The Surgeon General's
   Report on
  NUTRITION
  AND HEALTH

1988

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
           Public Health Service

DHHS (PHS) Publication No. 8840210

For sale by the Superintendent of Documents, U.S. Government Printing Of&e
            Washington. DC 20402
         GPO Stock Nuniber 017M)14O465-1


DEPARTMENT OF HEALTH & HUMAN SERVICES

The Surgeon General of the
Public Health Service
Waehington DC 20201

MESSAGE FROM THE SURGEON GENERAL

I am pleased to transmit to the Secretary of the Department of Health and
Human Services this first Surgeon General's Report on Nutrition and Health.
It was prepared under the auspices of the Department's Nutrition Policy
Board, and its main conclusion is that overconsumption of certain dietary
components is now a major concern for Americans. While many food
factors are involved, chief among them is the disproportionate consumption
of foods high in fats, often at the expense of foods high in complex
carbohydrates and fiber--such as vegetables, fruits, and whole grain
products--that may be more conducive to health.

I offer this Report in the context of the obligation of the Surgeon General to
inform the American public of developments in the science base that have
widespread implications for human health. Perhaps the classic example of
such reports is the one issued in 1964 during the tenure of one of my
predecessors, Dr. Luther Terry, which summarized the epidemiologic
evidence available at the time on the relationship of tobacco to health.  This
report called attention to the inescapable conclusion that cigarettes were a
major source of illness and death for those who smoked--at that time a
majority of adult men.

This Surgeon General's Report on Nutrition and Health follows the tradition
of the original report on smoking and health. It addresses an area of some
controversy and substantial misunderstanding. And the relative magnitude
of the associated health concerns is comparable, with dietary factors playing
a prominent role in five of the ten leading causes of death for Americans. In
addition, the depth of the science base underlying its findings is even more
impressive than that for tobacco and health in 1964, with animal and clinical
evidence adding to the epidemiologic studies.

On the other hand there are some fundamental differences. Most obvious is
the fact that food is necessary for good health. Foods contain nutrients
essential for normal metabolic function, and when problems arise, they
result from imbalance in nutrient intake or from harmful interaction with
other factors.  Moreover, we know today much more about individual
variation in response to nutrients than we know about possible variations in


response to tobacco. Some people are clearly more susceptible than others
to problems from diets that are, for example, higher in fat or salt.

Also, unlike the experience for tobacco in 1964, people are already making
dietary changes, as witnessed by the shift to products lower in saturated fats.
Nonetheless, the important effects of the dietary factors underlying
problems like coronary heart disease, high blood pressure, stroke, some
types of cancer, diabetes, obesity--problems that represent the leading health
threats for Americans--indicate the potential for substantial gains to be
accrued by the recommendations contained in this Report

It is important to emphasize that the focus of this Report is primarily on the
relationship of diet to the occurrence of chronic diseases. The Report is not
intended to address the problems of hunger or undernutrition that may
occur in the United States among certain subgroups uf the population. All
Americans should have access to an appropriate diet, but they do not. And
even though the size and numbers of problems related to inadequate access to
food are proportionately much smaller than those related to dietary excesses
and imbalances, the problems of access to food are of considerable concern
to me, personally, wherever they may occur.

The apparently sizable numbers of people resorting to the use of soup
kitchens and related food facilities, as well as the possible role of poor diet as
a contributor to the higher infant mortality rates associated with inadequate
income, suggest the need for better monitoring of the nature and extent of
the problem and for sustained efforts to correct the underlying causes of
diminished health due to inadequate or inappropriate diets.

This report was prepared primarily for nutritional policy makers, although
the eventual beneficiaries of better nutritional policy will be the American
people. I am convinced that with a concerted effort on the part of policy
makers throughout the Nation, and eventually by the public, our daily diets
can bring a substantial measure of better health to all Americans. I
commend to them the recommendations of this Report.

C. Everett Koop, M.D., Sc.D.
Surgeon General
U.S. Public Health Service


This first Surgeon General's Report on Nutrition and Health marks a key
event in the history of public health in the United States. While the Report
has been developed for use by policymakers, it offers lessons that can be
directly applied to the public. It responds to the increasing interest of
scientists, health professionals, and the American people in the role of diet
in health promotion. Within recent years, concerns about nutrition and
health have expanded beyond the need to prevent deficiencies to encom-
pass the effects of typical American dietary patterns on the incidence of
chronic diseases that are leading causes of death and disability in this
country. Although scientific research has provided substantial insight into
the ways specific dietary factors influence specific diseases, there are still
many uncertainties about diet-disease relationships. The Department of
Health and Human Services, through the Public Health Service and the
Surgeon General, welcomes the responsibility to evaluate the current state
of knowledge and to advise the public accordingly.

This Report reviews the scientific evidence that relates dietary excesses
and imbalances to chronic diseases. On the basis of the evidence, it
recommends dietary changes that can improve the health prospects of
many Americans. Of highest priority among these changes is to reduce
intake of foods high in fats and to increase intake of foods high in complex
carbohydrates and fiber.

The evidence presented here indicates the convergence of similar dietary
recommendations that apply to prevention of multiple chronic diseases.
The recommendation to reduce dietary fat, for example, aims to reduce the
risk for coronary heart disease, diabetes, obesity, and some types of
cancer. This advice is not new, But it is now substantiated by a large body of
evidence derived from many different kinds of research-a research base
that is now even more comprehensive than was the case for the pioneering
1964 Surgeon General's Report on Smoking and Health.

The weight of this evidence and the magnitude of the problems at hand
indicate that it is now time to take action. In the cause of good health for all
our citizens, I urge support for this Report's recommendations by every
sector of American society.

Otis R. Bowen, M.D.
Secretary

V


Preface

The Public Health Service of the Department of Health and Human Ser-
vices has long maintained an interest in the relationship between food and
health. In the 1970's, this interest began to focus on the ways in which
dietary excesses and imbalances increase the risk for chronic diseases.
With the publication in 1979 of Healthy People: The Surgeon General's
Report on Health Promotion and Disease Prevention, attention turned
toward environmental and behavioral changes that Americans might make
to reduce their risks for morbidity and mortality. Nutrition was one such
priority area. The 1980 report Promoting HealthlPreventing Disease: Ob-
jectives for the Nation included 17 specific, quantifiable objectives in
nutrition designed to reduce risks and to prevent illness and death. Also in
1980, the Department published, jointly with the U.S. Department of
Agriculture, the first edition of Dietary Guidelines for Americans. This
report, revised in 1985, includes seven recommendations that, taken to-
gether, address the relationship between diet and chronic diseases.

Diseases such as coronary heart disease, stroke, cancer, and diabetes
remain leading causes of death and disability in the United States. Substan-
tial scientific research over the past few decades indicates that diet can play
an important role in prevention of such conditions. The Public Health
Service has now reviewed this research and has produced a comprehensive
analysis of the relationship between dietary factors and chronic disease
risk. This Surgeon GeneralS Report on Nutrition and Health summarizes
research on the role of diet in health promotion and disease prevention. Its
findings indicate the great importance of diet to health. They demonstrate
that changes in present dietary practices of Americans could produce
substantial gains in the health of the population. The Public Health Service
is committed to improving the health of Americans through its programs in
education, services, and research.

One mechanism for improving the health of Americans is through the 1990
Health Objectives for the Nation. The role of nutrition in health will
continue to be a focus of national health priorities as we develop new
objectives for the year 2000. Federal, State, and local governments, the
American public, the food industry, and scientists and health professionals
can work together to encourage Americans to make healthy food choices
and to achieve national health goals.

vii


1 am pleased to commend to the American people this review of the
scientific evidence that links diet to chronic disease, and I urge that the
findings of this important Report be given your careful consideration.

Robert E. Windom, M.D.
Assistant Secretary for Health

. . .
vu1


Contents

  Foreword  ....................................................  v


  Preface  .....................................................  vii

  Nutrition Policy Board   ....................................... xiv

  Acknowledgments  ............................................ xv

  Summary and Recommendations  ................................  1

  Chapter 1: Introduction and Background  ........................ 2 1

  Chapter 2: Coronary Heart Disease  ............................. 83

  Chapter 3: High Blood Pressure  ............................... 139

  Chapter4:Cancer  ........................................... 177

  Chapter 5: Diabetes  .......................................... 249

  Chapter6:Obesity.. ......................................... 275

  Chapter 7: Skeletal Diseases  .................................. 3 11

  Chapter 8: Dental Diseases  ................................... 345

  Chapter9:KidneyDiseases  ................................... 381

  Chapter 10: Gastrointestinal Diseases  .......................... 403

  Chapter 11: Infections and Immunity  .......................... 427

  Chapter 12: Anemia .......................................... 465

  Chapter 13: Neurologic Disorders  ............................. 491

  Chapter 14: Behavior  ........................................ 509
,
  Chapter 15: Maternal and Child Nutrition  ...................... 539

  Chapter16:Aging  ........................................... 595

  Chapter 17: Alcohol .......................................... 629

  Chapter 18: Drug-Nutrient Interactions ......................... 67 1

  Chapter 19: Dietary Fads and Frauds  .......................... 695


   Index  ...................................................... 713


                           ix


Tables

1.

2.



l-l.

l-2.



l-3.

l-4.

l-5.

l-6.

l-7.

1-8.

l-9.

2-l.



2-2.

2-3.

2-4.

Recommendations..................................... 3

Estimated Total Deaths and Percent of Total Deaths for the 10
Leading Causes of Death: United States, 1987 . . . . . . . . . . . . .   4

Estimated Total Deaths and Percent of Total Deaths for the 10       +
Leading Causes of Death: United States, 1987 . . . . . . . . . . . . .  22

Selected Events in the History of Nutritional Science
to1950............................................... 25
Selected Federal Domestic Nutrition Policy Initiatives,
1862-1988 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  29

National Nutrition Surveillance Activities . . . . . . . . . . . . . . . .  38
Federal Dietary Recommendations for the General Public,
1917-1988 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  43

Food and Nutrition Board, National Academy of Sciences-
National Research Council Recommended Daily Dietary
Allowances, Revised 1980 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  49

Estimated Safe and Adequate Daily Intakes of Selected
VitaminsandMinerals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  52

Annual Per Capita Availability of Selected Commodities in
the U.S. Food Supply, 1%5-1985 . . . . . . . . . . . . . . . . . . . . . . . .  65

Mean Daily Intake of Food Energy, Nutrients, and Food
Components for Men, Women, and Young Children From the
Continuing Survey of Food Intakes by Individuals (CSFII),
1985 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  69

Death Rate for Coronary Heart Disease by Age, Race, and
Sex, United States, 1985  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  85

Prevalence of Coronary Heart Disease by Age, Race, and
Sex, United States, 1985  . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . .  86

National Cholesterol Education Program Adult Treatment
Panel Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  94

Estimates of Serum Cholesterol Change From Given Changes
in Dietary Lipids Based on Isocaloric Controlled
Experiments in Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  97

X


3-1.

3-2.

3-3.

3-4.

3-5.

3-6.

3-7.

4-l.

4-2.

4-3.

4-4.

4-5.

4-6.

4-7.

   4-8.
,

   4-9.

4-10.

Classification of Blood Pressure in Adults 18 Years or
Older ................................................  143
Estimated Prevalence of Cardiovascular Disease in the United
States ................................................  143

Control Mechanisms for Arterial Pressure  ................  145
Major Nutrients and Possible Mechanisms for Influencing
BloodPressure.. ......................................  147
Changes in Weight and Blood Pressure (Baseline to Followup)
in Treatment (Rx) and Control Groups of Five Randomized
ControlledTrials  ......................................  149

Studies of Cross-Sectional Association of Blood Pressure
With Alcohol Consumption  .............................  154
Prospective Observational Studies of the Association of Blood
Pressure With Alcohol Consumption  .....................  155
Proportions of Cancer Deaths Attributed to Various
Factors ...............................................  180
International Changes Since 1950 in Death Certification
Rates for Cancers of Stomach and Lung  ..................  181

Cancer Incidence Rates in the Philippines and Among
Filipinos and Caucasians in Hawaii  ......................  182
Reported Relationship Between Selected Dietary
ComponentsandCancer  ...............................  191

National Cancer Institute Dietary Guidelines ..............  192
Comparison of Dietary Guidelines for the
American Public  ......................................  193
Summary of Epidemiologic Studies Examining Dietary Fat
andBreastCancer .....................................  196
Retrospective Human Studies Relating Body Weight and
Cancer ...............................................  200
Summary of Epidemiologic Studies Examining Dietary Fiber
and Colon Cancer  .....................................  205
Dietary Vitamin A and Lung Cancer Risk: A Summary of
PreviousStudies  ......................................  211

xi


4-l 1. NCI-Sponsored Prevention Clinical Trials Related to
   VitaminA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  215

4-12.

5-l.

5-2.

5-3.

6-l.

6-2.

6-3.

7-l.

8-l.

Summary of Epidemiologic Studies on Selenium and
CancerRisk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  221
History of Dietary Composition (Relative Proportion of
Carbohydrate and Fat Calories) Used in Management of          ,
Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  251
Clinical Complications of Diabetes . . . . . . . . . . . . . . . . . . . . . . .  255

American Diabetes Association Dietary Recommendations
for Persons With Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  263
Comparison of Metropolitan Desirable Weights With Average
Weights From U.S. Cohort Studies . . . . . . . . . . . . . . . . . . . . . .  282
Body Mass Index (kg/m*) Used to Define Desirable Weight
and Overweight According to Three Different "Ideal"
Reference Populations  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  285
Mortality Ratios for All Ages Combined in Relation to the
Death Rate of Those 90 to 109 Percent of Average Weight . . .  290

Scientific Validity of Risk Factors . . . . . . . . . . . . . . . . . . . . , . . .  314
Supplemental Fluoride Dosage Scheduled (in mg F/day)
According to Fluoride Concentrations of Drinking Water . . .  359

10-I. Summary of Digestive Processes  . . . . . . . . . . . . . . . . . . . . . . . .  407

10-2.  Gastrointestinal Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  410

1 l-l.  Causes of Food-Associated Illness . . . . . . . . . . . . . . . . . . . . . . .  448

12-I. Estimates for Percent Prevalence of Impaired Iron Status:
  Average of Estimates Using Three Methods: NHANES II,
   1976-80 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  468

12-2. Total Body Iron and Storage Iron . . . . . . . . . . . . . . . . . . . . . . . .  471

14-1.  Behavioral and Psychologic Hypotheses to Explain
   Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  515

14-2. Diagnostic Criteria for Anorexia Nervosa and Bulimia . . . . . .  520

15-1. Selected National Objectives to be Achieved by the Year 1990
   Related to Maternal and Child Nutrition . . . . . . . . . . . . . . . . . .  545

xii


15-2. Content of Selected Nutrients in Human Milk, Commercial
  Formulas, and Other Milks Used for Feeding Normal Full-
   TermInfants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  565

Figures

l-l.  Dependence of Biologic Function or Tissue Concentration on
   Intake of a Nutrient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  47

2-l.  Diagram of an Atherosclerotic Plaque . . . . . . , . . . . . . . . . . . . .  88

4-l.  Range of Incidence Rates (International Comparisons) . . . . .  180

4-2.  Carcinogenesis........................................ 183

4-3.  Dietary Fat Intake in Relation to Breast Cancer-Related Death
   Rate................................................. 187

6-l.  A Nomogram for Determining Body Mass Index (BMI)  . . . .  284

8-l.  The Distribution of Mean Decayed and Filled Coronal
   Surfaces (DFS) by Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  348

8-2.  The Distribution of Mean Decayed and Filled Root Surfaces
   (DFS) by Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  349

8-3.  Percent of Persons by Severe Loss of Periodontal
  Attachment (Pocket Depths Measuring 4 mm or More)
   andAgeGroups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  351

8-4.  Comparison of the Percent of Edentulous Persons in the
  1985-86 NIDR Survey to That Reported From the NCHS
   Surveyof1960-62 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  351

8-5.  Schematic Cross-Section of a Typical Mandibular Molar
   Tooth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  352

9-l.  The Comparative Structures of Amino Acids, Ketoacids, and
  Hydroxyacids......................................... 391

. . .
Xl11


    Nutrition Policy Board
U.S. Department of Health and Human Services

J. Michael McGinnis, M.D. (Chairman), Deputy Assistant Secretary for
Health (Disease Prevention and Health Promotion), Public Health Service   -

Faye G. Abdellah, R.N., Ed.D., Sc.D., Deputy Surgeon General, Public
Health Service

W. Douglas Badger, M.Div., Deputy Assistant Secretary, Office of Human
Development Services

Mary M. Ever& M.B.A., Director, Office of Community Services, Family
Support Administration

Manning Feinleib, M.D., M.P.H., Dr.P.H., Director, National Center for
Health Statistics, Centers for Disease Control, Public Health Service

Allan L. Forbes, M.D., Director, Office of Nutrition and Food Sciences,
Center for Food Safety and Applied Nutrition, Food and Drug Administra-
tion, Public Health Service

William T. Friedewald, M.D., Associate Director for Disease Prevention,
National Institutes of Health, Public Health Service

Bernard I. Grosser, M.D., Director, Office of Science, Alcohol, Drug
Abuse, and Mental Health Administration, Public Health Service

John Porvaznik, M.D., F.A.C.S., Associate Director, Office of Health
Programs, Indian Health Service, Public Health Service
William A. Robinson, M.D., M.P.H., Chief Medical OBicer, Health Re-
sources and Services Administration, Public Health Service

xiv


Acknowledgments

The Surgeon General's Report on Nutrition and Health was prepared
under the general editorship of the Department of Health and Human
Services' Nutrition Policy Board, whose members are listed on the pre-
vious page. Managing Editor was Marion Nestle, Ph.D., M.P.H., Office of
Disease Prevention and Health Promotion. Special editorial assistance was
contributed by John Bailar III, M.D., Ph.D., Science Advisor, Office of
Disease Prevention and Health Promotion, and by Darla E. Danford,
M.P.H., D.Sc., R.D., National Institutes of Health. Project Officer during
early stages of preparation of the Report was Ann Sorenson, Ph.D., now
with the National Institutes of Health.

In addition to the guidance of the Nutrition Policy Board's Senior Editorial
Advisors and Staff Working Group, important editorial contributions were
made by Karen Donato, M.S., R.D., Nancy D. Ernst, M.S., R.D., Marilyn
E. Farrand,M.S.,R.D.,andVanS. Hubbard,M.D.,Ph.D.,oftheNation-
al Institutes of Health's Nutrition Education Subcommittee; and by Walter
H. Glinsmann, M.D., Marilyn G. Stephenson, M.S., R.D., John E. Van-
derveen, Ph.D., and Elizabeth Yetley, Ph.D., R.D., of the Food and Drug
Administration's Center for Food Safety and Applied Nutrition.

Senior Editorial Advisors to the Nutrition Policy Board were:

C. Wayne Callaway, M.D., Director, Center for Clinical Nutrition, George
Washington University Medical Center, Washington, D.C.

`Johanna T. Dwyer, D.Sc., Director, Frances Stem Nutrition Center, New
England Medical Center Hospitals, and Professor of Medicine, Tufts Uni-
versity Medical School, Boston, Massachusetts

Samuel Fomon, M.D., Professor of Pediatrics, University of Iowa, Iowa
City, Iowa

Richard L. Hall, Ph.D., Vice President, Science and Technology, McCor-
mick & Co., Inc., Hunt Valley, Maryland

Robert I. Levy, M.D., President, Sandoz Research Institute, East Hano-
ver, New Jersey

Walter Mertz, M.D., Director, Beltsville Human Nutrition Research Cen-
ter, U.S. Department of Agriculture, Beltsville, Maryland

xv


Malden C. Nesheim, Ph.D., Vice President for Planning and Budget,
Cornell University, Ithaca, New York

Sushma Palmer, D.Sc., Executive Director, Food and Nutrition Board,
National Academy of Sciences, Washington, D.C.

Irwin H. Rosenberg, M.D., Director, USDA Human Nutrition Research
Center on Aging, Tufts University, Boston, Massachusetts

Theodore Van Itallie, M.D., Professor of Medicine, Columbia University
College of Physicians and Surgeons, New York, New York

Nutrition Policy Board Staff Working Group members were:

Elizabeth Brannon, M.S., R.D., Clinical Nutrition Specialist, Bureau of
Maternal and Child Health and Resources Development, Health Resourc-
es and Services Administration, Rockville, Maryland

Darla E. Danford, M.P.H., D.Sc., R.D., Nutritionist, Nutrition Coordinat-
ing Committee, National Institutes of Health, Bethesda, Maryland

Willie M. Etheridge, M.S., Policy Analyst, Policy Planning and Legislation
Division, Office of Human Development Services, Washington, D.C.

James J. Heam, L.L.B., Chief, Community Food and Nutrition Program,
Office of Community Services, Family Support Administration, Washing-
ton, D.C.

M. Yvonne Jackson, Ph.D., R.D., Chief, Nutrition and Dietetics Section,
Indian Health Service, Rockville, Maryland

Linda D. Meyers, Ph.D., Nutrition Advisor, Office of Disease Prevention
and Health Promotion, Washington, D.C.

Marion Nestle, Ph.D., M.P.H., Director, Nutrition Policy Staff, Office of
Disease Prevention and Health Promotion, Washington, D.C.

Lana Skirboll, Ph.D., Special Assistant to the Director, Offtce of Science,
Alcohol, Drug Abuse, and Mental Health Administration, Rockville,
Maryland

Frederick Trowbridge, M.D., M.S., Director, Nutrition Division, Center
for Health Promotion and Education, Centers for Disease Control, Atlan-
ta, Georgia

xvi


Catherine E. Woteki, Ph.D., R.D., Deputy Director, Division of Health
Examination Statistics, National Center for Health Statistics, Centers for
Disease Control, Hyattsville, Maryland

Individuals who contributed to the writing of draft chapters or
portions of the Report were:

Margaret J. Albrink, M.D., M.P.H., Professor of Medicine, West Virginia
University Medical Center, Morgantown, West Virginia (Obesity)

William R. Beisel, M.D., Adjunct Professor, Department of Immunology
and Infectious Diseases, School of Hygiene and Public Health, The Johns
Hopkins University, Baltimore, Maryland (Infections and Immunity)

C. Wayne Callaway, M.D., Director, Center for Clinical Nutrition, George
Washington University Medical Center, Washington, D.C. (Alcohol)

Joseph E. Ciardi, Ph.D., Research Biochemist, Caries and Restoration
Materials Research Branch, Extramural Program, National Institute of
Dental Research, National Institutes of Health, Bethesda, Maryland (Den-
tal Diseases)

Phyllis A. Crapo, R.D., Department of Medicine, University of California
at San Diego, LaJolla, California (Diabetes)

Jeffrey A. Cutler, M.D., Chief, Prevention and Demonstration Research
Branch, National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland (High Blood Pressure)

Peter R. Dallman, M.D., Professor, Department of Pediatrics, University
of California, San Francisco, California (Anemia)

Barbara H. Dennis, R.D., Ph.D., Division of Heart and Vascular Diseases,
National Heart, Lung, and Blood Institute, National Institutes of Health,
Bethesda, Maryland (Coronary Heart Disease)

John Duguid, M.D., Ph.D., Neurologist, Massachusetts Institute of Tech-
nology, Cambridge, Massachusetts (Neurologic Disorders)

Robert Edelman, M.D., Chief, Clinical and Epidemiological Studies
Branch, Deputy Director, Microbiology and Infectious Diseases Program,
National Institute of Allergy and Infectious Diseases, National Institutes
of Health, Bethesda, Maryland (Infections and Immunity)

xvii


Nancy D. Ernst, MS., R.D., Nutrition Coordinator, National Heart,
Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary-
land (High Blood Pressure)

Lloyd J. Filer, Jr., M.D., Ph.D., Department of Pediatrics, University of
Iowa School of Medicine, Iowa City, Iowa (Maternal and Child Nutrition)

Mattie R.S. Fox, Ph.D., Chief, Nutrient Interaction Section, Experimental
Nutrition Branch, Division of Nutrition, Food and Drug Administration,
Washington, D.C. (Introduction and Background)
Philip J. Garry, Ph.D., Professor, Department of Pathology, University of
New Mexico School of Medicine, Albuquerque, New Mexico (Aging)

James Goodwin, M.D., Professor and Vice Chairman, Department of
Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin (Aging)

Sheila Gottschalk, M.D., Associate Professor of Pediatrics, Louisiana
State University School of Medicine, New Orleans, Louisiana (Maternal
and Child Nutrition)

,

Gregory E. Gray, M.D., Ph.D., Assistant Professor, Department of Psy-
chiatry and the Behavioral Sciences, Los Angeles County-University of
Southern California Medical Center, Los Angeles, California (Behavior)

Peter Greenwald, M.D., lX.P.H., Director, Division of Cancer Prevention
and Control, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland (Cancer)

John H. Growdon, M.D., Massachusetts Institute of Technology, Massa-
chusetts General Hospital, and Harvard Medical School, Cambridge, Mas-
sachusetts (Neurologic Disorders)

Margaret A. Hamburg, M.D., Special Assisiant to the Director, National
Institute of Allergy and Infectious Diseases-, National Institutes of Health,
Bethesda, Maryland (Infections and Immunity)

James P. Hat-wood, Ph.D., Executive Secretary, Scientific Review Office,
National Institute on Aging,-National Institutes of Health, Bethesda,
Maryland (Introduction and Background)

Michael Horan, M.D., Chief, Hypertension and Kidney Diseases Branch,
National Heart, Lung, and Blood Institute, National Institutes of Health,
Bethesda, Maryland (High Blood Pressure)

Richard D. Hurt, M.D., Mayo Clinic, Rochester, Minnesota (Alcohol)

. .
XVlll


Howard Jacobson, M.D., Institute of Nutrition, University of North Car-
olina, Chapel Hill, North Carolina (Maternal and Child Nutrition)

Mamie Y. Jenkins, Ph.D., Research Chemist, Bioavailability Section,
Experimental Nutrition Branch, Division of Nutrition, Food and Drug
Administration, Washington, D.C. (Introduction and Background)

Alexander Jordan, Ph.D., Supervisory Pharmacologist, Food and Drug
Administration, Rockville, Maryland (Drug-Nutrient Interactions)

George M. Kazzi, M.D., Chief, Department of Obstetrics and Gynecolo-
gy, Harper-Grace Hospitals, and Assistant Professor, Maternal-Fetal
Medicine, Wayne State University School of Medicine, Detroit, Michigan
(Maternal and Child Nutrition)

Joel D. Kopple, M.D., Professor of Medicine and Public Health, Univer-
sity of California at Los Angeles, Chief, Division of Nephrology and
Hypertension, Harbor-UCLA Medical Center, Torrance, California (Kid-
ney Diseases)

Markus J.P. Kruesi, M.D., Staff Psychiatrist, National Institute of Mental
Health, Alcohol, Drug Abuse, and Mental Health Administration, Rock-
ville, Maryland (Behavior)

Elaine Lanza, Ph.D., Diet and Cancer Branch, Division of Cancer Preven-
tion and Control, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland (Cancer)

Harris R. Lieberman, Ph.D., Department of Brain and Cognitive Sciences,
Massachusetts Institute of Technology, Cambridge, Massachusetts (Neu-

,  rologic Disorders; Behavior)

  Gardner C. McMillan, M.D., Division of Heart and Vascular Diseases,
  National Heart, Lung, and Blood Institute, National Institutes of Health,
  Bethesda, Maryland (Coronary Heart Disease)

Albert I. Mendeloff, M.D., M.P.H., Department of Medicine, The Johns
Hopkins University School of Medicine, Baltimore, Maryland (Gastroin-
testinal Diseases)

Linda D. Meyers, Ph.D., Nutrition Advisor, Office of Disease Prevention
and Health Promotion, Washington, D.C. (Introduction and Background)

Sanford A. Miller, Ph.D., Director, Center for Food Safety and Applied
Nutrition, Food and Drug Administration, Washington, D.C. (Introduction
and Background)

xix


Geraldine V. Mitchell, Ph.D., Chief, Bioavailability Section. Experimental
Nutrition Branch, Division of Nutrition. Food and Drug Administration,
Washington, D.C. (Introduction and Background)

Eliot N. Mostow, M.D., M.P.H., Medical Staff Fellow, Division of Cancer
Prevention and Control, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland (Cancer)

Jerrold M. Olefsky, M.D., Department of Medicine, University of Califor-
nia at San Diego, and San Diego Veterans Administration Medical Center,
San Diego, California (Diabetes)

Youngmee K. Park, Ph.D., Nutritionist, Clinical Nutrition Branch, Divi-
sion of Nutrition, Food and Drug Administration, Washington, D.C. (Intro-
duction and Background)

Jean A.T. Pennington, Ph.D., Assistant to the Director, Division of Nutri-
tion, Food and Drug Administration, Washington, D.C. (Introduction and
Background)

L. Ross Pierce, M.D., Group Leader, Food and Drug Administration,
Rockville, Maryland (Drug-Nutrient Interactions)

Peggy L. Pipes, M.P.N., R.D., Child Development Mental Retardation
Center, University of Washington, Seattle, Washington (Maternal and
Child Nutrition)

Ernest0 Pollitt, Ph.D., Department of Applied Behavioral Sciences, Uni-
versity of California, Davis, California (Maternal and Child Nutrition)

Leon Prosky, Ph.D., Deputy Chief, Experimental Nutrition Branch, Divi-
sion of Nutrition, Food and Drug Administration, Washington, D.C. (Intro-
duction and Background)

Jeanne I. Rader, Ph.D., Chief, Nutrient Toxicity Section, Experimental
Nutrition Branch, Division of Nutrition, Food and Drug Administration,
Washington, D.C. (Introduction and Background)

Lawrence G. Raisz, M.D., Professor of Medicine and Chief, Division of
Endocrinology and Metabolism, University of Connecticut School of Med-
icine, Farmington, Connecticut (Skeletal Diseases)

Judith L. Rapoport, M.D., Chief, Child Psychiatry Branch, National Insti-
tute of Mental Health, Alcohol, Drug Abuse, and Mental Health Adminis-
tration, Rockville, Maryland (Behavior)

xx


Merrill S. Read, Ph.D., Professor and Chairman, Human Nutrition and
Food Systems, College of Human Ecology, University of Maryland, Col-
lege Park, Maryland (Maternal and Child Nutrition)

Basil M. Rifkind, M.D., F.R.C.P., Division of Heart and Vascular Dis-
eases, National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland (Coronary Heart Disease)

Norman E. Rosenthal, M.D., Chief, Unit on Outpatient Studies, Clinical
Psychology Branch, National Institute of Mental Health, Alcohol, Drug
Abuse, and Mental Health Administration, Rockville, Maryland (Behav-
ior)

Neil L. Sass, Ph.D., Senior Scientist, ORice of Management, Center for
Food Safety and Applied Nutrition, Food and Drug Administration, Wash-
ington, D.C. (Introduction and Background)

Claudia Schuth, M.D., Associate Professor of Pediatrics, Louisiana State
University School of Medicine, New Orleans, Louisiana (Maternal and
Child Nutrition)

James H. Shaw, Ph.D., Professor of Nutrition Emeritus, Harvard School of
Dental Medicine, Boston, Massachusetts (Dental Diseases)

Alan J. Sheppard, Ph.D., Chief, Experimental Methods Research Section,
Nutrient Surveillance Branch, Division of Nutrition, Food and Drug Ad-
ministration, Washington, D.C. (Introduction and Background)

Solomon Sobel, M.D., Food and Drug Administration, Rockville, Mary-
land (Drug-Nutrient Interactions)

Robert J. Sokol, M.D., Professor and Chairman and Chief, Department of
Obstetrics and Gynecology, Wayne State University, Hutzel Hospital,
Detroit, Michigan (Maternal and Child Nutrition)

Marilyn G. Stephenson, M.S., R.D., Assistant to the Director, OfIice of
Nutrition and Food Sciences, Center for Food Safety and Applied Nutri-
tion, Food and Drug Administration, Washington, DC. (Dietary Fads and
Frauds)

Albert Stunkard, M.D., Professor of Psychiatry, University of Pennsylva-
nia School of Medicine, Philadelphia, Pennsylvania (Behavior)

Robert M. Suskind, M.D., Department of Pediatrics, Louisiana State
University School of Medicine, New Orleans, Louisiana (Maternal and
Child Nutrition)

xxi


Shyy Hwa Tao, Ph.D., Research Chemist, Nutrient Interaction Section,
Experimental Nutrition Branch, Division of Nutrition, Food and Drug
Administration, Washington, D.C. (Imroduction and Background)

Thomas Thorn, Statistician, Epidemiology and Biometry Research Pro-
gram, Division of Epidemiology and Clinical Applications, National Heart,
Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary-
land (Coronary Heart Disease)

Gloria Troendle, M.D., Deputy Director, Food and Drug Administration,
Rockville, Maryland (Drug-Nutrient Interactions)

Momtaz Wassef, Ph.D., Division of Heart and Vascular Diseases, National
Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda,
Maryland (Coronary Heart Disease)

Cora E. Weeks, J.D., Ph.D., Consumer Safety Officer, Division of Reg-
ulatory Guidance, Center for Food Safety and Applied Nutrition, Food and
Drug Administration, Washington, D.C. (Introduction and Background)

Robert W. Wissler, M.D., Ph.D., Donald N. Pritzker Distinguished Service
Professor of Pathology Emeritus, University of Chicago, Chicago, Illinois
(Coronary Heart Disease)

Philip A. Wolf, M.D., Professor of Neurology and Associate Research
Professor of Medicine, Preventive Medicine and Epidemiology, Boston
University School of Medicine, Boston, Massachusetts (Neurologic Disor-
ders)

Bonnie S. Worthington-Roberts, Ph.D., Professor, Nutritional Sciences,
University of Washington, Child Development Center, Seattle, Washington
(Maternal and Child Nutrition)

Catherine E. Woteki, Ph.D., R.D., Deputy Director, Division of Health
Examination Statistics, National Center for Health Statistics, Centers for
Disease Control, Hyattsville, Maryland (Introduction and Background)

Richard J. Wurtman. M.D., Professor, Department of Brain and Cognitive
Sciences, Director, Clinical Research Center, Massachusetts Institute of
Technology, Cambridge, Massachusetts (Neurologic Disorders; Behavior)

Elizabeth Yetley, Ph.D., R.D., Chief, Clinical Nutrition, Division of Nutri-
tion, Office of Nutrition and Food Sciences, Center for Food Safety and
Applied Nutrition, Food and Drug Administration, Washington, D.C. (In-
troduction and Background)

xxii


During preparation of the Report, chapters were subjected to six stages of
critical review, three by experts within the Public Health Service (internal
reviews) and three by scientists and professionals recommended as experts
by national scientific and nutrition professional organizations in the private
sector (external reviews). In addition, the senior editorial advisors and staff
to the Nutrition Policy Board listed above provided expert technical eval-
uation throughout the review process.

Individuals who reviewed chapters or potions of the Report were:

Phyllis B. Acosta, Dr.P.H., R.D., Director of Metabolic Diseases, Ross
Laboratories, Columbus, Ohio

Lawrence Agodoa, M.D., Coordinator, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, Bethesda,
Maryland

Duane F. Alexander, M.D., Director, National Institute of Child Health
and Human Development, National Institutes of Health, Bethesda, Mary-
land

Aaron M. Altschul, Ph.D., Diet Management and Eating Disorders Pro-
gram, Georgetown University, Washington, D.C.

Ronald A. Arky, M.D., Professor, Department of Medicine, Harvard
Medical School at Mt. Auburn Hospital, Cambridge, Massachusetts

Louis Avioli, M.D., Professor of Medicine and Oral Biology, Washington
University School of Medicine and Dental School, St. Louis, Missouri

David Badman, Ph.D., Hematology Program Director, National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, Bethesda, Maryland

John Bailar III, M.D., Ph.D., Science Advisor, Office of Disease Preven-
tion and Health Promotion, Washington, D.C.

David H. Baker, Ph.D., Professor of Nutrition and Metabolism, Univer-
sity of Illinois, Urbana, Illinois

Susan Blumenthal, M.D., Medical Oflicer and Chief, Behavioral Medicine
Program, National Institute of Mental Health, Alcohol, Drug Abuse, and
Mental Health Administration, RockvilIe, Maryland

Ronette Briefel, Dr.P.H., R.D., Nutritional Epidemiologist, Survey Plan-
ning and Development Branch, National Center for Health Statistics,
Centers for Disease Control, Hyattsville, Maryland

. . .
xx111


Benjamin Burton, Ph.D., Associate Director for Disease Prevention and
Technology Transfer, National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Ritva Butrum, Ph.D., Diet and Cancer Branch, Division of Cancer Preven-
tion and Control, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland

Charles E. Butterworth, Jr., M.D., Director, Clinical Nutrition Research
Unit, University of Alabama, Birmingham, Alabama

George F. Cahill, Jr., M.D., Howard Hughes Medical Institute, Boston,
Massachusetts

Doris H. Calloway, Ph.D., Provost Professor Schools and College, Uni-
versity of California, Berkeley, California

Richard Calve& M.D., Medical Research Nutritionist, Experimental Nu-
trition Branch, O&e of Nutrition and Food Sciences, Center for Food
Safety and Applied Nutrition, Food and Drug Administration, Washing-
ton, D.C.

Mona Calvo, Ph.D., R.D., Nutritionist, Clinical Nutrition, Division of
Nutrition, Office of Nutrition and Food Sciences, Center for Food Safety
and Applied Nutrition, Food and Drug Administration, Washington, D.C.
James P. Carlos, D.D.S., Chief, Epidemiology Branch, Epidemiology and
Oral Disease Prevention Program, National Institute of Dental Research,
National Institutes of Health, Bethesda, Maryland
Kenneth K. Carroll, Ph.D., Professor, Department of Biochemistry, Uni-
versity of Western Ontario, London, Ontario, Canada

Ranjit K. Chandra, M.D., F.R.C.P., Janeway Child Health Center, Immu-
nology Department, St. John's, Newfoundland, Canada

Lois Chatham, Ph.D., Director, Division of Basic Research, National
Institute on Alcohol Abuse and Alcoholism, Alcohol, Drug Abuse, and
Mental Health Administration, Rockville; Maryland

Aram V. Chobanian, M.D., Director and Professor, Cardiovascular Insti-
tute, Boston University School of Medicine, Boston, Massachusetts

Joginder G. Chopra, M.D., Special Assistant, Medical Affairs, Office of
Nutrition and Food Sciences, Center.for Food Safety and Applied Nutri-
tion, Food and Drug Administration, Washington, D.C.


Gregory Christenson, Ph.D., Special Population Studies Branch, Division
of Cancer Prevention and Control, National Cancer Institute, National
Institutes of Health, Bethesda, Maryland

Carolyn Clifford, Ph.D., Diet and Cancer Branch, Division of Cancer
Prevention and Control, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland

James D. Cook, M.D., Division of Hematology, University of Kansas
Medical Center, Kansas City, Kansas

Stephen B. Corbin, D.D.S., M.P.H., Senior Prevention Policy Advisor,
Prevention Policy Staff, OfIice of Disease Prevention and Health Promo-
tion, Washington, D.C.

Ann Coulston, M.S., R.D., Clinical Research Center, Stanford University
Hospital, Stanford, California

Frances Cronin, Ph.D., R.D., Chief, Diet Appraisal Research Branch,
Nutrition Education Division, Human Nutrition Information Service, U.S.
Department of Agriculture, Hyattsville, Maryland

Cheryl L. Damberg, M.P.H., Director of Marketing, General Health Inc.,
Washington, D.C.

Michele DeBartolo, M.P.H., R.D., Senior Clinical Research Associate,
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park,
Illinois

Hector F. DeLuca, Ph.D., Department of Biochemistry, College of Agri-
culture and Life Sciences, University of Wisconsin, Madison, Wisconsin

Dominick P. DePaola, D.D.S., Ph.D., Dean, University of Medicine and
Dentistry of New Jersey, New Jersey Dental School, Newark, New Jersey

Vincent T. DeVita, Jr., M.D., Director, National Cancer Institute, Nation-
al Institutes of Health, Bethesda, Maryland

Karen Donato, M.S., R.D., Nutritionist, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland

Allan L. Drash, M.D., Professor of Pediatrics, University of Pittsburgh
School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, Penn-
sylvania

XXV


Mary Dufour, M.D., Chief, Epidemiology Branch, Division of Biometry
and Epidemiology, National Institute on Alcohol Abuse and Alcoholism,
Alcohol, Drug Abuse, and Mental Health Administration, Rockville,
Maryland

Harriet P. Dustan, M.D., Veterans Administration Distinguished Physi-
cian and University Distinguished Professor Emeritus, Veterans Adminis-
tration Medical Center, University of Alabama at Birmingham, Bir-
mingham, Alabama

Mary Egan, R.D., M.S., M.P.H., National Center for Education in Mater-
nal and Child Health, Georgetown University, Washington, D.C.

Shirley Ekvall, Ph.D., R.D., Professor and Chief of Nutrition Services,
University of Cincinnati and University Affiliated Cincinnati Center for
Developmental Disorders, Children's Hospital Medical Center, Cincin-
nati, Ohio

Lillian Emmons, Ph.D., R.D., Comprehensive Psychiatric Services, Inc.,
Cleveland, Ohio

Arnold Engel, M.D., Commission Officer, Medical Statistics Branch,
National Center for Health Statistics, Centers for Disease Control, Hyatts-
ville , Maryland

Frank Falkner, M.D., F.R.C.P., School of Public Health, University of
California, Berkeley, California

Marilyn E. Farrand, M.S., R.D., Public Health Nutrition, Prevention and
Demonstration Research Branch, Division of Epidemiology and Clinical
Application, National Heart, Lung, and Blood Institute, National Insti-
tutes of Health, Bethesda, Maryland

Owen Fennema, Ph.D., Department of Food Science, University of Wis-
consin at Madison, Madison, Wisconsin

John D. Femstrom, Ph.D., Professor of Psychiatry and Behavioral Neuro-
science, University of Pittsburgh School of Medicine, Pittsburgh, Pennsyl-
vania

Willis R. Foster, M.D., Senior Staff Physician, Office of Disease Preven-
tion and Technology Transfer, National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Judith Fradkin, M.D., Chief, Endocrine and Metabolic Diseases Programs
Branch, National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, Maryland

xxvi


Victor Frattali, Ph.D., Deputy Director, Division of Nutrition, Offtce of
Nutrition and Food Sciences, Center for Food Safety and Applied Nutri-
tion, Food and Drug Administration, Washington, D.C.

Robert A. Fried, M.D., Associate Professor and Director of Clinical Af-
fairs, Department of Family Medicine, University of Colorado School of
Medicine, Denver, Colorado

Edward D. Frohlich, M.D., Alton Ochsner Distinguished Scientist and
Vice President for Academic Affairs, Alton Ochsner Medical Foundation,
Staff Member, Section on Hypertensive Diseases, Ochsner Clinic, New
Orleans, Louisiana

Peter Frommer, M.D., Deputy Director, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland

Margie Gallagher, Ph.D., R.D., School of Home Economics, Institute for
Coastal and Marine Resources, East Carolina University, Greenville,
North Carolina

Dian Gans, M.S., Research Assistant, Department of Nutritional Sci-
ences, University of Wisconsin at Madison, Madison, Wisconsin

Stanley M. Gam, Ph.D., Center for Human Growth and Development,
University of Michigan, Ann Arbor, Michigan

Peter Gergen, M.D., Commission Officer, Medical Statistics Branch, Na-
tional Center for Health Statistics, Centers for Disease Control, Hyatts-
ville , Maryland

Dorothy W. Gietzen, Ph.D., Assistant Research Neurophysiologist, De-
partment of Physiologic Sciences, School of Veterinary Medicine, Depart-
ment of Psychiatry, School of Medicine, University of California at Davis,
Davis, California

Susan Gilbert, M.P.A., Associate, Prospect Associates, Rockville, Mary-
land

Walter H. Glinsmann, M.D., Associate Director, Clinical Nutrition, Divi-
sion of Nutrition, Food and Drug Administration, Washington, D.C.

Vay Liang W. Go, M.D., Chairman, Nutrition Coordinating Committee,
National Institutes of Health, Bethesda, Maryland

Murray Goldstein, D.O., M.P.H., Director, National Institute of Neu-
rological and Communicative Disorders and Stroke, National Institutes of
Health, Bethesda, Maryland

xxvii


Dewitt S. Goodman, M.D., Professor of Medicine, Department of Medi-
cine, College of Physicians and Surgeons of Columbia University, New
York, New York

PhiUip Gorden, M.D., Director, National Institute of Diabetes and Di-
gestive and Kidney Diseases, National Institutes of Health, Bethesda,
Maryland

Enoch Gordis, M.D., Director, National Institute on Alcohol Abuse and
Alcoholism, Alcohol, Drug Abuse and Mental Health Administration,
Rockville , Maryland

Stephen L. Gordon, Ph.D., Director, Musculoskeletal Diseases Program,
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health, Bethesda, Maryland

Gilman D. Grave, M.D., Chief, Endocrinology, Nutrition, and Growth
Branch, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland

Jesse F. Gregory III, Ph.D., University of Florida, Food Science and
Nutrition Department, Gainesville, Florida

Joan Gussow, Ed.D., Mary Swartz Rose Professor of Nutrition and Edu-
cation, Department of Nutrition and Education, Teachers College, Colum-
bia University, New York

Wilbur Hadden, M.A., Chief, Programming Staff, National Center for
Health Statistics, Centers for Disease Control, Hyattsville, Maryland

Evan Hadley, M.D., Chief, Geriatrics Branch, National Institute on
Aging, National Institutes of Health, Bethesda, Maryland

Carole Haines, M.P.H., Data Analysis Coordinator, National Heart,
Lung, and Blood Institute, National Institutes of Health, Bethesda, Mary-
land

Judith G. Hallfrisch, Ph.D., Senior Staff Fellow, Metabolism Section of
the Gerontology Research Center, National Institute on Aging, National
Institutes of Health, Bethesda, Maryland

Charles H. Halsted, M.D., Ph.D., Chief, Division of Clinical Nutrition,
and Professor of Internal Medicine, School of Medicine, University of
California at Davis, Davis, California

Linda Harris, Ph.D., Special Assistant, Gflice of Disease Prevention and
Health Promotion, Washington, D.C.

  . . .
XXVlll


Tamara Harris, M.D., Service Fellow, Office of Analysis and Epidemiolo-
gy Program, National Center for Health Statistics, Centers for Disease
Control, HyattsviUe, Maryland

John N. Hathcock, Ph.D., Chief, Experimental Nutrition Branch, Division
of Nutrition, Food and Drug Administration, Washington, D.C.

Maureen Henderson, M.D., Cancer Prevention Research Program, Fred
Hutchinson Cancer Research Center, Seattle, Washington

Stephen P. Heyse, M.D., Director, Disease Prevention, Epidemiology and
Clinical Applications, National Institute of Arthritis and Musculoskeletal
and Skin Diseases, National Institutes of Health, Bethesda, Maryland

Jules Hirsch, M.D., Professor and Senior Physician, Rockefeller Univer-
sity, New York, New York

Gladys Hirshman, M.D., Director, Chronic Renal Disease Program, Na-
tional Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, Maryland

Peter R. Holt, M.D., Chief, Division of Gastroenterology, Professor of
Medicine, College of Physicians and Surgeons, St. Luke's Hospital, New
York, New York

Steven S. Hotta, M.D., Ph.D., Medical Gflicer, Clinical Nutrition Branch,
Division of Nutrition, Food and Drug Administration, Washington, D.C.

Anastacio M. Hoyumpa, M.D., Professor of Medicine, Division of Gas-
troenterology and Nutrition, University of Texas Health Science Center,
San Antonio, Texas

Van S. Hubbard, M.D., Ph.D., Director, Nutritional Sciences Branch,
National Institute of Diabetes and Digestive and Kidney Diseases, Nation-
al Institutes of Health, Bethesda, Maryland

Sandra Huckaby, R.N., M.S.N., Special Assistant, Maternal and Infant
Health Branch, Bureau of Maternal and Child Health and Resources
Development, Health Resources and Services Administration, RockviUe,
Maryland

James C. Hunt, M.D., Chancellor, University of Tennessee, Memphis,
Tennessee

Vince L. Hutchins, M.D., M.P.H., Deputy Director, Bureau of Maternal
and Child Health and Resources Development, Health Resources and
Services Administration, Rockville, Maryland

xxix


William T. Jan+, Ph.D., Professor of Health Education, Department of
Preventive Medicine, School of Medicine, Loma Linda University, Loma
Linda, California

Clifford Johnson, M.S.P.H., Chief, Nutrition Statistics Branch, National
Center for Health Statistics, Centers for Disease Control, Hyattsville,
Maryland

Norman Kaplan, M.D., Professor of Internal Medicine, University of
Texas Health Science Center, Dallas, Texas

Gerald T. Keusch, M.D., Professor of Medicine, Department of Medicine,
New England Medical Center, Boston, Massachusetts

Matthew Kinnard, Ph.D., Health Scientist Administrator, National Insti-
tute of Dental Research, National Institutes of Health, Bethesda, Mary-
land

Samuel Korper, Ph.D., Associate Director, Offtce of Planning, Analysis,
and Communications, National Institute on Aging, National Institutes of
Health, Bethesda, Maryland

David Kritchevsky, Ph.D., Associate Director of Anatomy and Biology,
Wistar Institute, Philadelphia, Pennsylvania

Robert Kuczmarksi, M.S.P.H., M.P.H., Dr.P.H., R.D., Health Statisti-
cian, Nutrition Statistics Branch, National Center for Health Statistics,
Centers for Disease Control, Hyattsville, Maryland

William Lands, Ph.D., Department of Biochemistry, University of Illinois
at Chicago, Chicago, Illinois

Lynn A. Larsen, Ph.D., Associate Director, Program Development, Divi-
sion of Nutrition, Office of Nutrition and Food Sciences, Center for Food
Safety and Applied Nutrition, Food and Drug Administration, Washington,
D.C.

Reva C. Lawrence, M.P.H., Epidemiologist, Data Systems, Program Of-
ficer, National Institute of Arthritis and Musculoskeletal and Skin Dis-
eases, National Institutes of Health, Bethesda, Maryland

Claude Lenfant, M.D., Director, National Heart, Lung, and Blood Insti-
tute, National Institutes of Health, Bethesda, Maryland

Gilbert A. Leveille, Ph.D., Staff Vice President, NABISCO Brands, Inc.,
East Hanover, New Jersey

xxx


Ephraim Y. Levin, M.D., Medical Officer, National Institute of Child
Health and Human Development, National Institutes of Health, Bethesda,
Maryland

Christine J. Lewis, Ph.D., R.D., Chief, Experimental Clinical Research
Section, Division of Nutrition, Oflice of Nutrition and Food Sciences,
Center for Food Safety and Applied Nutrition, Food and Drug Administra-
tion, Washington, D.C.

Charles S. Lieber, M.D., Director, Alcohol Research and Treatment Cen-
ter, Chief, Section of Liver Disease and Nutrition, Bronx Veterans Admin-
istration Medical Center, Professor of Medicine and Pathology, Mount
Sinai School of Medicine, New York, New York

Jane Lin Fu, M.D., Acting Chief, Genetic Services Branch, Bureau of
Maternal and Child Health and Resources Development, Health Resources
and Services Administration, Rockville, Maryland

Harald Lee, D.D.S., Director, National Institute of Dental Research,
National Institutes of Health, Bethesda, Maryland

Anne Looker, Ph.D., R.D., Health Statistician, Nutrition Statistics
Branch, National Center for Health Statistics, Centers for Disease Con-
trol, Hyattsville, Maryland

Susan K. Maloney, M.H .S., Director, Health Communication Staff, Office
of Disease Prevention and Health Promotion, Washington, D.C.

Alvin Mauer, M.D., University of Tennessee, Division of Hematology/
Oncology, Memphis, Tennessee

Donald B. McCormick, Ph.D., Chairman, Department of Biochemistry,
Emory University School of Medicine, Atlanta, Georgia

Gardner C. McMillan, M.D., Division of Heart and Vascular Diseases,
National Heart, Lung, and Blood Institute, National Institutes of Health,
Bethesda, Maryland

Marilyn McMillen, Ph.D., Statistician, Surveillance and Operations Re-
search Section, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland

Laura McNally, R.D., M.P.H., Nutrition Specialist, Child and Adolescent
Primary Care Services Branch, Bureau of Maternal and Child Health and
Resources Development, Health Resources and Services Administration,
Rockville, Maryland

xxxi


Marsel Mesulam, M.D., Professor of Neurology, Harvard Medical School,
Director, Division of Neuroscience and Behavioral Neurology, Beth Israel
Hospital, Boston, Massachusetts

Esteban Mezey, M.D., Professor of Medicine, Johns Hopkins Hospital,
Baltimore, Maryland

Angela D. Mickalide, Ph.D., Staff Coordinator, U.S. Preventive Services
Task Force, Office of Disease Prevention and Health Promotion, Washing-
ton, D.C.

William E. Mitch, M.D., Renal Division, Emory University School of
Medicine, Atlanta, Georgia

Elaine R. Monsen, Ph.D., R.D., University of Washington, Seattle, Wash-
ington

Steven R. Moore, M.P.H., Associate Chief of Staff, Office of the Surgeon
General, Rockville, Maryland

Hamish N. Munro, M.D., D.Sc., Senior Scientist, USDA Human Nutri-
tion Research Center on Aging, Tufts University, Boston, Massachusetts

Juan M. Navia, Ph.D., Professor and Chairman, Department of Public
Health Sciences, Schools of Public Health and Dentistry, University of
Alabama at Birmingham, Birmingham, Alabama

Buford L. Nichols, Jr., M.D., Children's Nutrition Research Laboratory,
Baylor School of Medicine, Houston, Texas

Phillip Nieburg, M.D., M.P.H., Medical Epidemiologist, Division of Nutri-
tion, Centers for Disease Control, Atlanta, Georgia

Daniel W. Nixon, M.D., Associate Director, Cancer Prevention Research
Program, National Cancer Institute, National Institutes of Health, Bethes-
da, Maryland

Marie U. Nylen, D.D.S., Dr. Odont. h.c., Director, Extramural Program,
National Institute of Dental Research, National Institutes of Health, Be-
thesda, Maryland

Carole A. Palmer, M.Ed., R.D., Associate Professor and Division Co-
Chairman, Division of Nutrition and Prevention Dentistry, Tufts Univer-
sity School of Medicine, Boston, Massachusetts

xxxii


Eugene Passamani, M.D., Director, Division of Heart and Vascular Dis-
eases, National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland

Penelope Pollard, M.S., M.B.A., Senior Research Associate, National
Health Policy Forum, Washington, D.C.

Donna V. Porter, Ph.D., R.D., Specialist in Life Sciences, Science Policy
Research Division, Congressional Research QIXce, Washington, D.C.

Roger J. Porter, M.D., Deputy Director, National institute of Neurological
and Communicative Disorders and Stroke, National Institutes of Health,
Bethesda, Maryland

Barbara Posner, D.P.H., R-D., Associate Professor and Director, Graduate
Nutrition Division, Boston University, Boston, Massachusetts

Ann Prendergast, R.D., M.P.H., Chief Nutritionist, Habilitative Services
Branch, Bureau of Maternal and Child Health and Resources Develop-
ment, Health Resources and Services Administration, Rockville, Mary-
land

Jeanne I. Rader, Ph.D., Chief, Nutrient Toxicity Section, Experimental
Nutrition Branch, Division of Nutrition, Food and Drug Administration,
Washington, D.C.

Edward Roccella, Ph.D., M.P.H., Program Coordinator, National High
Blood Pressure Education Program, National Heart, Lung, and Blood
Institute, National Institutes of Health, Bethesda, Maryland

Daphne A. Roe, M.D., Professor, Division of Nutritional Sciences, Cornell
University, Ithaca, New York

Quinton Rogers, Ph.D., Department of Physiological Sciences, School of
Veterinary Medicine, University of California at Davis, Davis, California

Daniel Rudman, M.D., Associate Chief of Staff, Geriatric Medicine, North
Chicago Veterans Administration Medical Center, North Chicago, Illinois

Robert Russell, M.D., USDA Human Nutrition Research Center on Aging
at Tufts University, Boston, Massachusetts

Anna A. Sandberg, Dr.P.H., Coordinator, Clinical Trial, Kidney-Urology
Branch, National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, Maryland

  . . .
xxx111


Harold H. Sandstead, M.D., Department of Preventive Medicine and
Community Health, University of Texas Medical Branch, Galveston,
Texas

Howerde Sauberlich, Ph.D., Department of Nutrition Science, University
of Alabama, University Station, Alabama

Christopher Sempos, Ph.D., Health Statistician, Nutrition Statistics
Branch, National Center for Health Statistics, Centers for Disease Con-
trol, Hyattsville, Maryland

Zekin Shakhashiri, M.S., M.D., M.P.H., Senior Medical Advisor, National
Institute of Neurological and Communicative Disorders and Stroke, Na-
tional Institutes of Health, Bethesda, Maryland

Lawrence E. Shulman, M.D., Ph.D., Director, National Institute of Arthri-
tis and Musculoskeletal and Skin Diseases, National Institutes of Health,
Bethesda, Maryland

Robert Silverman, M.D., Ph.D., Chief, Diabetes Programs Branch, Na-
tional Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, Maryland

Christine Hamilton Smith, Ph.D., R.D., Home Economics Department,
Food Science and Nutrition, California State University at Northridge,
Northridge, California

Dorothy D. Sogn, M.D., Chief, Asthma and Allergy Branch, Immunology,
Allergic and Immunologic Diseases Program, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Bethesda, Mary-
land

David A.T. Southgate, Ph.D., AFRC Institute of Food Research, Norwich
Laboratory, Norfolk, United Kingdom

Reynold Spector, M.D., Executive Director, Merck Sharp & Dohme Re-
search Laboratories, Rahway, New Jersey

Judith S. Stem, Sc.D., University of California at Davis, Davis, California

Eugene Streicher, Ph.D., Director, Division of Fundamental Neurosci-
ences, National Institute of Neurological and Communicative Disorders
and Stroke, National Institutes of Health, Bethesda, Maryland

Helene Swenerton, Ph.D., Nutritionist, Cooperative Extension, Depart-
ment of Nutrition, University of California at Davis, Davis, California

xxxiv


Jean K. Tews, Ph.D., Department of Biochemistry, University of Wiscon-
sin at Madison, Madison, Wisconsin

Jeanne L. Tillotson, R.D., M.A., Crofton, Maryland

Phillip P. Toskes, M.D., Professor of Medicine and Director, Division of
Gastroenterology, Hepatology and Nutrition, University of Florida Col-
lege of Medicine and Gainesville Veterans Administration Medical Center,
Gainesville, Florida

Pelagia Turyn-Einhom, M.D., Medical OfIicer, Clinical Nutrition Branch,
Division of Nutrition, Office of Nutrition and Food Sciences, Center for
Food Safety and Applied Nutrition, Food and Drug Administration, Wash-
ington, D.C.

Emestine Vanderveen, Ph.D., Associate Director for AIDS, Division of
Clinical Research, National Institute on Drug Abuse, Alcohol, Drug
Abuse, and Mental Health Administration, Rockville, Maryland

John E. Vanderveen, Ph.D., Director, Division of Nutrition, Food and
Drug Administration, Washington, D.C.

John Wallingford, Ph.D., Nutritionist, Clinical Nutrition Branch, Division
of Nutrition, Office of Nutrition and Food Sciences, Center for Food Safety
and Applied Nutrition, Food and Drug Administration, Washington, D.C.

Donald M. Watkin, A.B., M.D., M.P.H., Manager, Occupational Health
Division, Office of Aviation Medicine, Federal Aviation Administration,
U.S. Department of Transportation, and Research Professor, Department
of Medicine, School of Medicine and Health Sciences, The George Wash-
ington University, Washington, D.C.

Richard Weindruch, Ph.D., Health Scientist Administrator, National Insti-
tute on Aging, National Institutes of Health, Bethesda, Maryland

Gerald Wheeler, Commission Officer, Division of Health Examination
Statistics, National Center for Health Statistics, Centers for Disease Con-
trol, Hyattsville, Maryland

Philip L. White, Sc.D., Wilmette, Illinois, Director, Division of Applied
Medical Sciences, American Medical Association, Chicago, Illinois (Re-
tired)

T. Franklin Williams, M.D., Director, National Institute on Aging, Nation-
al Institutes of Health, Bethesda, Maryland

XXXV


David E Williamson, M.S., Ph.D., Analytic Epidemiologist, Centers for
Disease Control, Atlanta, Georgia

Myron Winick, M.D., R.R. Williams Professor of Nutrition and Pediatrics,
Columbia University College of Physicians and Surgeons, New York, New
York

Deborah Winn, Ph.D., Epidemiologist, Survey Planning and Development
Branch, National Center for Health Statistics, Centers for Disease Con-
trol, Hyattsville, Maryland

Maxwell M. Wintrobe, M.D., Ph.D., D.Sc., Distinguished Professor of
Medicine, University of Utah Medical School, Salt Lake City, Utah

Elisabeth I? Wirick, Food, Nutrition, and Dietetics, College of Health and
Human Services, University of Northern Colorado, Greeley, Colorado

Eleanor A. Young, Ph.D., R.D., L.D., Professor, Department of Medicine,
Division of Gastroenterology and Nutrition, University of Texas Health
Science Center at San Antonio, San Antonio, Texas

William J. Zukel, M.D., Deputy Director, Division of Heart and Vascular
Diseases, National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland

The editors gratefully acknowledge the contributions of the following
staff members and others who assisted in the preparation of this
Report:

o Office of Disease Prevention and Health Promotion

Nancy Chapman, R.D., M.P.H., President, N. Chapman Associates,
Washington, D.C.

Mary Jo Deering, Ph.D., Publications Manager

James A. Harrell, M.A., Deputy Director
Susan K. Maloney, M.H.S., Director, Health Communication Staff

David G. Schardt, M.S., Ph.D., Nutrition Consultant, Nutrition
Media Network, Washington, D.C.
Marilyn K. Schulenberg, Staff Assistant

Maureen Sullivan, M.P.H., M.I.A., Program Analyst, U.S. Food
and Drug Administration, New York, New York

xxxvi


Herbert Szeto, Intern, Nutrition Policy Staff
Sara L. White, M.S., Health Promotion Research Associate, Health
Communication Staff

o Technical Resources, Inc.

Joanna Fringer, M.A., Program Manager
Jeffrey Baughman, Graphic Artist
Colleen Bolton, Graphic Artist
Diane Cannon, Graphic Artist

James Dofflemyer, Graphic Artist

Dana Donofrio, Word Processor

Robin Fagan, Graphic Artist
Margaret Leahy, Editor

Cathy Merritt, Word Processor

Laura Pancoast, Word Processing Supervisor

Cherie Phillips, Graphic Artist

Theodora Radcliffe, Proofreader

William Rhodes, Graphic Artist

Joan Saunders, Writer/Editor
Channah Springer, M . F. A., Proofreader
David Tran, Information Specialist

o TRITON, Inc.

Clarence Johnson, Communications Manager

John Borstel, Senior Graphics Editor
Sharon Greenspan, Graphics Assistant

xxxvii


Summary and Recommendations

This Report addresses the substantial impact of daily dietary patterns on
the health of Americans. Good health does not always come easily. It is the
product of complex interactions among environmental. behavioral, social,
and genetic factors. Some of these are, for practical purposes, beyond
persona1 control. But there are many ways in which each of us can
influence our chances for good health through the daily choices we make.

In recent years, scientific investigations have produced abundant informa-
tion on the ways persona1 behavior affects health. This information can
help us decide whether to smoke, when and how much to drink, how far to
walk or climb stairs, whether to wear seat belts, and how or whether to
engage in any other activity that might alter the risk of incurring disease or
disability. For the two out of three adult Americans who do not smoke and
do not drink excessively, one personal choice seems to influence long-term
health prospects more than any other: what we eat.

Food sustains us, it can be a source of considerable pleasure, it is a
reflection of our rich social fabric and cultural heritage, it adds valued
dimensions to our lives. Yet what we eat may affect our risk for several of
the leading causes of death for Americans, notably, coronary heart dis-
ease, stroke, atherosclerosis, diabetes, and some types of cancer. These
disorders together now account for more than two-thirds of all deaths in the
United States.

Undernutrition remains a problem in several parts of the world, as well as
for certain Americans. But for most of us the more likely problem has
become one of overeating-too many calories for our activity levels and an
imbalance in the nutrients consumed along with them. Although much is
still uncertain about how dietary patterns protect or injure human health,
enough has been learned about the overall health impact of the dietary
patterns now prevalent in our society to recommend significant changes in
those patterns.

This first Surgeon General's Report on Nutrition and Health offers com-
prehensive documentation of the scientific basis for the recommended
dietary changes. Through the extensive review contained in its chapters,
the Report examines in detail current knowledge about the relationships
among specific dietary practices and specific disease conditions and sum-

1


O Nutrition and Health

marizes the implications of this information for individual food choices,
public health policy initiatives, and further research. The Report's main
conclusion is that overconsumption of certain dietary components is now a
major concern for Americans. While many food factors are involved, chief
among them is the disproportionate consumption of foods high in fats, often
at the expense of foods high in complex carbohydrates and fiber that may be
more conducive to health. A list of the key recommendations based on the
evidence presented in the Report is provided in Table 1.

Magnitude of the Problem

Diet has always had a vital influence on health. Until as recently as the
1940's, diseases such as rickets, pellagra, scurvy, beriberi, xerophthalmia,
andgoiter (caused by lack of adequate dietary vitamin D, niacin, vitamin C,
thiamin, vitamin A, and iodine, respectively).were prevalent in this coun-
try and throughout the world. Today, thanks to an abundant food supply,
fortification of some foods with critical trace nutrients, and better methods
for determining and improving.the nutrient content of foods, such "deti-
ciency" diseases have been virtually eliminated in developed countries.
For example, the introduction of iodized salt in the 1920's contributed
greatly to eliminating iodine-deficiency goiter as a public health problem in
the United States. Similarly, pellagra disappeared subsequent to the dis-
covery of the dietary causes of this disease. Nutrient deficiencies are
reported rarely in the United States, and the few cases of protein-energy
malnutrition that are listed annually as causes of death generally occur as a
secondary result of severe illness or injury, child neglect, the problems of
the house-bound aged, premature birth, alcoholism, or some combination
of these factors.

As the diseases of nutritional deficiency have diminished; they have been
replaced by diseases'of dietary excess and imbalance-problems that now
rank among the leading causes of illness and death in the United States,
touch the lives of most Americans, and generate substantial health care
costs. Table 2, for example, lists the 10 leading causes of death in the
United States in 1987.

In addition to the five of these causes that scientific studies have associated
with diet (coronary heart disease, some-types of cancer, stroke, diabetes
mellitus, and atherosclerosis), another three-cirrhosis of the liver, acci-
dents, and suicides-have been associated With excessive alcohol intake.

2


Summary and Recommendations O

   Table 1
Recommendations

Issues for Most People:

o Furs and cholesterol: Reduce consumption of fat (especially saturated fat) and
cholesterol. Choose foods relatively low in these substances, such as vegeta-
bles, fruits, whole gram foods, fish, poultry, lean meats. and low-fat dairy
products. Use food preparation methods that add little or no fat.

o Energy and weight control: Achieve and maintain a desirable body weight. To
do so, choose a dietary pattern in which energy (caloric) intake is consistent
with energy expenditure. To reduce energy intake, limit consumption of foods
relatively high in calories, fats, and sugars, and minimize alcohol consump-
tion. Increase energy expenditure through regular and sustained physical ac-
tivity.

o Complex carbohydrates andfiber: Increase consumption of whole grain foods
and cereal products, vegetables (including dried beans and peas), and fruits.

o Sodium: Reduce intake of sodium by choosing foods relatively low in sodium
and limiting the amount of salt added in food preparation and at the table.

o Alcohol: To reduce the risk for chronic disease, take alcohol only in modera-
tion (no more than two drinks a day), if at all. Avoid drinking any alcohol be-
fore or while driving, operating machinery, taking medications, or engaging in
any other activity requiring judgment. Avoid drinking alcohol while pregnant.

Other Issues for Some People:

o Fluoride: Community water systems should contain fluoride at optimal levels
for prevention of tooth decay. If such water is not available, use other appro-
priate sources of fluoride.

o Sugars: Those who are particularly vulnerable to dental caries (cavities). espe-
cially children, should limit their consumption and frequency of use of foods
high in sugars.

o Calcium: Adolescent girls and adult women should increase consumption of
foods high in calcium, including low-fat dairy products.

o Iron: Children, adolescents, and women of childbearing age should be sure to
consume foods that are good sources of iron, such as lean meats, fish, certain
beans, and iron-enriched cereals and whole grain products. This issue is of
special concern for low-income families.


0 Nutrition and Health

               Table 2
Estimated Total Deaths and Percent of Total Deaths for the
  10 Leading Causes of Death: United States, 1987

                                           Percent
                                        of Total
Rank  Cause of Death                      Number   Deaths

la   Heart diseases                     759,400    35.7
    (Coronary heart disease)              (511,700)  (24.1)
    (Other heart disease)                (247,700) (11.6)
2a   Cancers                        476,700    22.4
3a   Strokes                        148,700 7.0
4b   Unintentional injuries                 92,500
    (Motor vehicle)                   W8O'J  (E,
     (All others)                     (45,700)
5   Chronic obstructive lung diseases            78,000  %'
6    Pneumonia and influenza          68,600 3:2
78   Diabetes mellitus                   37,800 1.8
8b   Suicide                         29,600 1.4
9b   Chronic liver disease and cirrhosis           26,000 1.2
10s   Atherosclerosis                    23,100 1.1

. . .   AU causes                     2,125,100
causes of death in which diet plays a part.
Wauses of death in which excessive alcohol consumption plays a part.

100.0

Source: National Center for Health Statistics, Monthly Vital Statistics Report, vol. 37, no.
   1 ,April25,sticsReport,vol.37, no.
   1, April 25,1989.

Although the precise proportion attributable to diet is uncertain, these
eight conditions accounted for nearly 1.5 million of the 2.1 million total
deaths in 1987. Dietary excesses or imbalances also contribute to other
problems such as high blood pressure, obesity, dental diseases, os-
teoporosis, and gastrointestinal diseases. Together, these diet-related con-
ditions inflict a substantial burden of illness on Americans. For example:
o Coronary Heart Disease. Despite the recent sharp decline in the death
  rate from this condition, coronary heart disease still accounts for the
largest number of deaths in the United States. More than 1.25 million
  heart attacks occur each year (two-thirds of them in men), and more
than 500,000 people die as a result. In 1985, illness and deaths from
coronary heart disease cost Americans an estimated $49 billion in
direct health care expenditures and lost productivity.
o Stroke. Strokes occur in about 500,000 persons per year in the United
  States, resulting in nearly 150,000 deaths in 1987 and long-term dis-
ability for many individuals. Approximately 2 million living Americans
  suffer from stroke-related disabilities, at an estimated annual cost of
  more than $11 billion.
                        4


Summary and Recommendations 0

o High Blood Pressure. High blood pressure (hypertension) is a major
risk factor for both heart disease and stroke. Almost 58 million people
in the United States have hypertension, including 39 million who are
under age 65. The occurrence of hypertension increases with age and is
higher for black Americans (of which 38 percent are hypertensive)
than for white Americans (29 percent).

o Cancer. More than 475,000 persons died of cancer in the United States
in 1987, making it the second leading cause of death in this country.
During the same period, more than 900,000 new cases of cancer
occurred. The costs of cancer for 1985 have been estimated to be $22
billion for direct health care, $9 billion in lost productivity due to
treatment or disability, and $41 billion in lost productivity due to
premature mortality, for a total cost of $72 billion.

o Diabetes Meflitus. Approximately 11 million Americans have diabe-
tes, but almost half of them have not been diagnosed. In addition to the
nearly 38,000 deaths in 1987 attributed directly to this condition,
diabetes also contributes to an estimated 95,000 deaths per year from
associated cardiovascular and kidney complications. In 1985, diabetes
was estimated to cost $13.8 billion per year, or about 3.6 percent of
total health care expenses.

o Obesity. Obesity affects approximately 34 million adults ages 20 to 74
years in the United States, with the highest rates observed among the
poor and minority groups. Obesity is a risk factor for coronary heart
disease, high blood pressure, diabetes, and possibly some types of
cancer as well as other chronic diseases.

o Osteoporosis. Approximately 15 to 20 million Americans are affected
by osteoporosis, which contributes to some 1.3 million bone fractures
per year in persons 45 years and older. One-third of women 65 years
and older have vertebral fractures. On the basis of x-ray evidence, by
age 90 one-third of women and one-sixth of men will have suffered hip
fractures, leading to death in 12 to 20 percent of those cases and to
long-term nursing care for many who survive. The total costs of
osteoporosis to the U.S. economy were estimated to be $7 to $10
billion in 1983.

o Dental Diseases. Dental caries and periodontal disease continue to
affect a large proportion of Americans and cause substantial pain,
restriction of activity, and work loss. Although dental caries among
children, as well as some forms of adult periodontal disease, appear to
be declining, the overall prevalence of these conditions imposes a
substantial burden on Americans. The costs of dental care were esti-
mated at $21.3 billion in 1985.

5


O Nutrition and Health

o Diverticular Disease. Because most persons with diverticular disease
do not have symptoms, the true prevalence of this condition is un-
known. Frequency increases with age, and up to 70 percent of people
between the ages of 40 and 70 may be affected. In 1980, diverticulosis
was accountable for some 200,000 hospitalizations.
In assessing the role that diet might play in prevention of these conditions,
it must be understood that they are caused by a combination (and interac-
tion) of multiple environmental, behavioral, social, and genetic factors.
The exact proportion that can be attributed directly to diet is uncertain.
Although some experts have suggested that dietary factors overall are
responsible for perhaps a third or more of all cases of cancer, and similar
estimates have been made for coronary heart disease, such suggestions are
based on interpretations of research studies that cannot completely dis-
tinguish dietary from genetic, behavioral, or environmental causes.

We know, for example, that cigarette smoking exerts a powerful influence
on the occurrence of both coronary heart disease and some types of cancer.
We also know that some people are genetically predisposed to coronary
heart disease, stroke, and diabetes and that the interaction of genetic
predisposition with dietary patterns is an important determinant of individ-
ual risk. For these reasons, it is not yet possible to determine the propor-
tion of chronic diseases that could be reduced by dietary changes. None-
theless, it is now clear that diet contributes in substantial ways to the
development of these diseases and that modification of diet can contribute
to their prevention. The magnitude of the health and economic cost of diet-
related disease suggests the importance of the dietary changes suggested.
This Report reviews these issues in detail.

Nature of the Evidence

Whereas centuries of clinical observations and decades of basic and
clinical research prove that dietary deficiencies of single, identifiable nu-
trients can cause disease, research on the relationship of dietary excesses
and imbalances to chronic disease yields results that rarely provide such
direct proof of causality. Instead, investigators must piece together various
kinds of information from several kinds of sources. Nevertheless, the
quantity of current animal, laboratory, clinical, and epidemiologic evi-
dence that associates dietary excesses and imbalances with chronic dis-
ease is substantial and, when evaluated according to established princi-
ples, compelling.

Scientists must often draw inferences about the relationships between
dietary factors and disease from laboratory animal studies or human meta-

6


Summary and Recommendations O

bolic and population studies that approach the issues indirectly. Data
sources for such human studies include clinical and laboratory measure-
ments of physiologic indicators of nutritional status or risk factors, as well
as dietary intake data estimated for populations or individuals. Epi-
demiologic studies using these data compare dietary intake and disease
rates in different countries or in defined groups within the same country.

Interpretations of animal studies are limited by uncertainties about their
applicability to people. Clinical, laboratory, and dietary intake studies can
provide useful information, but each has limitations. Currently available
clinical and laboratory measurements reveal only a small part of the
complex physiological responses to diet, and they may reflect past rather
than current nutritional status. Dietary surveys depend on accurate recall
of the types and portion sizes of consumed foods as well as on the assump-
tion that the food intake during any one period represents typical intake.
Reported intake, however, is not always accurate, and intake reported for
a given period may differ significantly from that typical of longer time
periods. Dietary intake data provide useful indicators for populations, but
even when an association or correlation between a dietary factor and a
disease is observed, it is often ditllcult to prove that the dietary factor is an
actual or sole cause of that disease.

This difference between association and causation is basic to understand-
ing the scientific evidence that links diet to chronic disease. Uncertainties
in the ability to determine causation have sometimes made it difficult to
achieve consensus on appropriate public health nutrition policies. Estab-
lished principles require evaluation of the supporting evidence for a given
association between a dietary factor and a disease on the basis of its
consistency, strength, specificity, and biological plausibility. The evidence
showing that dietary intake of saturated fat raises blood cholesterol, which
in turn increases the chance of coronary heart disease, illustrates this
point. The similarity in results from laboratory, clinical, and epidemiologic
research, the apparent relationship between dose and effect in these stud-
ies, the observations that the increase in blood cholesterol level is ~p~ifk
to saturated fatty acids but not to other types, and the biological plausibility
of explanations for the observations, when taken together, provide consid-
erable support for concluding that the association is causal, at least for
some individuals.

For some of the other diseases reviewed in this Report, the available
evidence is less complete and less consistent. Nevertheless, much evi-
dence supports credible associations between a dietary pattern of excesses


u Nutrition and Health

and imbalances and several important chronic diseases. These associa-
tions, in turn, suggest that the overall health of Americans could be
improved by a few specific but fundamental dietary changes.

Key Findings and Recommendations

Even though the results of various individual studies may be inconclusive,
the preponderance of the evidence presented in the Report's comprehen-
sive scientific review substantiates an association between dietary factors
and rates of chronic diseases. In particular, the evidence suggests strongly
that a dietary pattern that contains excessive intake of foods high in
calories, fat (especially saturated fat), cholesterol, and sodium, but that is
low in complex carbohydrates and fiber, is one that contributes signifi-
cantly to the high rates of major chronic diseases among Americans. It also
suggests that reversing such dietary patterns should lead to a reduced
incidence of these chronic diseases.

This Surgeon General's Report on Nutrition and Health provides a com-
prehensive review of the most important scientific evidence in support of
current Federal nutrition policy as stated in the Dietary Guidelines for
Americans. These Guidelines, issued jointly by the Department of Agri-
culture and the Department of Health and Human Services, recommend:
o Eat a variety of foods.
o Maintain desirable weight.

o Avoid too much fat, saturated fat, and cholesterol.
o Eat foods with adequate starch and fiber.
o Avoid too much sugar.
o Avoid too much sodium.

o If you drink alcoholic beverages, do so in moderation.

Evidence presented in this Report expands the focus of these seven guide-
lines and provides considerable insight into priorities. Clearly emerging as
the primary priority for dietary change is the recommendation to reduce
intake of total fats, especially saturated fat, because of their relationship to
development of several important chronic disease conditions. Because
excess body weight is a risk factor for several chronic diseases, mainte-
nance of desirable weight is also an important public health priority.
Evidence further supports the recommendation to consume a dietary
pattern that contains a variety of foods, provided that these foods are
generally low in calories, fat, saturated fat, cholesterol, and sodium.

8


Summary and Recommendations O

Taken together, the recommendations in this Report promote a dietary
pattern that emphasizes consumption of vegetables, fruits, and whole grain
products-foods that are rich in complex carbohydrates and fiber and
relatively low in calories-and of fish, poultry prepared without skin, lean
meats, and low-fat dairy products selected to minimize consumption of
total fat, saturated fat, and cholesterol.

The evidence presented in this Report suggests that such overall dietary
changes will lead to substantial improvements in the nutritional quality of
the American diet. Consuming a higher proportion of calories from fruits,
vegetables, and grains may lead to a modest reduction in protein intake for
some people, but this reduction is unlikely to impair nutritional status.
Average levels of protein consumption in the United States, 60 grams per
day for women and 90 grams per day for men, are well above the National
Research Council's recommendations of 44 and 56 grams per day, respec-
tively .

The evidence also suggests that most Americans generally need not con-
sume nutrient supplements. An estimated 40 percent of Americans con-
sume supplemental vitamins, minerals, or other dietary components at an
annual cost of more than $2.7 billion. Although nutrient supplements are
usually safe in amounts corresponding to the Recommended Dietary Al-
lowances (and such Allowances are set to ensure that the nutrient needs of
practically all the population are met), there are no known advantages to
healthy people consuming excess amounts of any nutrient, and amounts
greatly exceeding recommended levels can be harmful. For example, some
nutrients such as selenium have a narrow range of safe level of intake.
Toxicity has been reported for most minerals and trace elements, as well as
some vitamins, indicating that excessive supplementation with these sub-
stances can be hazardous.

Finally, some recommendations for dietary change apply broadly to the
general public whereas others apply only to specific population groups.
These major findings and recommendations of The Surgeon General's
Report on Nutrition and Health are noted below.

Issues for Most People

0 Fats andcholesterol: Reduce consumption of fat (especially saturated fat)
and cholesterol. Choose foods relatively low in these substances, such as
vegetables, fruits, whole grain foods, bh, poultry, lean meats, and low-
fat dairy products. Use food preparation methods that add little or no
fat.

9


0 Nutrition and Health

High intake of total dietary fat is associated with increased risk for obesity,
some types of cancer, and possibly gallbladder disease. Epidemiologic,
clinical, and animal studies provide strong and consistent evidence for the
relationship between saturated fat intake, high blood cholesterol, and
increased risk for coronary heart disease. Conversely, reducing blood
cholesterol levels reduces the risk for death from coronary heart disease.
Excessive saturated fat consumption is the major dietary contributor to
total blood cholesterol levels. Dietary cholesterol raises blood cholesterol
levels, but the effect is less pronounced than that of saturated fat. While
polyunsaturated fatty acid consumption, and probably monounsaturated
fatty acid consumption, lowers total blood cholesterol, the precise effects
of specific fatty acids are not well defined.

Dietary fat contributes more than twice as many calories as equal quanti-
ties (by weight) of either protein or carbohydrate, and some studies indi-
cate that diets high in total fat are associated with higher obesity rates. In
addition, there is substantial, although not yet conclusive, epidemiologic
and animal evidence in support of an association between dietary fat intake
and increased risk for cancer, especially breast and colon cancer. Similar-
ly, epidemiologic studies suggest an association between gallbladder dis-
ease, excess caloric intake, high dietary fat, and obesity. More precise
conclusions about the role of dietary fat await the development of im-
proved methods to distinguish among the contributions of the high-calorie,
high-fat, and low-fiber components of current American dietary patterns.

At present, dietary fat accounts for about 37 percent of the total energy
intake of Americans-well above the upper limit of 30 percent recom-
mended by the American Heart Association and the American Cancer
Society, and above the percent consumed by many societies, such as
Mediterranean countries, Japan, and China, for example, where coronary
heart disease rates are much lower than those observed in the United
States. Consumption of saturated fat and cholesterol is also substantially
higher among many Americans than levels recommended by several expert
groups.

The major dietary sources of fat in the American diet are meat, poultry,
fish, dairy products, and fats and oils. Animal products tend to be higher in
both total and saturated fats than most plant sources. Although some plant
fats such as coconut and palm kernel oils also contain high proportions of
saturated fatty acids, these make minor contributions to total intake of
saturated fats in the United States. Dietary cholesterol is found only in
foods of animal origin, such as eggs, meat, poultry, fish, and dairy prod-

10


Summary and Recommendations tl

ucts. To help reduce consumption of total fat, especially saturated fat and
cholesterol, food choices should emphasize intake of fruits, vegetables,
and whole grain products and cereals. They should also emphasize con-
sumption of fish, poultry prepared without skin, lean meats, and low-fat
dairy products. Among vegetable fats, those that are more unsaturated are
better choices.

0 Energy and weight control: Achieve and maintain a desirable body
weight. To .do so, choose a dietary pattern in which energy (caloric)
intake is consistent with energy expenditure. To reduce energy intake,
limit consumption of foods relatively high in calories, fats, and sugars
and minimize alcohol consumption. Increase energy expenditure
through regular and sustained physical activity.
People are considered overweight if their body mass index, or BMI (a ratio
of weight to height described in the Report), exceeds the 85th percentile for
young American adults (approximately 120 percent of desirable body
weight); they are considered severely overweight if their BMI exceeds the
95th percentile (approximately 140 percent of desirable body weight).
Overweight individuals are at increased risk for diabetes mellitus, high
blood pressure and stroke, coronary heart disease, some types of cancer,
and gallbladder disease. Epidemiologic and animal studies have shown
consistently that overall risk for death is increased with excess weight,
with risk increasing as severity of obesity increases.

Type II (noninsulin-dependent) diabetes mellitus accounts for approxi-
mately 90 percent of all cases of diabetes and is strongly associated with
obesity. Clinical studies indicate that weight loss can improve control of
Type II diabetes.

Obesity increases the risk for high blood pressure, and consequently for
stroke; it also increases blood cholesterol levels associated with coronary
heart disease. In addition, it appears to be an independent risk factor for
coronary heart disease. Weight reduction has been shown to reduce high
blood pressure and high blood cholesterol. Most obese individuals who
achieve a more desirable body weight improve their cholesterol profile,
achieving a decrease in both total blood cholesterol and LDL (low density
lipoprotein) cholesterol.

Some studies have found an association between overweight and increased
risk for several cancers, especially cancer of the uterus and breast. In
addition, overweight increases the risk for gallbladder disease.

11


0 Nutrition and Health

More than a quarter of American adults are overweight. Black women age
45 and above have the highest prevalence, about 60 percent. Although
evidence suggests a genetic component to the tendency of many people to
become overweight, patterns of dietary caloric intake and energy expendi-
ture play a key role. Sustained and long- term efforts to reduce body weight
can best be achieved as a result of improving energy balance by reducing
energy consumption and raising energy expenditure through physical ac-
tivity and exercise.

Maintenance of desirable body weight throughout the lifespan requires a
balance between energy (calorie) intake and expenditure. Weight control
may be facilitated by decreasing energy intake, especially by choosing
foods relatively low in calories, fats, and sugars, and by minimizing alcohol
consumption. Energy expenditure can be enhanced through regular phys-
ical activities such as daily walks or by jogging, bicycling, or swimming at
least three times a week for at least 20 minutes.

0 Compk carbohydrates andfiber Increase consumption of whole grain
foods and cereal products, vegetables (includiug dried beaus and peas),
and fruits.

Dietary patterns emphasizing foods high in complex carbohydrates and
fiber are associated with lower rates of diverticulosis and some types of
cancer. The association shown in epidemiologic and animal studies be-
tween diets high in complex carbohydrates and reduced risk for coronary
heart disease and diabetes mellitus is, however, difficult to interpret. The
fact that such diets tend also to be lower in energy and fats, especially
saturated fat and cholesterol, clearly contributes to this difficulty. Some
evidence from clinical studies also suggests that water-soluble fibers from
foods such as oat bran, beans, or certain fruits are associated with lower
blood glucose and blood lipid levels. Consuming foods with dietary fiber is
usually beneficial in the management of constipation and diverticular
disease.

While inconclusive, some evidence also suggests that an overall increase in
intake of foods high in fiber might decrease the risk for colon cancer.
Among several unresolved issues is the role of the various types of fiber,
which differ in their effects on water-holding capacity, viscosity, bacterial
fermentation, and intestinal transit time.

Other food components associated with decreased cancer risk are com-
monly found in diets high in whole grain cereal products containing com-
plex carbohydrates and fiber. In addition, some epidemiologic evidence


Summary and Recommendations 0

suggests that frequent consumption of vegetables and fruits, particularly
dark green and deep yellow vegetables and cruciferous vegetables (such as
cabbage and broccoli), may lower risk for cancers of the lung and bladder
as well as some cancers of the alimentary tract. However, the specific
components in these foods that may have protective effects have not yet
been established. Current evidence suggests the prudence of increasing
consumption of whole grain foods and cereals, vegetables (including dried
beans and peas), and fruits.

o Sodium: Reduce intake of sodium by choosing foods relatively low in
sodium and limiting tbe amount of salt added in food preparation and at
the table.

Studies indicate a relationship between a high sodium intake and the
occurrence of high blood pressure and stroke. Salt contains about 40
percent sodium by weight and is used widely in the preservation, process-
ing, and preparation of foods. Although sodium is necessary for normal
metabolic function, it is consumed in the United States at levels far beyond
the 1.1 to 3.3 grams per day found to be as safe and adequate for adults by
the National Research Council. Average current sodium intake for adults
in the United States is in the range of 4 to 6 grams per day.

Blacks and persons with a family history of high blood pressure are at
greater risk for this condition. While some people maintain normal blood
pressure levels over a wide range of sodium intake, others appear to be
"salt sensitive" and display increased blood pressure in response to high
sodium intakes.

Although not all individuals are equally susceptible to the effects of so-
dium, several observations suggest that it would be prudent for most
Americans to reduce sodium intake. These include the lack of a practical
biological marker for individual sodium sensitivity, the benefit to persons
whose blood pressures do rise with sodium intake, and the lack of harm
from moderate sodium restriction.

Processed foods provide about a third or more of dietary sodium. Because
about another third of the sodium consumed by Americans is added by the
consumer, much can be done to reduce sodium consumption by using less
salt at the table and substituting alternative flavoring such as herbs, spices,
and lemon juice in the preparation of foods. In addition, choices can be
made of foods modiied to lower sodium content and less frequent choices
could be made of foods to which sodium is added in processing and
preservation.

13


O Nutrition and Health

o Alcohol: To reduce the risk for chronic disease, take alcohol only in
moderation (no more than two drinks a day), ifat all. Avoid drinking any
alcohol before or while driving, operating machinery, taking medica-
tions, or engaging in any other activity requiring judgment. Avoid
tkhking alcohol while pregnant.

Alcohol is a drug that can produce addiction in susceptible individuals,
birth defects in some children born to mothers who drink alcohol during
pregnancy, impaired judgment, impaired ability to drive automobiles or
operate machinery, and adverse reactions in people taking certain medica-
tions. In addition, alcohol abuse has been associated with disrupted family
functioning, suicides, and homicides.

Excessive use of alcohol is also associated with liver disease, some types of
cancer, high blood pressure, stroke, and disorders of the heart muscle.
Extensive epidemiologic and clinical evidence has identified alcohol con-
sumption as the principal cause of liver cirrhosis in the United States, at
least in part as a result of the direct toxic effects of alcohol on the liver.
Smoking and alcohol appear to act synergistically to increase the risk for
cancers of the mouth, larynx, and esophagus. Less conclusive and some-
what conflicting evidence suggests a role of alcohol in other types of
cancers such as those of the liver, rectum, breast, and pancreas.

Studies indicate a direct association between increased blood pressure and
the consumption of alcohol at levels beyond about two drinks" daily.
Extremely excessive alcohol consumption is associated with cardiomyop-
athy. Alcohol consumption by the mother during pregnancy has also been
associated with fetal malformations.

Although consumption of up to two drinks per day has not been associated
with disease among healthy men and nonpregnant women, surveys suggest
that at least 9 percent of the total population consumes two or more drinks
per day and those in this group need to reduce their alcohol consumption. A
threshold level of safety for alcohol intake during pregnancy has not been
established. Thus, pregnant women and women who may become preg-
nant should avoid drinking alcohol.

lone drink is defined as a 12 ounce beer, a 5 ounce glass of wine, or 1% fluid ounces (one
jigger) of distilled spirits, each of which contains about 1 ounce of alcohol.

14


Summary and Recommendations O

Other Issues for Some People

0 Fluoride: Community water systems should contain fluoride at optimal
levels for prevention of tooth decay. If such water is not available, use
other appropriate sources of fluoride.

The most efficient means of making fluoride available to the general public
to reduce dental disease is through drinking water. Numerous epidemio-
logic and clinical studies have attested to the efficacy, safety and cost-
effectiveness of systemic fluoride in the prevention of tooth decay. Life-
time use of water containing an optimal fluoride concentration of approxi-
mately 1 part per million has been shown to reduce the prevalence of dental
caries by more than 50 percent. Water fluoridation is considered one of the
most successful public health efforts introduced in the United States.

For children living in areas with inadequate concentrations of fluoride in
the water, supplementary fluoride sources should be used at dosages that
depend on the fluoride content of the local water supply and the age of the
child. The effectiveness of prenatal fluoride administration, however, is
uncertain because clinical studies of its effects on subsequent caries inci-
dence have been equivocal. Excessive fluoride should be avoided because
it may cause mottling of developing teeth.

0 Sugurs: Those who are particularly vulnerable to dental caries (cavities),
especially children, should limit their consumption and frequency of use
of foods high in sugars.

Although genetic, behavioral, and other dietary factors also influence
dental health, the major role of sugars in promotion of tooth decay is well
established from animal, epidemiologic, clinical, and biochemical studies.
Newly erupting teeth are generally more vulnerable to decay than mature
teeth.

Research has shown that three conditions must exist for the formation of
dental caries: the presence of fermentable carbohydrate, acid-producing
bacteria, and a susceptible tooth. Caries-producing bacteria metabolize a
range of sugars (glucose, fructose, maltose, lactose, and sucrose) to acids
that demineralize teeth. The unique role of sucrose (common table sugar)
in dental caries is related to its special ability to be converted by these
bacteria into long, complex molecules that adhere firmly to teeth and form
plaque.


0 Nutrition and Health

The most important diet-related interventions are fluoridation of drinking
water, or the use of other means of fluoride administration, and control of
intake of sugars. While fluoride is the most important factor overall in
dental caries prevention, reduction in the frequency of consumption and in
the quantity of sugar-rich foods in the diet will also help reduce decay.
Sticky sweet foods that adhere to the teeth are more cariogenic than those
that wash off quickly. The longer cariogenic foods remain in the mouth, the
more they are likely to increase the initiation and progression of tooth
decay.

0 Calcium: Adolescent girls and adult women should increase consumption
of foods high in calcium, including low-fat dairy products.

Inadequate dietary calcium consumption in the first three to four decades
of life may be associated with increased risk for osteoporosis in later life.
Osteoporosis, a chronic disease characterized by progressive loss of bone
mass with aging, occurs in both women and men, although postmenopausal
women are twice as likely as men to have severe osteoporosis with conse-
quent bone fractures. Evidence shows that chronically low calcium intake,
especially during adolescence and early adulthood, may compromise de-
velopment of peak bone mass. In postmenopausal women, the group at
highest risk for osteoporosis, estrogen replacement therapy under medical
supervision is the most effective means to reduce the rate of bone loss and
risk for fractures. Maintenance of adequate levels of physical activity and
cessation of cigarette smoking have also been associated with reduced
osteoporosis risk.

Although the precise relationship of dietary calcium to osteoporosis has
not been elucidated, it appears that higher intakes of dietary calcium could
increase peak bone mass during adolescence and delay the onset of bone
fractures later in life. Thus, increased consumption of foods rich in calcium
may be especially beneficial for adolescents and young women. Food
sources of calcium consistent with other dietary recommendations in this
Report include low-fat dairy products, some canned fish, certain vegeta-
bles, and some calcium-enriched grain products.

o Iron: Children, adolescents, and women of childbearing age should be
  sure to consume foods that are good sources of iron, such as lean meats,
  fish, certain beans, and iron-enriched cereals and whole grain products.
  This issue is of special concern for low-income families.
Dietary iron deficiency is responsible for the most prevalent form of
anemia in the United States. Iron deficiency hampers the body's ability to
produce hemoglobin, a substance needed to carry oxygen in the blood. A

16


Summary and Recommendations O

principal consequence of iron deficiency is reduced work capacity, al-
though depressed immune function, changes in behavior, and impaired
intellectual performance may also result. Because of the serious conse-
quences of iron deficiency, continual monitoring of the iron status of
individuals at high risk-particularly children from low-income families,
adolescents, and women of childbearing age-is vital, as is treatment of
those identified to be iron deficient.

Proper infant feeding-preferably breastfeeding, otherwise use of iron-
fortified formula-is the most important safeguard against iron deficiency
in infants. Among adolescents and adults, iron intake can be improved by
increasing consumption of iron-rich foods such as lean meats, fish, certain
kinds of beans, and iron-enriched cereals and whole grain products. Also,
consuming foods that contain vitamin C increases the likelihood that iron
will be absorbed efficiently.

Policy Implications

Dietary Guidance

General Public

Educating the public about the dietary choices most conducive to preven-
tion and control of certain chronic diseases is essential. Educational efforts
should begin in primary school and continue throughout the secondary
grades, and should focus on the dietary principles outlined in this Report-
the potential health benefits of eating a diet that is lower in fat (especially
saturated fat) and rich in complex carbohydrates and fiber. The importance
of adequate physical activity should also be stressed. Efforts should con-
tinue throughout each stage of life to promote the principles outlined in the
Dietary Guidelines for Americans.

Special Populations

A disproportionate burden of diet-related disease is borne by subgroups in
our population. Black Americans, for example, have higher rates of high
blood pressure, strokes, diabetes, and other diseases associated with
obesity (but lower rates of osteoporosis) than the general population. Some
groups of Native Americans exhibit the highest rates of diabetes in the
world. Pregnant and lactating women also have special nutritional needs.
Particular effort should be made to identify and remove the barriers to
optimal health and nutritional status in such high-risk groups, using meth-
ods that take into consideration their diverse cultural backgrounds.

17


O Nutrition and Health

Many older persons suffer from chronic diseases that can reduce functional
independence; many take multiple medications that may adversely interact
with nutrients. Sound public education directed toward this group-and
professional education directed toward individuals who care for older
Americans-should focus on dietary means to reduce risk factors for
chronic disease, to promote functional independence, and to prevent ad-
verse consequences of use of medications.

Health Professionals

Improved nutrition training of physicians and other health professionals is
needed. Training should emphasize basic principles of nutrition, the role of
diet in health promotion and disease prevention, nutrition assessment
methodologies and their interpretation, therapeutic aspects of dietary in-
tervention, behavioral aspects of dietary counseling, and the role of dieti-
tians and nutritionists in dietary counseling of patients.

Programs and Services

Food Labels

Food labeling offers opportunities to inform people about the nutrient
content of foods so as to facilitate dietary choices most conducive to
health. Food manufacturers should be encouraged to make full use of
nutrition labels. Labels of processed foods should state the content of
calories, protein, carbohydrate, fats, cholesterol, sodium, and vitamins
and minerals. To the extent permitted by analytical methods, manufactur-
ers should disclose information where appropriate on the content of satu-
rated and unsaturated fatty acids and total fiber in foods that normally
contain them. Descriptive terms such as "low calorie" and "sodium re-
duced" in compliance with the Food and Drug Administration's regula-
tions for food labeling may also be helpful, and the expanded use of these
terms should be encouraged.

Nutrition Services

Health care programs for individuals of all ages should include nutrition
services such as, when appropriate, nutrition counseling for individuals or
groups, interpretation and implementation of prescribed therapeutic diets
tailored to individual food preferences and lifestyle, referral to appropriate
community services and food assistance programs, monitoring of prog-
ress, and appropriate followup. These services should routinely incorpo-
rate assessment of nutritional status and needs based on established crite-

18


Summary and Recommendations O

ria to identify individuals with nutritional risk factors who would profit
from preventive measures and those with nutritional disorders who need
remedial care.

Food Services

Lack of access to an appropriate diet should not be a health problem for any
American. Wherever food is served to people or provided through food
assistance programs, it should reflect the principles of good nutrition stated
in this Report. Whether served in hospitals, schools, military installations,
soup kitchens, day care centers, or nursing homes, or whether delivered to
homes, food service programs offer important opportunities for improving
health and providing dietary education. Such programs should pay special
attention to the nutritional needs of older people, pregnant women, and
children, especially those of low income or other special dietary needs.
Because a large proportion of the population takes meals in restaurants and
convenience food facilities, improvements in the overall nutritional bal-
ance of the meals served in such places can be expected to contribute to
health benefits.

Food service programs should also take particular care to ensure that
special diets lower in fat, especially saturated fat, are provided to people
with elevated blood cholesterol, heart disease, or diabetes; that diets low in
sodium are provided to individuals with high blood pressure; and that
protein-restricted diets are made available to people with end-stage kidney
disease.

Food Products

The public would benefit from increased availability of foods and food
products low in calories, total fat, saturated fat, cholesterol, sodium, and
sugars, but high in a variety of natural forms of fiber and, perhaps, certain
minerals and vitamins. Food manufacturers can contribute to improving
the quality of the American diet by increasing the availability of palatable,
easily prepared food products that will help people to follow the dietary
principles outlined here. Because the public is becoming increasingly
conscious of the role of nutrition in health, development of such products
should also benefit the food industry.

Research and Surveillance

Impressive evidence already links nutrition to chronic disease. However,
much more information is needed to continue to identify changes in the

19


O Nutrition and Health

national diet that will lead to better health for the Nation. Gaps in our
knowledge of nutrition suggest future research and surveillance needs.
Examples are:

o The role of specific dietary factors in the etiology and prevention of
chronic diseases.

o The childhood dietary pattern that will best prevent later development
of chronic diseases.

o The effects of maternal nutrition on the health of the developing fetus.
o The nutrient and energy requirements of older adults.
o How nutrient requirements translate into healthful dietary patterns.
o The development of biodhemical markers of dietary intake to monitor
better the effects of dietary intervention.
o The identification of effective educational methods to translate dietary
recommendations into appropriate food choices.
o The establishment of a nutrition surveillance system that will enhance
the monitoring of population-specific and State-specific trends in the
occurrence of nutrition-related risk factors and conditions.

20


Chapter 1

Introduction and Background

Power of nutriment reaches to bone and to
all the parts of bone, to sinew, to vein, to
artery, to muscle, to membrane, to flesh,
fat, blood, phlegm, marrow, brain, spinal
marrow, the intestines, and all their parts: it
reaches also to heat, breath, and moisture.
   Hippocrates (-377 B.C.)

Introduction

It has long been understood that optimal health depends on adequate
nutrition, yet knowledge of the ways in which specific dietary factors affect
the risk for disease is incomplete. Dietary deficiencies can be manifested in
various ways. A deficient intake of energy or nutrients can lead to protein-
energy malnutrition or to classic deficiency diseases such as rickets, pel-
lagra, or iron deficiency anemia. Protein-energy malnutrition and diseases
due to deficiencies of various nutrients are prominent causes of premature
death and disability in developing countries but, with a few exceptions,
appear to have been eliminated in the United States.

When nutrient deficiencies are reported in this country, they are most often
observed to be associated with poverty, the additional nutrient require-
ments of pregnancy or infancy (IOM 1985), the abuse or neglect of children
or older persons, or some combination of these factors. They also are
observed to result from the restricted food intake that sometimes accom-
panies aging, alcohol or drug abuse, unusually severe and prolonged injury
or illness (including prolonged hospitalization), excessive dieting, or re-
strictive dietary practices. Thus, pregnant women, young infants, chil-
dren, older persons, alcohol and drug abusers, and chronically ill and
disabled individuals are at greatest risk for malnutrition due to dietary
deficiencies, especially if their income is low. Whatever its root cause,
inadequate nutrition retards normal growth, lowers resistance to infectious
disease, impairs maternal and child health, and may adversely affect the
ability to function at peak physical and mental capacity. These issues are
discussed in detail in the relevant chapters of this Report.

21


O Nutrition and Health

As problems of nutritional deficiency have diminished in the United States,
they have been replaced by problems of dietary imbalance and excess.
These imbalances and excesses have contributed to the increased preva-
lence and severity of chronic diseases that are major causes of death and
disability among Americans. Table l-1 lists the 10 leading causes of death
in this country. Among them, five-coronary heart disease and generalized
atherosclerosis, stroke, some types of cancer, and diabetes-have been
associated with dietary excesses or imbalances, and another three-cir-
rhosis of the liver, accidents, and suicides-are often the result of exces-
sive alcohol intake. Together, these conditions account for as much as 70
percent of annual deaths among Americans (Collins 1986; NCHS 1986).
Dietary excesses or imbalances also have been associated with high blood
pressure, obesity, dental diseases, osteoporosis, and, perhaps, kidney and
gastrointestinal diseases. Such conditions also contribute to much illness,
disability, and death in the United States, and thus to substantial human
and economic costs to society.

Table l-l

Estimated Total Deaths and Percent of Total Deaths for the
  10 Leading Causes of Death: United States, 1987

Rank     Cause of Death

Number

Percent
of Total
Deaths

la

2a
3a
4b

5
6
7a
8b
9b
IO=

Heart diseases                759,400
(Coronary heart disease)         (511,700)
(Other heart disease)           (247,700)
Cancers                   476,700
Strokes                    148,700
Unintentional injuries             92,500
(Motor vehicle)              W5,800)
(All others)                (45,700)
Chronic obstructive hmg diseases       78,ooO
Pneumonia and influenza           w600
Diabetes mellitus               37,800
Suicide                    29,600
Chronic liver disease and cirrhosis      26,000
Atherosclerosis                23,100

35.7
(24.1)
(11.6)
22.4
7.0
(i::,
(2.2)
3.7
3.2
1.8
1.4
1.2
1.1

. . .      All causes                 2,125,loo
BCauses of death in which diet plays a part.
Wauses of death in which excessive alcohol consumption plays a part.

100.0

Source: National Center for Health Statistics 1988.

22


Introduction and Background cl

Much about the ways in which excessive intake of energy and nutrients
might affect health remain to be elucidated. Yet despite uncertainties,
much has been learned about diet-disease relationships. This first Surgeon
General's Report on Nutrition and Health examines the current state of
knowledge of associations among dietary patterns, nutrients, and certain
disease conditions. Its purpose is to review the available research evidence
that relates diet to health to establish a basis for policies that promote
dietary means to improve health.

Development and Organization of the Report

This Surgeon General's Report on Nutrition and Health has been devel-
oped in response to the increasing interest of the public, health profession-
als, and policy leaders in the role of diet in health promotion and prevention
of chronic disease. In preparing the Report, the Public Health Service
(PHS) reviewed past and current research related to diet and disease as a
basis for examination of the implications for public policies on nutrition
education, services, and research.

The Report reviews current knowledge of the influence of dietary factors
on specific aspects of health. This first chapter introduces the major
themes of the Report in their historical context; it also reviews and synthe-
sizes basic information about essential nutrients in the human diet, the
levels of intake required for human health, and American dietary patterns,
and it explains the criteria used to examine the various kinds of research
studies that are reviewed throughout the Report. Chapters 2 through 14
describe the scientific research that has examined associations between
specific dietary factors and selected disease conditions in the United States
(Coronary Heart Disease, High Blood Pressure, Cancer, Diabetes,
Obesity, Skeletal Diseases, Dental Diseases, Kidney Diseases, Gastroin-
testinal Diseases, Infections and Immunity, Anemia, Neurologic Disor-
ders, and Behavior). Chapters 15 (Maternal and Child Nutrition) and 16
(Aging) review the special nutritional challenges at especially vulnerable
stages of the human life cycle. The interactions between nutrients and
alcohol and between nutrients and drugs, and the effects of these sub-
stances on human nutritional status, are reviewed in chapters 17 and 18,
respectively. The Report closes with a final chapter on dietary fads and
frauds.

Most of the chapters follow a common format. Each begins with a brief
introduction and a section entitled Historical Perspective that is designed
to establish a historical context for the area under review. A section on

23


O Nutrition and Health

Significancefor Public Health contains information currently available on
the incidence, prevalence, and cost to the Nation of each of the conditions
under review. Many of the chapters contain a further introductory Scien-
tific Background section that summarizes technical information needed to
understand the research issues reviewed in the Report.

The major part of the chapters is devoted to a review of Key Scientific
Issues that summarizes current knowledge about possible associations
between dietary factors and disease that are most relevant to public policy.
Each chapter closes with a section entitled Implications for Public Health
Policy that summarizes the signiftcance of the research evidence for di-
etary guidance and education, nutrition programs and services, and nutri-
tion research and surveillance. Finally, Literature Cited provides an exten-
sive list of references to support the scientific findings in each chapter.

Historical Perspective

Throughout history, human societies have observed relationships between
the consumption of certain foods and the preservation of good health or the
prevention or treatment of diseases. Although the word "diet" occurs
frequently in writings attributed to Hippocrates and to Galen, the term
"nutrition" did not appear as an English word until the mid-1400's and was
used infrequently until the second half of the 19th century (Todhunter
1973). The modem concept of nutrition-that human life depends on a
steady intake of a variety of specific dietary substances in defined
amounts-is less than 200 years old.

Development of Nutritional Science

Conditions related to nutritional deficiency, such as beriberi, rickets, or
scurvy, were described in very early writings, but the identification of the
specific dietary factors required to prevent or treat these conditions began
to occur only in the late 18th century and did not approach completion for
another 150 years. Some of the major events in this gradual development of
nutrition as a science from the earliest records to 1950 are listed in Table
l-2. The chapters of this Report review the great expansion of nutrition
research and knowledge that has occurred since then.

The earliest efforts to establish the scientific basis of nutrition are usually
attributed to the French chemist Lavoisier, who demonstrated in 1789 that
the oxygen breathed in air was consumed in the body to produce carbon
dioxide and water, and that this central metabolic process was measurable,
variable, and related to both the level of physical activity and the amount of

24


Introduction and Background 0

               Table 1-2
Selected Events in the History of Nutritional Science to 1950

c. 1500 B.C.

c. 400 B.C.

c. 300 B.C.

c. 200 A.D.

1250

1614

1650

1730

1747

1752

1780

1789

17%

1807

1810-23
1810

1816

1827

1833

1838

1839

1840

Papyrus Ebers contains prescription believed to refer to diabetes.
Hippocrates wrote of relationship of diet to health.
Beriberi described in ancient Chinese texts.
Arataeus gave the name diabetes to the condition of "too much
passing of urine."

Joinville described scurvy among troops of Louis IX at the siege
of Cairo.

Sanctorius published studies relating body weight to food intake.
Glisson described rickets in De Rachitide.
Casal described pellagra, calling it "ma1 de la rosa."
Lind proved that citrus fruits cure scurvy in first controlled
human dietary experiment. Menghini established presence of iron
in blood.

Reaumur published experiments on digestion in birds.
Spallanzani produced evidence that digestion was the chemical
action of gastric juices.

Lavoisier and Seguin make first measurements relating oxygen
consumption to human energy metabolism. Cod liver oil used as
treatment for rickets.

Lemon juice offtcially introduced in British Navy to prevent
SCUNY.

Davy isolated sodium, potassium, calcium, magnesium, sulphur,
and boron.

Chevreul studied chemistry of animal fats.
WolIaston isolated cystic oxide (later named cystine) from
urine--first amino acid discovered.
Magendie identified dietary nitrogen requirements in dogs.
Prout classified food constituents as saccharine, oily, and
albuminous (sugar, fat, and protein).
Beaumont reported observations and experiments on digestion in
his patient St. Martin.
Mulder introduced the term "protein."
Boussingault conducts first nitrogen balance studies in animals.
Liebig published Animal Chemistry, stating basic principles of
metabolism.

25


O Nutrition and Health

Table l-2 (continued)

1843

1848

1849-57

1850

1850-52

186641

1867

1877

1885

18%

1897

1902

1909-28

1912

1914

1916

1918

1919-22

1921-24

1922

1928

1929

1931-37

1932

1933

Chossat studied the effect of starvation on the body using
pigeons.

Addison described pernicious anemia.
Bernard elucidated digestive action of pancreatic juices and
glycogenic function of liver.

Livingstone described xerophthalmia (due to vitamin A
deficiency) in Africa.

Chatin in France used iodine to prevent goiter.
Voit and Pettenkofer explained protein metabolism.
Boussingault recognized iron as essential nutrient.
Pavlov began classic studies on digestion in dogs.
Takaki demonstrated in controlled dietary experiments with
Japanese Navy sailors that beriberi could be prevented.
Atwater and Bryant introduced their basic reference, Chemical
Composition of American Food Materials.
Eijkman published his work on causes of beriberi.
Rubner showed that food components increased metabolism by
different amounts.

Osborne and Mendel studied the nutritive value of protein.
Funk coined the term "vitamine."
Goldberger established dietary cause of pellagra.
McCollum and Davis and Osborne and Mendel discovered
accessory dietary factors "fat-soluble A" and "water-soluble B."
Mellanby showed that experimental rickets in dogs is due to lack
of fat-soluble vitamin.

Water-soluble B factor shown to be more than one factor.
Blindness in children shown to be result of lack of vitamin A.
McCollum identified vitamin D in cod liver oil.
Goldberger identified pellagra-preventing factor in yeast.
Role of intrinsic and extrinsic factors in pernicious anemia
discovered.
Fluoride content of drinking water identified as cause of mottled
enamel of teeth and prevention of tooth decay.
Vitamin C isolated from lemon juice. Warburg and Christian
identified riboflavin and defined its molecular function.
Williams identified kwashiorkor as a nutritional disease.

26


Introduction and Background O

Table l-2 (continued)

1938

1941

Rose classified amino acids as essential and nonessential.
Evidence provided for the influence of prenatal diet on the health
of the newborn infant.

! 944-46

Keys and coworkers studied effects on young men of
experimentally induced semistarvation and methods of dietary
rehabilitation.

I945


1948-49

Grand Rapids. Michigan. becomes the first city in the world to
fluoridate its drinking water to prevent tooth decay.
Crystalline vitamin B,, isolated from liver extract and shown to
contain cobalt.

1949     Framingham Study of coronary heart disease risk factors begins.
Sources: Darby 1985; McCollum 1957; Murlin 1948; Olson 1978; Todhunter 1962, 1973,
     1976.

food ingested (Lusk 1933). In the 19th century, European and American
scientists isolated and began to identify the major groups of nutrients in the
diet, to develop the first estimates of nutrient requirements, and to explore
the basics of energy metabolism. For example, in 1816, Magendie of
France established that nitrogen-containing compounds were essential in
the diet of dogs; in 1838, these compounds were given the name protein
(from the French word for "primary substance"). In 1814, the French
chemist Chevreul discovered that fats consisted of fatty acids attached to a
glycerol molecule. By 1834, the London physician Prout was able to
introduce the idea that food consists of substances called saccharine, oily,
and albuminous-today called carbohydrates, fats, and proteins
(Todhunter 1959). Later in the century, Rubner ofGermany and Atwater of
the United States established the energy values of these substances as
approximately 4, 9, and 4 kcal/g, respectively (McCollum 1957).

Thus, from the time of Lavoisier to the end of the 19th century, knowledge
of nutritional science grew to encompass the metabolic basis of energy
production from food, the classification of nutrients and sources of energy,
the dependence of energy requirements on physical activity, the influence
of diet on body weight and of fevers on metabolism of food substances, the
principles of metabolic homeostasis, and the roles of specific essential
nutrients in human physiology (Murlin 1948). During this period, lemon
juice was found to prevent scurvy, iodine to prevent goiter, and in-
completely milled rice to prevent beriberi. Despite these advances, the
most fundamental concepts about nutrition were still poorly developed at
the beginning of the 20th century. It was not until the first half of this

27


O Nutrition and Health

century that scientists identified human nutritional requirements, charac-
terized the nutritional value of proteins, and identified the amino acids,
vitamins, fatty acids, and minerals essential in the human diet (Todhunter
1976). For example, Osborne and Mendel of Yale University elucidated the
differences between complete and incomplete proteins during the first
decades of this century. Later, Rose of the University of Illinois estab-
lished which of the amino acids were essential and estimated how much of
each was required each day.

The diseases of scurvy, beriberi, rickets, and pellagra had been described
in very early writings, but their specific causes were not identified until
after 1900. In 1906, Hopkins of Cambridge University suggested that food
contained certain accessory factors necessary for prevention of these
conditions. In 1912, Funk named these factors "vitamines," later called
vitamins as more was learned about their chemical structure (Rosen 1958).

Early in the century, the dietary cause of pellagra was established by
Goldberger, a PHS physician, and fat- and water-soluble vitamins were
isolated and characterized (McCollum 1957). Also during this period,
kwashiorkor was identified as a nutritional disease and the importance of
prenatal diet on the health of newborn infants began to be appreciated
(Darby 1985). Over the next three decades, all of the vitamins were
identified, starting with the isolation of a fat-soluble substance in egg yolk
by McCollum at the University of Wisconsin, now known as vitamin A,
and continuing with the discoveries of folic acid, vitamin Br2, and other B
vitamins in the 1930's and 1940's (McCollum 1957). The essential nature of
trace elements such as selenium and zinc were finally recognized in the
1950's and 1960's (Darby 1985).

After World War II, the major focus of attention in nutrition began to shift
away from acute nutrient deficiency diseases. The advent of improved
transportation systems and home refrigeration and frozen foods expanded
the year-round availability of fresh and wholesome foods, and food for-
tification helped to increase the availability of previously scarce nutrients.
At the same time, vaccines, antibiotics, and other advances in medicine
and health prevented and controlled many of the infectious diseases that
had previously shortened the human lifespan. Thus, chronic degenerative
diseases became more important as causes of illness and death. Nutrition
scientists began to examine the relationship of modem dietary patterns and
practices to these chronic diseases-cardiovascular disease, cancer, and
diabetes, for example-that were becoming increasingly prevalent among

28


Introduction and Background cl

Americans in middle and late life, and attention shifted to the effects of
specific nutrients and dietary factors on the long. slow development of
these conditions.

Evolution of .Federal Nutrition Policy

As knowledge developed in the nutrition sciences and on the health effects
of food, and as food availability and consumption patterns became more
apparent, nutrition assumed an increasingly visible role in pubtic policy.
By 1979, the Federal Government was involved in efforts to ensure an
adequate, safe, and nutritious food supply for Americans through spon-
sorship of more than 350 programs in key areas of nutrition policy: agricul-
tural support, food safety and regulation, food fortification, food assis-
tance, nutrition services and training, food intake and nutritional status
monitoring, food and nutrition research, and food and nutrition education
(Comptroller General 1979). Some of these programs had rdots that
reached back to the turn of the century. but since World War I1 the
Government's efforts have increasingly focused on meeting the needs of
high-risk groups and on the role of-diet in health promotion and disease
prevention. Table l-3 presents a chronological listing of selected events in
the development of Federal domestic nutrition policies; the history of
Federal initiatives in the major areas of nutrition policy is reviewed below.

Table 1-3

Selected Federal Domestic Nutdtion Policy Initiatives, 1862-1988

1862


1867


1887



1889

U.S. Department of Agriculture (USDA) created. Morrill Act
establishes land grant colleges.
O&e of Education established-wi;h responsibilities for
nutrition education within public schools.
Hatch Act establishes agricultural experiment stations.
Federal research laboratory established at Staten Island.
Name is changed to the National Institute of Health in 1930.
U.S. Public Health Service Commissioned Corps authorized
for duty on communicable, nutritional, and other diseases.

1893


1906




1914

1916

USDA authorized by Congress to conduct research on
agriculture and human nutrition.
The Pure Food and Drug (Wiley) Act prohibits interstate
commerce and misbranded and adulterated foods, drinks, and
drugs. Federal Meat Inspection Act passed.
Cooperative Extension Service created as part of USDA.
USDA publishes Food for Young Children, first dietary
guidance pamphlet.

29


u Nutrition and Health

Table l-3 (continued)

1917

1921-29

1924

1927

1930

1933

1935

1936-37

1938

1939


1940


1941

1946

1947

1954

U.S. Food Administration established to supervise World Wa,
I food supply. First dietary recommendations issued by
USDA-Five Food Groups.
Maternity and Infancy Act enabled State health departments
to employ nutritionists.

Addition of iodine to salt to prevent goiter is first U.S. food
fortification program.

Food, Drug, and Insecticide Administration established. Name
is changed to Food and Drug Administration (FDA) in 1932.
USDA and Federal Emergency Relief Administration buy and
distribute surplus agricultural commodities as food relief.
Public Health Service Hygienic Laboratory designated as
National Institute of Health (later changes to National
Institutes of Health).

Agricultural Act amendments permit purchase of surplus
commodities for donation to child nutrition and school lunch
programs.

Food Distribution Program established. Social Security Act
authorizes grants to States for nutrition services to mothers
and children .

USDA conducts first Nationwide Food Consumption Survey
(NFCS).

The Food, Drug and Cosmetic (FD&C) Act includes
provisions for food standards. FDA nutrition research
program established. Social Security Act provides support for
role of nutrition in health.

Federal Surplus Commodities Corporation initiates
experimental Food Stamp Program.
National Defense Advisory Commission draws attention to
malnutrition in the United States.
President Roosevelt calls National Nutrition Conference, with
announcement of the first Recommended Dietary Allowances
by the Food and Nutrition Board. FDA promulgates standards
for enrichment of flour and bread with B-complex vitamins
and iron.

National School Lunch Program established.
Laboratories of Nutrition, Chemistry, and Pathology of the
National Institutes of Health incorporated into Experimental
Biology and Medicine Institute.
Special Milk Program established.

30


Introduction and Background 0

Table 1-3 (continued)

1955

1956

1958

1961

1%3 and 1965

1%5




1966







1966-70








1968


1968-70




I%9





1971-74

Interdepartmental Committee on Nutrition for National
Defense established (discontinued 1%7).

Title VII of the Public Health Service Act authorizes funds to
support graduate training in public health nutrition.
Food Additives Amendment to FD&C Act prohibits use of a
food additive until safety established by manufacturer.
Delaney Clause prohibits carcinogenic additives. GRAS
(Generally Recognized As Safe) list established.
President Kennedy expands the use of surplus food for needy
people at home and abroad and announces a new pilot Food
stamp Program.

Maternal and Child Health and Mental Retardation Planning
Amendments to the Social Security Act allow for an expanded
number of nutritionists in health care programs.

Food Stamp Act passed by Congress. Nationwide Food
Consumption Survey collects first data on dietary intake of
individuals.

Child Nutrition Act passed. School Breakfast Program
established. President Johnson outlines Food for Freedom
Program, the "war on hunger." Allied Health Professions
Personnel Training Act includes support for training of
dietitians.

The Department of Health, Education, and Welfare (DHEW),
which later becomes the Department of Health and Human
Services (DHHS), sponsors a National Academy of Sciences
study, Maternal Nutrition and the Course of Pregnancy, which
makes major recommendations related to the role of nutrition
in human reproduction.

U.S. Senate Select Committee on Nutrition and Human Needs
established.

DHEW sponsors Preschool and Ten-State Nutrition Surveys
that report evidence of hunger and malnutrition in poverty
groups in the United States.

President Nixon calls White House Conference on Food,
Nutrition, and Health. Secretary of Agriculture establishes the
Food and Nutrition Service to administer Federal food
assistance programs.

The National Center for Health Statistics conducts the first
National Health and Nutrition Examination Survey
(NHANES) to measure the nutritional status of the U.S.
population. This is followed by NHANES II in 1976-80,
Hispanic HANES in 1982-84, and NHANES III in 1988.

31


0 Nutrition and Health

1974

1975


1977

1978

1979

1980

1981

1984

1985

Table l-3 (continued)

1972

USDA establishes Special Supplementary Food Program for
Women, Infants, and Children (WIC). Agriculture and
Consumer Protection Act provides price supports to farmers.
Amendments to the Older Americans Act of 1%5 establish a
congregate and home-delivered meals program for older
Americans.

U.S. Senate Select Committee on Nutrition and Human Needs
issues Guidelines for a National Nutrition Policy, prepared by
the National Nutrition Consortium. Safe Drinking Water Act
passed.

National Institutes of Health establishes Nutrition
Coordinating Committee.

U.S. Senate Select Committee on Nutrition and Human Needs
issues two editions of Dietary Goals for the United States.
Food and Agricultural Act and Child Nutrition and National
School Lunch Amendments passed.

Joint Subcommittee on Human Nutrition Research established
in Office of Science and Technology Policy (in 1983 becomes
Interagency Committee on Human Nutrition Research under
joint direction of USDA and DHHS). DHEW and USDA
submit proposal to Congress for National Nutrition Monitoring
System.

DHEW establishes Department-wide Nutrition Policy Board
and issues Healthy People: The Surgeon General's Report on
Health Promotion and Disease Prevention.

USDA and DHHS jointly issue Nutrition and Your Health:
Dietary Guidelines fcr Americans. A second edition follows in
1985. DHHS issues Promoting Health/Preventing Disease:
Objectives for the Nation, which contains 17 nutrition
objectives to be achieved by the year 1990. The Surgeon
General's Workshop on Maternal and Infant Health makes
recommendations about improving nutrition for these
vulnerable groups.

DHHS and USDA issue Joint Implementation PIan for a
Comprehensive National Nutrition Monitoring System,
revised in 1987 as the Operational Plan for the National
Nutrition Monitoring System. The Select Panel for the
Promotion of Child Health, created by Public Law 95-626,
submits to Congress and the Secretary of DHHS its report,
which includes recommendations on nutrition.

The Surgeon General's Workshop on Breastfeeding and
Human Lactation develops strategies for promoting
breastfeeding.

USDA initiates Continuing Survey of Food Intakes by
Individuals. repeated in 1986.

32


Introduction and Background O

Table l-3 (continued)

1986

DHHS and USDA issue Nutrition Monitoring in the United
States, the report of the Joint Nutrition Monitoring Evaluation
Committee.

1988

DHHS publishes The Surgeon General's Report on Nutrition
and Health.

Agricultural Support. The earliest Federal nutrition policies in this area
were designed to strengthen the agricultural production system and to
ensure a consistent and adequate food supply. In 1862. the U.S. Depart-
ment of Agriculture (USDA) was created, and the Morrill Act established
land grant universities as sites for agricultural training and research. The
Hatch Act of 1887 authorized the creation of agricultural experiment
stations. As a result of these and other policies. food production increased
and farmers began to produce more food than could be consumed. Even-
tually, a system of commodity price and income supports was developed to
stabilize the economic condition of the farm sector. The Agricultural and
Consumer Protection Act of 1973 and the Food and Agriculture Act of 1977
established the basis for current agricultural support policies (Stucker and
Boehm 1978; Boehm 1979).

Food Safety and Regulation. The pure food movement of the late 1800's,
led by Dr. Harvey Wiley, chief of the Government's Bureau of Chemistry,
and popularized by the publication of Upton Sinclair's novel of 1906, The
Jungle, led Congress to pass the Pure Food and Drug Act of 1906-then
known as the Wiley Act-which prohibited interstate transport and sale of
misbranded or adulterated foods (Ziporyn 1985). This Act and the Federal
Meat Inspection Act, also passed that year, extended Federal responsibil-
ity into the arena of food safety. Significant revisions to the legislation
occurred in 1938 when the Food, Drug, and Cosmetic Act established
standards of identity and quality for certain foods, required ingredient
listings on food labels, and prohibited sales of foods that were determined
to be harmful to health. In 1958, the Food Additives Amendment to the
1938 Act shifted the burden of proof of safety to the manufacturer, required
that additives known to cause cancer in either humans or animals be
deemed unsafe (the Delaney Clause), and established the list of ingredients
in common use that were "Generally Recognized As Safe" (GRAS) for
human consumption. A 1960 Color Additives Amendment applied the
Delaney Clause to all chemical food coloring agents. Since 1969, a major
review has been under way of the safety of substances on the GRAS list
(Smith and Rulis 1981). Regulation of food safety is a shared responsibility

33


u Nutrition and Health

of several Federal agencies, primarily the USDA for plant, animal,
poultry production; the Food and Drug Administration (FDA) for all c
foods and additives; and the Environmental Protection Agency
pesticide contaminants.

The food labeling provisions of the 1906 and 1938 Acts were designe
protect consumers against fraudulent misbranding of foods, and this pc
was extended by the Fair Packaging and Labeling Act of 1%6, which cz
for accurate ingredient labeling on foods in interstate commerce (PC
1987). More recently, interest has grown in the use of food labels to edu
consumers about the nutritional quality of food and the role of nutritic
health. Regulations published in 1973 authorized voluntary nutrition la
ing and required nutrition labeling for fortified foods and those for WI
nutritional claims were made (Hutt 1981). In 1987, the FDA proposed a
policy for public health messages on food labels to permit health claim
package labels when the information is true and certain criteria are
(FDA 1987). Responsibility for regulating labeling and marketing prc
dures related to foods is shared by the USDA (meat, poultry, eggs), F
(all other foods) and, for advertising, the Federal Trade Commission (.
ter 1987).

Food Fortrjication. The onset of World War I brought new nutritic
concerns and focused attention on the need for an overall improvemer,
the availability of nutrients to the general population. The first food
tification program, instituted in 1924, was the addition of iodine to sal
prevent goiter. During the Second World War, this program was extendel
include enrichment of wheat flour with iron and the vitamins thian
niacin, and riboflavin. Also during the 1940's, milk was fortified v
vitamin D and margarine with vitamin A.

Food Assisrunce. As early as 1918, the idea of targeting food assistance
vulnerable population groups was proposed in the Children's Bureau p
lication Milk-The Indispensable Food for Children. Milk supplies 1
decreased and prices increased due to the effects of World War I, and
Children's Bureau advocated that children be given priority in allocat
milk supplies. Charitable organizations established milk stations and cc
munity kitchens to provide food supplements to the poor and to help peo
with limited income choose and prepare an adequate diet (Egan 1980

Widespread unemployment anda overty during the 1930's stimulated I
development of new Federal programs to provide food assistance to i
poor. At first, these programs focused exclusively on distribution of surp
agricultural commodities. In 1930, for example, the USDA and the Fede

34


Introduction and Background 0

Emergency Relief Administration began a distribution program as food
relief. The donation of surplus foods to child nutrition and school lunch
programs was authorized by amendments to the Agricultural Act in 1933.
The more formally organized Food Distribution Program was established
in 1935. An experimental Food Stamp Program was initiated by the Surplus
Commodities Corporation in 1939. The National School Lunch Program
was established in 1946, and the Special Milk Program was added in 1954
(U.S. Senate 1976).

In the early 1960's, as a result of surveys and assessments indicating special
needs among low-income populations (Citizens' Board 1968), the Federal
Government expanded its involvement in income support and direct deliv-
ery of food services. A pilot study in 1961 led to the Food Stamp Act of
1965, which authorized a small-scale program to meet limited needs for
food assistance. The Child Nutrition Act of 1966 established the School
Breakfast Program. Following the 1969 White House Conference on Food,
Nutrition, and Health (White House Conference 1970), eligibility and
benefits were enlarged for the Food Stamp, School Lunch, School Break-
fast, Special Milk, and Summer Food Programs; the Special Supplemental
Food Program for Women, Infants, and Children (WIG) was created;
general assistance reimbursements were increased (for the School Break-
fast and School Lunch Programs); and the Nutrition Program for the
Elderly was established through an amendment to the Older Americans
Act. From I%9 to 1977, Federal expenditures for these programs increased
from about $1.2 to $8.3 billion (U.S. Senate 1977a). By 1986, as many as 50
million Americans (the exact number is uncertain due to overlapping
benefits) were served by food assistance programs administered by the
USDA. The cost of these programs exceeded $18.8 billion in 1986 and $20
billion in 1987 (Matsumoto 1987).

Nutrition Services and Training. In the 1920's under the Federal Maternity
and Infancy Act, nutrition services were launched in nine State depart-
ments of public health. Enactment of the Social Security Act in 1935,
authorizing grants-in-aid to the States for health services for mothers and
children, was a major impetus for the further development of nutrition
services in State health agencies. By 1945, all but three States had one or
more nutrition consultant positions included in their budgets. Nutrition
services began to extend beyond maternal and child health during the late
1950's and early 1960's in response to new mental retardation, chronic
disease control, home health service, and nursing home and other ex-
tended care programs. Initiatives in primary health care, family planning,
and comprehensive health planning during the 1970's further expanded the
availability of nutrition services (Nutrition Services Project Committee

35


cl Nutrition and Health

1983), as did establishment of the Community Food and Nutrition Program
(CFN) in the 1980's to provide nutrition services to low-income popula-
tions (Office of Community Services 1987).

To ensure an adequate supply of health professionals to serve the popula-
tion, the Federal Government also supports health professions education
in primary care as well as public health practice. Since the 1940's, funds
have been available from Title V of the Social Security Act for nutrition
training of health professionals, and since 1957, various authorities under
Title VII of the Public Health Service Act have supported health profes-
sions students and curriculum development in applied nutrition, including
capitation grants to schools of public health that support traineeships for
public health nutrition students.

Food Intake and Nutrition Status Monitoring. The involvement of the
Federal Government in monitoring of food intake dates back to 1893 when
the USDA received an appropriation for this purpose (Porter 1986). The
USDA first began to collect data on the wholesale availability or "disap-
pearance" of food commodities in 1909. The subsequent annual collection
of such data has provided an important source of information on trends in
the availability of food, an indirect indicator of food use by the population
(Bunch 1987). Attempts to estimate actual food intake by the population
began in the 1930's. For example, household food purchases were exam-
ined by the USDA in 1936-37 through the first Nationwide Food Consump-
tion Survey (NFCS); such surveys have been conducted about every 10
years since, most recently in 1987-88 (USDA 1986,1987a, 1987b). Estima-
tions of the per capita nutrient content of the food supply began in the
1940's and are now reported annually (Marston and Raper 1986). The first
collections of data on the food consumption habits of individuals in
sampled households were performed by the USDA in 1%5 (NRC 1984).
Examples of food intake and availability data are given later in this chapter
in the section on dietary patterns.

Assessment of nutritional status emerged as a concern as early as 1918
when infants and children were weighed and measured during the opening
event of the Children's Year Campaign (initiated to "protect children from
the effects of war"). The impetus for this activity was the high percentage
of Selective Service rejections in World War I caused by conditions that
might have been prevented or corrected by adequate nutrition in early
childhood. The first studies of nutrition and child health were conducted by
the Children's Bureau in a mountainous section of Kentucky in 1920 and in
the industrial area of Gary, Indiana, in 1922 (Egan 1980).

36


Introduction and Background O

Much of the recent expertise in measuring human nutritional status was
developed through the work of the Interdepartmental Committee on Nutri-
tion for National Defense, which conducted nutrition surveys in more than
30 countries during the 1950's and 1960's. Attempts to evaluate the nutri-
tional status of the U.S. population began in 1956 when Congress autho-
rized the Department of Health, Education, and Welfare (DHEW) to
conduct periodic national health examination surveys; with the addition in
1971 of additional status measures, including a dietary intake component,
these surveys evolved into the National Health and Nutrition Examination
Surveys (NHANES). The first NHANES was conducted from 1971-74,
the second from 1976-80, and the Hispanic HANES from 1982-84 (DHHS/
USDA 1986). The third NHANES started in 1988. In l%8-70, in response
to increasing concern about the nutritional status of low-income popula-
tions, DHEW sponsored the Preschool (Owen et al. 1974) and Ten-State
(DHEW 1972) Nutrition Surveys and identified evidence of malnutrition in
these populations.

The dietary intake, health, and nutritional status surveys and surveillance
systems listed in Table l-4 and described above are components of the
National Nutrition Monitoring System-a complex assortment of inter-
connected activities that provide regular information about dietary intake
and nutritional status to the health of the American people and about
factors that affect diet and nutritional status (DHHS/USDA 1987). The
present system was proposed in 1978 in response to a congressional re-
quest in the 1977 Food and Agriculture Act that the Secretaries of Agri-
culture and of Health, Education, and Welfare, now Health and Human
Services (DHHS), develop a joint proposal for a comprehensive system
that would monitor the nutritional status of the American people. In 1981, a
Joint implementation Pfun (revised in 1987) committed the two Depart-
ments to close coordination of survey methods and to submission of
reports to Congress every 3 years on information gained from monitoring
activities. The National Nutrition Monitoring System includes efforts by
several Federal agencies to provide information about health and nutri-
tional status, food consumption, food composition, dietary knowledge and
attitudes, and food safety and quality.

Food and Nutrition Research. The Federal role in nutrition research began
in 1887 with the development of the forerunner of the National Institutes of
Health (NIH) as a one-room laboratory on Staten Island. In 1893, the
USDA was authorized to perform agricultural and human research. The
PHS Hygienic Laboratory developed into the first National Institute of
Health in 1930; subsequently, it was joined by other laboratories to create

37


        Table 14
National Nutrition Surveillance Activities

0
2
1.

Category          Activity

Departmenta  Agencya    Population     Timing        g.
                                                         J

Health and Nutritional
Status Measurements

National Health and
Nutrition Examination
Surveys
NHANES 1
NHANES I1
Hispanic HANES
NHANES III

DHHS      CDC/NCHS

National Health        DHHS
Interview Survey
NHIS Special Topics     DHHS
NHANES I Epidemiologic DHHS
Followup
National Survey of Family DHHS
Growth

National Maternal and    DHHS
Infant Health Survey
National Mortality Survey DHHS

CDC/NCHS

CDCR'XHS

CDC/NCHS

CDC/NCHS

CDC/NCHS              Planned 1988

CDCMCHS

Vital Statistics        DHHS      CDC/NCHS

U.S. population,
special groups

l-74 yrs       1971-74
6 mo-74 yrs     1976-80
6 mo-74 yrs     1982-84
2 mo+        1988-94

U.S.         Annual

U.S.       Selected topics
NHANES I older  1982-84, 1986,
persons       1987

Women 15-44 yrs 1976, 1983, 1987

Annual l%l-68,
1986

U.S. States,
counties, local
areas

Annual


Health and Nutritional
Status Measurements
(continued)

Coordinated State
Surveillance System

Behavioral Risk Factor
Surveillance System
Nutrition Research in
Support of Nutrition
Monitoringb

Food Consumption
Measurements

Nationwide Food
Consumption Survey
(NFCS)
Continuing Survey of
Food Intakes by
Individuals (CSFII)
1985 and 1986

1989 and beyond

NHANES

DHHS

CDCKHPE  Pregnant women, Continuous
        children

CDCKHPE   Adults

Continuous

DHHS
USDA

NIH       Varies      Ongoing
ARS
CDCKHPE
FDA

USDA      HNIS

U.S., low-income Every 10 years,
sample       current 1987-88

USDA      HNIS

DHHS

CDCINCHS

Women 19-50,   Annual
their children,
men, low-income
sample               zi
U.S. population,  Annual (planned)    E
low-income                         a
sample, other            !?
U.S. population  1971-74, 1976-80,
         1982-84, 1988-94  g
                 s
         ii


Table 14 (continued)

Food Consumption     Total Diet Study
Measurements (continued)
               Vitamin/Mineral
            Supplement Adverse
                Reactions

Food Composition
Measurements

Nutrient Data Bank

Nutrient Composition
Laboratory
Food Labeling and
Package Survey
Total Diet Study
Fiber, Carotenoid, and
Vitamin A Comp. Studies;
Taurine and Biotin Comp.
Studies

Dietary Knowledge     Health and Diet Survey
and Attitude Assessment
            Survey of Infant Feeding
                Practices

Survey of Weight-Loss
Practices

Cholesterol Awareness
Survey

DHHS

FDA

DHHS      FDA

USDA

USDA

DHHS

DHHS

DHHS

DHHS

DHHS

DHHS

DHHS

HNIS

ARS

FDA

FDA

NIH/NCI

NIHI
NIDDK

FDA

FDA

FDA
NIHI
NHLBI

NIHI
NHLBI
+ FDA

Specific age-sex Annual
groups
U.S.         Continuous



          Continuous


          Continuous

Annual and
biennial parts
Annual
Ongoing

Ongoing

U.S. adults     .18-22 mo intervals

Pregnant women  1988 or 1989


U.S. adults     1987 or 1988



Physicians      1986

Adults


e

Dietary Knowledge and
Attitude Assessment
(continued)

Nursing and Dietitian
Survey

NHIS Special Topics
Health Promotion/
Disease Prevention

.

VitMn Supplement
Cancer Control

Food Supp!y
-

CSFII Followup
(Consumer Perceptions
Survey)
Physician Knowledge
Survey on Hypertension
Cancer Prevention
Awareness Program
Demand Studies

DHHS      NIH/
        NHLBI

DHHS     CDC/NCHS   U.S. adults

        + NIH/NCI
USDA/DHHS HNIS
        FSIS
         FDA

DHHS      NIH/NHLBI

DHHS      NIH/NCI

USDA      ERS

Nurses, dietitians 1986, 1987

1985

           1986

           1987
U 3. population  Planned 1989-%



Physicians      1978-88


U.S. adults    1984 + ongoing

U.S. population Continuous

Determinations

aARS = Agricuftural Research Service, CDC = Centers for Disease Control, CHPE = Center for Health Promotion and Education, DHHS =
Department of Health and Human Services, ERS = Economic Research Service, FDA = Food and Drug Administration, FSIS = Food Safety
and Inspection Service, HNIS = Human Nutrition information Service, NCHS = National Center for Health Statistics, NCI = National Cancer
Institute, NHIS = National Health Interview Survey, NHLBI = National Heart, Lung, and Blood Institute, NIDDK = National Institute of Diabetes
and Digestive and Kidney Diseases, NIH = National Institutes of Health, USDA = U.S. Department of Agriculture.
blncludes research on nutritional status assessment and requirements throughout the life cycle. The nutritional status research focuses on (1)
indices of nutritional status, (2) micromethods to measure nutrient concentrations in various tissues and plasma, and (3) methods that improve
accuracy of dietary intake data.

Source: U.S. Department of Health and Human Services and U.S. Department of Agriculture 1987.


n

u Nutrition and Health

the present research enterprise of NIH (Simopoulos 1986). In 1975, the
NIH Nutrition Coordinating Committee was established to address NIH
nutrition issues that span the goals and purposes of 12 Institutes, 2 Divi-
sions, and 2 Centers within the agency. The FDA began conducting nutri-
tion research in 1938. By 1976, Federal expenditures for nutrition research
and research training exceeded $73 million (U.S. Senate 1976). The amount
was reported as nearly $200 million by 1979 (JSHNR 1980) and $270 million
in 1984, of which nearly $200 million represented research supported by
NIH (ICHNR 1986; NIH 1987). In 1987, NIH expended a total of $261
million, reinforcing its longstanding position as the major Federal agency in
biomedical and behavioral nutrition research and training support. This
nutrition research encompasses a broad range of topics, including health
maintenance, human development throughout the life cycle, disease pre-
vention, and disease treatment.

The Interagency Committee on Human Nutrition Research (ICHNR) was
established by the Secretaries of DHHS and USDA to succeed the Joint
Subcommittee on Human Nutrition Research that operated out of the
White House Office of Science and Technology Policy to coordinate all
Federal nutrition research activities. The ICHNR produced a 5-year plan
for human nutrition research that reviewed the research activities of eight
Federal agencies, listed research priorities, and identified six areas for
expanded research investigation: nutritional requirements at various
stages of the life cycle, nutrition interactions and bioavailability, nutrition
and chronic diseases, energy regulation and eating disorders, nutrition
monitoring, and nutrition education methodology (ICHNR 1986).

Dietary Guidance and Nutrition Education. The Federal Government has
supported efforts to teach the public about nutrition since 1867 when the
Office of Education was established with responsibility for nutrition educa-
tion within the public schools. The Children's Bureau of the Department of
Labor published Prenatal Care in 1913 and Znfant Care in 1914 to provide
dietary guidance to mothers. These books have been in publication ever
since and are all-time best sellers of the U.S. Government Printing Offtce.

The USDA also had an early role and published its first food selection
guide, designed to help parents meet the nutritional needs of young chil-
dren, in 1916 (Hunt 1916). Since that time, federally supported dietary
guidance materials have been issued and revised regularly to meet the
needs of specific target audiences and to reflect emerging knowledge of
nutritional science. A list of Federal dietary guidance publications for the
general public since 1917 is presented in Table l-5.

42


e

                 Table l-5
Federal Dietary Recommendations for the General Public, 1917-1988

Recommendationa

Year   Agencyb

Publication

     Maintain Include
      Ideal    Starch            Limit
     Body    and   Limit Limit Choles- Limit   Limit
Variety  Weight   Fiber  Sugar   Fat    terol    Salt   Alcohol

1917 USDA

1942 USDA

1943 USDA


1946 USDA


1946 USDA

1958 USDA

1977 U.S. Senate
1979 USDA

1979 DHEW

1979 DHEWINCI

What the Body Needs-
Five Food Groups
Food for Freedom-
Daily Eight
National Wartime Nutrition
Guide-Basic Seven
National Food Guide-
Basic Seven
Food for Growth-
Four Food Groups
Food for Fitness-
Four Food Groups
Dietary Goats for the U.S.
Building a Better Diet-
Five Food Groups
Healthy People: The Surgeon General's
Report on Health Promotion and
Disease Prevention
Statement on Diet, Nutrition,
and Cancer--Prudent
Interim Principles

+


+

+

      + * *


       +            *



       +            *



       +            *



       +


       +


+       +      +     +      +      +
+       +      +     +      +      +      +


+       +      +     +      +      +      t

-I-       t           +                  +


Year   Agencyb

Publication

                           0
                                                   z
                                            5
Table l-5 (continued)                      g
                                  Ei
                      Recommendationa              5
           Maintain Include
            Ideal    Starch             Limit       i

          Body and   Limit Limit Choles- Limit        2

    Variety  Weight   Fiber  Sugar   Fat    terol   salt  Limit 5
                                           Alcohol

   1980 USDA/DHHS  Dietary Guidelines for Americans        +       +       +      +     +      +      +      +
   1980 DHHS      National 1990 Nutrition Objectives        +       +       +      +     +      +      +      +
   I984 DHHS/NHLBI Recommendations for Control                  +                   +            +      +

% 1985 USDA/DHHS   of High Blood Pressure
              Dietary Guidelines for Americans,        +       +       +      +     +      +      +      +
                  2nd edition
   I986 DHHS/NCI   Cancer Control Nutrition Objectives              +       +           +                  +
                  for the Nation: 1985-2000
   1987 DHHS/NHLBI National Cholesterol Education         +       +       +           +      +            +
               Program Guidelines
   1988 DHHS/NCI    Dietary Guidelines for Cancer           +       +       +           +            +      +
                   Prevention

`!7ecommended for inclusion in the daily diet, as opposed to subsequent recommendations to limit intake.
aOther recommendations include: increased consumption of foods containing vitamins and minerals (USDA 1917-l 958; NCI 1988) increased
physical activity (USDA/DHHS 18881985; DHHS 1980). and reduced intake of salt-cured or smoked foods (NC1 1988).
bUSDA = U.S. Department of Agriculture, U.S. Senate = U.S. Senate Select Committee on Nutrition and Human Needs, DHEW = Department
of Health, Education, and Welfare, DHHS = Department of Health and Human Services, NCI = National Cancer Instiiute. NHLBI = National
Heart, Lung, and Blood Institute.


Introduction and Background O

The earliest federally sponsored guidelines advised the public to consume
portions from a variety of food groups every day to obtain sufficient energy
and to avoid nutritional deficiencies. As more was learned about nutrients
essential in the diet, recommendations began to emphasize consumption of
foods containing vitamins, minerals, and other "protective" dietary com-
ponents (Hertzler and Anderson 1974). In response to the economic crisis
of the 1930's, the USDA began to develop meal plans for consumers at
different levels of income to address issues of cost (Haughton, Gussow,
and Dodds 1987).

The first Recommended Dietary Allowances (RDA's) for intake of energy
and eight nutrients were developed by the National Research Council and
adopted at the wartime National Nutrition Conference in 1941 (Roberts
1958). RDA's have been published periodically since; the most recent
(ninth) edition appeared in 1980 (NRC 1980). Its recommendations are
reviewed later in this chapter. Also in 1941, the USDA, in cooperation with
the Offtce of Education and the PHS, published the first Federal guide to
incorporate information on specific vitamins and minerals and the first to
use the term "enriched." Meal plans and dietary guidelines published since
the 1940's have been designed increasingly to translate the RDA's into
terms usable by consumers (Hertzler and Anderson 1974). The USDA's
1958 Food for Fitness-A Daily Food Guide, written in terms of four food
groups, was the first to promote intake of specific nutrients-alcium,
vitamin A, and vitamin C-that were commonly consumed in amounts
substantially below RDA levels (Haughton, Gussow. and Dodds 1987).

Typically, an adequate diet has been defined as providing the basic food
groups that would contain amounts of essential nutrients-protein, vi-
tamins, and minerals-sufficient to prevent deficiency diseases. In the
mid-1970's, however, the focus of national policy objectives expanded to
encompass the role of overconsumption of fat, cholesterol, salt, sugar, and
alcohol as dietary factors associated with chronic disease. The increasing
scientific interest in these relationships led the U.S. Senate to hold hear-
ings on diet and health from 1973 through 1977 (U.S. Senate 1977a).
Expanding knowledge of the role of diet in health maintenance also led to
the development in 1975 of a DHEW Policy Statement on Health Aspects
of Nutrition (U.S. Senate 1976). Thus, dietary adequacy began to include
consideration of the most reasonable proportions of dietary factors for
prevention of chronic-rather than deficiency--diseases.

This new perspective was reflected in the two editions of the 1977 report
Dietary Goals for the United States, produced by the Senate Select Com-
mittee on Nutrition and Human Needs (U.S. Senate 1977b. 1977~). These


u Nutrition and Health

reports recommended significant changes in average dietary intake pat-
terns to improve protection against the principal chronic diseases. To
accomplish this goal, they established quantitative targets for consumption
of complex carbohydrates and naturally occurring sugars (greater than 48
percent of energy), refined and processed sugars (10 percent of energy),
total fats (less than 30 percent of energy), saturated fat (less than 10 percent
of energy), cholesterol (less than 300 mglday), and salt (less than 5 g/day)
(U.S. Senate 1977~).

These principles, although not the quantitative targets, were supported and
expanded in the 1979 report Healthy People: The Surgeon General's
Report on Health Promotion and Disease Prevention (DHEW 1979) and by
the 1980 publication Nutrition and Your Health: Dietary Guidelines for
Americans, jointly issued and revised in 1985 by the Departments of
Agriculture and of Health and Human Services (USDAIDHHS 1985). The
Guidelines recommend:

o Eat a variety of foods.
o Maintain desirable weight.
o Avoid too much fat, saturated fat, and cholesterol.
o Eat foods with adequate starch and fiber.
o Avoid too much sugar.
o Avoid too much sodium.
o If you drink alcoholic beverages, do so in moderation.

This approach reflects the increase in interest in the relation between
nutrition and prevention of chronic diseases, a development that has
shaped and mandated Federal nutrition education activities of the past
decade (see Table l-4) and is the principal focus of the discussion, conclu-
sions, and recommendations of this Report.

Scientific Background

Human Nutritional Requirements

Essential nutrients must be obtained from the diet in the proper amounts
and proportions to maintain good health and to prevent deficiency dis-
eases. A deficiency of an essential nutrient causes signs and symptoms that
can be prevented or cured by an increased intake of the nutrient. Such
deficiencies may be due to inadequate dietary intake, or they may be

46


Introduction and Background 0

induced by either inherited or acquired inabilities to absorb, transport,
store, or metabolize nutrients or by excessive losses of nutrients from the
body (for example, from vomiting, bleeding, or diarrhea).

Just as a deficiency of a nutrient can cause disease, too much of a nutrient
can also lead to disease. For example, as discussed throughout this Report,
the excessive consumption of energy, fat (especially saturated fat), and
alcohol have been associated with the development of specific chronic
disease conditions in some individuals. Excessive intake of some vitamins
and most of the minerals also has been shown to result in either acute or
long-term disorders. For most nutrients, there appears to be a safe and
adequate range of dietary intake that satisfies nutritional requirements but
does not cause untoward symptoms. This concept is illustrated in Figure
l-1. Ideally, the diet should contain energy and all of the essential nutrients
in amounts that fall within these ranges of intake.

I ( )I Y'o

                        .:.:.:.:.:.:.:.:.:.:.:.~..:.~.~:.:.~:.~.~: .:
                        .........................................
                      . .
                     ........ . .          ......................... , . .
                       . . ..:.1:.:.~:.:.:.:.:.:.:.:.: .:.
                        . . . . . . ...... . . . . . . ... . ...... . . . . . . ... . ............................
                      .....................................
                     ......................................
                      ..........................................................................
C                    :.:2..~:.:.~:.~:.:.:.:.:.:.:.~..~:.:.:.~:.:.:.:.:.:.:.:.:.:.: .
                     ......................................
.z                ..............................................................................
                      . ..... . . . . . . . . . . . ...... . ... . . . . . . . .... . . . . . . . . . . . . ...... . . . . . . . . . . ......
                      ......................................
                     . . .....................................
5                     ....................................
                      .....................................
                      .................................... . .
C                   :.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.~:.:.:.:.:.~:.:.~.~.:.~~ ...
                      .....................................
3                 .:::::::~::::::::~~::::::::::::::::::::::::::~::::~.::::~:::
L                    . ........................................
                      . . . .... . . . . . . ... . . ..... .................................................
                      .....................................
                      . .....................................
                      ....................................
                      .................................... . .
                      .....................................
                     .....................................
                      ..................................... .
                      .......................................
                      . . . . . . . . .... . . . . . .               .
                           ......................................................
                      .....................................
              .................................................
                        . . . . . . . . . .               .
                           .......................................................
                   ... . .
                   ... ......
                      ...... . ... . . . . ............................................................
                      . . . . . . -. . .
                        . . . .
                         . . . .... ... ..... . . .
                           ........ .
                        . . . . . . .   ..................................................
                             . . . . ...... . . . . . . .... ...... . . . ... .... . . ........ .
                     .........  ............................................................
                      ..................................... .
                     ....................................
                     .:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:        . .
                                 .............................
                                  ...............
                     ~:.:.~:.:.~..:.:.:.:.:.:.:.:.:.:.:.~:.:.~:.:.:.~:.:.~..:.:.:.: .:

*   Concrnkltion or intake of nutrient -

Figure l-l. Dependence of biologic function or tissue concentration on in-
     take ol a nutrient. For nutrients and energy sources, there is a
    range of intake that confers optiil physiologic function. Below
    thII range, deficiincies can cause dii or death. Excecrsive
     intake also can lead to increasiing symptoms of toxkity. The op-
     timal range varies for each nutrient and is affected by many
      indiiidual and environmental factors.

Source: Merlz, W. 1981. The essential trace elements. Science 213:1332-38. Copy-
   right 1981 by the American Association for the Advancement of Science, re-
    printed with permission.

47


u Nutrition and Health

Recommended Dietary Allowances

The need to establish goals for good nutrition in the United States was
recognized in the 1930's and led to the establishment in 1940 of the
Committee on Food and Nutrition, now called the Food and Nutrition
Board, of the National Research Council, National Academy of Sciences.
The Committee's initial purpose was to make sure that the population was
adequately nourished during World War II, and one of its early functions
was to recommend quantities of nutrients that should be provided to the
Armed Forces and the general population. These recommendations led to
the development of goals for intake of nine specific nutrients that would
meet the known nutritional requirements of men, women, and children of
varying ages. These first RDA's were adopted in 1941 (Roberts 1958), and
they have been published at 5- to lo-year intervals since 1943. Although the
original purpose of the RDA's was to promote nutritional health during
wartime, their purpose has expanded over the years to include use for
development of standards for food assistance programs, food labels, and
evaluation of dietary adequacies.

Because research on human nutritional requirements is often incomplete
or inconsistent, and because of variability in individual nutrient require-
ments, the RDA's represent an estimated, rather than an absolute, stan-
dard of dietary adequacy, and they are revised periodically to reflect
current scientific evaluation of the available nutrition research. The most
recent revision was published in 1980 and is presented in Table l-6 (NRC
1980). The RDA's are defined as ". . . the levels of intake of essential
nutrients considered, in the judgment of the Committee on Dietary Allow-
ances of the Food and Nutrition Board on the basis of available scientific
knowledge, to be adequate to meet the known nutritional needs of prac-
tically all healthy persons." Thus, each RDA is deliberately set higher than
the.actual requirement for that nutrient in most individuals.

Specific RDA's have been established for protein, 10 vitamins, and 6
minerals; they are presented in categories that vary according to body size.
gender, and energy consumption (NRC 1980). RDA's are usually higher for
males than for females, except for women who are pregnant or lactating.
For 12 additional nutrients, research has been too limited to establish
specific RDA's and the Food and Nutrition Board has proposed ranges of
daily intake that are considered "safe and adequate." These are presented
in Table l-7. The RDA's are designed to exceed the nutrient requirements
of most individuals, but the allowances for energy are designed to reflect
average needs for people of different heights and weights, ages, and activi-
ty levels.

48


                               Table l-6
              Food and Nutrition Board, National Academy of Sciences-
       National Research Council Recommended Daily Dietary Allowances,a Revised 1960
     Designed for the maintenance of good nutrition of practically all healthy people in the U.S.A.

                                              Fat-Soluble Vitamins
         Age       Weight        Height       Protein    Vitamin A    Vitamin D     Vitamin E
        (years)    (kg)    (lb)    (cm)    (in)     w     ha REJb     (CLkT)C     (mg a-TE)d


   Infants   0.0-0.5                  60     24    kgx2.2       420        IO           3
          0.5-I .o   x   s      71     28    kgx2.0       400        IO           4
   Children    1-3      13      29      90     35       23        400        IO          5
                   20      44     112     44       30        500        IO           6
    7%      28      62     132     52       34        700        IO           7
   Males     11-14      45      99     157     62       45        loo0        IO          8
%          15-18      66      145     176     69       56        looo        IO          IO
           B-22            154     177     70               loo0        7.5         10
          23-50   z     154     178      i:        loo0         5          IO
           51+      70     154     178  ::       56        loo0         5          IO    $
   Females   11-14      46      101     157     62       46        800        IO           8   1
           15-18      55     120     163     64       46        800        IO
           19-22     55     120     163     64       44        800        7.5    t         0
                                                      g.
          23-50      55      120     163             44        800         5           8         1
           51+      55      120     163  iii       44        800         5           8     B
    Pregnant                                     +30       +200        +5         +2         e
   Lactating                                +20       +400        +5         +3         m
                                                                    R
  aThe allowances are intended to provide for individual variations among most normal persons as they live in the United States under usual en-  9
   vironmental stresses. Diets should be based on a variety of common foods to provide other nutrients for which human requirements have been
    less well defined.                                               s
   Wetinol equivalents; 1 RE = 1 kg retinol or 6 pg $ carotene.
   CAs cholecalciferol; 10 pg cholecalciferol = 4000 IU of vitamin D.
   da-tocopherol equivalents: 1 mg d-a tocopherol = 1 a-TE.


                        Table l-6 (continued)                    0
                                     2
                           Water-Soluble Vitamins
        Age Weir&                                      s:
                     Height   Vitamin C Thiamin Riboflavin  Niacin  Vitamin B, Folacinr Vitamin B,,
        (years) (kg) (lb) (cm) (in)   b-fg)    (mg)    (mg)   (mg NEP   (mg)    h3)    (Ia)     iz
                                                           E
    infants   0.0-0.5 6 13                                                                           0.
                        60 24     35      0.3      0.4      6       0.3      30     0.5g      X
          0.5-1.0 9 20   71 28     35      0.5      0.6      8       0.6      45      1.5     i!
   Children    l-3       29   90 35     45      0.7      0.8      9       0.9      loo    2.0 g
       :i   44 II2 44      45      0.9      1.0      II       1.3      200      2.5
    7% 28   62 132 52     45       1.2      1.4      I6       1.6      300     3.0
    Males     II-14 45   99 I57 62     50       I.4      1.6     18              400      3.0
          15-18 66 I45 176 69     60       I.4      1.7     I8   :*:      400      3.0
           19-22  70 154 177 70      60      1.5      1.7     19    212      400      3.0

3          23-50 70 154 178 70     60       I.4      1.6      18       2.2
           51+   70 154 I78 70     60       1.2      I.4     16       2.2   z   :-I
   Females   II-14 46 IO1 157 62     50       I.1      1.3     I5       1.8      400    3:o
            15-18   55 120 163 64      60      I.1      1.3     14       2.0      400      3.0
           19-22   55 120 163 64             I.1      1.3      14       2.0             3.0
          23-50 55 I20 163 64  2      1.0      1.2     I3      iti      3.0
            51+   55 120 163 64     60       1.0      1.2     I3   El     400      3.0
    Pregnant                       +20     +0.4     + 0.3     +2      + 0.6     +400     +1.0
    Lactating                      +40     +0.5     +0.5     +5      +0.5     +100    +1.0
  eNiacin equivalent; 1 NE = 1 mg of niacin or 60 mg of dietary tryptophan.
  f The folacin allowances refer to dietary sources as determined by Lactobacillus casei assay after treatment with enzymes (conjugates) to make
   polyglutamyl forms of the vitamin available to the test organism.
  @Ihe recommended dietary allowance for vitamin B12 in infants is based on average concentration of the vitamin in human milk. The allowances
  after weaning are based on energy intake (as recommended by the American Academy of Pediatrics) and consideration of other factors, such
    as intestinal absorption.


Table l-6 (continued)

Age
(years)

                   Minerals

Weight     Height     Calcium   Phosphorus   Magnesium   Iron   Zinc   Iodine
(kg)   (lb)   (cm)   (in)    bud      (mid      @x3)    kg)   bf3)   (I%)

   Infants     0.045    6     13    60    24      360       240         50     10   :     40
            0.5-1.0    9     20        28      540       360         70      15           50
   Children     l-3     13     29  iz    35     800       800        150      15     10     70
     7%  20 28  44 62  112 132  44 52   800 800   800 800    200 250   IO 10  IO IO  120 90
   Males      11-14    45  1:    157    62     1200      1200        350      18     I5     150
             15-18    66         176    69     1200      1200        400      18     15     150

Y            19-22    70    154    177    70      800       800        350      10     15     150
            23-50    70    154    178    70     800       800        350      IO     15     150
            51+     70    154    178    70      800       800        350      10     15     I50
   Females     II-14    46    101    157    62     1200      1200        300      I8     I5     150
            15-18    55    120    163    64     1200      1200        300      I8     I5     150  z
            19-22    55    120    163    64     800       800        300      18     I5     I50   8
            23-50    55    120    163    64      800       800        300      I8     I5     I50    E
             51+     55    120    163    64      800       800        300      IO     I5     I50   g
    Pregnant                              +400      +400       + I50       h     +5    + 25      3
    Lactating                              +400      +400       + I50       h    + 10    +50   B
                                                                           a
  hThe increased requirement during pregnancy cannot be met by the iron content of habitual American diets nor by the existing iron stores of       m
   many women; therefore, the use of 3040 mg of supplemental iron is recommended. Iron needs during lactation are not substantially different    Pi
   from those of nonpregnant women, but continued supplementation of the mother for 2-3 months after parturition is advisable to replenish
   stores depleted by pregnancy.                    f

   Source: National Research Council 1980.                                       bi
                                              0


O Nutrition and Health

          Table 1-7
Estimated Safe and Adequate Daily Intakes
  of Selected Vitamins and Mineralsa

Age
(years)

Vitamins



Vitamin K
(PIit)

Biotin
(Ia)

Panto-
thenic
Acid
(mg)

Infants         O-O.5       12           35         2
            0.5-l       lo-20         50         3
Children and      l-3        15-30         65          3
Adolescents   30       20-40         85         3-4
                     30-60         120        4-5
              11+        50-100        100-200      47
Adults                   70-140        100-200      &7

    Trace Element+
         Man-                 Molyb-
Age  Copper ganese Fluoride Chromium Selenium denum
Wars) (mg)   (mg) (mg)   (mg)    (mg)    Ow)

Infants     O-O.5  0.5-0.7 0.5-0.7 0.14.5  0.014.04  0.01-0.04 0.03-0.06
        0.5-l  0.7-1.0 0.7-1.0 0.2-1.0  0.02-0.06  0.02-0.06 0.0.08
Children and l-3    1.0-1.5  1.0-1.5 0.5-1.5  0.02-0.08  0.02-0.08 0.05-0.1
Adolescents  4-6    1.5-2.0  1.5-2.0 l&2.5  0.03-0.12  0.03-0.12 0.06-0.15
        7-10   2.0-2.5  2.0-3.0 1.5-2.5  0.05-0.2   0.05-0.2  0.10-0.3
        II+   2.0-3.0 2.5-5.0 1.5-2.5  0.05-0.2   0.05-0.2  0.15-0.5
Adults          2.0-3.0 2.5-5.0 1.54.0  0.05-0.2   0.05-0.2  0.15-0.5 -

                 Electrolytes
          Age       Sodium      Potassium     Chloride
         (years)    (mg)       (mg)       (mg)

Infants         O-O.5       I 15-350      350-925       275-700
            0.5-l       25fL750      425-1275      400-1200
Children and     l-3        325-975      550-1650      500-1500
Adolescents   EO       450-1350      775-2325      700-2100
                     600-1800     100&3000      925-2775
            11+       900-2700     1525-4575     14Ot+t200
Adults                 1100-3300     1875-5625     1700-5100
aBecause there is less information on which to base allowances, these figures are not
given in the main table of RDA and are provided here in the form of ranges of recom-
mended intakes.
Wecause the toxic levels for many trace elements may be only several times usual in-
takes, the upper levels for the trace elements given in this table should not be habitually
exceedad.

Source: National Research Council 1980.

52


Introduction and Background 0

The fact that most RDA's are intentionally established to exceed the
nutrient requirements of most people means that a dietary intake below the
RDA is not necessarily inadequate for an individual whose requirement for
a nutrient is average or even above average (NRC 1980). It also means that
the small percent of persons who- have unusually high nutrient require-
ments may not meet nutritional needs even when they consume nutrients at
RDA levels. The RDA's are estimates of the nutrient requirements for
populations rather than for individuals. In addition, RDA's may need to be
modified for people who are ill or injured.

Translating the RDA's into a single, universally applicable, ideal pattern of
food choices that best supports health and longevity is, for many reasons,
difficult. As noted above, individual nutrient requirements depend upon
complex interactions between genetic and environmental factors and the
stage of physiologic development. The nutritional needs of infants. young
adults, and older persons vary, and dietary habits and preferences differ
markedly from culture to culture and from individual to individual.

A definition of the food choices that best fu!fill nutrient requirements has
been a goal of the many Federal agencies and private health organizations
that have developed sets of dietary recommendations during the past
decade (Dwyer 1983; McNutt 1980). Some of these recommendations are
noted in Table 1-5; the evidence on which they are based is presented
throughout this Report. Most current recommendations emphasize that it
is the overall dietary pattern that determines whether or not nutrient
intakes are likely to fall within desirable ranges. Public health concerns
about specific nutrients, therefore, usually are directed to the kinds and
amounts of foods consumed and to the genetic, behavioral, and environ-
mental factors that affect food choices.

The diet must contain adequate energy, all essential nutrients, and certain
other dietary factors to sustain normal growth, development, and health.
The nutrients and dietary factors discussed in this Report include carbohy-
drates, fats, and proteins-the macronutrients-which are sources of ener-
gy as well as of essential fatty acids and amino acids that either cannot be
synthesized or are synthesized in amounts inadequate to meet body needs;
micronutrients-vitamins and mineral elements-which are necessary in
small amounts; and substances such as fiber, which does not fall into either
category but is nonetheless beneficial for good health. This section defines
these nutrients as background for this Report. Basic information on essen-
tial nutrients has been reviewed extensively (see, for example, Nutrition
Reviews 1984; Passmore and Eastwood 1986; Schneider, Anderson, and
Coursin 1983; Shils and Young 1988).

53


LJ Nutrition and Health

Energy

The diet must supply sufficient energy to support growth and development,
maintain basic physiologic functions, meet the demands of muscle activity,
and repair damage caused by illness or injury. In the United States, energy
intake and expenditure are measured in kilocalories, abbreviated as kcal,
and referred to as Calories or, commonly, calories. In international usage,
the term is kilojoules, abbreviated kJ (1 kcal=4.184 kJ). In this Report, the
terms energy and calories are used interchangeably to refer to the general
concept of energy; specific measures of energy intake or expenditure or the
energy value of food are given in kilocalories.

The body obtains chemical energy from food from the oxidation (chemical
burning) of protein, fat, carbohydrate, and, when it is consumed, alcohol.
The oxidation within the body of 1 g each of these substances in pure form
yields about 4,9, 4, and 7 kcal, respectively. Thus, fat contains more than
twice the caloric value of either protein or carbohydrate. The health signiti-
cance of the relatively high energy value of alcohol is discussed in the
chapter devoted to this topic.

Body weight depends on complex physiologic controls of the balance
between energy intake and energy expenditure. Both intake and expendi-
ture are equally important in regulation of body weight. Weight increases
when more energy is consumed than expended. Over time, such an imbal-
ance can lead to obesity. The physiologic controls of that balance and the
ways in which diet and exercise affect body weight are reviewed in the
chapter on obesity.

Carbohydrates

Carbohydrates are sources of energy for vital metabolic processes and also
are constituents of cellular substances such as nucleic acids, glycoproteins,
and enzyme cofactors and structural components of cell walls and cell
membranes. Carbohydrates are classified as monosaccharides, disac-
charides, and polysaccharides. Monosaccharide and disaccharide sugars
are referred to as simple carbohydrates and the polysaccharides (starches
and fibers) as complex carbohydrates.

Monosaccharides. Monosaccharides are simple sugars that do not need to
be further digested to be absorbed. The most important dietary monosac-
charides are glucose, fructose, and galactose. Glucose and fructose are
found in fruits, vegetables, and honey. They are also products of the
digestion of sucrose (table sugar) and, in the case of glucose, other disac-
charides. The glucose obtained from corn starch can be converted by

54


Introduction and Background O

enzymatic processes to fructose to produce high fructose corn sweeteners.
As discussed below, galactose is a subunit of the disaccharide lactose.

Disaccharides. Sugars formed from two monosaccharides are called disac-
charides. Sucrose, common table sugar, is composed of glucose and fruc-
tose. It is found in many fruits and vegetables but occurs in especially high
concentrations in sugar beets and sugar cane. Maltose is a disaccharide of
two glucose molecules and is found in beer, glucose syrups, and cereals.
Lactose, the sugar of milk, is composed of one molecule of glucose and one
of galactose.

Polysaccharides. Starch, glycogen, and most types of fiber are large. high-
molecular weight polysaccharides. Starch and glycogen are composed of
glucose molecules. Fiber includes a variety of carbohydrates and other
components. These molecules differ from each other in the ways their
monosaccharide units are linked to each other and, therefore, in their
ability to be digested to sugars that can be absorbed into the body. The
chemical linkages in starch and glycogen can be split by human intestinal
enzymes, but those of polysaccharides found in fiber are, by definition,
indigestible although some fiber components can be broken down by
enzymes released by bacteria in the digestive tract to short-chain fatty
acids that can be reabsorbed and furnish small amounts of energy.

Fiber. Dietary fiber is a term used to describe a heterogeneous group of
plant food components that are resistant to human digestive enzymes
(LSRO 1987). Not all are fibrous in the usual sense of the word, and some
are even soluble. Dietary fiber includes some of the structural components
of plant cell walls (e.g., cellulose and noncellulosic polysaccharides such as
hemicellulose) and certain nonstructural components of cells such as pec-
tins, gums, brans, mucilages, algal polysaccharides, and modified cel-
lulose.

Specific types of dietary fiber are often classified as soluble or insoluble on
the basis of their response to extraction methods. In general, the soluble
fibers include gums, mucilages, and some pectins and hemicelluloses,
while insoluble fibers include cellulose, lignin, and other pectins and
hemicelluloses. Although all fruits, vegetables, and grains contain these
fiber components, some are especially good sources of one or another type.
Oat bran and beans, for example, contain relatively large proportions of
soluble fibers whereas wheat bran is a good source of insoluble fiber. In
general, diets that contain large amounts of fiber add bulk and may confer
greater feelings of satiety.

55


The effect\ of the WI'WU~ fiber types on intestinal function differ, however.
Insoluble fibers that adsorb water increase stool weights. Some soluble
fibers have been found in short-term studies to reduce blood cholesterol,
enhance glucose tolerance, and increase insulin sensitivity (LSRO 1987).
These issues are reviewed in appropriate chapters of this Report.

Lipids

Dietary fats or lipids include a variety of substances soluble in organic
solvents, such as chloroform or benzene, but insoluble in water. Food lipids
include triglycerides (composed of fatty acids and glycerol), phospholipids,
and cholesterol. Any excess of energy in the body, whether derived from
carbohydrate, fat, protein, or alcohol, can be converted to fatty acids and
stored in adipose tissue triglyceride, but dietary fat is essential because it
supplies linoleic acid (an essential fatty acid) and it is a vehicle for absorp-
tion of fat-soluble substances such as the vitamins A, D, E, and K (NRC
1980).

Lipids are concentrated sources of energy as well as structural components
of cell membranes and are molecular precursors for the synthesis of hor-
mones and other substances. In adults, these functions usually can be met
by a daily intake of 15 to 25 g of fat (NRC 1980), a level well below that
typical of current American diets. In addition, fats impart characteristic
mouth-feel and flavors to foods and increase the feeling of satiety after
meals by delaying the passage of food from the stomach to the small
intestine. The reservoirs of fat stored in the body protect the body's organs,
provide insulation from heat loss, and maintain energy production during
long periods of reduced food consumption, such as in starvation, dieting, or
serious illness or injury.

Furt.v Acids. Fatty acids are molecules containing carbon. hydrogen, and
oxygen with chain lengths ranging from 4 to about 25 carbon atoms. A small
amount of food fat occurs as phospholipid. Most fat in food, however,
occurs as triglycerides, three fatty acid chains attached to a glycerol
molecule. Triglycerides are called fats or oils depending on whether they
are solid or liquid at room temperature. Both provide concentrated sources
of metabolizable energy, about 9 kcal/g, more than twice the level of either
proteins or carbohydrates. Recent studies suggest that the caloric value of
fat may appear even higher in growing rats, reflecting greater efficiency of
utilization under certain circumstances (Donato and Hegsted 1985; Donato
1987).

56


Introduction and Background 0

The fatty acids commonly found in food are usually composed of an even
number of carbon atoms, usually 12 to 22, and contain from 0 to 6 double
bonds-sites where additional hydrogen atoms can be attached. The
number of double bonds determines the degree of saturation of fats. Fatty
acids with no double bonds are saturated, those with one double bond are
monounsaturated, and those with two or more double bonds are polyun-
saturated.

Although all dietary fats consist of a mixture of saturated, monounsatu-
rated, and polyunsaturated fatty acids, fatty acids in foods of animal origin
are more often saturated, while those in plants are more likely to be
monounsaturated and polyunsaturated. There are some important excep-
tions to this generalization. Coconut oil and palm kernel oil contain a high
proportion of saturated fatty acids even though they are derived from
plants, and as discussed below, certain fish are good sources of polyunsatu-
rated fatty acids.

The location of double bonds along the carbon chain is also of physiologic
importance. The site of the double bonds is used to categorize unsaturated
fatty acids into three groups-the omega-3, omega-6, and omega-9 fatty
acids. In the metabolism of fatty acids, the end of the carbon chain
containing the methyl group (whose carbon atom is known as the omega
carbon) tends to remain unchanged, whereas enzymes can add or subtract
carbon atoms or double bonds starting from the end of the molecule that
contains the carboxyl group. For convenience, the chemical features of
fatty acids are usually described in terms of the structure at the methyl end
of the chain. Oleic acid has nine carbon atoms between its methyl omega
carbon atom and its closest double bond, so it belongs to the omega-9
family of fatty acids. Linoleic acid and the compounds to which it is
connected in the body have six carbons between their omega carbons and
closest double bonds, and they are omega-6 fatty acids. Linolenic acid and
its derivatives have three carbons between the omega carbon and the
closest double bond and are omega-3 fatty acids.

Monounsaturated omega-9 fatty acids such as oleic and palmitoleic acids
are not essential in the human diet because they can be synthesized
biochemically within the body. Linoleic acid, an omega-6 fatty acid, can-
not be synthesized by the human body and must be consumed in the diet. It
is a component of cell membranes and is required for the synthesis of
arachidonic acid, the major precursor of prostaglandins, prostacyclins,
thromboxanes, and leukotrienes that influence many physiologic pro-

51


0 Nutrition and Health

cesses, including blood vessel dilation, platelet aggregation, smooth mus-
cle contraction, inflammation, and reproduction. Linoleic acid is widely
distributed in the fatty portion of both plant and animal foods. Vegetable
seed oils are especially rich sources. Symptoms of its deficiency have been
reported among infants restricted to skim milk and among children and
adults fed intravenous solutions lacking fat (Rivers and Frankel 1981).
Linoleic acid deficiency can be prevented by consuming about 3 to 5 g of
linoleic acid a day, an amount considerably less than that consumed by the
average adult in the United States. Thus, essential fatty acid deficiencies
are reported rarely in the United States (NRC 1980).

The role of omega-3 fatty acids, particularly eicosapentaenoic acid and
docosahexaenoic acid, in human nutrition and health is under active inves-
tigation. Omega-3 fatty acids are present in the human brain, retinal lipids,
and phosphoglycerides of synaptic membranes. Of current interest are the
potential health effects of these highly polyunsaturated fatty acids derived
from linolenic acid (omega-3).

Recent epidemiologic, clinical, and experimental data suggest that
omega-3 fatty acids may have important physiologic effects that cannot be
met by omega-6 or omega-9 fatty acids. Some of these effects are reviewed
in the chapter on coronary heart disease.

Cholesterol. Cholesterol is a fatty substance required for synthesis of sex
hormones, bile acids, and vitamin D, and it is an important constituent of
all cell membranes. It is both synthesized in the body (endogenous) and
obtained from the diet (exogenous) and is not, therefore, an essential
nutrient. In normal individuals, endogenous synthesis of cholesterol is
reduced when blood cholesterol levels are high. When the physiologic
mechanisms that regulate this feedback mechanism are insufficient, blood
cholesterol levels can rise and increase the risk for coronary heart disease
(see that chapter). Dietary cholesterol is found only in foods derived from
animals (meat, poultry, fish, eggs, and dairy products); it is not present in
plants.

Protein

Body proteins serve many functions; they include structural components
of cells and tissues, enzyme catalysts of biochemical reactions, peptides
and hormone messengers, and components of the immune system. The
amino acids in proteins can also serve as sources of energy, and most can
be used to synthesize glucose when dietary carbohydrate is inadequate.
Some amino acids are needed for the synthesis of special compounds;

58


Introduction and Background 0

tryptophan, for example, is required for synthesis of serotonin (a neu-
rotransmitter) and niacin (a vitamin).

Proteins are formed from various combinations of amino acids that are
linked together in chains ranging from several to hundreds in length. Each
plant and animal species has its own characteristic proteins that are distin-
guished by the sequence of amino acids. Plants can synthesize all of their
amino acids from the elements carbon, oxygen. hydrogen, nitrogen, and
sulfur, but humans lack the ability to synthesize at least eight amino acids
and must obtain them from the diet. The rest are called nonessential amino
acids because, although needed for protein synthesis, they are not required
in the diet. Essential amino acids include isoleucine, leucine, lysine, methi-
onine, phenylalanine, threonine, tryptophan, and valine. The amino acid
cystine can replace part of the requirement for methionine, and tyrosine
can replace part of the requirement for phenylalanine. Histidine is an
essential amino acid for infants, but its essentiality for adults has not been
conclusively demonstrated (NRC 1980).

The proteins in different foods vary in their biologic value due to their
content and balance of amino acids. When the concentration of one essen-
tial ammo acid is low relative to the others, that amino acid is considered
limiting and the protein is said to be incomplete. The presence of limiting
amino acids in incomplete proteins can be compensated for at least par-
tially by dietary intake of complementary proteins, those with different
limiting amino acids. When consumed together or within a short time (the
exact length of time has not been defined), such proteins can meet require-
ments for essential amino acids. This explains, in part, why strict vege-
tarians can maintain good health without eating foods derived from ani-
mals. The addition of even a small amount of protein from animal foods can
improve amino acid intake. The RDA's for protein intake of men, women,
and children of different ages are given in Table l-6.

Vitamins

Vitamins are organic (carbon-containing) compounds that are essential in
very small amounts for health, growth, and reproduction. They must be
obtained from the diet either because they cannot be synthesized at all by
the body or because the amounts made are insufficient to meet require-
ments. Vitamins are classified according to their solubility in fat or water,
and this property affects their occurrence in foods as well as their absorp-
tion, transport, storage, and metabolism.

59


t.~,r-.~,,/rr/~/e C'itclmins. The fat-soluble vitamins are vitamins A, D, E, and
k. These vitamins are generally found in high concentrations in the fatty
portions of food and are absorbed, transported, metabolized, and stored
along with fat. Their absorption requires bile and dietary fat. They are
transported in the body by the same mechanisms by which fat is trans-
ported, are bound to lipoproteins or specific transport proteins, and are
stored in liver and fat tissue. Fat-soluble vitamins are excreted into the
intestine in bile and are either reabsorbed or are eliminated in feces. They
are not excreted to any appreciable extent in urine. Because excretion of
fat-soluble vitamins is minimal, excess intake is more likely to cause
toxicity symptoms. For the same reason, deficiencies are reported rarely
among healthy adults, although they are observed among children who are
growing rapidly and who lack adequate fat stores and among children or
adults who have disease conditions that interfere with fat metabolism, such
as malabsorption, biliary obstruction, or renal or liver disease. The RDA's
for vitamins A, D, and E are given in Table 1-6; the estimated safe and
adequate intake of vitamin K is shown in Table l-7.

Vitamin A is present in the diet both as the vitamin and its precursor.
Retinol, or preformed vitamin A, is found in foods derived from animals
(milk, butter, egg yolks, liver) and, when bound to a fatty acid, is used to
fortify many foods. Retinol occurs in foods primarily in the ester form.
Certain carotenoids (pigments found in many dark green, yellow, and
orange vegetables, fruits, and egg yolks) can be converted by the body into
retinol. The conversion of beta-carotene into retinol occurs mainly in the
intestinal mucosa. Retinol circulates in the plasma bound to a specific
transport protein called retinol-binding protein. Excess amounts are stored
in the liver. Bxcessive intake of retinol has caused toxic symptoms (head-
ache, skin and bone disorders, and renal failure) among people consuming
abnormally large amounts of vitamin supplements, or-less commonly-
liver from animals with high vitamin A levels (Selhorst et al. 1984; Ma-
honey et al. 1980). High intakes of retinol supplements have also been
associated with birth defects (Rosa 1986); synthetic retinoid analogs, used
to treat a variety of skin disorders (Bollag 1983), can cause fetal malforma-
tions. They are hazardous to pregnant women or women planning to
become pregnant (Lammer et al. 1985) and should be used only under
medical supervision. Excess amounts of beta-carotene are stored in body
fat deposits. Excessive intake of foods rich in beta-carotene, such as
carrots, is not known to cause toxic effects. It raises levels of carotene in
the blood and can cause the skin to take on an orange color that disappears
when the carotene consumption declines. Vitamin A is essential for visual
processes, for the normal differentiation of epithelial tissue, for the regula-
tion of cell membrane structure and function, and for the maintenance of

60


Introduction and Background O

immunocompetence. Vitamin A deficiency, through adverse effects on eye
epithelial tissues, is a major cause of blindness among children in many
developing countries, and it is also responsible for substantial additional
illness. Recent studies of children consuming inadequate levels of retinol
or carotenes suggest that retinol supplementation may improve their sur-
vival (Sommer et al. 1986; Tarwotjo et al. 1987).

Vitamin D, (cholecalciferol or calciol) is synthesized from a precursor (7-
dehydrocholesterol) in skin that becomes activated by exposure to ultra-
violet light from the sun. It is essential in the diet only when exposure to sun
is inadequate. The vitamin is converted by the liver to 25-dihydrox-
yvitamin D (calcidiol) and then further converted by the kidney to 1,25-
dihydroxyvitamin D (calcitriol), the metabolically active form. Excess
vitamin D can be toxic, especially to children and adults who have kidney
disease or certain metabolic disorders. The metabolism and functions of
vitamin D are reviewed in detail in the skeletal diseases chapter.

Vitamin E functions as an antioxidant. Its principal dietary sources are
vegetable seed oils. Its deficiency has been associated with a hemolytic
anemia in premature infants and with neurologic symptoms in adults.
Vitamin K functions as an activator of blood clotting proteins, proteins in
bone and kidney, and the formation of other proteins that contain gamma-
carboxyglutamic acid (GLA). It is synthesized by intestinal bacteria. Thus,
deficiencies generally occur only in infants whose intestinal flora has not
yet been established, in children and adults receiving antibiotic or anti-
coagulant therapy (see chapter on drug-nutrient interactions), and in indi-
viduals with disease conditions that interfere with intestinal absorption.
Vitamins E and K are less toxic than vitamins A or D.

Water-Soluble Vitamins. The water-soluble vitamins include vitamin C
(ascorbic acid) and those of the B-complex group: biotin, folate, niacin,
pantothenic acid, riboflavin, thiamin, vitamin B,, and vitamin B,,. The
RDA's for vitamin C, thiamin, riboflavin, niacin, vitamin B,, folacin, and
vitamin B,, are presented in Table 1-6; the safe and adequate ranges of
intake of biotin and pantothenic acid are given in Table l-7. These vitamins
are generally found in whole grain cereals, legumes, leafy vegetables, and
meat and dairy foods. The two exceptions are vitamin C, which can be
obtained in adequate amounts only from fruits and vegetables, and vitamin
B,,, which is made by bacteria and found only in foods of animal origin.
Water-soluble vitamins are absorbed from the intestine, and most are
stored in a form that is bound to enzymes or transport proteins and
excreted in urine. Thus, they should be supplied in adequate amounts in the
daily diet even though tissue depletion may take as long as weeks or
months.

61


0 Nutrition and Health

Water-soluble vitamins are essential components of enzymes and enzyme
systems that catalyze a wide variety of biochemical reactions in cellular
energy production and biosynthesis. Thus, deficiencies of these vitamins
particularly affect tissues that grow or metabolize rapidly, such as skin,
blood, and the cells of the digestive tract and nervous system. Common
deficiency symptoms are skin disorders, anemia, malabsorption and diar-
rhea, neurologic disorders, and defects in tissues of the mouth. Specific
vitamin deficiencies infrequently occur in the United States. When defi-
ciencies occur, they usually are found along with other deficiencies and are
due to diseases or to consumption of highly restricted diets or excessive
amounts of alcohol or drugs that interfere with vitamin metabolism. The
risk for deficiencies is greater in growing infants (see maternal and child
nutrition chapter) and, perhaps, in older persons (see chapter on aging).
Substantial intake of these vitamins causes toxicity infrequently, although
severe toxic reactions have been reported from very excessive intakes of
niacin and vitamin B,.

Minerals

Minerals perform a number of roles in the body. They function as inorganic
components of enzyme systems that catalyze the metabolism of protein,
carbohydrate, and lipids. Some act to regulate fluid and electrolyte bal-
ance, to provide rigidity to the skeleton, and to regulate the function of
muscles and nerves. Minerals also work together with vitamins, hormones,
peptides, and other substances to regulate the body's metabolism.

Essential minerals are often classified as macrominerals, required in
amounts from several hundred milligrams to 1 or more grams a day (cal-
cium, phosphorus, magnesium, sodium, potassium, and chloride), or as
trace elements-iron, zinc, iodine, copper, manganese, fluoride, chro-
mium, selenium, molybdenum, and cobalt (as a component of vitamin
B&-which are required in small amounts (Underwood 1977). Other
minerals such as nickel, vanadium, silicon, or boron have been shown to be
essential under rigorous conditions for experimental animals but do not
have well-established functions in humans. Still others, such as lead or
mercury, are potentially toxic. RDA's for six minerals are given in Table
1-6. Ranges of dietary intake considered safe and adequate are given for
nine others in Table l-7.

Minerals are distributed in a variety of foods, but they usually are present
in limited amounts. Thus, diets must contain enough of a variety of foods to
meet daily requirements. People consuming diets low in energy for pro-

62


Introduction and Background 0

longed intervals are at risk of developing mineral deficiencies. Deficiencies
can also result from therapy with medications that interfere with mineral
absorption and metabolism; alcoholism, renal disease, or gastrointestinal
diseases (see relevant chapters); and causes of mineral loss such as bleed-
ing or diarrhea. Toxic symptoms can result from consumption of excessive
amounts of almost any mineral or as a result of defective regulation of
absorption or inadequate excretion.

Dietary Patterns

There are two types of data for monitoring dietary patterns: food availabili-
ty and dietary intake. Food availability data are derived from annual
estimates of per capita availability of selected commodities in the food
supply. These data are useful in examining changes over time in the
availability of agricultural commodities. Estimates of dietary intake come
from periodic national food consumption surveys of individuals.

Time Trends in the Availability of Foods

Food availability data are produced by the USDA and are derived from
annual production and marketing estimates of food products that are then
usually adjusted for imports, exports, and stock changes. Such data have
been collected since 1909 and have been published as a historical series
from 1909 to the mid-MO's (USDA 1968). Data for the most recent 20
years are published annually (Bunch 1987). Per capita estimates of food
availability are derived by dividing the total amount of food available by the
total U.S. population. These data represent economic rather than phys-
iologic consumption because they estimate the amount of food available at
wholesale and retail levels rather than actual intake by individuals. Certain
limitations restrict use of such data as proxies for consumption--for exam-
ple, the difficulty in correcting for wastes and losses that occur before
consumption by individuals, for inedible food components and food for
human consumption fed to pets, or for variabilities in intakes of population
subgroups.

Nonetheless, food availability data provide useful information when used
within their appropriate limits of interpretation. Time trend changes in
availability of foods are best estimated from these data because the data
have been available on an annual basis for many years. At the current time,
these data are also the best source of information for tracking changes in
the use of commodities or products that can be substituted for one another
(e.g., partial substitution of high-fructose corn syrup for refined sugar).

63


O Nutrition and Health

A summary of the recent trends is noted below, taken mainly from the data
of the last two decades as presented in Table 1-8 (Bunch 1987), but in part
from the early data series as well (USDA 1968).

Overall, total per capita availability of meat, poultry, andfish increased by
about 10 percent since 1965-67, primarily due to increases in poultry and
fish and shellfish. Availability of red meat increased substantially after
World War II (USDA 1968) but, after peaking in about 1970, has since
declined to approximately 1965-67 levels.

Egg availability reached its peak about 1950. During the past 20 years, it
has declined by about 18 percent; this is approximately equivalent to a
decrease of one egg per week per person (from about six to five eggs per
week).

The availability of fluid whole milk declined by 48 prp"nt from 1965-67,
while available levels of low-fat milk and milk products (including yogurt)
more than doubled from 1%547 to 1983-85. Cheese availability also more
than doubled during this period.

Availability off&s and oils increased by approximately 23 percent since
1965-67, primarily due to a 77 percent increase in salad and cooking oil and
a 36 percent increase in shortening. Butter availability was about 18 lb per
capita per year in 1909 (USDA 1968) and has declined to about 5 lb,
including about a 20 percent decline since 1965-67 (Bunch 1987). Availabil-
ity of total animal fat also declined by 1983-85, to levels approximately 80
percent of those in 1%5-67, but with a slight recent increase. Over the two
decades, vegetable sources increased from 67 percent to 79 percent of all
fats and oils-in marked contrast to the first half of the century when
animal sources provided most of the fats and oils (USDA 1968).

As noted earlier, these data represent availability of commodities and thus
do not necessarily reflect changes in actual intakes of fats and oils by the
U.S. population. For example, there is no correction for losses of fats and
oils used for deep fat frying, which are discarded after use rather than
consumed. Second, the bulk data represent only fats and oils that are added
to foods or used in table spreads; they do not include "hidden" fats in foods
such as marbled fat in meats or the fats in nuts.

Vegetable undfruit availability increased from 1%567 by 19 percent and 7
percent, respectively, primarily due to increases in availability of fresh
produce. There was, however, no consistent change in availability of
legumes (beans, peas, and nuts) or starchy vegetables (potatoes and sweet
notatoes).

64


                              Table 1-8
            Annual Per Capita Availability of Selected Commodities in the
                    U.S. Food Supply, 198!%1989
                         (pouts)

             Meat, Poultry, and Fishb                     Dairy Productsd
                                                     Low-fat Milke
                                              Fluid      and Milk
                      Fish and                Whole      Products
   Year      Meat   Poultry    Shellfish   Total Ew     Milk      (fluid)      Cheese'    Totab

   1965-67    123.6     30.6      10.8     165.0 40.0     240.3        41.7         9.8     343.9
z   1968-70    130.8     33.0      11.3     175.1     39.5     219.5        54.6        11.0     334.6
   1971-73    129.5     35.1      12.3     176.9    38.2     199.2        69.3        12.9     327.7
   1974-76    128.7     35.5      12.4     176.6    35.1     176.0        82.9        14.9     317.1
   1977-79    126.2     40.1      13.0      179.3    34.6     155.9        95.3        16.8     310.2   g
  1980-82    120.9     44.2      12.7      177.8     33.9     138.1       101.7        18.7     299.7
   1983-85    120.9     47.6      13.8     182.3    32.8     125.3       111.4       21.5     301.7    &
                                                                           C
  aTotals may include more categories than the selected commodities.                                 a.
  bMeat (beef, veal, pork, lamb), poultry, and fish, edible weight. Fish excludes game fish (Bunch 1987, Table 9, p. 15).             B
  cEggs, retail weight. Weight of a dozen eggs is assumed to be 1.57 lb (Bunch 1987, Table 8, p. 14).
  d Dairy products are for civilian population, except fluid milk and cream data, which use U.S. resident population (Bunch 1987, Table 10. p. 16).    f2
  BLOW-fat and other milk products include low-fat, skim, buttermilk, flavored drinks, and yogurt.                2
  `Cheese is whole and part-whole milk cheese, excluding pot, baker's, and cottage cheese.                            6
  gTotal dairy products calculated as total retail product weight minus butter (Bunch 1987, Table 10, p. 16). Includes frozen dairy products, cot-  g
  tage cheese, and other products not indicated in table. The amount of calcium contributed by this food group has actually increased slightly
  during the 20-year period shown, as a result of increases in products such as dry milk powder.                     g
                                              0


Table l-8 (continued)

Year

1965-67
I 968-70

g:   1971-73
   1974-76
   1977-79
   1980-82
   1983-85

                     Fats and Oil@

    Animal                Vegetable
                                Salad and
          Total                Cooking    Total
Butter Lard Animal Margarine  Shortening     Oil    Vegetable Total

5.9    5.7    16.9     10.3       15.4       12.6      35.2    52. I
5.5    5.0    16.0     10.7       16.9       14.4      38.8    54.9
4.9    3.7    14.1     11.0       17.2       16.7      41.9    56.0
4.5    2.9    II.6     Il.4       17.2       18.5      44.8    56.4
4.4    2.3    II.6     Il.3       17.9      20.0      46.3    57.9
4.4    2.5    12.8     II.2       18.4       21.6      48.1    60.9
4.9    2.0    13.5     10.5      20.9      22.3      50.6    64.1

Fruit@        2.

Fresh  Processed   Total

79.0     35.3     114.3
77.1     37.6     114.7
75.5     39.4     114.9
79.9
80.4  2:    120.5
            120.2
84.8   37:1     121.9
87.9    34.8     122.7

hFood fats and oils calculated on a total population basis except butter, which is based on civilian population (Bunch 1987; animal and vegeta-
ble fats are from Table 2, p. 7; butter, lard, margarine, shortening, and salad and cooking oil are from Table 12, p. 18). The animal and vegeta-
ble categories are not strictly distinct because some margarines and shortenings include animal fats.
I Selected fruits, retail weights. Include fruits for which data are available for the entire series: oranges, tangerines, tangelos, lemons and limes,
grapefruit, apples, avocados, bananas, cherries, grapes, nectarines, peaches, pears, pineapples, plums and prunes, strawberries, minor fruits,
and a variety of canned, frozen, and chilled fruit and juices (Bunch 1987, Table 2, p. 7).


Table l-8 (continued)

          Vegetablesi                          Sugar and Sweeteners'
                                Potatoesk
                       Beans,     and    Flour and   Refined             Total
                    Peas, and   sweet    Cereal     Cane      Corn     Caloric   Coffee, Tea
   Year    Fresh Processed Total   Nuts    Potatoes   Pruducts   and Beet   Sweeteners Sweeteners   and Cocoa

   1%5-67   62.6    41.4    104.0    14.8     84.5     143.8      97.6      15.5      114.8      15.1
%   1968-70  65.2    45.4    110.6   14.8     85.1     141.9      100.6      18.2      120.4      14.5
   1971-73   66.1    45.9   112.0    14.2      80.6     138.5     101.7      21.8      125.0      14.2
   1974-76  68.9    46.1    115.0   15.1      81.5     143.6      92.7      27.3      121.4      13.1
   1977-79  71.7    46. I    117.7    14.3     81.5     145.8      91.7      33.8      126.X      II.1
   1980-82  74.3    44.2    118.6   * 14.0      76.3     150.2      78.9      44.4      124.6      II.3   $
   1983-85  79.7    44.7    123.3    14.6     79.5     150.5      67.4      58.3      127.1      II.6        0
  I Selected vegetables: fresh vegetables for which data are available for entire series include broccoli, carrots, cauliflower, celery, corn, lettuce,   g
  onions and shallots, and tomatoes; 1985 data for processed vegetables are unavailable (Bunch 1987, Table 2, p. 7).             g.
  kPotatoes and sweet potatoes: data not comparable to pre-1980 figures. Data revised to reflect conversion from processed weight to fresh-        1
  weight equivalent to dehydrated potatoes, frozen potatoes, chips, and shoestrings (Bunch 1987, Table 2, p. 8).                E
                                                                           a
  1 Sugars and sweeteners, dry weight basis (Bunch 1987, Table 27, p. 33).                     r


m Nutrition and Health

Availability of jlour and cereal products showed both decreasing and
increasing fluctuations during the 20-year period; 1983-85 levels were
approximately 5 percent higher than 1%5-67 levels. Availability of grains
was at its lowest point this century in 1971-73, but has since increased by
about 9 percent.

Availability of sugars and sweeteners increased by about 11 percent since
1965-67. It should be noted that the availability data for sugars and sweet-
eners are for bulk commodity forms only; they do not include estimates of
sugars that are consumed as a natural constituent of food products, for
example, lactose in milk or sugars naturally present in fruits.

Availability of coffee, tea, and cocoa decreased approximately 25 percent
since 1%5-67.

Current Dietary Intakes

Food consumption surveys can be used to estimate food and nutrient
intakes of populations and population subgroups. The most recent nation-
ally representative survey is the first Continuing Survey of Food Intakes by
Individuals (CSFII), conducted by the USDA in 1985. Data are limited to
three subgroups: children 1 through 5 years and adult men and women 19
through 50 years of age. Results are presented based on 1 day of intake
(Table l-9). When applicable, estimated mean intakes are compared with
recommendations in the latest report on RDA's (NRC 1980). In interpret-
ing results, it should be noted that the RDA's (except for energy) have a
margin of safety above average requirements. Thus, diets that do not meet
the RDA's do not by themselves provide conclusive evidence of nutritional
deficiencies. Corroborating health data are needed.

Food Energy. Men and children had estimated mean intakes of more than
90 percent of the Recommended Energy Intakes (REI); for women, the
estimated mean intake was 82 percent of the REI.

Total Fat, Fatty Acids, and Cholesterol. Fat contributed 34 percent of total
energy intake for children and 36 to 37 percent for men and women. The
relative fatty acid contributions were approximately 40 percent saturated,
40 percent monounsaturated, and 20 percent polyunsaturated. Cholesterol
intakes ranged from a mean of 254 mglday for children to 304 and 435 mg for
women and men, respectively.

Protein. For men, women, and children, estimated mean intakes were 140
percent or more of the RDA. Protein contributed approximately 16 percent
of total energy intakes.

68


Introduction and Background cl

Table l-9

Mean Daily Intake of Food Energy, Nutrients, and Food
Components for Men, Women, and Young Children From the
Continuing Sutvey of Food Intakes by Individuals (CSFII), 198!jb
                     Men   Women        Children
Total Food Energy (% REW       (94)     (82)          (loo)

Fat [% total energy]
  Total fat
Saturated fatty acids
Monounsaturated fatty acids
polyunsaturated fatty acids
Cholesterol mg
Protein
[(9$ tgflrgyl
Carbohydrates I% total energy]
Dietary Fiber g
Vitamins (% RDA)
Vitamin A
Vitamin E
Vitamin C
  Thiamin
Riboflavin
  Niacin
Vitamin B,
Vitamin B,*
  Folacin
Minerals (% RDA)
  Calcium
Phosphorus
  Iron
  Zinc
Magnesium
Minerals (ESADDI)'
Sodium
Potassium

1361
t131
(141
171
435

1163
(175)
[451
18

(122)
(98)
(182)
(124
(129)
(146)
(85)
(245)
(76)

(115)     (78)
(192)    (126)
(159)     (61)
(94)     (60)
(94)     (72)

(exceeds)
(within)

(within)
(within)

(371
[I31
If41
t71
304

[161
(144)
1461
12

(127)
(97)
(133)
(110)
(115)
(130)
(61)
(156)
(51)

[341
[I41
1121
161
254

[161
(222)
1521
10

(215)
(108)
(186)
(153)
(197)
(151)
(127)
(192)
(157)

(105)
(132)
(88)
(84)
(121)

    (exceeds)
(l-3 years exceeds)
(4-5 years within)

(below)

(below)

Copper              (below)
+&mated mean daily intake is expressed in several ways: amount of intake, percent of
total energy intake, percent of Recommended Dietary Allowance, or comparison wrth Es-
timated Safe and Adequate Daily Dietery Intake.
bData based on 1 -day dietary recalls obtained by personal interview for !58 men 19 to 50
years of age for 1 459 women 19 to 50 yeers of age, and for 489 of !herr chrldren.1 to 5
years of age'in 19& (unweighted numbers). Nutrient Intakes do not Include vrtamln and
mineral supplements or sodium from salt added at the table.
~Recommended Energy Intake (NRC 1980); Source of percentages: NFCS, CSFII Report
Nos. 85-l and 85-3 (USDA 1985,1986).
dRecommended Dietery Allowance (NRC 1980); Source of percentages: NFCS, CSFII Re-
port Nos. 65-1 and 85-3 (USDA 19851989).
*Estimated Safe and Adequate Daily Dietary Intake (NRC 1980).

69


O Nutrition and Health

Diel<ip WM. Estimated mean intakes were 10 g/day for children, 12 g for
women. and 18 g for men. For all three groups, these intake values
corresponded to levels of about 7 g/l,000 kcal.

Calcium. Children and men had estimated mean intakes of 105 and 1 IS
percent of the RDA, respectively. For women, estimated mean intakes
were 78 percent of the RDA.

Iron. For women and children, estimated mean intakes were 61 percent
and 88 percent of the RDA, respectively. For men, the estimated mean
intake was 159 percent of the RDA.

Sodium and Potassium. For men and children, estimated mean intakes of
sodium from foods alone (excluding salt added at the table) exceeded the
upper limit of the Estimated Safe and Adequate Daily Dietary Intake
(ESADDI) (Table l-7). For women, the estimated mean intake of sodium
was within the ESADDI. For children 1 to 3 years, the estimated mean
intake of potassium exceeded the ESADDI. For children 4 to 5 years, men,
and women, the estimated mean intake of potassium was within the ESADDI.

Other Nutrients. The estimated mean intakes for the following nutrients
were close to or above 100 percent of the RDA for men, women, and
children: vitamin A, vitamin E, vitamin C, thiamin, riboflavin, niacin,
vitamin B,,, and phosphorus.

Nutrients for which estimated mean intakes were below recommended
levels for one or more groups were vitamin B, (women had a mean intake of
less than 70 percent of the RDA; men had mean intake of less than 90
percent of the RDA), folacin (women had a mean intake of less than 60
percent of the RDA; men had a mean intake of less than 90 percent of the
RDA), zinc (women had a mean intake of less than 70 percent of the RDA;
children had a mean intake of less than 90 percent of the RDA), and copper
(men, women, and children had mean intakes below the lower limit of the
ESADDI).

Use of Nutrient Supplements

Between 35 and 40 percent of the U.S. population took vitamin or mineral
supplements in the late 1970's and early 1980's (Koplan et al. 1986; Stewart
et al. 1985). In the 1985 CSFII, 58 percent of women and 60 percent of
children reported using supplements on a regular or occasional basis,
levels that are 19 and 12 percentage points higher, respectively, than those
for comparable age and gender groups in the 1977-78 NFCS (USDA 1985).

70


Introduction and Background _1

An FDA telephone survey on the levels of 21 nutrients consumed from
supplements indicated that median intake ranged from the RDA level to
about six times the RDA. For some nutrients, intake levels for some people
were as much as 60 times the RDA. The most commonly consumed
nutrient (91 percent of users) was vitamin C, either used alone or as a
component of other supplements (Stewart et al. 1985).

Supplement use is higher among females than among males, higher in the
West than in other regions of the United States, and higher in whites than in
nonwhites (Koplan et al. 1986; Read et al. 1981; Read et al. 1986; Schutz et
al. 1982; Stanton 1983; Worthington-Roberts and Breskin 1984; Block et al.
1988). Higher use of vitamin supplements is also associated with older ages,
higher incomes, and higher educational levels (Koplan et al. 1986; Carry et
al. 1982; Read and Graney 1982). Limited information is available on
supplement use by children. The National Health Interview Survey re-
ported that 36 percent of children to age 17 took a vitamin/mineral supple-
ment during a 2-week period in 1981. Use of supplements was highest
among younger children (46 percent of children to age 2 and 49 percent of
children ages 3 to 6) and was higher in the winter than in any other season
(Kovar 1985).

NHANES II data show a correlation between dietary intake of nutrients
and nutrient supplementation. Persons with higher nutrient intakes from
foods alone are more likely to take supplements than those with deficient
intakes, even after adjusting for the effects of other variables (Koplan et al.
1986). Analysis of types of foods consumed by people who take nutrient
supplements showed similar results. Supplement users tended to consume
more of all types of fruits and vegetables and, therefore, more dietary
vitamin C (Looker et al. 1987). A recent review of surveys of supplement
usage in the United States concluded further that use of supplements is
frequently inappropriate, that exceptionally high intake among certain
population groups raises concerns about the potential for toxicity, and that
nutrition education and research are needed to combat supplement abuse
(McDonald 1986).

Criteria for Scientific Judgment

Research on the relationship of dietary factors to disease is often compli-
cated by the complexity of the variables, the intricacy of the interactions,
and the disparate nature of the analytical tools. Thus, for many nutritional
research questions, proof of causality in the classic scientific sense (i.e.,
uniform causality or absolute protection) is often not attainable. Whereas

71


0 Nutrition and Health

classic nutritional disorders such as beriberi, pellagra, or scurvy could be
clearly and directly demonstrated to be deficiencies of single identifiable
nutrients, it has proved far more diflicult to demonstrate that associations
between specific dietary factors and chronic diseases are causally related.

Development of the major chronic disease conditions-coronary heart
disease, stroke, diabetes, or cancer-is affected by multiple genetic, en-
vironmental, and behavioral factors among which diet is only one-albeit
an important+omponent. These other factors interact with diet in ways
that are not completely understood. In addition, foods themselves are
complex; they may contain some factors that promote disease as well as
others that are protective. The relationship of dietary fat intake to causation
of atherosclerotic heart disease is a prominent example. An excess intake
of total fat, if characterized by high saturated fat, is associated with high
blood cholesterol levels and therefore an increased risk for coronary heart
disease in many populations. A higher proportion of mono- and polyun-
saturated fats in relation to saturated fats is associated with lower blood
cholesterol levels and, therefore, with a reduced risk for coronary heart
disease.

Because of these complexities, definitive scientific proof that specific
dietary factors are responsible for specific chronic disease conditions is
difficult-and may not be possible-to obtain, given available technology.
An ideal study to demonstrate a causal association between a specific
dietary factor and cancer, for example, would feed otherwise identical diets
varying only in that factor to two large groups of children with comparable
family histories, environments, and behavioral patterns. The study would
then compare cancer rates in each group for the 30 to 50 years or more that
it might take the disease to develop. Although this study would constitute a
direct test of the hypothesis, it is evident that such research would be
impractical and prohibitively expensive, as well as slow in yielding results.

For these reasons, researchers generally identify a relationship between a
dietary factor and disease from studies in laboratory animals and from
observations in humans. Data sources for human studies include laborato-
ry measurements of blood nutrient levels or other biochemical measures of
nutritional or risk status, population estimates of dietary intakes, and
estimates of individual dietary intake based on recall. Epidemiologic stud-
ies using these data sources can compare dietary intake and disease rates in
different countries or in defined groups within the same country (ecologic
correlation studies). Another approach compares levels of dietary or bio-
chemical indicators in persons with a specific condition to those observed

72


Introduction and Background O

in persons without the condition (case-control studies). And it is sometimes
possible to conduct prospective studies that compare dietary intake and
disease rates in defined groups over time.

Biochemical, epidemiologic, and dietary intake studies can provide useful
information, but each has important limitations. Interpretation of animal
studies is always limited by uncertainties about their applicability to hu-
mans. Laboratory measurements reveal only a small part of the complex
physiologic processes involved and do not always reflect current nutri-
tional status. Dietary surveys depend on recall of the types and portion
sizes of consumed foods (Basiotis et al. 1987). Epidemiologic studies can
only demonstrate an association or correlation between a dietary risk
factor and a disease; they cannot prove that the dietary factor causes the
disease. For example, a study might show that populations consuming
high-fat diets have higher rates of breast cancer than populations consum-
ing low-fat diets. Although such a study demonstrates an association be-
tween fat and breast cancer, it may be that some genetic, environmental, or
other dietary factor might be the true cause of the apparent relationship
between fat and breast cancer. Prospective studies must be conducted with
precisely comparable populations under strictly controlled conditions that
may be difficult to achieve or to maintain for a sufftciently long period of
time to observe significant differences in disease rates.

For these reasons, the relationship between diet and disease is usually
inferred from the totality of existing laboratory, animal, dietary, genetic,
metabolic, and epidemiologic evidence. Such inferences must be based on
the application of established principles for making determinations of the
quality of scientific evidence (Lilienfeld and Lilienfeld 1980). These princi-
ples include:

Consistency of the Associafion. Evidence gathered from a range of bio-
chemical, animal, epidemiologic, and clinical studies should all produce
results that support the possibility that a dietary factor is causally associ-
ated with increased disease risk. Repeated findings in different population
groups and in different countries should consistently yield similar results.

Strength ofrhe Association. The more powerful the correlation between
dietary intakes and a health outcome, the more convincing the evidence. A
causal relationship between dietary fat and coronary heart disease. for
example, would be more credible if all individuals with coronary heart
disease-but no healthy individuals-routinely consumed high-fat diets.
Most diseases, however, are caused by multiple factors. and perfect corre-

73


O Nutrition and Health

spondence cannot be expected. Instead, the strength of association is
expressed as a correlation between levels of exposure and disease rates in a
population. The greater the correlation between dietary fat and coronary
heart disease in a population, the more that correlation supports an in-
ference that dietary fat increases coronary risk. Strength of association
also can be expressed as a relative risk-the ratio of disease rates in the
population exposed to the dietary factor (e.g., consuming high-fat diets) to
the population that has not been exposed (e.g., consuming low-fat diets). A
high relative risk supports an inference that a dietary factor increases
disease risk.

Specificity of rhe Association. Demonstration of specificity in an associa-
tion makes a causal hypothesis more convincing. Complete specificity only
occurs, however, when a single cause is totally responsible for one-and
only one-disease or condition and is, therefore, both necessary and
sufficient. Because few nutritional factors act in complete independence of
other factors, and many have roles in more than one disease, this criterion
has limited applicability to evaluation of nutritional evidence.

Degree ofExposure to a Factor. If a dietary factor causes a disease, the risk
for developing the disease should increase with the degree of exposure to
the factor. The higher the fat intake in a population, for example, the greater
should be the rate of coronary heart disease. While evidence of such dose-
response relationships increases the plausibility of associations between
dietary factors and disease, dose responses are often difficult to demon-
strate because of variations in dietary intake and uncertainties in evaluating
food and nutrient consumption.

Biological Credibility. There should be a reasonable physiologic explana-
tion for the relationship between the dietary factor and the health outcome.
Exposure to the dietary factor should precede the onset of disease, with
appropriate latent or induction periods.

Experimentation and elucidation of physiologic and molecular mecha-
nisms provide the most direct evidence for a causal relationship between a
dietary factor and a specific disease condition. Epidemiologic studies
provide evidence in support of such associations. Although this evidence
usually is indirect, it can accumulate in quantity and quality to the point
where a causal relationship appears sufficiently probable to provide a
reasonable basis for public health action.

Application of these principles to development of a dietary recommenda-
tion for reduction of risk for a given disease must consider the effect of that

74


Introduction and Background O

recommendation on the risk for other chronic diseases and on require-
ments for energy and nutrients. The evidence presented in this Report
suggests that similar dietary patterns affect the risk for several chronic
diseases. For example, diets containing a large proportion of calories from
foods high in fat but low in complex carbohydrates and fiber are associated
not only with increased risk for coronary heart disease. but also with
increased risk for some types of cancer, diabetes. and obesity. Evidence
also suggests that potentially competing risks can be accommodated within
recommended changes in such patterns. For example. the recommenda-
tions to consume adequate calcium yet reduce overall fat intake can be
accommodated by advice to select low-fat dairy products. Consequently,
the interdependent nature of dietary changes to reduce disease risk have
been considered along with the criteria described above in developing the
overall findings and recommendations of this Report.

75


O Nutrition and Health

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Owen, G.M.; Kram, K.M.; Garry, P.J.; Lowe, J.E.; and Lubin, A.H. 1974. A study of
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Passmore. R., and Eastwood. M.A. 1986. Davidson and Passmore human nutrition and
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Porter, D. 1986. A National Nutrition Monitoring System: briefbackgroundand bill compari-
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Introduction and Background O

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Rosa, F.W. 1986. Retinoic acid embryopathy. New England Journal of Medirine 315: 262.

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0 Nutrition and Health

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Chapter 2

Coronary Heart Disease

The heart in itself is not the beginning of life:
but it is a vessel formed of thick muszle.
vivified and nourished by the artery and vein
     as are the other muscles.
   Leonardo da Vinci ( 1452-I 5 19)
    The Notebooks of Leonardo

Introduction

Coronary heart disease (CHD) is a term used to identify several cardiac
disorders resulting from inadequate circulation of blood to local areas of
heart muscle. This deficiency is nearly always a consequence of focal
narrowing of the coronary arteries by atherosclerosis. Atherosclerosis is a
progressive disease that often begins in childhood. The earliest lesions
probably arise in the lining of the coronary arteries or in the aorta, often by
ages 10 to IS. They appear first as fatty streaks. some of which may later
progress to fatty or fibrous plaques and, eventually. large complicated
lesions (Berenson 1986). The result of the progressive narrowing of the
vessels may be angina pectoris, myocardial infarction (heart attack). or
sudden death. These are the most common manifestations of CHD. Else-
where in the body, the same process may lead to serious and sudden
decrease of the blood supply to the brain (ischemic stroke). peripheral
vascular disease, or serious problems caused by weakening of the lower
abdominal aorta. The development of CHD is a silent process generally
lasting decades before the onset of symptoms. Of the half-million heart
attack deaths that occur annually, approximately 60 percent occur sud-
denly or outside of a hospital before treatment can be administered (Kannel
and Thorn 1984). Thus, much attention is directed at the prevention of CHD
by identifying and modifying risk factors before clinical disease develops.

The causes of CHD are multifactorial. It is generally accepted that high
blood cholesterol, high blood pressure, and cigarette smoking play causal
roles in the development of atherosclerosis. which leads in turn to narrow-
ingof the arteries and development of CHD. Diet plays an important role in

a3


O Nutrition and Health

the regulation of blood cholesterol levels and influences other risk factors
for CHD as well. For millions of Americans, the most effective CHD
preventive strategies are to avoid smoking cigarettes, to control high blood
pressure, and to lower high blood cholesterol.

This chapter focuses on the influence of diet on the development, treat-
ment, and prevention of CHD. The role of diet in hypertension is reviewed
in the chapter on high blood pressure.

Historical Perspective

Interest in atherosclerosis and its relationship to dietary factors can be
traced to observations made in 18th and 19th century medicine. During that
period, the fatty nature of the plaque was described and cholesterol was
identified in the blood (see historical review, Stamler 1967). In the early
20th century, atheromatous aortas were found to contain excessive
amounts of cholesterol (Windaus 1910). These observations led to a series
of experiments to induce atherosclerosis in animals by feeding them a diet
rich in fats and cholesterol. In 1912-13, typical arterial atherosclerosis was
produced in rabbits by feeding pure cholesterol dissolved in vegetable oil
(Anitschkow 1967).

At that time, another line of investigation was based on the theory that
atherosclerosis was caused by toxic products of protein metabolism. Nutri-
tional experiments, in which large amounts of foods rich in animal protein
were fed to rabbits, produced changes in the aorta similar to those in
humans. The observed effects were later attributed to the high cholesterol
content of the experimental diets (Anitschkow 1967).

Early observations by clinicians and pathologists working in the colonies of
British India, Indonesia, Africa, and Latin America were consistent with
the pathologic and experimental findings. More than 50 years ago, these
workers observed the relative rarity of CHD among the native populations
compared with European and North American populations and associated
this finding with the nature of the habitual diets. Whereas native groups
consumed diets composed mainly of vegetable products, the Westernized
population consumed large quantities of eggs and butter (Raab 1932).

Subsequent epidemiologic studies, including long-term prospective stud-
ies, of CHD mortality among many national, occupational, racial, and

84


Coronary Heart Disease _I

religious subgroups have established three major modifiable risk factors for
developing CHD: cigarette smoking, high blood pressure. and high levels
of blood cholesterol.

Significance for Public Health

Deaths from CHD are declining in this country, and this decline has been
attributed both to improved medical care and changes in lifestyle. Thus,
from 1964 to 1985, the age-corrected CHD death rate has dropped by more
than 42 percent, resulting in 350,000 fewer deaths in 1986 than would
otherwise have occurred. A recent analysis of the effects of changes in
medical intervention and changes in lifestyle attributes 30 percent of this
decline to reductions in plasma cholesterol (Goldman and Cook 1984).

Despite this decline, however, CHD still accounts for more deaths an-
nually than any other disease or group of diseases. More than 1.25 million
heart attacks occur each year (two-thirds occur in men), and more than
500,000 people die as a result (NHLBI 1984). Death rates for CHD in men
under age 65 and in women under age 75 are higher among blacks than
among whites, the reverse being true in older persons (Tables 2-l and 2-2).
Available data show lower rates for CHD in the Hispanic population than
in non-Hispanic whites (Heckler 1985).

          Table 2-1
Death Rate for Coronary Heart Diseese
by Age, Race, and Sex, United States, 1985

Age (ye-)
Total
Under 45
454
G-74

  Death Rate per 100,000 Population=
White Men   Black Men   White Women

  180.8       164.9        82.9
   8.2        13.2         1.7
  294.5       317.8        85.1
1.132.6      990.6        SC%.0

Black Women

   100.8
    4.3
   161.1
   645.9

75 &d over

'
3,071x

2,205.o      2,010.2       1,717s

BAge-adjusted to the U.S. population, 1940.

Source: National Center for Health Statistics. In press.

85


O Nutrition and Health

         Table 2-2
Prevalence of Coronary Heart Disease
by Age, Race, and Sex, United States, tg85

Age (Years)

Prevalence per 1,000 Persons

Men       Women       White      Black

Total           32.9        24.1
Under 45         0.9a         1.e
45-64           80.9         44.4
65-74           175.6        107.0
75 and over       169.0        124.6
aFigure does not meet standards of reliability or precision.

31.8        11.3a
1.3'        l.la
65.1        46.3
143.9        62.2
154.7           a

Source: National Center for Health Statistics 1 W6a.

CHD ranks fast as the reason for Social Security disability (Social Security
Administration 1982), third after arthritis and hypertension for limitation of
activity (Collins 1986), and third after mental illness and all forms of cancer
for total hospital bed days (NCHS 1987). According to information from
the National Heart, Lung, and Blood Institute (NHLBI), morbidity and
mortality from CHD cost the United States an estimated $49 billion a year
in 1985 in direct health care expenditures and lost productivity. Further-
more, it has been estimated that unless there are reductions in risk factors
or improvements in the efficacy of therapies, CHD prevalence and inci-
dence will increase in the future because of the aging of the population,
especially with maturation of the post World War II baby boom generation
(Weinstein et al. 1987).

High Blood Cholesterol (Hypercholesterolemia) and CHD Risk
An extensive body of clinical evidence supported by animal, epidemiolog-
ic, and metabolic studies has established the relationship between high
blood cholesterol and increased CHD risk (Grundy 1986). The relationship
is strong, continuous, and graded.

Until recently, it was unclear whether this relationship held only for blood
cholesterol levels above a threshold value of about 200 to 220 mg/dl.
However, data from the 361,000 men ages 35 to 57 screened for the
Multiple Risk Factor Intervention Trial indicate that the association is
apparent at even lower levels-about 180 mg/dl (Stamler, Wentworth, and
Neaton 1986; Martin et al. 1986).

Average blood cholesterol levels for adult American men and women are
211 and 215 mg/dl, respectively (NCHS 1986b). Individuals whose choles-
terol levels are within the top 25 percent of the cholesterol distribution

86


Coronary Heart Disease 0

(above 240 mg/dl) have been defined as being hypercholesterolemic and at
substantially higher risk (Consensus Development Panel 1985).

Scientific Background

The effects of dietary factors on circulating lipids in blood were among the
earliest observations of factors influencing lipid metabolism and the ath-
erogenic process. A voluminous literature has accumulated over the past
75 years on the relationship between diet, lipoproteins, atherogenesis, and
CHD. The primary conclusions of this research are (I) that the higher the
total blood cholesterol level, the greater the severity of atherosclerosis and
the greater the risk for CHD, (2) that dietary saturated fat and cholesterol
raise total blood cholesterol and low density lipoprotein (LDL) cholesterol
levels, and (3) polyunsaturated fat lowers total blood cholesterol and LDL
cholesterol levels (Levy et al. 1979). Monounsaturated fat also appears to
lower blood cholesterol (Grundy et al. 1986).

Atherogenesis

Atherosclerosis is a combination of changes in the inner lining of arteries
that occur in response to vessel injury and repair. These changes, as well as
elevations in the blood lipids, including cholesterol, permit the excessive
entry of proteins and lipoproteins, especially LDL, from the blood into
focal regions of the artery wall. In general, LDL is thought to enter intact,
but some may have been modified by oxidation or by glycosylation (as in
diabetes). They may also undergo alteration, which makes them more
atherogenic, after entering the artery wall. Some evidence suggests that
very low density lipoproteins (VLDL) may also injure the vessel wall in
some individuals with hyperlipidemia (Bradley, Gotto, and Gianturco
1985).

Injury of the blood vessel may also allow certain cells from the blood to
adhere to its lining or to enter it, causing low-grade chronic inflammation,
which helps to stimulate the proliferation of the arterial cells. The resulting
arterial plaque is made up mostly of these modified and rapidly dividing
arterial smooth muscle cells, proteins from the blood (especially lipopro-
teins and their transported fats, including cholesterol), and other cells such
as platelets and monocyte/macrophages from the blood. Smooth muscle
cells multiply in the plaque, apparently partly in response to growth factors
carried to them by blood platelets and released at the site where the
platelets adhere when they aggregate. The proliferating cells produce an
excessive amount of collagen, elastin, and intercellular matrix. Throm-
botic processes probably also participate in the progression of the plaque,
especially when endothelial injury becomes more severe.

87


O Nutrition and Health

Figure 2- 1 illustrates the microscopic appearance of arterial plaque created
as a result of the interaction of these various mechanisms. The smooth
muscle cell proliferation in conjunction with cellular accumulations of
cholesterol and fat-filled macrophages or foam cells results in a tissue mass
with a fibrous layer, or cap, on the lumen (interior) side of the artery.
Within the plaque, dead cells and lipid debris, which represent the break-
down of earlier stages of plaque growth, form acentral core. This is the soft
cholesterol ester-rich component from which the lesion derives its name
(athero-"gruel") (Wissler 1985).

Lipoprotein Metabolism

The link between high blood cholesterol and atherogenesis has been eluci-
dated through studies of lipoprotein metabolism. Lipoproteins are the
protein carriers of lipids in the blood. Four classes of plasma lipoproteins
are generally recognized. They are designated according to their density,
which depends on their relative proportions of protein and lipid; those that
contain the greatest proportion of lipid are the lightest. Chylomicrons, the
lightest lipoproteins, contain mostly triglyceride (90 percent) and originate
when dietary fats are delivered to the blood stream via the intestinal lymph.
Very low density.lipoproteins mainly manufactured by the liver, are also
rich in triglyceride (65 percent). The low density lipoproteins normally
carry 60 to 70 percent of the circulating cholesterol. High density lipopro-
teins (HDL) are the heaviest lipoprotein particles because they contain a

    Necrotic Center
   (cell debris, cholesterol
   crystals, cholesterol
;/ esters, calcium)

    Ehdothelium

Fibrous Cap
(proliferated smooth
muscle cells. collagen,
extracellular and
intracellulai lipid,
including foam cells)

Media

Adventitia

Fgure 2-1. Diagram d an athenrsclerotic plaque The advanced atherosclerotic
szr -the t2ho&Wd- and
                necroWcoreandIheiibrouscap.

Source: Conner, W.E., and Bristow, J.D., eds. 1985. Coronary heart disease: Prevention,
    complications and treatment, p. 194. Philadelphia, PA: Lippincott.
    Reprinted with permission.

88


Coronary Heart Disease 0

relatively higher proportion of protein (approximately 50 percent by
weight) (Rifkind 1982). All of these lipoproteins contain cholesterol but in
varying amounts. All contribute to the total blood cholesterol level. An
increase in any of them therefore contributes to high blood cholesterol.
Lipoproteins are generally measured in the blood as the cholesterol frac-
tion, for example, HDL cholesterol.

The metabolism of lipoproteins is largely determined by the composition of
their protein components, or apoproteins. Some apoproteins serve pri-
marily a structural role in lipid transport; others serve as functional units
that are recognized by and bind to cell receptors. Still other apoproteins
appear to act as cofactors for enzyme systems involved in catalyzing the
intravascular changes in lipoproteins or their entry or exit from cells.
Advances in techniques for measuring the composition and structure of
lipoproteins are providing new insights into mechanisms controlling lipid
metabolism and the process of atherogenesis. Although much information
is available on how diet affects circulating levels of lipoproteins and the
process of atherogenesis, less is known about its effects on the underlying
mechanisms.

Low Density Lipoproreins. Low density lipoprotein is the major atherogen-
ic lipoprotein and usually accounts for most of the CHD risk associated
with elevated plasma total cholesterol (Gordon et al. 1977b). The level of
LDL in the blood is an important determinant of the rate at which choles-
terol is deposited in the artery walls. Low density lipoprotein levels are
also influenced by other risk factors such as diabetes, cigarette smoking,
and obesity (Schwarz et al. 1982).

The level of circulating LDL is determined by specialized proteins called
LDL receptors, located on the surface of cells in the liver and other tissues
(Goldstein, Kita, and Brown 1983). The number of receptors is determined
by the cholesterol needs of the cell. Although cells are capable of making
their own cholesterol, their receptors can also bind cholesterol-rich LDL
particles and remove them from the circulation, leading to the incorpora-
tion of their cholesterol into the cell. If uptake of cholesterol by this route is
decreased, as when the number of receptors is deficient, the cell increases
its own synthesis of cholesterol. When the cholesterol is not withdrawn by
the cells, LDL accumulates in the plasma and may be taken up by the
arterial wall cells by mechanisms that do not involve LDL receptors.

Although the synthesis of cholesterol by the liver is under feedback regula-
tion from dietary cholesterol, a reduction in dietary cholesterol intake to
lower levels (~300 mg/day) will cause a net plasma cholesterol decrease

89


O Nutrition and Health

despite increased endogenous synthesis (Ernst and Levy 1980). The ability
with which dietary cholesterol suppresses endogenous cholesterol syn-
thesis varies greatly among individuals (Quintao, Grundy, and Ahrens
1971). Dietary cholesterol appears to suppress LDL receptor function in
humans (Appelbaum-Bowden et al. 1984).

Much information about the consequences of diminished LDL receptor
production has come from studies of individuals with familial hyper-
cholesterolemia (FH) (Goldstein, Kita, and Brown 1983). This disease is
caused by a genetic inability to synthesize normally functioning LDL
receptor protein, causing very high circulating levels of LDL cholesterol,
severe atherosclerosis, and often death in early adulthood from heart
attack. In the most severe form of FH, accelerated and clinically cata-
strophic CHD occurs in early childhood in the absence of any other risk
factors and is caused solely by elevated LDL cholesterol. Although the
receptor defect in FH is genetically determined, other factors, such as
increasing age and high-fat diets, may also lead to diminished receptor
function in normal individuals (Brown, Kovanen, and Goldstein 1981).

Baboons, rabbits, and dogs maintained on low-fat diets have a high number
of LDL receptors, and their circulating LDL levels are much lower than
those of humans. When dogs and rabbits are fed high-fat diets, receptor
activity is decreased by as much as 90 percent and circulating LDL levels
rise (Brown and Goldstein 1984). At birth, infants have blood LDL con-
centrations similar to newborns of other species, apparently because of
their ability to produce LDL receptors. In Western societies, LDL levels
rise threefold to fourfold by adulthood. Clinical studies have suggested that
this increase is attributable to a decrease in the numberof receptors (Brown
and Goldstein 1984). The cause of this receptor deficiency is not known, but
a high-fat diet may be an important contributing factor. Diets high in
saturated fat and cholesterol cause cholesterol to accumulate in cells and
the liver, which could lead to a reduction in the number of LDL receptors.
In some animals, dietary cholesterol has been reported to inhibit LDL
receptor function by 30 percent, even in the presence of added polyunsatu-
rated fat, and saturated fat may depress receptor function by as much as 90
percent (Spady and Dietschy 1985).

Experiments with cultured cells suggest that LDL receptor activity oper-
ates optimally at an LDL blood concentration of 25 mg/dl (Brown and
Goldstein 1986). Average LDL cholesterol levels of 120 mg/dl in adult
Western populations far exceed optimal levels (Goldstein and Brown 1977).
This suggests that the human LDL receptor system evolved to function at
low LDL levels and that a substantial portion of humanity may not be

90


Coronary Heart Disease 0

genetically adapted to the relatively recent introduction of high dietary fat
intake (Tiger 1980). This hypothesis is consistent with epidemiologic tind-
ings relating elevated LDL cholesterol to dietary fat intake (Brown and
Goldstein 1984).

High Density Lipoproteins. High density lipoprotein is considered to pro-
tect against CHD. Numerous epidemiologic studies have shown that the
higher the HDL cholesterol level, the lower the risk for CHD (Heiss et al.
1980). Female sex, estrogen use, exercise, moderate alcohol consumption,
and weight loss have been associated with higher levels of HDL: in con-
trast, obesity and cigarette smoking have been associated with lower levels
(Heiss et al. 1980). Some components of the HDL fraction may be involved
in removing cholesterol from cells (reverse cholesterol transport) and
inhibiting deposition of cholesterol in arteries, but the precise role of HDL
is not well understood.

Very Low Density Lipoproteins. Very low density lipoprotein consists
primarily of triglyceride of endogenous origin. The relationship between
triglyceride and CHD is complex (NIH 1983). Although triglyceride levels
are positively associated with an increased risk ofCHD in most prospective
population studies, they are closely associated with attributes such as
obesity, total cholesterol, HDL levels, hypertension, and cigarette smok-
ing and generally not independently predictive of CHD risk (Hulley et al.
1980). Elevated triglyceride may be an independent risk factor in older
women (Gordon et al. 1977a).

However, almost all case-control studies of survivors of myocardial infarc-
tion have shown higher triglyceride levels in the affected patients, and
many diseases associated with high triglyceride levels, such as diabetes
mellitus, chronic renal disease, and certain primary hyperlipidemias, are
associated with an increase in risk for cardiovascular disease (NIH 1983).
Moreover, plasma triglyceride levels between 250 and 500 mg/dl may be a
marker of lipoprotein abnormalities that are more directly associated with
atherosclerosis, such as low HDL cholesterol. Alternatively, elevated tri-
glycerides may reflect the presence of abnormal, triglyceride-rich lipopro-
tein particles or their metabolic products that may enhance atherogenesis.
Whether or not triglycerides are directly involved in the atherogenic pro-
cess, the identification of elevated levels may help to identify persons with
increased CHD risk.

Expert Reports and Recommendations
Numerous expert bodies have examined the evidence relating diet to CHD
and its implications for public health. Although there are many determi-

91


Ll Nutrition and Health

nants of blood cholesterol levels, no modifiable factor has been shown to
influence cholesterol and LDL more profoundly than diet. The average
adult American currently consumes a diet in which about 37 percent of the
total calories is contributed by fat and 13 percent of calories by saturated
fat. Dietary cholesterol is estimated to be about 300 to 400 mg/day (USDA
1985a, 1985b). These levels of saturated fat and cholesterol, the major
determinants of blood cholesterol, exceed those in countries with low CHD
rates, indicating the need for vigorous promotion and dissemination of
appropriate dietary guidance.

Federal recognition of this need is demonstrated in the USDA/DHHS Di-
em-y Guidelinesfor Americans issued in 1980 and revised in 1985 (USDA/
DHHS 1985). The guidelines, which are being widely distributed and
promoted in the public and private sectors, emphasize the reduction of fat,
saturated fat, and cholesterol in diets for healthy Americans and suggest
some ways to reduce these components through appropriate food selec-
tion.

A national preventive strategy to reduce the risk of CHD was enunciated in
the 1980 DHHS report Promoting Health, Preventing Disease: Objectives
for the Nation (DHHS 1981). Specific objectives are aimed at controlling
high blood pressure, stopping smoking, lowering blood cholesterol levels,
and reducing the prevalence of obesity. By 1990, the report states, the mean
cholesterol level in the adult population ages 18 to 74 should be at or below
200 mg/dl.

In 1984, the NHLBI and the National Institutes of Health Office of Medical
Applications of Research convened a consensus development conference
on Lowering Blood Cholesterol to Prevent Heart Disease (Consensus
Development Panel 1985). After reviewing much of the available data, the
consensus panel of lipoprotein experts, cardiologists, primary care physi-
cians. epidemiologists, nutrition scientists, biostatisticians, experts in pre-
ventive medicine, and lay representatives unanimously concluded, despite
consideration of some dissenting views (Ahrens 1985) that elevated blood
cholesterol is a major cause of CHD and that the risk for heart attacks due
to CHD should be reduced by lowering elevated blood cholesterol levels.
specifically, blood levels of LDL cholesterol. The panel members sug-
gested that although the benefits of blood cholesterol reduction had been
demonstrated most conclusively in men with elevated levels, the evidence
justified the conclusion that women with elevated levels would be afforded
similar protection. The panel further recommended designation of individ-
uals with blood cholesterol levels above the 75th percentile (the upper 25
percent of values) as being at special risk and requiring vigorous treatment

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Coronary Heart Disease O

with dietary measures. It also recognized that dietary treatment of elevated
blood cholesterol in children requires special consideration to ensure
adequate nutrients for growth and development and to meet energy needs.
Older persons, who are at increased risk for malnutrition. may also require
special care to ensure adequate intake of essential nutrients.

The panel members asserted that the average blood cholesterol level in the
United States is too high. largely because of high intakes of calories,
saturated fat, and cholesterol. They recommended that all Americans,
except children under age 2, adopt a diet with total dietary fat intake of 30
percent of total calories, with less than 10 percent of calories from saturated
fatty acids; limit polyunsaturated fat intake to a maximum of IO percent of
calories; and limit daily cholesterol intake to 250 to 300 mg or less. These
dietary recommendations are compatible with food intakes of countries
with low CHD prevalence. The panel further advised that caloric intake be
reduced if necessary to correct for obesity and that it be adjusted to
maintain ideal body weight (Consensus Development Panel 1985).

Although the consensus panel considered the moderate-fat, moderate-
cholesterol diet recommended for the genera1 public to be suitable for all
members of the family over 2 years of age, special concern was expressed
about promotion of cholesterol-lowering diets for children because such
diets might inadvertently compromise their nutritional needs (Ahrens
1985). The American Academy of Pediatrics has recommended modera-
tion with respect to decreases in saturated fat and cholesterol, noting that
30 to 40 percent of calories from fat seems sensible for adequate growth and
development (AAP Committee on Nutrition 1986; see chapter on maternal
and child nutrition). Diets that avoid extremes, it states, are safe for
children for whom there is no evidence of specific vulnerability.

National Cholesterol Education Program

The NHLBI is providing the focus for a national effort to reduce cholester-
ol levels through the National Cholesterol Education Program (NCEP),
initiated in 1985. The NCEP has issued detailed guidelines for treatment of
adults with high blood cholesterol (NCEP 1988a) and recommendations for
improvements in the measurement of blood cholesterol (NCEP 1988b).
Future panel reports will provide recommendations for the general public
and for treatment of high blood cholesterol in children and adolescents
(Lenfant 1987).

The report of the NCEP Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults (NCEP 1988a) defined
categories of risk according to measurement of total cholesterol and, when

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0 Nutrition and Health

indicated, subsequent evaluation of LDL cholesterol (Table 2-3). Patients
with borderline high blood cholesterol (200 to 239 mg/dl) and no other risk
factors should be given cholesterol-lowering dietary information and
should be reevaluated annually. Lipoprotein analysis is recommended for
patients either with high blood cholesterol (240 mg/dl or greater) or with
borderline high blood cholesterol and CHD, or with two other risk factors
(one of which can be male sex). The LDL cholesterol is the basis for
initiating treatment. Persons with borderline high LDL cholesterol levels
(130 to 159 mg/dl) and CHD or two other risk factors and persons with LDL
cholesterol levels of 160 mg/dl or greater should be treated to lower their
cholesterol.

The report recognized that diet is the cornerstone of therapy to reduce
borderline and high-risk blood cholesterol levels whether or not drug
therapy is eventually added to the regimen; in general, drug therapy is not
recommended without at least 6 months on optimal diet. The advent of
highly effective drugs for the treatment of elevated blood cholesterol levels
may stimulate widespread use as an alternative to diet therapy. Concerns
have been raised about this potential trend because all lipid-lowering drugs
have potential side effects, and adverse effects may not become manifest
for many years (Grundy 1986). Many patients can reduce their cholesterol
levels substantially with diet alone (see Dietary Guidance, Special Popula-
tions section). When drugs are required, concomitant modification of the
diet may reduce their dosage requirements, cost, and potential side effects.
Based on the NCEP adult treatment guidelines (NCEP 1988a), it is esti-
mated that over 40 million adult Americans could be candidates for dietary
education or treatment.

Other Reports

A compilation of 47 major reports addressing the public health issues of
habitual diet and CHD risk issued since 1968 reveals a common theme-
recommendations for less total fat, less saturated fat, and control of

         Table 2-3
National Cholesterol Education Program
Adult Treatment Panel Classification

                 Total Cholesterol
                mg/dl
Desirable               <200
Borderline high           2W239
High                  >240
                         -
Source: National Cholesterol Education Program 1988a.

LDL Cholesterol
  mg/dl
   Cl30
  130-159
   >160
    -

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Coronary Heart Disease 0

obesity-and most of the reports also recommend a reduction in dietary
cholesterol and partial replacement of saturated with polyunsaturated fat
(Truswell 1983).

In response to a congressional directive, DHHS and USDA jointly spon-
sored an assessment of the existing evidence relating dietary cholesterol to
blood cholesterol and human health, as well as recommendations for
further research. Their report to Congress, The Relationship Between
Dietary Cholesterol and Blood Cholesterol and Human Health and Nutri-
tion (1986). concluded that high blood cholesterol is one of the major risk
factors for CHD and that cholesterol in the diet, but even more the amount
and types of fat in the diet, affect blood cholesterol; dietary cholesterol
raises blood cholesterol in most people; in some there is a small response
and in others the increase is more pronounced. The prevalence of different
degrees of response in the population is not known. A broad program of
research was recommended.

The National Research Council of the National Academy of Sciences
recently conducted a 3-year review of the role of animal products in the
American diet (NRC 1988). Its report, Designing Foods. Animal Product
Options in the Marketplace, concluded that nutrition-related health prob-
lems affect nearly every American family and recommended measures to
reduce the quantity of animal fat in the diet and to increase consumers'
access to fat and cholesterol information.

Key Scientific Issues

o Role of Dietary Fat and Cholesterol in CHD
o Role of Other Dietary Factors in CHD
o Efficacy of Dietary Interventions in CHD

Role of Dietary Fat and Cholesterol in CHD

Of the many dietary factors that have been studied, the strongest and most
consistent evidence relates to dietary fat. Systematic examination of the
diet-blood cholesterol-CHD link through clinical, epidemiologic, and ani-
mal research implicates both the amount and nature of dietary fats as
important determinants of plasma cholesterol levels.

Clinical Studies
Clinical studies have addressed the role of dietary fat and cholesterol upon
CHD through their effects upon blood cholesterol and by their effects upon

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13 Nutrition and Health

development and severity of heart disease. The latter type of clinical
studies is summarized in the section on Efficacy of Dietary Interventions in
CHD, while studies on blood cholesterol are summarized below.

A variety of clinical studies carried out over the past several decades have
shown that the type of fat and amount of cholesterol in the diet affect blood
cholesterol levels. In these studies, the composition of the diet is controlled
so that the effects of single constituents can be tested. Fatty acid sources
examined include butter fat, olive oil, cottonseed oil, sunflower oil, hy-
drogenated coconut oil, sardine oil, safflower oils, margarines, and cocoa   1
butter(Keys, Grande, and Anderson 1974). Typically, saturated fatty acids
were shown to raise and polyunsaturated fatty acids to lower plasma
cholesterol levels in comparison with monounsaturated fatty acids, which
were considered to be neutral. The degree of response to saturated fatty
acids depends on the individual fatty acid content. Myristic (14 carbon
atoms, C:14) and lauric acids (C:12) have a more powerful effect than
palmitic acid (C: 16), but palmitic acid is more abundant in the food supply.
Saturated fatty acids with more than 18 or fewer than 10 carbon atoms
appear to have little or no effect on plasma cholesterol levels (Keys 1967).
Likewise, stearic acid (C: 18) has been reported not to raise blood choles-
terol levels or, when substituted for palmitic acid, to lower blood cholester-
ol levels (Bonanome and Grundy 1988). Trans fatty-acids are isomers of
naturally occurring cis unsaturated fatty acids. They are produced in fats as
a result of commercial hydrogenation of cooking oils and also occur in
ruminant fats, including milk fat, beef fat, and lamb fat. Trans fatty acids as
consumed in hydrogenated vegetable oil appear to be the equivalent of
oleic acid in their cholesterolemic properties in humans. In this respect,
they are similar to stearic acid, but dissimilar to palmitic, myristic, and
lauric acids (LSRO 1985).

Equations to estimate the change in serum cholesterol from changes in
dietary fats and cholesterol (Keys, Anderson, and Grande 1965; Hegsted et
al. 1965) derived from such clinical experiments are presented in Table 2-4.
They show that saturated fatty acids are about twice as powerful in raising
plasma cholesterol levels as polyunsaturated fatty acids are in lowering
them, while dietary cholesterol has a smaller effect (Blackbum 1979). It has
been estimated that increasing the dietary cholesterol intake by 100
mg/1,000 kcal increases the plasma total cholesterol by about 10 mg/dl
(Grundy et al. 1988). Thus, if a person consuming 2,000 calories per day
increases his or her dietary cholesterol from 300 to 500 mg/day, plasma
cholesterol will rise about 10 mg/dl.

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Coronary Heart Disease O

Table 2-4

Estimates of Serum Cholesterol Change From Given Changes in
Dietary Lipids Based on kocaMc Controlled Experknents in
                Humans

Keys (Minnesota) equation:

ACHOL = 1.35(2AS - AP) + 1.52AZ

Hegsted (Harvard) equation:

ACHOL = 2.16AS - 1.65AP + 0.0677AC - 0.53

Where A CHOL = estimated change in serum cholesterol in mg/dl; A S =
change in percent daily calories from saturated fat; A P = change in percent
daily calories from polyunsaturated fat; A 2 = change in the square root of daily
dietary cholesterol in mg/l,OOO calories; and A C = dietary cholesterol in mg/
day.

Source: Blackbum, Ii. 1979. Diet and mass hyperlipidemia: public health considerations-
   a point of view. In Nutrition, lipids, and coronary heat7 disease, ed. Ft. Levy, 8.
   Riind, 8. Dennis, and N. Ernst, pp. X9-47. New York: Raven. Reprinted with
   permission from Raven Press, New York.

Numerous studies have predicted group mean plasma cholesterol levels on
the basis of the dietary content of saturated and polyunsaturated fatty acids
and cholesterol alone (Keys, Grande, and Anderson 1974). Other clinical
studies have shown that although saturated fat raises and polyunsaturated
fat lowers plasma cholesterol levels, the magnitude of the change differs
from that predicted by the equations. Results of six European experiments
were compared with those predicted by equations such as those shown in
Table 2-4 (Grande 1983). The predicted changes in serum cholesterol were
generally in agreement with the observed changes, with some variability.
For example, in the Finnish Mental Health Study, a dietary change that
was predicted to raise cholesterol 33 mg/dl produced an average elevation
of 49 mg/dl. In another experiment, the cholesterol-lowering effect of corn
oil and olive oil were compared with a control diet. Mean serum cholesterol
reductions were 50 mg/dl and 38 mg/dl, respectively, whereas the equa-
tions predicted the same decrease for both diets, 43 mg/dl. In another
experiment, the effect of dietary cholesterol added to a diet rich in polyun-
saturated fat was in agreement with the predicted value but was underesti-
mated when cholesterol was added to a diet high in saturated fat.

More recently, the effects of high-oleic safflower oil (monounsaturated),
high-linoleic safflower oil (polyunsaturated), and palm oil (saturated) on

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cl Nutrition and Health

blood cholesterol levels were compared in normal and hypertriglyceridem-
ic patients. Both the high monounsaturated and high polyunsaturated fatty
acid oils achieved similar lowering of total cholesterol (35 mg/dl), compared
with 78 mg/dl predicted for the high polyunsaturated and 45 mg/dl predicted
for the high monounsaturated fat diets (Mattson and Grundy 1985).

In another study, beef fat, coconut oil, and safflower oil were isocalorically
exchanged in the diets of healthy normal volunteers (Reiser et al. 1985).
Mean plasma total cholesterol was 21 mg/dl lower on the safflower oil diet
compared with the habitual diet. Mean plasma total cholesterol on the beef
fat diet was 14 mg/dl higher than on the diet containing safflower oil and 13
mg/dl lower than on the diet containing coconut oil. The authors suggested
that the relatively higher proportion of stearic acid in the beef fat might
contribute to these differences.

Despite some inconsistencies in the degree of plasma cholesterol re-
sponses, clinical studies have generally shown a fall in response to polyun-
saturated fat and a rise in response to saturated fat. However, the above two
experiments suggest that the interaction of dietary factors in regulating
blood cholesterol levels may be more complex than can be accounted for
solely by the amount of saturated and polyunsaturated fats and dietary
cholesterol. Other factors that might contribute to inconsistencies across
studies include differences in baseline plasma cholesterol levels, composi-
tion and form (food vs. liquid formula) of the diet, age, metabolic status of
the participants, and duration of the experiment (Mattson and Grundy
1985).

Most clinical studies have noted a high degree of individual variability in
response to dietary cholesterol, a characteristic also noted among some
animal species (Jokinen, Clarkson. and Prichard 1985). Humans are gener-
ally less sensitive to dietary cholesterol than most animal species, and the
high degree of individual variability in plasma cholesterol responses to
dietary cholesterol suggests that some people may be overly sensitive to
dietary cholesterol while others are relatively resistant. The proportion of
the population that might be cholesterol-sensitive and the factors that
contribute to that sensitivity are not well understood. The response to
dietary cholesterol may be affected by such factors as previous diet, age, or
genetic makeup (McGill 1979) and the relative proportions of other nu-
trients in the diet. For example, one controlled clinical study compared the
effects of adding three or six eggs to basal diets containing 40 percent fat
and 300 mg of cholesterol and differing ratios of polyunsaturated to saturat-
ed fat (P/S). At P/S ratios of 0.25 and 0.4, the addition of three and six eggs
raised LDL cholesterol by 16 mg/dl and 25 mg/dl, respectively. At P/S

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Coronary Heart Disease- 0

ratios of 0.8 and 2.5, the addition of three eggs had little effect, but the
addition of six eggs at the P/S ratio 0.8 raised LDL cholesterol 17 mgidl. On
the diet with a P/S of 2.5, neither three nor six eggs produced significant
changes. Thus, both the cholesterol content and the P/S ratios were impor-
tant in determining LDL level (Schonfeld et al. 1982). Another example
suggests that type of protein may influence response to dietary cholesterol.
In a controlled dietary study in Type II hypercholesterolemia patients.
substitution of soybean for animal protein caused a reduction in serum
cholesterol concentrations, and the decrease was about the same with or
without the addition of 500 mg of cholesterol to the diet (Sir-tori, Gatti. and
Mantero 1979).

A total of 75 studies were carried out in 50 male outpatient volunteers fed
high cholesterol (approximately 800 mg/dl) versus low cholesterol (approx-
imately 250 mg/dl) in a diet containing 35 percent of calories as either
polyunsaturated or saturated fat. In 69 percent of the studies. participants
compensated for the increased dietary cholesterol by decreasing cholester-
ol absorption or endogenous synthesis. The type of dietary fat had a larger
and more consistent effect on plasma cholesterol (McNamara et al. 1987).

The main effect of dietary cholesterol on lipoproteins is to raise LDL
levels, but it also affects other lipoprotein fractions. For example, human
volunteers who ate three to six eggs per day showed increased binding
activity of an HDL subfraction that might be associated with increased risk
for the development of atherosclerosis (Mahley et al. 1978). It is hypothe-
sized that dietary cholesterol might increase the cholesterol content of
chylomicron and VLDL remnants, making them more atherogenic; these
changes would not be detected in fasting blood samples. indicating the need
for information on postprandial lipoproteins (Grundy et al. 1988).

Epidemiologic Studies

Extensive evidence relating diet to high blood cholesterol has been
amassed in a variety of observational-epidemiologic studies. These investi-
gations involve comparisons of different populations, comparisons of mi-
grant with native populations, and comparisons of groups within popula-
tions.

Between-Population Studies (International Comparisons). In one type of
international analysis, nutrient and food commodity data from Food and
Agriculture Organization food balance sheets have been compared with
World Health Organization CHD mortality data for sets of countries
(Stamler 1983). Univariate analyses consistently showed statistically sig-

99


O Nutrition and Health

nificant positive associations of CHD mortality with calories, total fat,
animal fat, saturated fat, dietary cholesterol, total protein, animal protein,
animal products (dairy products, meat, poultry, and eggs), and refined
sugars. Similar analyses have also shown an inverse association between
vegetable products and CHD mortality. Since many of these variables
occur together, the independent effect of a single nutrient cannot be
determined in such analyses. When the data were reanalyzed, combining
the saturated and polyunsaturated fatty acids and dietary cholesterol into a
single score based on defined equations (see Table 2-4) and using analysis
of variance to control separately for the influence of sugar, vegetable
products, and fat, the significant effects of dietary fats persisted while
sugar and vegetable products no longer related to CHD mortality (Liu et al.
1982).

In a second type of international comparison, autopsy records were used to
compare the degree of atherosclerosis with dietary data. The most system-
atic study was the International Atherosclerosis Project (McGill 1%8), in
which severity of atherosclerosis was quantified in autopsies of 23,000
people in 12 countries. The percent of calories consumed as fat ranged from
10 to I5 percent in Costa Rica and Guatemala to nearly 50 percent in the
United States. Dietary composition was estimated from available survey
data and subjective judgment. The countries were ranked on the basis of
severity of disease, dietary indices, and serum cholesterol. The results
showed that the percentage of calories from dietary fat was related to the
severity of the atherosclerosis (r = 0.67) and to population levels of blood
cholesterol (r = 0.74).

A third type of international comparison involves the direct measurement
of cardiovascular risk factors and dietary assessment. These epidemiologic
surveys provide further descriptive data on dietary factors associated with
the prevalence of heart disease in the populations studied. For example,
the Seven Countries Study (Keys 1970) has involved 12,000 men from I8
populations sampled in Finland, Greece, Italy, Japan, the Netherlands, the
United States, and Yugoslavia. Fourfold differences in prevalence and
incidence of CHD were shown among these populations. The highest
incidence rates were recorded for Finland and the United States and the
lowest for Japan and three populations in Greece (Co&, Crete, and
Dalmatia). Seven-day food records supplemented by chemical analyses of
the diets consumed by study participants showed wide variability across
population samples in both amount and type offat. Saturated fat intake was
highest in Finland, the United States, and the Netherlands (I7 to 22 percent
of calories, compared with 5 to 9 percent of calories in the other countries).
Saturated fat intakes and 5-year CHD incidence rates for these populations
were highly and significantly correlated (r = 0.84), as were saturated fat and

100


Coronary Heart Disease LJ

serum cholesterol levels (r = 0.89) and serum cholesterol levels and CHD
incidence rates (r=O.81) (Keys 1972). Followup after 10 years still support-
ed these findings (Stamler 1979).

International migration studies are yet another type of cross-country com-
parison. The movement of population groups from less affluent to more
affluent societies provides a special opportunity to evaluate changes in risk
factors among persons sharing the same genetic and cultural background.
Such observations have helped to dispel the view that atherosclerosis and
CHD essentially represent an immutable aging process, with most of the
variations representing the inherited population pattern, or that the choles-
terol levels encountered in most people in the United States can be re-
garded as normal. They indicate that as populations move and show a rise
in dietary fat and saturated fat intake, they move from areas with low
incidence of CHD to high incidence. They also display concurrent eleva-
tions in serum cholesterol. For example, the Ni-Hon-San Study, initiated
in 1%5 with middle-aged men of Japanese ancestry residing in Japan,
Honolulu, and the San Francisco Bay area, showed intakes of saturated fat
to be about 7 percent, 12 percent, and 14 percent, respectively. Average
dietary cholesterol intakes were 464,545, and 533 mg/day, and mean body
weights were 55, 63, and 66 kg for the respective populations. Compared
with Japan, serum cholesterol was 12 percent higher in Hawaii and 21
percent higher in San Francisco, and CHD mortality was 1.7 times higher
in Hawaii and 2.8 times higher in San Francisco (Kato et al. 1973; Marmot
et al. 1975; Robertson, Kato, Gordon, et al. 1977; Robertson, Kato, Rho-
ads, et al. 1977; Worth et al. 1975).

Within-Population Studies. The existence of groups within populations
who consume diets different from the rest of the population provides
another opportunity to examine the relationship between diet, serum cho-
lesterol, and CHD. For example, studies in the United States comparing
serum cholesterol levels in communities of omnivores (consuming animal
and vegetable products), vegans (consuming only vegetable products), and
lacto-ovo vegetarians (consuming milk, egg, and vegetable products)
showed that vegans, who habitually consume a low saturated fat and
cholesterol-free diet, had mean serum cholesterol levels 29 percent lower
than omnivores, and those of lacto-ovo vegetarians were 16 percent lower
(Hardinge and Stare 1954). Seventh-day Adventists who consume lacto-
ovo vegetarian diets have lower mean serum cholesterol levels than the
general American population. A dyear prospective study of 20.044 Sev-
enth-day Adventists in California showed that CHD mortality rates among
those 35 to 64 years of age and over age 65 were 72 percent lower and 50
percent lower, respectively, than rates found in the general population.

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O Nutrition and Health

Among Seventh-day Adventists, risk for CHD in nonvegetarian males 35 to
64 years of age was threefold greater than in vegetarian males (Phillips,
Lemon, and Kuzma 1978).

All these types of epidemiologic studies involve analysis of data for groups.
Despite the strength and consistency of results of group comparisons
across and within populations, it has been difficult in studies of individuals
within a given population to demonstrate similar relationships of dietary fat
with either the plasma cholesterol level or CHD. While studies of individu-
als have revealed strong relationships between plasma cholesterol and
CHD, only weak associations of dietary factors with plasma cholesterol
levels or CHD have been shown.

In the Puerto Rico Heart Study, for example, baseline serum cholesterol
levels in the urban sample were positively related to percent of calories
from protein, fat, and saturated fat, and serum cholesterol was negatively
related to percent of calories from total carbohydrate and complex carbo-
hydrate (Garcia-Palmieri et al. 1977). In the Honolulu Heart Study, baseline
serum cholesterol was positively related to dietary cholesterol, animal
protein, and saturated fat and to percent of calories from total protein, total
fat, animal protein, and saturated fat; it was negatively associated with
percent of calories from complex carbohydrate and total carbohydrate
(Kato et al. 1973). Multivariate analysis controlling for age, relative weight,
systolic blood pressure, serum cholesterol, and cigarette smoking showed
CHD incidence after 6 years to be inversely related to alcohol, starch, and
caloric intake per kilogram of body weight (Gordon et al. 198 1). Followup of
the Honolulu cohort after 10 years showed that percentage of calories from
fat, saturated fat, and dietary cholesterol was related directly to CHD
mortality, although percentage of calories from fat was inversely related to
total mortality, cancer mortality, and stroke mortality (McGee et al. 1985).

The Western Electric Study examined diet, serum cholesterol, and other
variables in 1,900 middle-aged men, who were examined at entry, 1 year
later, and 20 years later. Changes in the intake of saturated fat and dietary
cholesterol between entry and l-year visits were positively related to
change in the level of serum cholesterol. The dietary data collected at the
first two visits were averaged to provide baseline estimates of intake for the
followup study analysis. Results showed that the 19-year risk for death
from CHD was inversely related to polyunsaturated fat intake and
positively related to dietary cholesterol intake. These correlations per-
sisted after adjustment for baseline serum cholesterol, body mass index,
systolic pressure, cigarette smoking, monthly alcohol intake, and age
(Shekelle et al. 1981). After 25 years of followup, dietary cholesterol was

102


Coronary Heart Disease O

still positively and independently related to risk for death from CHD
(Shekelle and Stamler 1988).

The Ireland-Boston Heart Study reported within-population analyses
showing that individuals who died of CHD had a higher intake of saturated
fatty acids and cholesterol and a lower intake of polyunsaturated fatty
acids. Mean total fat intake was higher(39.4 percent vs. 38.5 percent) in the
group who died of CHD, but the difference was not statistically significant.
Fiber intake was significantly lower among those who died of CHD (Kushi
et al. 1985).

Although these epidemiologic studies have shown that diet. particularly the
amount and type of fat in the diet, influences the level of plasma cholester-
ol, other studies of individuals within populations. such as Framingham,
Tecumseh, and Evans County, have failed to find any association of diet
with plasma cholesterol or CHD (Kannel and Gordon 1970; Nichols et al.
1976; Cassel 1971; Gordon et al. 1981).

Difficulties in establishing a consistent correlation between diet and plasma
cholesterol in individuals within a given population (short of such extremes
as comparing vegetarians with the general public) have been attributed to
several factors. First, most methods used for measuring habitual dietary
patterns in free-living populations have a high degree of technical error
(Bingham 1982). Daily variability in dietary intakes of individuals is greater
than the variability among individuals. Hence, methods that measure
dietary intake only over 1 day, as was done in Puerto Rico (Garcia-Palmieri
et al. 1980), Honolulu (Katoet al. 1973), andTecumseh (Nichols et al. 1976),
can result in considerable misclassification of individuals on the basis of
long-term dietary patterns (Liu et al. 1978).

Intake of fat, especially saturated fat, and cholesterol tends to be uniformly
high in Western industrialized countries. Under such circumstances, possi-
ble fallacies may arise (Rose 1985). If nearly everyone in a population is
exposed to a causal agent such as smoking or high saturated fat intake, then
the presence of disease in an individual will appear to be attributable to
individual genetic and personal characteristics, and traditional case-con-
trol and cohort methods will fail to identify the causal agents. Under these
circumstances, causal agents are better revealed by differences between
populations or by contrasting changes within populations over time (Rose
1985).

Other problems arise from the variability and error in measurement of
factors such as plastia cholesterol. These dificulties weaken considerably

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O Nutrition and Health

any attempt to correlate diet with other CHD indices (Liu et al. 1978).
Conversely, epidemiologic correlations based on group averages of popula-
tions, such as the international comparisons cited earlier, tend to overesti-
mate the true effect (McGill, McMahn, and Wene 1981). Thus, the true
contribution of diet to plasma cholesterol levels probably lies somewhere
between the estimates obtained in comparisons between groups and be-
tween individuals within a group.

Animal Studies

Animal models extend the observations made in humans by providing
opportunities to explore directly mechanisms by which dietary factors
mediate the development, progression, and regression of atherosclerotic
lesions. Such studies often cannot be done in humans because the disease
develops slowly over a long period of time, and techniques to measure the
severity of the disease carry risk and have technical limitations. The
advantages and disadvantages of the use of various animal models in
atherosclerosis research have been reviewed (Jokinen. Clarkson, and
Prichard 1985). Because no single animal model can duplicate the range of
human arterial lesions that develop over long periods of time, several
animal species have been used, depending on the mechanism to be investi-
gated. These species vary in the natural occurrence and sensitivity to
induction of experimental atherosclerosis.

Hyperlipidemia, which leads to the development of atherosclerosis, is
readily produced in rabbits, pigeons, chickens, turkeys, Japanese quail,
pigs, and some nonhuman primates by feeding diets high in cholesterol and
saturated fats. Dogs and rats have generally been considered to be resistant
to both naturally occurring and experimentally induced atherosclerosis,
although, even in these species, advanced atherosclerotic lesions have
been produced by adding to the diet cholesterol and coconut oil (dogs) and
cholesterol and cholic acid (rats). Of all the animal models, many breeds of
pigs and several species of nonhuman primates tend to resemble humans
most closely in lipoprotein patterns and the pathologic components of the
lesion (Jokinen, Clarkson, and Prichard 1985).

For example, studies in miniature pigs fed hog chow supplemented with
cholesterol and either lard or beef fat showed elevations in plasma choles-
terol. Myocardial infarctions were observed, and the diet-induced athero-
sclerosis was very similar to the proliferative lesions of human atheroscle-
rosis. As in humans, individual variability in response to diet was observed
(Mahley 1979).

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Coronary Heart Disease 0

Nonhuman primates have several characteristics that make them valuable
as animal models: They are phylogenetically close to human beings; they
develop arterial lesions similar to those seen in humans; and dietary
manipulation can produce hyperlipidemia that, in some species. resembles
that of humans. Some nonhuman primates develop atherosclerosis in their
natural habitat, but their lesions are minimal compared with monkeys that
consume diets like humans consume in Western societies. Both human and
nonhuman primates are variable in their response to dietary cholesterol
and subsequent amount of atherosclerosis that develops. Atherogenic
diets--high in saturated fatty acids and dietary cholesterol-have reported-
ly been associated with myocardial infarction in rhesus monkeys and
cynomolgus monkeys (Jokinen, Clarkson, and Prichard 1985). Baboons are
apparently relatively resistant to diet-induced hyperlipidemia in compari-
son with other nonhuman primates and rabbits (McGill, McMahn. Kruski,
Kelley, et al. 1981) but they develop experimental atherosclerosis, which is
positively associated with LDL cholesterol concentrations and inversely
associated with HDL cholesterol concentrations (McGill, McMahn,
Kruski, and Mott 1981).

Although much of the diet-induced atherosclerosis in animals has been
achieved with extreme diets and is thus not directly applicable to humans,
some studies illustrate the effects of more moderate diets. Rhesus monkeys
fed diets resembling the typical American diet compared with those fed a
"prudent" ration reduced in calories, cholesterol, fat, and saturated fat had
much higher cholesterol levels and more frequent and more severe athero-
sclerotic lesions. The lesions seen in the animals fed the average American
regimen resembled those seen in autopsy examination of the coronary
arteries and aorta of young adult Americans (Wissler et al, 1983). Cholester-
ol feeding of rhesus monkeys-at levels that do not elevate plasma choles-
terol above those achieved on a cholesterol-free diet-may also stimulate
atherosclerosis (Armstrong, Megan, and Warner 1974).

Regression of diet-induced atherosclerosis by the reduction of serum cho-
lesterol to normal levels has been demonstrated in pigs, dogs, fowl, and
nonhuman primates (Vesselinovitch and Wissler 1978). Extensive investi-
gation of lesion regression has been conducted in rhesus monkeys. Over a
dozen studies in at least five centers found that lesions undergo substantial
regression on cholesterol lowering regimens (Wissler and Vesselinovitch
1984; Malinow et al. 1983). Rhesus monkeys fed rations containing 25
percent peanut oil and 2 percent cholesterol or 25 percent coconut oil-
butter fat and 2 percent cholesterol for 12 to 14 months developed severe

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hyperlipidemia and aortic and coronary artery atherosclerosis typical of
advanced atherosclerosis in humans (Vesselinovitch and Wissler 1978). A
subsequent change to a l2- to ICmonth diet in which calories, cholesterol,
and fat were reduced to resemble levels recommended by the American
Heart Association resulted in a prompt and sustained low serum cholester-
ol level and a substantial arrest and reversal of advanced aortic and coro-
nary atherosclerosis. Similar evidence of regression was seen when choles-
tyramine was added either to the low-fat, low-cholesterol diet or to the
atherogenic diet.

Regression of atherosclerosis has also been demonstrated in swine. Ad-
vanced atherosclerosis was produced by a combination of mechanical
injury and a 4-month high-cholesterol, high-fat diet. Fourteen months after
the animals were returned to their normal mash diet, significant regression
had occurred (Fritz et al. 1976).

A new animal model for endogenous hypercholesterolemia has become
available through the discovery of a strain of rabbits designated Watanabe

heritable hyperlipidemic (WHHL). In these animals,. severe hyper-
cholesterolemia results from a single genetic defect, and fulminant athero-
sclerosis occurs despite the ingestion of a cholesterol-free diet. The
WHHL-rabbit has the same defect in the LDL receptor gene that occurs in
persons with familial hypercholesterolemia (Goldstein, Kita, and Brown
1983).

Effects of Fatty Acids on Thrombosis

Because atherosclerosis is a multifactorial disease, diet may have effects on
CHD that are not mediated through plasma cholesterol and lipoprotein
levels. Arterial thrombosis is induced by vascular injury and the response
of blood platelets. Dietary studies have shown that platelet reactivity is
associated with the fatty acid composition of the diet.

Epidemiologic studies in France and Great Britain (Renaud 1987) have
shown that clotting activity of platelets and their response to thrombin-
induced aggregation were more closely related to the intake of saturated
fatty acids than to serum cholesterol levels. Intervention studies also show
that replacement of dietary saturated fat with polyunsaturated vegetable
oils is associated with decreased platelet aggregation and clotting activity
(Hornstra 1980; Renaud 1987). In animal studies, most saturated fatty acids
were found to induce platelet aggregation and arterial thrombosis and to
increase plasma cholesterol levels, whereas unsaturated fatty acids tended
-to reduce platelet-aggregation and also tended to lower plasma cholesterol
levels. (Goodnight et al. 1982).

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Coronary Heart Disease O

While long-chain saturated fatty acids tend to induce thrombosis in animal
studies, long-chain unsaturated dietary fats are either neutral or antithrom-
botic. In rats, the most thrombogenic fatty acid is stearic acid (Renaud
1969) despite its apparent neutral effect on serum cholesterol (Keys 1967:
Bonanome and Grundy 1988). One study in rats showed that palm oil
(containing about 50 percent saturated fat) was similar to polyunsaturated
vegetable oils in thrombotic tendency. The reasons for this anomaly are not
clear but might be related to some other constituents in palm oil that
counteract the thrombogenic properties of the saturated fatty acids
(Hornstra and Lussenberg 1975). Oleic acid, the major dietary monoun-
saturated fatty acid, seems to have little or no effect on thrombosis (Good-
night et al. 1982). The mechanisms by which dietary fatty acids may affect
thrombosis are poorly understood but may be related to prostaglandin
metabolism (Goodnight et al. 1982).

Linoleic acid, the most common dietary polyunsaturated fatty acid, is the
precursor of arachidonic acid and prostaglandins that regulate platelet
aggregation and, accordingly, thrombogenesis. Prostacyclin (PGI,). for
example, has been shown to be the most potent in rli\vo vasodilator and
antiaggregatory agent in animals and in humans, and to inhibit white cell
adherence to vessel walls, nylon fibers, and endotheliel monolayers in l&-o
(Moncada 1982). Its effects are counterbalanced by another prostaglandin,
thromboxane A,, a powerful vasoconstrictor and platelet aggregator. It is
theorized that arterial thrombosis may depend partly on the ratio between
these two prostaglandins.

Linoleic acid is also incorporated directly into membrane phospholipids,
thereby altering the structure and the function of the platelet membrane.
This process affects the fluidity and, therefore, the permeability of the cells
and influences processes including thrombus formation. Contrary to ex-
pectation, increasing the dietary intake of linoleic acid does not increase
the synthesis of arachidonic acid in platelet membranes, perhaps because
of competitive inhibition of certain enzymes. Increased dietary intake of
linoleic acid, however, has been associated in humans with significant
reduction in platelet aggregability (Hornstra et al. 1973: Jakubowski and
Ardlie 1978).

Fish Oils. The consumption of fish and other marine animals may confer
special benefits in reducing CHD mortality (Kromhout, Bosschieter. and
Coulander 1985). The fatty acids in these species are rich in long-chain
polyunsaturated fatty acids of the omega-3 series. particularly eicosapen-
taenoic acid and docosahexaenoic acid. Most polyunsaturated fatty acids
commonly found in vegetables belong to the omega-6 series. The differ-

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ences in chemical structure between omega-3 and omega-6 fatty acids
affect several metabolic processes related to blood platelet function,
thrombosis, and lipid metabolism that may relate to CHD.

Early observations in Greenland suggested that Eskimos who habitually
consumed large quantities of fish and other marine animals had a low
incidence of CHD despite a high fat and cholesterol intake (Kromann and
Green 1980; Dyerberg and Jorgensen 1982). Similar observations have been
made in other maritime communities (Kagawa et al. 1982; Yotakis 1981).
Subsequent examinations of Greenland Eskimos showed that they have
lower serum triglycerides and cholesterol levels and higher HDL levels
than Danes consuming a Western-type diet. The blood of Eskimos also
takes longer to clot. It has been hypothesized that the low incidence of
atherosclerosis and thrombosis in Greenland Eskimos is partly attributable
to the high proportion of omega-3 fatty acids in traditional Eskimo diets
(Dyerberg and Jorgensen 1982).

A recent prospective study of Dutch men showed that 20-year mortality
from CHD was reduced by 50 percent in men who consumed at least 1 oz of
fish per day (Kromhout, Bosschieter, and Coulander 1985). Whether the
benefit shown in this study can be attributed to omega-3 fatty acid intake or
to some other factor associated with fish consumption is uncertain. Men
who consumed low-fat fish derived the same benefit as those consuming
higher fat varieties. The effect of fish consumption on CHD mortality has
been examined in other large prospective studies. One found no relation-
ship (Vollset, Heuch, and Bjelke 1985). In another, fish consumption at
entry into the study was inversely associated with 25year risk of CHD
(Shekelle et al. 1985), and in the third study, CHD death rate was higher in
the group that consumed no fish compared with the group that consumed
fish (Curb and Reed 1985).

Early clinical experiments in which different sources of fat were given
showed that fish oils were at least as effective as polyunsaturated vegetable
oils in reducing serum cholesterol levels. More recently, fish oils have been
studied in relation to their effects on lipoprotein metabolism and other
CHD parameters. Clinical studies in normal volunteers and patients with
hypertriglycetidemia who were fed diets enriched in omega-3 fatty acids
generally showed variable reductions in total cholesterol and LDL choles-
terol. In some cases, LDL increased; HDL levels were either unchanged or
increased (Phillipson et al. 1985; von Lossonczy et al. 1978). The most
consistent and striking effect of fish oil on lipoprotein metabolism has been
a reduction in triglyceride and VLDL levels, an effect not observed with
vegetable oils (von Lossonczy et al. 1978; Saynor, Verol, and Gillott 1984;
Harris and Connor 1980; Nestel et al. 1984).

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Coronary Heart Disease O

Most experimental studies have used rather large amounts of fish (200 to
300 g/day) or fish oil (more than 20 g/day). One study sought to determine
the effects of more moderate fatty fish consumption. One hundred male
volunteers each consumed 3 oz or more of fatty fish at least twice a week for
3 months and little or no fatty fish for another 3 months. Mean plasma
triglyceride concentration decreased significantly, by nearly 7 percent, on
the fish diet. There were no significant changes in plasma total cholesterol,
HDL, or LDL (Fehily et al. 1983).

Another line of investigation involves studies on the effects of fish oils on
the vessel wall. A (i-week study in seven healthy men indicated that diets
supplemented with 18 g of fish oil per day may have anti-inflammatory
properties that could diminish infiltration of lipids in the vessel wall in
response to tissue injury (Lee et al. 1985).

In another study, the effect of cod liver oil on the development and progres-
sion of atherosclerosis in a hyperlipidemic swine model was assessed. All
animals were fed an atherogenic diet, 7 were given a cod liver oil supple-
ment, and 11 controls did not receive the supplement. Significantly less
disease was seen in coronary arteries from the animals fed cod liver oil
despite severe hyperlipidemia. Differences in the extent of coronary ath-
erosclerosis were not related to differences in plasma lipid levels. Pros-
taglandin synthesis from arachidonic acid was markedly reduced in the oil-
fed group (Weiner et al. 1986).

Role of Other Dietary Factors in CHD

Obesity

Obesity is associated with many important CHD risk factors such as
hypertension, low levels of HDL, elevated plasma glucose levels, high
blood cholesterol, and hypertriglyceridemia (see chapter on obesity) and
hence increases the risk for CHD. Data from the Framingham Heart Study,
in which 5,209 men and women were observed for 26 years for the develop-
ment of CHD, showed that relative weight was a significant independent
long-term predictor of CHD incidence, especially in women (Hubert et al.
1983). The association of weight with CHD incidence was most pronounced
in those under age 50. Weight gain in adulthood conveyed an added risk.
Total calorie consumption has been associated with CHD prevalence in
international comparisons. However, studies within populations have
shown that a greater caloric intake is associated with a reduced risk for
CHD, but increased body weight is associated with increased CHD risk.
This suggests that increased energy expenditure, which would tend to
increase caloric requirements, may be related to reduced risk for CHD

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(Gordon et al. 1981). Current evidence suggests that leanness and avoid-
ance of weight gain before middle age are advisable goals in the prevention
of CHD for most men and women (Hubert et al. 1983; Bray 1983). In
addition, weight loss often improves the status of other risk factors such as
diabetes and high blood pressure (see respective chapters).

Alcohol

The relationship between alcohol consumption and CHD is complex
(Hulley and Dzvonik 1984). High alcohol intake has been associated with
CHD deaths, as well as deaths from other causes (see chapter on alcohol),
but some epidemiologic studies have shown an association between light to
moderate alcohol intake and a decreased incidence of CHD (LaPorte,
Cresanta, and Kuller 1980). In these studies, light intake is generally
considered to be more than one drink per month but fewer than one per day
and moderate intake is 1 to 3 oz per day. Numerous cross-sectional studies
have shown positive correlations of alcohol intake with HDL cholesterol
levels (Castelli et al. 1977), with the response related to doses of alcohol
ranging from 0 to 3 oz per day (Ernst et al. 1980; Haskell, Camargo, and
Williams 1984). Thus, it has been postulated that the decreased incidence of
CHD in those who consume moderate amounts of alcohol might be attrib-
utable to an ethanol-induced increase in HDL cholesterol levels. Recent
reports suggest, however, that moderate alcohol consumption induces
compositional changes in HDL that are inconsistent with current under-
standing of the anti-atherogenic properties of HDL subfractions, because it
increases HDL-3 levels but not those of the antiatherogenic HDL-2 sub-
fractions (Haskell, Camargo, and Williams 1984). The significance of alco-
hol-induced changes in apoprotein fractions (Camargo et al. 1985) is also
uncertain. Since heavy drinking has numerous adverse effects, including
several on the cardiovascular system (Burch and Giles 1971), the use of
alcohol, even in moderate quantities, for its possible beneficial effects on
CHD is not recommended.

Carbohydrate

Major dietary carbohydrates include starch, fiber, and sugars. Customary
diets containing 60 to 70 percent of calories from starch, such as those
consumed in Asian countries, are associated with low plasma cholesterol
levels and a low risk for CHD (Keys 1970). Such diets tend to be relatively
high in fiber and very low in fat and thus have been widely advocated for the
treatment of hypercholisterolemia. Epidemiologic studies cited previously
have shown that intake of starch (Gordon et al. 1981) and intake of fiber
(Kushi et al. 1985) were negatively related to CHD. Furthermore, the effect
of starch did not appear to be an indirect effect of lowered fat intake. On the

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Coronary Heart Disease O

other hand, total carbohydrate was inversely associated with HDL choles-
terol-and positively associated with LDL cholesterol-in cross-sectional
studies, but these correlations were very weak (U.S.-U.S.S.R. Steering
Committee 1984). Some experimental studies have shown that hyper-
triglyceridemia can be induced with high-starch (70 percent of calories)
diets, but the effect is temporary and appears to occur mainly after chang-
ing from a high-fat to a high-carbohydrate diet (Little, McGuire. and
Derksen 1979; Ahrens 1986).

The water-soluble fiber fractions, as found in oat bran. guar gum, psyllium
seeds, certain beans, and pectin, for example, have been shown to have
hypocholesterolemic effects in humans (Jenkins et al. 1975: Kirby et al.
1981; Anderson et al. 1984). Addition of fiber to high-carbohydrate diets has
been reported to prevent triglyceride elevation on high-carbohydrate diets
(Anderson, Chen, and Sieling 1980). A high fiber intake is often associated
with low-fat diets, and the net effect may provide additional benefits in
cholesterol reduction.

The role of sugars in CHD is unclear. A high sucrose intake has been
claimed to play a causal role in CHD (Yudkin and Roddy 1964). but there is
little evidence to sustain this view. Although some animal studies have
suggested that substitution of sucrose for other sources of calories in-
creases atherogenesis, the major epidemiologic studies of diet and CHD
risk have failed to identify an association with sucrose intake (Glinsmann,
Irausquin, and park 1986). Sucrose and fructose have been shown experi-
mentally to promote hypertriglyceridemia in susceptible (carbohydrate-
sensitive) individuals. Men appear to be more susceptible than pre-
menopausal women, older persons more than younger persons, and hyper-
triglyceridemic persons more than normal triglyceridemic persons (Reiser
et al. 1981; Coulston et al. 1987). Recommended treatment for patients with
elevated plasma triglyceride and VLDL levels includes weight control,
alcohol restriction, increased physical activity, and restriction of saturated
fat and cholesterol. Substitution of carbohydrate for fat is favored; al-
though increasing dietary carbohydrate may raise triglycerides, the re-
sponse is usually transient and triglyceride levels (and VLDL) later decline
(NIH 1983).

Protein

In animals, high protein levels accelerate the formation of atheromatous
lesions. Casein appears to be more atherogenic than soy protein (Kritchev-
sky 1979). Recent studies on rabbits showed that LDL receptors were
suppressed after feeding a cholesterol-free diet composed of carbohydrate
and casein (Goldstein, Kita, and Brown 1983). The low levels of plasma

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cholesterol observed among strictly vegetarian populations (West and
Hayes 1%8) may be attributable to the quantity and quality of protein.
However, their diets also tend to be lower in saturated fat and cholesterol
and higher in complex carbohydrate and fiber than diets of lacto-ovo
vegetarian or nonvegetarian groups (Sacks et al. 1985; Sacks et al. 1975;
Burslem et al. 1978). Studies involving the substitution of soy protein and
other vegetable proteins for animal protein in the diets of hyperlipidemic
patients have shown a marked reduction in serum cholesterol levels (Des-
covich et al. 1980; Sirtori, Gatti, and Mantero 1979) but only a small change
in persons with normal plasma cholesterol levels (Forsythe, Green, and
Anderson 1986). The mechanism for these effects has not been established.

coffee

Evidence relating coffee consumption to increases in serum total and LDL
cholesterol levels or to CHD has been inconsistent. Recent reports from
cross-sectional epidemiologic studies in Norway, Israel, and the United
States have shown an independent, positive, linear association with serum
cholesterol, nearly all of which can be accounted for by LDL cholesterol
(Thelle, Amesen, and Forde 1983; Kark et al. 1985; Williams et al. 1985).
One study associates coffee drinking (five or more cups per day) with
increased risk for CHD (LaCroix et al. 1986). The effect of coffee drinking
on serum cholesterol has also been examined in controlled experiments.
Coffee taken in amounts of six cups or more per day has been reported to
increase serum cholesterol levels (Arnesen, Forde, and Thelle 1984). De-
caffeinated coffee has also been reported to be associated with such eleva-
tions in some studies (Naismith et al. 1970), although not all (Mathias et al.
1985); in most studies, tea did not affect blood cholesterol levels (Frineas et
al. 1980; Little et al. 1%6; Kark et al. 1985). Such findings would appear to
rule out caffeine as a causal factor (Klatsky et al. 1985). Other studies have
found no association between coffee and cholesterol (Kovar, Fulwood, and
Feinleib 1983) or different effects in men and women (Shirlow and Mathers
1983). Inconsistencies in the results of different studies have been attribut-
ed to confounding effects of cigarette smoking and diet as well as to
variations in method of preparation. At present, the information regarding
the relationship between coffee intake and blood cholesterol levels is
insufflcient to allow conclusions to be drawn.

Vitamins and Minerals

The relationship of micronutrients (vitamins and minerals) to cardiovascu-
lar disease risk has been studied to a much lesser extent than the macronu-
trients. except in the case of sodium and hypertension (see chapter on high
blood pressure). Although dietary patterns that promote high plasma cho-

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lesterol levels would be expected to be different in micronutrient content
from dietary patterns associated with low plasma cholesterol levels, there
is at present no strong evidence linking vitamin and mineral intake to high
plasma cholesterol levels or to CHD.

Virumin E. Vitamin E was once widely advocated for prevention and
treatment of CHD (Shute and Taub 1972). Early studies supporting these
claims were marred by lack of controls and doubtful diagnosis of CHD, and
subsequent studies have failed to confirm them (Hodges 1979).

Vitumin C. Vitamin C (ascorbic acid) deficiency results in scurvy, which is
sometimes associated with cardiac abnormalities. Observations that high
doses of ascorbic acid reduce serum cholesterol in cholesterol-fed rabbits
and guinea pigs have led to the idea that high doses of vitamin C might
reduce blood cholesterol levels in patients with elevated levels. To date,
uncontrolled clinical trials have yielded conflicting results. and there is no
convincing evidence that vitamin C is related to CHD (Hodges 1979;
Anonymous 1984).

Thiumin. Thiamin deficiency leads to beriberi, and congestive heart failure
is associated with the "wet" form of this disease. Cardiac impairment is
generally completely reversible with appropriate administration of thiamin.
Thiamin deficiency is uncommon in the United States today, largely be-
cause of effective food enrichment programs. Nevertheless, inadequate
intakes are sometimes observed among persons with faulty dietary pat-
terns or among hospitalized patients who have been ill for prolonged
periods (Hodges 1979).

Niacin. Niacin (nicotinic acid) in pharmacologic (large) doses far in excess
of its requirements for vitamin function exerts HDL-raising and lipid-
lowering effects, principally in the VLDL fraction (Fredrickson and Levy
1972). The long-term followup of patients treated with niacin in the Coro-
nary Drug Project (as mentioned in the section on Effkacy of Dietary
Interventions in CHD) showed significant reduction in coronary and total
mortality. In a recent study, nicotinic acid in combination with colestipol
and a cholesterol-lowering diet slowed progression of coronary artery
lesions in men who had undergone coronary bypass surgery (Blankenhom
et al. 1987). There is no evidence, however, that niacin ingested at phys-
iologic levels exerts any protective effect against factors that elevate blood
lipid levels.

Calcium. High serum cholesterol levels have been observed in calcium-
deficient rats. and calcium-deficient rabbits and rats fed an atherogenic diet

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significantly increased their serum cholesterol and triglyceride levels over
control animals fed a stock ration. Supplementation of experimental diets
with calcium reduced the plasma lipid levels to near or below the levels of
the control group but also was associated with increased incidence of
kidney and heart lesions (Mertz 1979). In humans, an uncontrolled study of
10 hyperlipidemic subjects showed that the addition of 800 mg of calcium
(as calcium carbonate) daily over 1 year reduced blood cholesterol levels
by 25 percent, and another uncontrolled study in older women showed that
750 mg of daily calcium supplementation reduced cholesterol levels 36 mg/
dl from a mean 266 mg/dl (Mertz 1979). Such observations remain to be
confirmed by controlled clinical trials. The possible role of calcium con-
tinues to be a subject of investigation (Renaud 1987).

Magnesium. Magnesium therapy may correct some cardiac arrhythmias,
although it is uncertain whether magnesium deficiency causes them (Laban
and Chorbon 1986). Magnesium and calcium may interact with dietary fat
in the promotion of atherosclerotic lesions. In animals, the increased
incidence of kidney and heart lesions associated with very high intake of
calcium is reduced or eliminated by high levels of dietary magnesium. This
protective effect, however, was evident only at very high dietary calcium
levels (0.6 percent by weight) and only in the presence of elevated serum
cholesterol (Mertz 1979).

Copper. Copper deficiency has been associated with cardiovascular dam-
age and abnormalities in cholesterol metabolism in animals. In one human
study, copper deficiency was shown to produce a rise in plasma cholesterol
concentrations, perhaps because copper is a cofactor for enzymes involved
in cholesterol synthesis and lipoprotein degradation (Klevay et al. 1984).

Zinc. Because dietary zinc increases the copper requirement (Sandstead et
al. 1982) it has been postulated that a high ratio of zinc to copper in the
modem American diet could be a risk factor for CHD (Klevay 1975). Long-
term zinc supplementation in children, however, has not been associated
with any detectable rise in plasma cholesterol levels (Mertz 1979). Al-
though administration of high-dose zinc supplements has been reported to
reduce blood levels of HDL cholesterol in human subjects (Hooper et al.
1980) more physiologic doses had no effect on blood lipid values (Crouse et
al. 1984).

Selenium. In China, very low levels of dietary selenium have been associ-
ated with juvenile cardiomyopathy (Chen et al. 1980). Although a causal
role has not been firmly established, epidemiologic studies have also
suggested a role for selenium deficiency in CHD. Cardiovascular disease

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Coronary Heart Disease cl

mortality rates are significantly lower in areas of the United States with
high selenium soils. In Sweden, the lowest death rate from cardiovascular
diseases was reported in the city of Malmo, which has a higher selenium
content of tap water than Stockholm or Gothenburg. Other studies. how-
ever, have failed to demonstrate any differences in selenium concentrations
in serum and urine of patients with hypertension or in the coronary arteries
of persons who died from myocardial infarction and atherosclerosis as
compared with control groups (Thomson and Robinson 1980).

Human platelets contain more selenium than other human tissues. suggest-
ing that selenium deficiency may affect thrombosis. Experimental se-
lenium deficiency reduces platelet antioxidant activity, and this activity is
restored by selenium supplementation (Levander 1982).

A low serum selenium concentration has been associated with increased
clinical manifestations of CHD in a prospective study in Finland (Salonen
et al. 1982), yet a subsequent longitudinal case control study in another
Finnish population showed that levels of selenium in blood were highly
correlated to blood levels of eicosapentaenoic acid. Because fish is a major
source of selenium in the Finnish diet, it is difficult to distinguish the
antiatherogenic effects of selenium from those of polyunsaturated fatty
acids in these studies (Miettinen et al. 1983).

Efficacy of Dietary Intervention in CHD

Clinical studies in free-living populations over long periods of time have
been conducted to determine the potential of dietary change,to influence
blood cholesterol and CHD. In general, large-scale diet studies have
achieved 10 to 15 percent blood cholesterol reductions (Rifkind et al. 1983),
compared with about 25 percent in controlled metabolic ward studies,
probably because of less rigorous adherence to the diet. For example, the
National Diet-Heart Study, in which the experimental diets contained
either 30 percent fat with 15 percent polyunsaturated fatty acids or 40
percent fat with 18 to 20 percent polyunsaturated fatty acids, showed that
reductions in serum cholesterol were proportional to the degree of ad-
herence to the diets and that excellent adherence produced an average
serum cholesterol reduction of about 13 percent in free-living adults (Na-
tional Diet-Heart Research Group 1968). The Oslo Study achieved 13 to 15
percent reductions (Hjermann et al. 1981).

The Multiple Risk Factor Intervention Trial (MRFIT) was a randomized
primary prevention trial to test the effect of a multifactor intervention
program on CHD mortality in 12.866 men in the upper 10 percent of risk on

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account of their levels of cigarette smoking, blood cholesterol, and blood
pressure. It resulted in a 5 percent reduction in blood cholesterol in the
special care (diet and other intervention) group and 3 percent in the usual
care group, suggesting that many people were making changes in their diets
even in the absence of direct intervention (MRFIT Research Group 1982).
The results of this study were further complicated because of the cholester-
ol raising effect of diuretics in the hypertensive group and because the men
who stopped smoking were less successful in weight control than the men
who continued to smoke. Greater reductions in cholesterol were achieved
among MRFIT men with elevated cholesterol who were nonhypertensive
and nonsmokers over the 6-year intervention trial (Dolecek et al. 1986).

The impact of dietary-induced cholesterol lowering on CHD incidence has
also been assessed in several other clinical trials. They have generally
reported some reduction in CHD incidence and, taken together, have
shown a consistent relationship between degree of cholesterol lowering and
CHD risk reduction (Mann and Marr 1981). However, the ability to draw
definite conclusions from such trials is made difftcult by problems such as
small sample size, failure to randomize subjects into treatment and control
groups, failure to mask treatment assignment (a pervasive and essentially
insoluble problem in all large-scale diet studies), and inadequate followup
(Cornfield and Mitchell 1%9), as well as the type of problems cited above in
the MRFIT.

The Finnish Mental Hospital Study was a trial conducted in two hospitals,
one of which replaced whole milk and butter with a skim milk emulsion
containing soy oil and a high polyunsaturated margarine while the other
retained the usual diet. After 6 years, the diets were reversed, and the study
continued an additional 6 years. The study involved the total hospital
population in each site and encompassed 29,217 person-years of experi-
ence. Results showed that mean serum cholesterol values were reduced 12
to 18 percent and that death rates from all cardiovascular diseases for men
and women were 39 percent and 14 percent lower, respectively, on the
experimental diet. All-cause mortality for men was 12 percent lower on the
experimental diet, but for women it was similar on both diets (Miettinen et
al. 1972). The authors attribute the findings in women to an exceptionally
low death rate experienced in one hospital during the control period follow-
ing transfer of chronic cases to another hospital.

The dietary trial conducted in a Veterans Administration domiciliary
facility in Los Angeles used a double-blind experimental design in which
846 middle-aged and older male participants were randomly assigned to
either a control or a cholesterol-lowering diet group. Although the results

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suggested that a diet low in saturated fats and cholesterol and high in
polyunsaturated fats reduced coronary events, the experimental and con-
trol groups did not differ in overall mortality (Dayton et al. 1969). The
excessive mortality rate from cancer observed at first in the intervention
group has been reinterpreted, and subsequent analysis of the data and
those of four similar trials has found no association of cholesterol-lowering
diets with any increase in either cancer incidence or mortality rate (Ederer
et al. 1971).

The Oslo Study was a primary prevention trial designed to test whether
lowering serum lipids by dietary measures and smoking reduction would
reduce incidence of new CHD in 1,232 high-risk participants studied over 5
years. The dietary intervention consisted of advice to substitute polyun-
saturated fats for saturated fat, to increase intake of whole grain cereals,
and to reduce energy intake (in cases of elevated triglyceride levels). At the
completion of the trial, mean serum cholesterol levels were reduced 13
percent in the intervention group, and the combined incidence of myocar-
dial infarction and sudden death was significantly reduced in the treated
group by 47 percent compared with controls. Statistical analysis identified
the predominant effect as the decrease in plasma total cholesterol by diet
(Hjermann et al. 1981).

It is widely accepted that diet is a major cause of high blood cholesterol and
high LDL levels and that these play a causal role in atherosclerosis.
Evidence from animal-experimental studies has shown that reducing diet-
induced hypercholesterolemia, whether by diet or other means, reverses
the atherosclerotic process. The consistency of these studies supports the
conclusion that blood cholesterol lowering per se rather than a specific
action of the cholesterol-lowering agent produces the benefit. Hence,
consideration of evidence from the clinical trials using drugs to lower
cholesterol is relevant to assessment of the efficacy of dietary intervention
to lower CHD risk.

The Coronary Drug Project assessed the long-term efficacy of live lipid-
influencing drugs in 8,341 middle-aged men. Treatment with niacin signifi-
cantly decreased nonfatal recurrent myocardial infarction but not coronary
mortality during the treatment phase of the study (Canner et al. 1986).
However, followup at 9 years beyond the study demonstrated that total
mortality was reduced in the niacin-treated group.

The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-
CPPT) was a double-blind placebo-controlled clinical trial in high-risk
middle-aged men to test the efficacy of lowering cholesterol levels for the

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O Nutrition and Health

primary prevention of CHD. The LRC recruited 3,806 men with primary
hypercholesterolemia, free of symptomatic CHD at entry, but at high risk
for CHD due to elevated LDL cholesterol levels. The study participants
were randomly assigned to two groups that were similar in baseline charac-
teristics. The treatment group received the bile acid sequestrant cholesty-
ramine, and the control group received a matched placebo. Although the
LRC-CPPT was not designed as a dietary intervention trial, both groups
followed a diet plan calculated to achieve a 3 to 5 percent reduction in
plasma cholesterol. A net reduction in plasma cholesterol of 9 percent in
the treatment group resulted in a 19 percent reduction in fatal and nonfatal
myocardial infarctions. Corresponding reductions in angina pectoris, elec-
trocardiographic abnormalities, and bypass surgery were also found in the
treatment group (Lipid Research Clinics Program 1984a, 1984b).

The Helsinki Heart Study reported substantial benefit in reducing the
incidence of CHD by drugs (Frick et al. 1987). The study was a randomized
double-blind placebo-controlled primary prevention trial involving 4,081
middle-aged men in a j-year followup. To qualify, participants had to have
LDL plus VLDL cholesterol concentrations equal to or greater than 200
mg/dl. Treatment with gemfibrozil resulted in several changes in plasma
lipids: modest (8 percent) reductions in total and LDL cholesterol, a more
pronounced (34 percent) decrease in triglycerides, and a moderate (greater
than 10 percent) increase in HDL cholesterol. At the end of 5 years,
nonfatal myocardial infarction alone was reduced by 37 percent and CHD
mortality alone by 26 percent. These results were obtained despite an
incidence of CHD in the placebo group that was considerably lower than
expected. Total mortality, however, was not significantly affected.

Another approach to assessing benefit of cholesterol lowering is to measure
changes in atherosclerotic lesions. Early studies in nonhuman primates
demonstrated regression of atherosclerotic lesions with cholesterol-lower-
ing diets or with drugs (Armstrong, Warner, and Connor 1970; Wissler and
Vesselinovitch 1984). The effect of cholesterol lowering on coronary ar-
teries can now be assessed with serial angiograms in humans.

In the Leiden Study, 39 men with stable angina pectoris and advanced
arteriosclerosis, as assessed by coronary angiography, were prescribed a
vegetarian diet containing a polyunsaturated-to-saturated-fatty-acid ratio
of 2, and dietary cholesterol of less than 100 mg/day. Mean serum cholester-
ol decreased IO percent from a baseline value of 267 mg/dl. Since there was
no control group, the effect of dietary intervention could not be assessed
directly. However, angiographic examination performed after 24 months
showed no progression of disease in the group that had maintained lower

118


Coronary Heart Disease 0

values for the ratio of total cholesterol to HDL cholesterol throughout the
trial or who significantly lowered their ratio of total cholesterol to HDL
cholesterol (Amtzenius et al. 1985).

Another double-blind placebo-controlled trial, the NHLBI Type II Coro-
nary Zntervention Study, evaluated the efficacy of reduction in cholesterol
levels induced by cholestyramine on progression of coronary artery dis-
ease. The rate of progression, defined angiographically, was compared in
patients treated with cholestyramine plus diet with that of patients treated
with placebo plus diet. When the relationship between coronary artery
disease progression and lipid changes was examined independent of a
specific treatment group, a significant inverse relationship was found be-
tween progression at 5 years and the combination of an increase in HDL
and a decrease in LDL. These trends were observed in both the placebo-
treated and the cholestyramine-treated group (Levy et al. 1984).

The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a random-
ized placebo-controlled angiographic investigation of the ability of drugs
(colestipol and niacin) and diet to reduce blood cholesterol levels and to
cause regression of atherosclerosis in the coronary arteries. Participants
were 162 men who had undergone coronary bypass surgery. The study
reported 26 and 43 percent reductions in total blood cholesterol and LDL,
respectively, in the treatment plus diet group compared with 4 and 5
percent reductions, respectively, in the placebo plus diet group. There was
also a considerable increase in HDL and considerable decrease in triglycer-
ides in the drug plus diet group. These changes were associated with
significantly less progression of overall coronary disease in both the grafts
and the native coronary arteries with some suggestive evidence of regres-
sion (Blankenhom et al. 1987).

Despite some deficiencies in definition of lesions, control groups, and small
numbers of patients, these coronary angiographic studies support the
benefit of intervening with blood cholesterol reduction in the presence of
established disease.

Aggregate Analysis of Clinical Trials of Blood Cholesterol Lowering
Many of the clinical trials of blood cholesterol lowering to prevent CHD
have been hampered by small numbers and modest cholesterol lowering
(Mann and Marr 1981; Oliver 1985). However, additional information has
been obtained by evaluating them in aggregate.

Joint analysis of dietary trials has shown a linear relationship of cholesterol
lowering to risk reduction, with a 1 to 1.5 percent reduction in relative risk

119


13 Nutrition and Health

found for each 1 percent reduction in blood cholesterol (Hulley et al. 1981:
Mann and Marr 1981). When the various drug studies are analyzed, the
results are almost comparable, with a 2 percent reduction in risk resulting
from a I percent reduction in cholesterol (Lipid Research Clinics Program
1984b). This relationship is close to that predicted from the results of
prospective epidemiologic studies such as the Framingham study.

In the Helsinki Heart Study, a greater effect was observed: An 8 percent
reduction in total cholesterol resulted in a 34 percent reduction in CHD
incidence. This suggests that the moderate increase in HDL cholesterol
and marked fall in triglycerides might also have contributed to the benefit
(Frick et al. 1987).

Taken together, these clinical trials provide compelling evidence that lower-
ing plasma cholesterol reduces CHD morbidity and mortality. However,
the total mortality has generally not been reduced in these studies. A small
increase in noncardiovascular deaths was observed in the Los Angeles
Veterans Administration Trial, the Helsinki Mental Hospital Study, the
WHO Clotibrate Trial, the LRC-CPPT (Oliver 1981; Lipid Research Clinics
Program 1984a), and the Helsinki Heart Study (Frick et al. 1987). There is a
lack of consistency in the various noncardiovascular causes of death in
these studies; in some studies, more cancers have occurred, while in
others, more accidental or violent deaths. In the drug trials, some of the
observed mortality from various noncoronary causes may have been spe-
cific to the drug itself. One study has reported a significant reduction in
total mortality. In the Coronary Drug Project, total mortality in the niacin-
treated group was 11 percent lower than in the placebo group, a benefit that
became evident during a 9-year followup after termination of the trial
(Canner et al. 1986). This raises the possibility that the effect of cholesterol
lowering on mortality takes longer to emerge than its impact on nonfatal
heart attacks. The difficulties in showing an effect on total mortality may
reflect the problem that no clinical trial to date has had a sample size
sufficiently large to address this issue with adequate statistical power.

Implications for Public Health Policy

Dietary Guidance

General Public
High blood cholesterol is one of the three major modifiable risk factors for
CHD. The principal nutritional factors identified with high blood cholester-
ol and the development of CHD are dietary fat, particularly saturated fatty

120


Coronary Heart Disease O

acids and cholesterol, and energy imbalance leading to obesity. Other
dietary constituents, such as fiber or alcohol, may interact with these
factors in ways that are not clearly understood.

The relationship of dietary fat and cholesterol to CHD is supported by
extensive and consistent clinical, epidemiologic, metabolic, and animal
evidence. These studies strongly indicate that the formation of atheroscle-
rotic lesions in coronary arteries-contributing to the risk for CHD-is
increased in proportion to levels of total and LDL cholesterol in blood,
which, in turn, are increased by diets high in total and saturated fat but
decreased by diets containing polyunsaturated and/or monounsaturated
fat. International epidemiologic comparisons and migration studies have
revealed strong associations of fat, especially saturated fat, intake to
development of elevated blood cholesterol levels, atherosclerosis, and
CHD. Evidence from studies within a given population has been less
consistent but points in a similar direction. Dietary intervention trials in
men with elevated blood cholesterol levels have demonstrated small but
significant proportionate improvements such that each 1 percent reduction
in total blood cholesterol is accompanied by about a 1.5 percent reduction
in heart disease risk. Intervention to lower elevated blood cholesterol
levels has been shown in both human and animal studies to reduce CHD
risk and to slow lesion progression. Animal studies have shown lesion
regression, and there is suggestive evidence from some clinical studies that
this also occurs in humans.

Taken together, these studies provide strong support for recommendations
for an overall considerable decrease in dietary fat intake by the general
public from the present level of 37 percent of total caloric intake and
decrease in saturated fat from the present level of about 13 percent of total
caloric intake.

Although the effect of dietary cholesterol on blood cholesterol is somewhat
weaker and more variable among individuals than that for dietary saturated
fatty acids, a reduction in the amount of cholesterol consumed by the
general public from present average levels of approximately 305 mg/day for
women and 440 mg/day for men seems appropriate.

Obesity is associated with such CHD risk factors as elevated LDL and total
blood cholesterol, lower HDL cholesterol, high blood pressure, and di-
abetes melhtus. It is also a significant independent predictor of CHD,
especially in women and in persons under age 50. Thus, current evidence
suggests that an overall decrease in the prevalence and severity of over-
weight in the population, through both a decrease in caloric intake and an


Ll Nutrition and Health

increase in caloric expenditure, is advisable on the basis of the relationship
of obesity to heart disease risk.

Studies of animal protein, coffee, and sugar have shown variable associa-
tions with increased blood lipid levels, but present evidence of their rela-
tionship to CHD, if any, is too weak and insufficient to draw implications
for changes in the consumption of these substances. Likewise, evidence
from some studies that certain components of dietary fiber and omega-3
fatty acids from fish oils reduce blood cholesterol levels and heart disease
risk is too preliminary to recommend changes in average intake of these
substances. In addition, advice concerning vitamin and mineral supple-
ments on the basis of their relationship to CHD is unwarranted.

Special Populations

There is a need to identify those individuals with high cholesterol levels,
who are therefore at greatest risk. For individuals whose high total and
LDL cholesterol levels warrant treatment, the first line of intervention is
diet therapy. The recently released National Cholesterol Education Pro-
gram guidelines on the treatment of high blood cholesterol in adults recom-
mend that intensive dietary treatment should generally be carried out for at
least 6 months. As indicated in this Report, only after that period of time,
and if the cholesterol level remains significantly high, should the addition
of drugs to the dietary regimen be considered. Even then, continuation of
diet therapy can reduce the need for drugs and thus their risk of side effects
and cost. Furthermore, studies in persons with CHD suggest that diets low
in fat, saturated fat, and cholesterol can retard the progression of the
disease, including recurrent heart attacks, and perhaps induce regression
of atherosclerotic lesions. Persons with such high blood cholesterol levels
should receive dietary guidance by qualified health professionals.

Adults with total cholesterol levels of 240 mg/dl or above (whose LDL
cholesterol levels are also significantly elevated), and those with total
cholesterol levels of 200 to 239 mg/dl with CHD or two or more CHD risk
factors should begin a program of supervised dietary treatment. The NCEP
guidelines recommend starting dietary therapy with a step-one diet, in
which the intake of total fat is less than 30 percent of calories, saturated fat
is less than 10 percent of calories, and cholesterol is less than 300 mg/day. If
after 3 months on this diet cholesterol lowering is insufficient, the person
should progress to a step-two diet, in which saturated fat is further reduced
to less than 7 percent of total calories and cholesterol intake is further
reduced to less than 200 mg/day.

122


Coronary Heart Disease 0

Although in epidemiologic studies light to moderate alcohol consumption is
associated with reduced heart disease risk, a cause-and-effect relationship
has not been proved. Since heavy drinking has numerous adverse health
consequences (see chapters on maternal and child nutrition and on alco-
hol), including several on the cardiovascular system, the use. even in
moderate quantities, of alcohol for its possible beneficial effects on CHD is
not recommended.

Nutrition Programs and Services

Food I .abels

Evidence related to the role of dietary factors in CHD supports the need for
manufacturers to increase the number of food labels with their total fat,
fatty acids, and cholesterol content.

Food Services

Evidence related to the role of dietary factors in CHD suggests that the
public would benefit from increased availability of foods low in fat, saturat-
ed fat, and cholesterol in food service programs. The need is critical for the
one in four persons with cholesterol levels that put them at appreciably high
risk for CHD.

Food Products

Evidence related to the role of dietary factors in CHD suggests that food
manufacturers should increase availability of foods and food products that
are low in fat, saturated fat, and cholesterol.

Special Populations

Persons with high blood cholesterol and their food preparers should be
given access to counseling by qualified health professionals and assistance
in the development of diets low in fat, saturated fat, and cholesterol as well
as in the appropriate balance of caloric intake and expenditure. Education
and training opportunities for health professionals should be expanded to
meet this need.

Research and Suweillance

Research and surveillance issues of special priority related to the role of
diet in CHD should include investigations into:

123


0 Nutrition and Health

o The identification and management of individuals with high blood
cholesterol in the general population.
o The most effective educational and dietary intervention strategies to
reduce blood lipid levels and heart disease risk.
o Improved methods for assessing American dietary patterns in relation
to CHD risk.

o Refinement of current dietary recommendations, including evaluation
of other potentially efficacious dietary regimens, evaluation of dietary
fiber, and optimal intakes of omega-3 and omega-6 fatty acids to
prevent CHD.

o The mechanisms by which alterations in dietary fatty acids affect
atherogenesis and the risk for CHD, including degree of saturation,
chain length, and fatty acid series.
o Clarification of the role of dietary cholesterol in atherogenesis, includ-
ing variability in response, effects on cholesterol metabolism in both
fasting and postprandial states, and interactions of postprandial
lipoproteins and lipoprotein remnants with cells of the arterial wall.

124


Coronary Heart Disease 0

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Weiner. B.H.; Ockene. I.S.: Levine. PH.: Cuenoud. H.F.: Fisher, M.: Johnson. B.F.: Daoud.
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Weinstein. M.C.: Coxson, P.G.: Williams. L. W.: Pass. T.M.: Stason. W.B.: and Goldman. L.
1987. American Journal of Public Health 77: 1417-25.

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vegetarians and nonvegetarians in a Seventh-day Adventist Group. American Journal of
Clinical Nutrition 21S53-62.

Williams,P.T.;Wood,P.D.;Vranizan.M.A.;Albers,J.J.;Garay,S.C.;andTaylor.C.B. 1985.
Coffee intake and elevated cholesterol and apolipoprotein B levels in men. Journal of the
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Wissler, R.W.; Vesselinovitch. D.; Hughes, R.; Thmer, D.; and Frazier, L. 1983. Arterial
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Chapter 3

High Blood Pressure

  Hence if too much salt is used in food.
       the pulse hardens.
Huang Ti (the Yellow Emperor, 2697-2597 B.C.)
   The Yellow Emperor's Classic of
        Internal Medicine

Introduction

Hypertension, the medical name for high blood pressure, is a common
chronid medical problem in the United States responsible for a major
portion of cardiovascular disease. In recent years. public health efforts
have increased public awareness and knowledge of the risks and appropri-
ate treatment of this condition. As a result, almost the entire adult U.S.
population has had at least one blood pressure measurement and 73 percent
of Americans have had their blood pressure checked within the previous 6
months. By 1985,77 percent of the public identified high blood pressure as
the factor that most increases a person's chances of having a stroke, and 91
percent indicated that high blood pressure increases a persons chances of
getting heart disease (Lenfant 1987). The proportion of hypertensive per-
sons who have their high blood pressure under control more than doubled
from the early 1970's to 1980 (Subcommittee 1985). The significant de-
crease in cardiovascular disease deaths and disability that has occurred
since the 1970's is believed by many experts to be due to the increased
detection and treatment of high blood pressure.

This success in the control of hypertension is generally credited to a
combination of improved detection and the use of antihypertensive medi-
cation. However, the implications of long-term drug therapy for millions of
Americans are unknown. There are documented side effects of the anti-
hypertensive drugs. Thiazide diuretics, for example, can induce short-term
increases in serum cholesterol, low density lipoproteins (LDL), and tri-
glyceride levels in some persons. Some studies suggest that these effects

139


O Nutrition and Health

decrease or disappear with long-term therapy, although some clinical trials
have shown persistence of the adverse effects (JNC IV 1988). Beta-block-
ers tend to lower high density lipoprotein (HDL) levels. These and other
risks of drug therapy call attention to the potential benefits of nonphar-
maceutical treatment of high blood pressure (Kaplan 1985).

Currently, three nondrug methods-weight control, alcohol restriction,
and sodium restriction-are recommended as part of the treatment for
established hypertension (JNC IV 1988). These measures have also gained
support as likely to aid in the prevention of high blood pressure, particu-
larly for those at high risk.

Historical Perspective

The first successful dietary treatment of human hypertension has been
attributed to Kempner's rice-fruit diet that provided 20 g of protein, less
than 5 g of fat, 150 mg of sodium, 200 mg of chloride, and 3,000 mg of
potassium per day (Kempner 1944). Other studies confirmed that a very
low sodium intake, for example, 200 mg/day, was effective in lowering
blood pressure, although the effect on blood pressure of a moderate sodium
intake, for example, 2,000 mg/day, was inconsistent (Watkin et al. 1950).
Such studies laid the groundwork for subsequent investigations into the
role of sodium in the development of hypertension.

The positive association between body weight and blood pressure was
documented more than 60 years ago (Faber 1924). Clinical treatment of
hypertension with weight reduction was reported over 60 years ago by
Rose, who documented lower blood pressure and relief of edema in obese
patients who lost weight (Rose 1922). The historical evidence for dietary
associations with high blood pressure has been reviewed extensively
(McCarron and Kotchen 1983; McCarron, Filer, and Van Itallie 1982;
Horan et al. 1985).

A review of the development of U.S. public health policy on nutrition and
hypertension indicates that in a rather brief time period, the focus shifted
from acceptance of the association between sodium intake and blood
pressure-an emphasis of the 1969 White House Conference on Food,
Nutrition, and Health-to congressional attention on the topic of sodium
labeling and FDA action to promote sodium labeling to the 1980 issuance of
the DHHS/USDA recommendation in the Dietary Guidelines for Ameri-

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High Blood Pressure tl

~XVLV to avoid excessive sodium intake. The relatively fast pace of this
nutrition policy development can be appreciated by contrasting it with the
history of recommendations for dietary change for high blood cholesterol
levels (see chapter on coronary heart disease). A few milestones in the
development of nutrition-hypertension policy are noted here.

The role of dietary salt in hypertension was a major issue at the White
House Conference on Food, Nutrition, and Health and at the Senate Select
Committee hearings in I%9 (Mayer 1969). Subsequently, a committee of
the National Academy of Sciences recommended that no more than 0.25
percent salt be added to the commercial preparation of infant food (Sub-
committee 1970). In 1970, the infant food industry initiated restriction of
added salt.

In 1974, the American Academy of Pediatrics Committee on Nutrition
recommended dietary modification of sodium intake for the pediatric
population at risk for hypertension. The committee also favored the devel-
opment of guidelines for reducing the use of salt by food processors and
recommended that information about the amount of salt added to pro-
cessed food be made available to consumers (AAP Committee on Nutrition
1974).

The Food and Drug Administration (FDA) sponsored a review of the health
implications of added salt as part of an evaluation of substances designated
"Generally Recognized As Safe" for use in foods. This evaluation, com-
pleted in 1979 by a committee of the Federation of American Societies for
Experimental Biology, concluded that consumption of sodium chloride in
the United States should be reduced, guidelines should be developed for
restricting salt in processed foods, and the sodium content of processed
foods should be labeled (Select Committee on GRAS Substances 1979).
Subsequently, the FDA proposed that more information on the sodium
content of foods be provided as part of nutrition labeling (U.S. Congress
1981; FDA 1982).

Sodium labeling is part of the FDA's five-point sodium program that
involves collaboration between the food industry and Government. The
effort intends to achieve changes in food labeling and to encourage the food
industry to reduce the amount of sodium added to processed foods and to
market a greater variety of foods with lowered sodium. The FDA will
encourage consumer education about the relationship between sodium and

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hypertension. It is intended to monitor changes in the marketplace to see
whether efforts to reduce sodium in the food supply and to increase sodium
labeling are successful. Legislation to mandate sodium labeling might be
considered if voluntary efforts fail (Forbes and Stephenson 1985).

Appropriate caloric intake to maintain desirable weight and avoidance of
excessive sodium intake are goals included in the Surgeon General's
Report on Health Promotion and Disease Prevention (DHEW 1979) and
the nutrition component of the 1990 Objectives for the Nation (DHHS
1980). These goals are also recommended by the Food and Nutrition Board
of the National Academy of Sciences (NRC 1980) and are consistent with
the Dietary Guidelines for Americans, published by the Departments of
Agriculture and Health and Human Services (USDA/DHHS 1980, 1985).

In recognition of the clear social need to reduce illness, disability, and
death from uncontrolled hypertension, the National High Blood Pressure
Education Program (NHBPEP) was initiated in 1972, led and coordinated
by the National Heart, Lung, and Blood Institute. This program includes
an extensive network of Federal agencies and major national health organi-
zations. During the time the NHBPEP has been in operation, age-adjusted
death rates for stroke and coronary heart disease have substantially de-
clined. The activities of the NHBPEP on improving hypertension control
are believed to have contributed to this decline (Lenfant and Roccella
1984).

Significance for Public Health

In the United States, hypertension is a public health problem of enormous
magnitude. Estimates of the prevalence of hypertension vary, however,
depending upon differences in interpretation and extrapolation of the data.
Current definitions of hypertension are listed in Table 3-l. A change in the
blood pressure threshold from 160/95 mm Hg (systolic/diastolic measure-
ments in millimeters of mercury) to 140/90 mm Hg was recommended in
1984 (JNC III 1984) and is maintained in the most recent report (JNC IV
1988). According to this definition, almost 58 million individuals have been
found to have elevated blood pressure or have reported taking antihyper-
tensive drugs prescribed by a physician (Table 3-2). About 39 million of
these people are under the age of 65; less than 3 percent are children.
Prevalence of hypertension increases with age in the U.S. population and is
higher for black Americans (38 percent) than for white Americans (29
percent) (Subcommittee 1985).

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High Blood Pressure O

               Table 3-l
Classification of Blood Pressure' in Adults 18 Years or Older

Range, mm Hg
Diastolic

-=c 85

85-89

90-104

105-l 14

> 115
Systolic, when diastolic blood
pressure is < 90

< 140

14&159

> 160

Categoryb


Normal blood pressure
High normal blood pressure
Mild hypertension
Moderate hypertension
Severe hypertension



Normal blood pressure
Borderline isolated systolic hypertension
Isolated systolic hypertension

aBased on the average of two or more readings on two or more occasions.
bA classification of borderline isolated systolic hypertension (SBP 140 to 159 mm Hg) or
isolated systolic hypertension (SBP > 180 mm Hg) takes precedence over high normal
blood pressure (diistolii blood pressure 85 to 89 mm Hg) when both occur in the same
person. High normal blood pressure (DBP 85 to 89 mm Hg) takes precedence over a
classification of normal blood pressure (SBP < 140 mm Hg) when both occur in the same
person.

Source: 1988 Joint National Committee.

           Table 3-2
Estimated Prevalence of Cardiovascular Disease
        in the United States

Hypertension (> 140/90 or on Rx)                   57,700,ooo
Rheumatic fever with or without heart disease             1,500,ooo
Coronary heart disease                         6,700,OW
Cardiac arrhythmias                           1.4WooO

Cerebrovascular disease                        2,700,OOO
Sources: Subcommittee on Definition and Prevalence of the 1984 Joint National
    Committee on Detection, Evaluation, and Treatment of High Blood Pressure
    1985; National Center for Health Statistics 1988.

Hypertension is a major risk factor both for heart disease, which is the
leading category of causes of death in the United States, and for stroke,

143


0 Nutrition and Health

which is the third most frequent cause of death. All of the cardiovascular
diseases are highly prevalent in this country (Table 3-2). A high proportion
of end-stage renal failure is due to hypertension. The magnitude of the high
blood pressure problem is demonstrated by the fact that in 1980 and 1981,
the estimated annual number of visits to physicians' o&es by patients
with cardiovascular disease was over 56 million. The largest subgroup was
for hypertension, a total of 29 million visits (Ezzati and McLemore 1980;
NCHS 1984).

Scientific Background

Regulation of Blood Pressure

Blood pressure is regulated by a complex process involving the interac-
tions of multiple factors that are not completely understood. Ultimately,
the regulation of blood pressure reflects the interaction of cardiac output
(the amount of blood the heart pumps per unit of time) and total peripheral
resistance (the resistance to flow that blood encounters in the arteries and
arterioles). Therefore, hypertension is an imbalance of the mechanisms
that affect either output or resistance, or both. Some of the many mecha-
nisms that affect these functions and, therefore, blood pressure are listed in
Table 3-3. These include alterations in hemodynamic factors (plasma vol-
ume, cardiac output, and arterial pressure); central nervous system mecha-
nisms that influence the hemodynamic mechanisms; interactions of the
renin-angiotensin and adrenergic system that elevate arterial pressure;
adrenal hormone secretion and maintenance of water, sodium, and other
electrolyte balance; and various other hormonal influences.

In over 95 percent of individuals with high blood pressure, the specific
cause cannot be determined, and the condition is referred to as primary or
essential hypertension. Primary hypertension may sometimes represent
nonspecific disturbances in blood pressure regulation, and the specific
mechanism is not always identifiable.

Methodological Issues

Each approach to investigating the effects of diet on blood pressure has
limitations. Animal experimentation provides optimal control over intake
of specific nutrients, and hypotheses generated from animal models have
been useful in the study of human primary hypertension. Different mecha-
nisms, however, may be important in humans. Epidemiologic studies that
compare customary diets and average blood pressure levels among popula-
tions or among smaller groups within populations can lead to inferences
about the relative importance of various nutritional factors, particularly if

144


High Blood Pressure O

Table 3-3

Control Mechanisms for Arterial Pressure

Mechanical (posture, etc.)
Hemodynamic
Autonomic nervous system
Central nervous system

Gastrointestinal system (absorption of fluids and electrolytes)
Renal parenchymal function
Maintenance of sodium and fluid balance
Regulation of excretion of other electrolytes
Renin-angiotensin-aldosterone system
Other hormonal factors

      Adrenal cortical hormones
     Vasopressin
       Growth hormone

       Parathormone
     Thyroid hormone
     Kallikrein-kinin system
     Prostaglandin system
     Histaminergic mechanisms
!%urcx: Adapted from Frohlii 1963.

data are collected longitudinally. Cross-sectional studies have two key
drawbacks: (1) only a few observations may be used to characterize factors
that often have large individual fluctuations (e.g., diet, blood pressure),
and (2) they do not consider whether the observed dietary intake is typical
of long-term habits, reflects an aberration in usual intake, or reflects a
dietary pattern that has been recently modified in response to health
concerns.

Observational studies cannot distinguish between the effects of highly
correlated dietary constituents. For example, in an observational study,
both a low intake of potassium and a high intake of sodium may be
associated with high blood pressure. A well-designed human intervention
study can yield information on the independence or interaction of the
nutrients. Such studies require reliable dietary assessment and use of
objective measures whenever feasible as well as standardized blinded
blood pressure measurements, adequate length of followup. and control of
potentially confounding variables such as other nutrients or weight change.

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O Nutrition and Health

Nutritional Correlates

Research on diet and hypertension is complicated by the need to assess the
relative importance of about 50 essential nutrients, dietary fiber, and
nutrition-related factors such as obesity in the face of serious meth-
odological problems inherent in studies of the role of diet in chronic disease
(Reed et al. 1985). Although certain individual nutrients are implicated in
hypertension, future nutrition research may need to focus more on the
interrelationships among dietary factors than to consider each separately
(Hegsted 1985).

Several symposia have reviewed the role of nutrition in blood pressure
regulation as well as the mechanisms by which dietary factors are known or
thought to influence blood pressure regulation (McCarron, Filer, and Van
Itallie 1982; Horan et al. 1985). The major dietary factors thought to
influence blood pressure and the mechanisms by which they may do so are
summarized in Table 3-4. The complexity of these interactions explains
why ". . . even where there is general agreement about the importance of a
specific nutrient's effect on blood pressure, there is not necessarily con-
sensus on the mechanisms involved" (McCarron, Filer, and Van Itallie
1982).

Key Scientific Issues

o Role of Obesity in Hypertension
o Role of Sodium in Hypertension
o Role of Alcohol in Hypertension
o Role of Other Minerals in Hypertension
o Role of Macronutrients in Hypertension
o Role of Caffeine in Hypertension
Of the many dietary factors listed in Table 3-4 that affect blood pressure.
three-obesity, sodium, and alcohol-have a role that is well supported by
scientific evidence (JNC IV 1988). At present, research on the effects of
other dietary factors is suggestive but not conclusive.

Role of Obesity in Hypertension

As was noted in a special supplement on nutrition and blood pressure
control (Dustan 1983; Havlik et al. 1983), early studies on the association
between body weight and blood pressure have been confirmed in epi-
demiologic studies of primitive as well as developed populations. In many

146


High Blood Pressure 0

          Table 3-4
Major Nutrients and Possible Mechanisms
  for Influencing Blood Pressure

Calories and Macronutrients

rotal calories

Possible Mechanisms

Obesity
Energy generation

carbohydrates (and alcohol)

Energy metabolism
Membrane synthesis
insulin regulation-sodium excretion
Catecholamine regulation-vascular tone

Proteins

Lipids

Electrolytes and Minerals

ProteinIpeptide synthesis
Control of cellular function
Membrane transport systems

Energy source
Cell membrane components
Prostaglandin synthesis

Sodium

Potassium

Intravascular volume
Hormone regulation
Membrane potential

Vascular tone
Hormone regulation
Cation transport

Calcium

Receptor-ligand binding
Hormone synthesis/release
Vascular tone
Contractile protein interactions

Magnesium

Regulation of calcium channels
ATP production
Contractile protein interaction

Phosphorus

Membrane structure
ATP-energy metabolism
CAMP component

Trace elements           Copper-vascular integrity
                Manganese-energy metabolism
                 Chromium-lipid metabolism
                Vanadium-sodium/potassium ATPase
Source: Adepted from McCerron. Henry, and Morris 1982.

147


0 Nutrition and Health

populations where body weight does not increase with age, neither does
blood pressure. Further connection between hypertension and obesity has
been demonstrated in the Hypertension Detection and Follow-Up Pro-
gram, which reported that 60 percent of the participants with hypertension
were more than 20 percent overweight (Hypertension Detection and Fol-
low-Up Program Cooperative Group 1977).

Evidence for the effect of weight reduction on blood pressure began to
accumulate in the early part of this century. This association has now been
investigated in many epidemiologic studies and several clinical trials (as
reviewed by MacMahon et al. 1987). Although a few studies have reported
that treatment of hypertension with weight loss did not result in lower
blood pressure, many investigators have reported significant reduction of
elevated blood pressure by weight loss (Table 3-5).

Complicating the relationship of obesity to blood pressure is the role of
sodium. An early hypothesis was that obese individuals with hypertension
are sensitive to the blood pressure-raising effects of a high sodium intake
associated with long-term calorie excess (Dahl, Silver, and Christie 1958).
However, other investigators have dissociated the two factors and demon-
strated that weight loss is effective in lowering blood pressure even in the
absence of sodium restriction (Reisen et al. 1981; Maxwell et al. 1984).

In conclusion, increased body weight is related to increased blood pres-
sure. Furthermore, a fall in blood pressure can be expected with weight
reduction. Further studies may help to define other factors such as the
distribution of body fat (Kalkhoff et al. 1983; Krotkiewski et al. 1983;
Berchtold 1985) or specific mechanisms by which obesity might be in-
volved in the development of hypertension,

Weight loss is recommended for all overweight persons, particularly for
those with hypertension. It has been suggested that control of obesit)
would eliminate hypertension in 48 percent of whites and 28 percent of
blacks (Tyroler, Heyden, and Hames 1975). Even when weight loss does
not reduce blood pressure to normal, health risks may be reduced, and
smaller doses of antihypertensive medication may be needed as a result.

Role of Sodium in Hypertension

Definitions

In most human studies, sodium intake is estimated from reported dietary
intake of salt (sodium chloride) among the study participants. A more

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                     Table 3-5
Changes in Weight and Blood Pressure (Baseline to Followup) in Treatment (Rx)
     and Control Groups of Five Randomized Controlled Trials

   N     Followup  Weight Change (kg)  Systolic BP Change  Diastolic BP Change
Rx  Control (months) Rx     Control Rx     Control Rx      Control

  Diet trials
    Reisin et al.          57    26       4     - 14.9     - 1.2    - 37.4     -6.9   -23.3      -2.5
   Heyden et al.         63     64      12     -8.1     -1.9    - 18.0     - 12.0   - 13.0      -8.0
   Ramsay et al.         15     34      12      -5.1     -2.4    -11.9     -8.9    -6.9      -4.4
   Haynes et al.         30    30       6      -4.1     -0.8    +4.8     -0.2    + 1.4      -0.1
    MacMahon et al.       20     18       5      -7.4     +0.5   - 13.3      -7.4    -9.8      -3.1

  Pooled estimatesa
i
D  (Rx vs. control)
    Diet trials          185    172                -9.2           -6.3            -3.1
   (95% confidence limits)                   (-8.2, - 10.2)     (-3.3, -9.4)      (- 1.5, -4.7)
  Pooled estimatesa
  (Rx vs. control)
    All trials           336    254                -8.7           -5.3           -3.3
   (95% confidence limits)                  (-7.9, -9.5)     (-3.4, -7.31,      (- 1.8, -4.7)     s
  Gee MacMahon et al. 1987 for methods.                                          B

  Source: Adapted from MacMahon et al. 1987.                     B
                                         `Z
                                                                           3
                                                                           E
                                                                5


O Nutrition and Health

precise measure of sodium intake is 24-hour urinary sodium output, con-
sidered to be an accurate reflection of recent dietary sodium intake in
persons with normal kidney function. An average urinary sodium output
can be estimated to be about 150 mEq/24 hours. Dietary sodium intakes are
commonly reported in mEq, mM, or g. One mEq or one mM of sodium
equals 23 mg, and 1 g of sodium equals 44 mEq or mM and is equivalent to
2.5 g of sodium chloride (table salt). The average daily sodium intake of
adults is about 4 to 6 g (175 to 265 mEq).

Research Evidence

Epidemiology. A relationship of sodium to hypertension is supported by
several lines of evidence. In non-western populations with low salt con-
sumption, blood pressure does not rise with age. Populations with low
blood pressure generally do not consume much salt. These associations
have been reported among numerous populations such as the Bushmen of
Kalahari, Indian tribes in Brazil, and other groups in New Guinea, Malay-
sia, the Polynesian Islands, and Solomon Islands.

Salt intake is positively correlated with average systolic and diastolic blood
pressures in samples of men and women from 25 diverse populations,
regardless of methods of measurement (Gleibermann 1973; McCarron,
Henry, and Morris 1982); significant positive associations have not been
observed in other populations (see review, Subcommittee 1986). Associa-
tions among individuals within a population have been less consistent,
perhaps for methodological reasons (Liu et al. 1979).

Cfinical Studies. Many studies have examined the effect of moderate
restriction of sodium consumption on blood pressure in adults. One non-
randomized crossover study, for example, found that a diet considered to
be moderate in sodium restriction-that is, "avoiding all foods which had
sodium added during preparation"- reduced sodium excretion from 191 to
93 mEq and was accompanied by reductions in systolic and diastolic blood
pressure that averaged 7.7 and 4.4 mm Hg, respectively (Parijs et al. 1973).

A randomized study of 37 hypertensive patients with initial diastolic blood
pressures of 90 to 110 mm Hg reported that dietary restriction to 50 mEq of
sodium/day for 15 to 21 months produced reductions in systolic and di-
astolic blood pressure that were similar to those achieved by drug treat-
ment (Magnani et al. 1976). Long-term studies have shown that 39 percent
of hypertensive patients could control blood pressure with sodium intakes
below 50 mEq/day and close supervision by a dietitian and physician, and
about one-third of patients with mild hypertension could control blood
pressure with a sodium intake of 75 mEq/day or less (Hunt 1977).

150


High Blood Pressure 0

.4dditional studies suggest that even smaller reductions in sodium intake
over an extended period may reduce blood pressure, as discussed below.
In a 2-year controlled trial, 31 hypertensive patients were instructed to
reduce sodium intake by about 70 to 100 mEq. Although sodium excretion
declined only from 191 to 157 mEq, indicating a much smaller reduction in
intake, the average diastolic blood pressure fell by 7.3 mm Hg, a result
similar to that obtained by drug treatment (Morgan et al. 1978).

Similar results have been obtained in even shorter time periods. In a 12-
Lveek randomized trial, one-half of 90 drug-treated hypertensive patients
:vere placed on a no-added-sodium diet (estimated to be equivalent to a
maximum intake of about 100 to 150 mEq, or 2,300 to 3,450 mg of sodium).
Among the salt-restricted patients, sodium excretion decreased from 150
.o 37 mEq and diastolic blood pressure decreased by 6.3 mm Hg (compared
with a fall of 2.9 mm Hg in the drug-treated control group), and four of five
patients were able to discontinue or reduce medication (Beard et al. 1982).

In a randomized 8-week crossover study of 19 hypertensive patients,
dietary restriction was associated with a reduction in sodium excretion
`ram 191 to 83 mEq and a fall in mean blood pressure of 7.6 mm Hg
MacGregor, Markandu, et al. 1982). During a later double-blind phase of
.he trial, a level of sodium excretion of 76 mEq was associated with a mean
31ood pressure of 7.1 mm Hg lower than that of the control group (Mac-
Sregor, Smith, et al. 1982). Results of a nearly identical trial, however,
showed no difference in patients' blood pressures (Watt et al. 1983). The
.lifferences between these results may be related to a somewhat lower
llood pressure at entry, to a slight difference in average sodium excretion,
3r to chance variation.

4 recent review of 13 randomized clinical trials concluded that moderate
37 to 153 mEq/day) sodium restriction does reduce blood pressure, at least
:o some small extent, and that this practice is most effective for systolic
pressures, for older hypertensive patients, and for patients with higher
nitial blood pressures (Grobbee and Hofman 1986a).

3evention

The important question of whether reduction in sodium intake might
?revent the rise in blood pressure with age has been addressed in a few
short-term studies of adults, children, and infants with normal blood pres-
cures (normotensives). Blood pressure response to moderate sodium re-
itriction (to 60 mEq) for 3 months in 16 healthy normotensive husbands and
wives was associated with a decrease in sodium excretion from 152.7 to
59.5 mEq/day and significant decreases in systolic and diastolic blood

151


u Nutrition and Health

pressure of 4 and 3 mm Hg, respectively (Miller et al. 1983). In a ran-
domized double-blind trial, 23 1 infants fed a diet reduced in sodium content
by two-thirds during the first 6 months of life had a mean systolic blood
pressure that was significantly lower (2.1 mm Hg) than that of 245 infants
fed a customary diet (Hofman, Hazebrock, and Valkenburg 1985). These
two studies indicate that apparently normal blood pressures can be re-
duced by dietary sodium restriction, and they suggest that this practice
might prevent age-related increases in blood pressure. To date, however,
no reported studies have tested this hypothesis directly.

Variability in Response

The disparate blood pressure responses to sodium intake in animals at-
tributed to genetic influence (Dahl, Heine, and Tassinari 1%2) have led to
the proposal that dietary sodium and blood pressure relationships are
controlled by similargenetic factors in humans (DahIl972). Support for the
concept of individual variability in human blood pressure response has
been provided by a study of 20 hypertensive patients in hospital metabolic
units who were fed daily sodium intakes of 9 mEq, 109 mEq, and 249 mEq.
Investigators were able to distinguish a salt-sensitive group, whose blood
pressures fell in response to sodium restriction, and a salt-resistant group,
whose blood pressures tended not to be influenced by changes in salt intake
(Kawasaki et al. 1978). It has not yet been possible, however, to identify a
way to consistently distinguish salt-sensitive from salt-resistant persons
other than by measuring the blood pressure response itself.

While acknowledging that there are some hype,tiensive individuals whose
blood pressures do not respond to sodium restriction, some investigators
believe that patients who continue to consume low-salt diets have a more
benign course than those who revert to a high salt intake (Dahl 1977).

Two dietary intervention studies suggest that weight loss or sodium restric-
tion or both can retard the return of high blood pressure in patients who
have achieved normal blood pressure levels through drug treatment. The
Dietary Intervention Study in Hypertension assessed whether hyperten-
sive patients whose hypertension was controlled with drugs could discon-
tinue these medications with or without dietary therapy. The 415 patients
who discontinued medications were randomized, stratified by body
weight, either to control, weight loss (mean loss of 10 lb), or sodium
restriction (mean decrease of 40 mEq/day). The patients in the dietary
intervention groups were more than twice as successful as those in the
control group in maintaining normal blood pressure. At the end of 56
weeks, 50 percent of these patients remained normotensive without medi-
cation. This success rate was higher for patients with pretreatment mild

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hypertension than for those with pretreatment severe hypertension. In the
former group, 71.5 percent in the weight loss group and 78 percent in the
nonobese sodium restriction group remained normotensive (Langford et
al. 1985).

Similar results were noted in a 4-year trial, the Hypertension Control
Program. Among patients with pretreatment mild hypertension who dis-
continued antihypertensive medications but who restricted calories and
sodium and alcohol intake, 39 percent maintained normal blood pressure
after 4 years. In contrast, only 4 percent of those patients who did not
receive nutritional intervention remained normotensive (Stamler et al.
1987).

It should be noted that in the two studies previously described, the patients
had relatively mild hypertension that had been controlled successfully with
drugs for the preceding 5 years. Although the long-term effectiveness of
dietary intervention in persons with more severe elevations in blood pres-
sure remains to be established, these studies have important implications
for the millions of Americans who are being treated for high blood pressure
or who have elevated diastolic blood pressure. Many persons who adhere
to a dietary regimen to control blood pressure can reduce or stop drug
therapy, with potential economic and health advantages.

Role of Alcohol in Hypertension

Epidemiologic studies have shown that individuals who regularly consume
large amounts of alcohol have higher blood pressure than people who
abstain from alcohol or who drink only moderate amounts. The epi-
demiologic literature for the existence and nature of an association be-
tween blood pressure and alcohol consumption has been reviewed (Mac-
Mahon 1987). In the 12 cross-sectional North American studies reviewed
(Table 3-6), with the exception of the Canada Health Study, all reports
showed a significant positive association that was independent of age,
relative body weight, exercise, and smoking status. In most U.S. studies, a
J-shaped or U-shaped association is observed between blood pressure and
alcohol consumption, with blood pressure greater in nondrinkers than in
those consuming one to two drinks per day. It is not clear whether this
might be partially explained by other factors, such as obesity. A more
consistent finding was elevation of blood pressure at levels of three drinks
or more per day. The prospective, observational studies of the association
of blood pressure with alcohol consumption (Table 3-7) have also been
reviewed (MacMahon 1987). In this group of investigators, only the Hono-
lulu Heart Study failed to show a positive association with either systolic or

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           Table 3-6
Studies of the Cross-Sectional Association of
Blood Pressure With Alcohol Consumption

Year       Studya

No. of       Male      Age
Subjects   Subjects (o/o)    (years)

1967    Los Angeles Heart         865        100
1977    Chicago W. Electric      1,899        100
1977    Kaiser-Permanente I     83,947        45
1980    Tecumseh           3,390        47
1981    Lipid Research Clinics     4,783        52
1981    Honolulu Heart        8,006        100
1983    Stanford Five City       1,842        48
1983    Framingham          5,209        42
1985    Canada Health         1,418         51
1985    NHANES           9,553         45
1986    Kaiser-Permanente II     66,510        44
1986    Albany             1,910        100

21+
40-55
15-79
18+
20+
46-68
20-74
29-62
20+
18-74

-
38-55

1974
1980
1982
1983
1984
1985
1985

European
Copenhagen          5,249
Yugoslavia          11,121
Lyon             1,134
North KarelialKuopio     8,479
Munich Blood Pressure    3,198
Wurttemberg         3,351
Zutphen               794

Australian and New Zealand

100       40-59
100       35-62
100       20-59
50       30-64
33       30-69
88       20-65
100       a59

1980
1981
1982
1982
1984
1984
1985
1985

Tasmania
CSIRO
Sydney Hospital
Perth
Medicheck
Australian RFPS
Milton
Auckland

Japanese

  85
350
20,920
491
11,000
5,550
901
1.429

loo
100
65
100
75
::
66

36"
23b
18-70
2Od5
43b
19+
19+
35-64

1984    OsakalAkita            887        100       40-69
1984    Minamikawachi         3,083         37       53b

North American

aCSlR0 = Commonwealth Scientific and Industrial Research Organization; NHANES =
National Health and Nutrition Examination Survey; RFPS = Risk Factor Prevalence
Study.
Wean age.

Source: Adapted from Macblahon 1987.

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             Table 3-7
Prospective Observational Studies of the Association of
   Blood Pressure Wii Alcohol Consumption

Year       Studv

No. of
Subiects

1977  Chicago People's Gas   1,340       100
1981  Chicago W. Electric     871       100
1982   Honolulu Heart      6,858      loo
1983  Framingham        5,209       42
1985  Zutphen             794      100
1986   Albanv            I .910      loo

Subjects (%)

Age   Followup
(years)   (years)

40-59
40-55   t
46-68      6
29-62      4
40-59     10
38-55     18

Source: Adapted from MacMahon 1987.

diastolic blood pressure at followup with alcohol intake either at baseline
or followup. This evidence, in summary, indicates the potential impor-
tance of alcohol restriction in blood pressure control.

Role of Other Minerals in Hypertension

Potassium

One of the earliest observations of the association of dietary potassium
with reduced blood pressure concluded that "potassium salt regularly
produced a decline in blood pressure, while sodium salt just as regularly
produced a rise" (Addison 1928). It was later observed that potassium
lowered blood pressure in individuals with hypertension even when dietary
salt intake remained high (McQuarrie, Thompson, and Anderson 1936).
This protective effect has also been observed in rats (Meneely, Ball, and
Youmans 1957). These inverse associations have been reviewed exten-
sively (Meneely and Battarbee 1976; Tannen 1983; Prineas and Blackbum
1985).

Population studies have shown both a positive relationship between so-
dium intake and blood pressure and an inverse relationship between po-
tassium intake and blood pressure (Maddocks 1967; Sinnett and Whyte
1973; Bulpitt et al. 1986). Although the Framingham study showed no
relationship between urinary potassium levels and blood pressure (Dawber
et al. 1%7), potassium intake was more strongly correlated than any other
dietary factor to blood pressure in a Hawaii study (Reed et al. 1985). In
disease prevalence studies in Evans County, Georgia, hypertension was
more strongly associated with lower potassium intake in black adults than
in white adults with similar sodium intakes (Grim et al. 1980). In a Southern
California cohort of 859 men and women ages 50 to 79 years, an inverse
relationship was observed between dietary potassium, estimated by 24-

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hour dietary recall at the baseline examination, and death from stroke,
identified by examination of death certificates, in the 1Zyear followup
(Khaw and Barrett-Connor 1987).

Intervention trials have attempted to lower blood pressure in hypertensive
patients with the use of potassium supplements. The effect of 60 mEq of
potassium supplementation was compared with that of placebo and was
documented in a double-blind 4-week crossover trial in 23 patients with
hypertension. A small but significant lowering of both systolic and diastolic
blood pressure occurred in the supplementation period compared with the
placebo period (MacGregor, Smith, et al. 1982). In another double-blind
crossover trial, 20 normotensive subjects taking a 64 mEq of potassium
supplement reduced diastolic blood pressure significantly (by 2.4 mm Hg)
in 2 weeks compared with subjects taking a placebo (Khaw and Thorn
1982). A double-blind clinical trial that enrolled 116 adults with mild
hypertension for 8 weeks found a 3.4 mm Hg greater decrease in systolic
blood pressure and a 1.8 mm Hg greater decrease in diastolic blood
pressure in the group taking potassium supplements of 120 mEq/day than in
the group taking placebo. A much greater decrease was observed in the five
black patients taking potassium compared with placebo (Svetkey et al.
1987). In a 15-week clinical trial that randomized 37 mildly hypertensive
patients, there was a mean difference (lower) of 14 mm Hg in systolic blood
pressure and 10.5 mm Hg in diastolic blood pressure in the patients taking
48 mEq/day of potassium compared with placebo (Siani et al. 1987). These
beneficial effects of potassium on blood pressure in hypertensive patients
have been confirmed in another randomized blinded crossover study of 19
hypertensive patients with diuretic-induced potassium depletion. Po-
tassium supplements of 60 mEq/day reduced mean blood pressures by 5.5
mm Hg (Kaplan, Carnegie, and Raskin 1985). In contrast to these findings,
an unblinded crossover study of 12 mildly hypertensive subjects showed
no influence of potassium supplementation on blood pressure (Richards et
al. 1984). One extensive review of the literature concluded that a high
potassium intake has no effect on blood pressure in normotensive animals
or humans, although a potassium intake of 120 to 175 mEq/day appears to
reduce blood pressure in hypertensive patients by 3 to 10 percent (Tannen
1983).

If potassium does have an effect, it is likely influenced by sodium. In a
randomized 12-week crossover study of increased sodium intake and
added potassium in hypertensive and normotensive adults, blood pressure
rose in both hypertensive and normotensive subjects who consumed in-
creased sodium, but among hypertensives who consumed supplemental
potassium, blood pressure fell (Parfrey et al. 1981).

I56


High Blood Pressure Ll

The relationship between sodium, potassium, and blood pressure in nor-
motensive adults has been found to be dependent on family history of
hypertension (Pietinen, Wong, and Altschull979). The response to dietary
potassium and sodium has been assessed in male medical students with and
without a family history of hypertension. In just the group with a positive
family history, diastolic blood pressure was reduced by about 11 mm Hg
when sodium intake was lowered in the presence of high potassium intake
compared with 7 mm Hg with reduced sodium intake alone (Parfrey et al.
1981). A reanalysis of these data confirmed this effect of potassium (Holly
et al. 1981). Also consistent with these data that show a lack of potassium
influence in those with a negative family history of hypertension are two
trials that failed to find a blood pressure-lowering effect of potassium in
those persons who achieved substantial reduction of sodium intake (Mor-
gan et al. 1983; Smith et al. 1985). Because the duration of the majority of
these studies has been only weeks or months, longer term intervention
studies have been recommended to evaluate the effects on blood pressure
of both increased potassium and reduced sodium (Prineas and Blackbum
1985).

Calcium

A possible role for dietary calcium in the regulation of blood pressure is
suggested by experimental studies in animals, epidemiologic studies, and
clinical studies, including clinical trials (Kaplan and Meese 1986).

Experimental studies in spontaneously hypertensive rats have suggested
that supplemental dietary calcium may prevent the development of hyper-
tension (Ayachi 1979; McCarron, Henry, and Morris 1982; Schleiffer et al.
1984). One study, however, reported no such effect (Stem et al. 1984).

An association between calcium and blood pressure was suggested by
reports that "hard" drinking water (containing calcium) was associated
with reduced prevalence of cardiovascular disease (Schroeder 1960). This
association between calcium and blood pressure is supported by observa-
tions from the Puerto Rico Heart Health Program that individuals who
drank no milk (which is high in calcium) had twice the prevalence of
hypertension as those who consumed a quart of milk or more per day
(Garcia-Pahnieri et al. 1984). An analysis of data for 5,050 adults in South-
em California surveyed for heart disease risk factors as part of a Lipid
Research Clinics population study indicated that hypertensive men, but
not hypertensive women, had a significantly lower intake of calcium from
milk than normotensive individuals; in men, diastolic blood pressure de-
creased significantly with reported increasing milk consumption (Ackley,
Barrett-Connor, and Juarez 1983). In a case-control study, dietary calcium

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intake assessed by 24-hour dietary recall in 46 hypertensive patients and
normotensive controls showed that calcium intake was 22 percent less in
the hypertensive group (McCarron, Morris, and Cole 1982).

An analysis of the National Health and Nutrition Examination Survey I
(NHANES I) data found an inverse, although inconsistent, association
between dietary calcium and blood pressure; the lower blood pressures
were correlated with higher levels of serum calcium (Harlan et al. 1984).
Although a subsequent examination of a subset of NHANES I data also
suggested an inverse relationship between dietary calcium intake and
blood pressure (McCarron et al. 1984), the analysis was hindered by
methodological shortcomings: the salt added in food preparation and at the
table were excluded from dietary intake data; the results were examined
using only systolic blood pressure measures; and the analyses did not
control consistently for age, race, sex, and body mass index (Feinleib,
Lenfant, and Miller 1984). Subsequent analyses of both NHANES I and II
data have failed to identify a relationship between dietary calcium and
blood pressure except among black males in NHANES I (Sempos et al.
1986).

In a randomized placebo-controlled clinical trial, normotensive adults
taking 1,000 mg of calcium per day for 8 weeks had blood pressures that
were 6 to 9 percent lower than those receiving placebos (Belizan et al.
1983). In an uncontrolled clinical study, 2,000 mg of oral calcium carbonate
taken for 5 days lowered blood pressure in people with low plasma renin
activity (Resnick, Nicholson, and Laragh 1984). A blood pressure-lower-
ing effect of calcium has been noted after 5 months in an uncontrolled study
of individuals with mild-to-moderate hypertension (Resnick, Nicholson,
and Laragh 1984).

Another randomized placebo-controlled crossover trial provided 1,000 mg/
day of oral calcium for 8 weeks to 48 hypertensive and 32 normotensive
individuals. In the hypertensive group, standing systolic and diastolic
pressures were significantly reduced (by 6 and 2 mm Hg, respectively), as
was supine systolic (by 3 mm Hg)-but not diastolic-pressure. Among
normotensive persons, only supine diastolic blood pressure was signifi-
cantly lowered with calcium (McCarron and Morris 1985). Supplements of
1,500 mg of calcium per day produced modest (2 to 3 mm Hg) reductions of
systolic and diastolic pressures in both white and black normotensive men
in a recent study (Lyle et al. 1987). An oral calcium supplement of 10 or 20
mM/day was given for 2 months in a double-blind randomized crossover
study involving 5 1 hypertensive and 5 1 normotensive patients. There was
an apparent trend for lower systolic blood pressure. The diastolic blood


High Blood Pressure 0

pressure did not change significantly. In the normotensive group, there
were no significant changes in blood pressure (Nowson and Morgan 1986).
The effect of 1 g of calcium lactate gluconate or calcium carbonate in 23
patients with mild-to-moderate hypertension was observed for 8 weeks in
another double-blind crossover study. These investigators reported no
evidence that oral calcium supplements lowered blood pressure in these
patients (Zoccali et al. 1986).

Analyzed collectively, the preceding evidence suggests that a disturbance
in cellular calcium metabolism may contribute to the development of
hypertension, although the physiologic mechanism for this effect is as yet
unknown (Pak 1985). The possibility that calcium supplements may lower
blood pressure only in patients with mildly elevated levels of parathyroid
hormone that have occurred as a result of abnormally high kidney excre-
tion of calcium (and consequent lowering of blood calcium levels) has been
proposed on the basis of a study of 90 hypertensive patients (Grobbee and
Hofman 1986b). At present, the role of calcium in blood pressure regula-
tion must be considered uncertain and the clinical evidence considered
inconclusive (Kaplan and Meese 1986).

Chloride

In early studies, the blood pressure-raising effect of sodium chloride was
attributed to its chloride portion. Since the mid-1950's, however, the
sodium component of sodium chloride typically has been considered more
important (Dahl and Love 1954).

The effect of dietary chloride on the pathogenesis of sodium-dependent
hypertension has been examined in experimental animals. Steroid-treated
rats with one kidney removed developed hypertension when fed sodium
chloride but not when they were fed sodium bicarbonate. These different
responses could not be explained by differences in caloric intake, weight
gain, or the balance of sodium, water, or potassium (Kurtz and Morris
1983).

The observation that salt-sensitive hypertension depends on the presence
of both chloride and sodium has induced some investigators to suggest that
chloride-rather than sodium-induces hypertension. In one study of salt-
sensitive rats, for example, blood pressures were shown to be significantly
higher after 5 weeks of loading with sodium chloride, but they remained
normal when sodium bicarbonate was substituted for sodium chloride in
the diet (Kotchen, Luke, and Ott 1983). The effect of a nonchloride sodium
salt on blood pressure was recently tested in five hypertensive men. At 10
mEq/day of sodium chloride, blood pressure was normal. A 230 mEq of

159


0 Nutrition and Health

sodium chloride supplement induced a significant increase in blood pres-
sure, which was reversed with a supplement of an equimolar amount of
sodium as sodium citrate (Klutz, Al-Bander, and Morris 1987). This study
again raises the possibility that the chloride ion may independently contrib-
ute to the sodium chloride-induced increases in blood pressure. The need
for further investigation is reinforced by the report that chloride concentra-
tions and activity are decreased in erythrocytes of humans with essential
hypertension (Kurtz and Morris 1985).

Magnesium

An early study showed that clinical administration of magnesium salts
lowered blood pressure (Blackfan and Hamilton 1925), and recent epi-
demiologic data have rekindled an interest in this effect (Joffres, Reed, and
Yano 1987). Because magnesium, along with calcium, is present in "hard"
drinking water, an association between dietary magnesium and blood
pressure is also suggested by the finding of lower rates of cardiovascular
disease in hard-water areas. The possible association between magnesium
and blood pressure is supported to some extent by an observation that
magnesium-deficient rats had both higher blood pressure levels and re-
duced diameter of tiny blood vessels than control animals (Altura et al.
1984).

Among elderly people in Denmark, low serum magnesium concentration
has been associated with increased blood pressure (Petersen et al: 1977),
and magnesium intakes have been found to be reduced among hyperten-
sive patients (McCarron 1982). One randomized study of 18 patients taking
diuretic medications for hypertension or congestive heart failure showed
that magnesium supplementation was followed by a significant fall in both
systolic (by 12 mm Hg) and diastolic (by 8 mm Hg) blood pressure (Dyck-
ner and Webster 1983). As stated in the chapter on drug-nutrient interac-
tions, thiazide diuretics have been associated with magnesium depletion,
and this may be a factor in the blood pressure changes seen during magne-
sium supplementation. However, in another study in which patients with
mild to moderate hypertension not on diuretics were given either magne-
sium supplements or a placebo, blood pressures did not fall in either group,
despite a significant increase in plasma magnesium concentration and in
urinary magnesium in the group taking the supplement (Cappuccio, Mark-
andu, and Beynor 1985). The inconsistency of data regarding magnesium
and blood pressure levels indicates that there are many unanswered ques-
tions regarding the role of magnesium in hypertension.

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High Blood Pressure 0

Trace Elements

Little is known about the role of trace elements in the regulation of blood
pressure. Because trace elements such as zinc, copper, and iron participate
in enzyme reactions related to blood pressure regulation, they could be
factors in the development of hypertension, although they are unlikely to
be its primary cause (Saltman 1983). In a comprehensive review of this
topic, cadmium was the only trace element that appeared to be related to
blood pressure (Mertz 1985), and experimental data from animals and the
results of some human studies are consistent with a potential causative role
for this element. This role, however, lacks confirmation and is complicated
by the many interactions of cadmium with selenium, copper, zinc, and
lead. Epidemiologic and animal data also suggest a direct relationship
between lead levels and blood pressure (Pirkle et al. 1985), but existing data
do not support a major role for this or any other trace element in the
pathogenesis of hypertension.

Role of Macronutrients in Hypertension

Carbohydrates

There is some evidence that carbohydrates may play a role in blood
pressure regulation. Studies in rats have indicated that dietary sucrose
increases blood pressure, whereas starch decreases it (Ahrens et al. 1980).
Normotensive humans who supplemented their diets with 200 g/day of
sucrose had diastolic blood pressures 5 mm Hg higher than those who
consumed no added sucrose (Ahrens 1974). Both a high sucrose and a high
glucose solution-but not galactose or lactose-consumed after an over-
night fast produce transient increases in blood pressure in normotensive
men. These observations suggest that carbohydrates might influence blood
pressure-regulating hormones in rats, but investigations conducted to date
have failed to find a similar effect in humans (Hodges and Rebello 1985).

Fiber

There is some indication that plant fiber may reduce blood pressure levels
(Anderson 1983; Anderson and Tietyen-Clark 19861, but it is uncertain
whether dietary fiber plays a role in blood pressure regulation that is
independent of other concomitant dietary changes, such as replacement of
fat or facilitation of lower sodium intake (Mendeloff 1985).

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Fat

The effect of dietary fats on blood pressure has been recently reviewed
(Sacks et al. 1987). Neither the effect of total fat content nor responses to
major changes in fatty acid intake have been sufficiently studied with
desirable methodology, controlling potentially confounding variables for
an adequate time period.

Polyunsaturated Fatty Acids. Considerable interest has focused on obser-
vational studies indicating that an increased intake of polyunsaturated fatty
acids is associated with lower blood pressure (Iacono, Puska, and Dough-
erty 1983; Puska et al. 1985). Although it is uncertain whether the lower
blood pressures were attributable to the change in the type of dietary fat, an
action of the fatty acids on blood pressure might be mediated through
changes in prostaglandin metabolism caused by increased intake of the
polyunsaturated fatty acid, linoleic acid. Some prostaglandin metabolites
influence salt and water excretion and can cause contraction or dilation of
small blood vessels, thereby affecting blood pressure (Iacono et al. 1981).
A single-blind randomized control experiment among hypertensive and
normotensive men and women in North Karelia, Finland, found that a low-
fat diet with a P/S ratio of 1 .O was associated with reductions in systolic and
diastolic blood pressure of 8.9 and 7.6 mm Hg, respectively, reductions
greater than those observed in parallel control groups receiving sodium
restriction or no dietary change (Puska et al. 1983). Another team of
investigators has shown that compared with the baseline diet, decreasing
saturated fats and increasing polyunsaturated fats are associated with
lower blood pressure (Iacono et al. 1975; Iacono et al. 1981; Iacono,
Dougherty, and Puska 1982).

No significant change in blood pressure was observed after feeding either a
low-fat diet (22 percent of calories from fat) or a diet high in polyunsatu-
rated fatty acids (19 percent of calories from polyunsaturated fatty acids-
compared with the U.S. average of about 7 percent) to 15 to 18 normoten-
sive young adults (Brussaard et al. 1981). A double-blind randomized
control trial of 6 weeks studying 21 mildly hypertensive patients found that
increasing the polyunsaturated fatty acid linoleate from 4.6 to 13 percent of
calories and reducing saturated fatty acids from 16 to 10 percent failed to
produce any significant changes in blood pressure (Sacks et al. 1987).

Monounsaturated Fatty Acids. An association between increased con-
sumption of the monounsaturate oleic acid and reductions in both systolic
and diastolic blood pressures has been observed recently in a cross-
sectional survey that examined 3-day food records and resting blood

162


High Blood Pressure O

pressure in 76 normotensive men. Although no physiologic explanation for
this association is evident, it is consistent with the lower prevalence of
hypertension among Mediterranean populations who consume diets rich in
oleic acid-containing olive oil; Mediterranean populations also have a high
carbohydrate intake and low saturated fatty acid intake compared with the
U.S. population (Williams et al. 1987).

Omega-3 Fatty Acids. The role of omega-3 fatty acids in blood pressure
lowering has also received attention. Investigators have reported that the
ingestion of enough fish to provide 5 g of omega-3 fatty acids per day for 2
weeks caused a significant fall in blood pressure, and the lower blood
pressure could be maintained subsequently by the weekly consumption of
20 oz of fish that provided 1.2 g/day of omega-3 fatty acids (Singer et al.
1986).

In summary, these results indicating that the type of fat intake may influ-
ence blood pressure level require further investigation to resolve inconsis-
tencies, confirm the observations, and establish their clinical significance
(Iacono, Dougherty, and Puska 1982).

Protein

The possibility of an effect of protein level on blood pressure regulation and
whether specific amino acids might have an antihypertensive role has
received little scientific study. In a study of spontaneously hypertensive
rats, those rats fed American rat chow containing 25.3 percent protein,
compared with rats fed Japanese rat chow containing 19.7 percent protein,
developed a lower incidence of stroke (30 percent versus 80 percent).
When the rats previously fed American rat chow were fed the Japanese
diet, an accelerated rate of cerebral lesions and stroke occurred. This
observation led to a search for specific amino acids in proteins that might
affect blood pressure; tryptophan and tyrosine, as well as total protein
intake, were cited as leading possibilities. Taurine has been demonstrated
as having an antihypertensive effect in patients with hypertension
(Kohashi et al. 1983) as well as in rats (Abe et al. 1987). One hypothesis is
that amino acids or protein may affect blood pressure either at the vascular
level or through changes in neuronal control of the cardiovascular system
(Yamori et al. 1984), but this idea has yet to be confirmed.

Role of Caffeine in Hypertension

The consumption of 150 mgof caffeine (two to three cups of brewed coffee)
may promote an increase in blood pressure by 5 to 15 mm Hg within 15

163


0 Nutrition and Health

minutes that is maintained for as long as 2 hours. These short-term effects
are primarily mediated by an increase in cardiac output, with systolic
pressure usually rising more than diastolic; they are demonstrable both in
individuals who do not habitually consume caffeine and in those who do
habitually ingest caffeine if they abstain for 12 hours or more. The cause of
these effects is uncertain; short-term effects are not directly attributable to
rises in plasma catecholamines, vassopressin, or renin activity (Izzo et al.
1983).

Chronic caffeine consumption, however, neither maintains high blood
pressure nor is it associated with increased rates of hypertension
(Robertson et al. 1984). Prolonged administration of caffeine-as much as
504 mg/day for 4 weeks-has not been associated with significant rises in
blood pressure either in normotensive (Ammon et al. 1983) or hypertensive
individuals (Robertson et al. 1984). Thus, there appears to be adaptation or
tolerance to the hemodynamic effects of caffeine.

Implications for Public Health Policy

Dietary Guidance

General Public

Dietary factors that clearly contribute to high blood pressure include
obesity and excessive intake of sodium and alcohol. The average daily
sodium consumption of 4 to 6 g by adult Americans is substantially above
the National Research Council's recommended range of 1.1 to 3.3 g for safe
and adequate intake and is 5 to 10 times higher than the amount required.
Many individuals are able to maintain normal blood pressure levels over a
large range of sodium intake; the lack of known harm from moderate
sodium restriction, however, and the potential benefit to people whose
blood pressures rise with increased sodium intake suggest that those who
ingest excess sodium-most Americans-should consider reducing their
dietary sodium intake.

The strong association between obesity and hypertension and the demon-
strated reduction in blood pressure that occurs with weight loss suggest
that maintenance of desirable body weight should be a goal for the popula-
tion.

Similarly, there is a direct association between blood pressure and alcohol
consumption beyond about two standard-sized drinks daily. (One stan-
dard-sized drink is defined as 12 oz of regular beer, 5 oz of wine, or 1 `/z oz of
distilled spirits.)

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High Blood Pressure O

Some evidence indicates that a reduction in blood pressure is associated
with increased dietary intake of potassium, calcium, magnesium, and fiber.
This evidence is, as yet, too preliminary to recommend increased intake of
these factors for the general population for the purpose of hypertension
control. Likewise, although increased intake of certain lipids (e.g.,
omega-6 or omega-3 polyunsaturated fatty acids) may decrease blood
pressure, additional research is needed before any recommendations can
be made.

Special Populations

Achieving and maintaining desirable body weight and moderating sodium
and alcohol intake can lower blood pressure in patients with mild and
moderate hypertension and reduce the need for antihypertensive medica-
tions. Such patients should be informed of the likely benefit ofthese dietary
practices, along with the importance of adequate caloric expenditure
through exercise, and the moderation of fat intake, especially saturated
fatty acids, to reduce high blood cholesterol levels and the risk for heart
attack.

Nutrition Programs and Services

Food Labels

Evidence related to the role of dietary factors in hypertension supports the
need for nutrition labeling on a wide selection of foods so that the consumer
has the option of choosing foods with known amounts of calories and
sodium.

Food Services

Evidence related to the role of dietary factors in hypertension suggests that
food service programs should provide adequate choices of foods that
provide essential nutrients and energy to maintain desirable body weight
and should include foods that are low in sodium.

Food Products

Evidence related to the role of dietary factors in hypertension suggests that
food manufacturers should continue to reduce sodium in products and
continue the research and development of products low in calories and
sodium.

Special Populations

Counseling and assistance in the selection and preparation of foods low in
sodium and calories and assistance with the development of dietary pat-

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terns that control energy, sodium, and alcohol should be available to
individuals whose blood pressure places them in the mild-to-moderate as
well as high range of hypertension.

Research and Surveillance

Special priority is attached to the following research and surveillance tasks
related to the role of diet in hypertension:

o Development of practical methods for the rapid and reliable identifica-
tion of individuals at high risk for hypertension because they are salt
sensitive.

o Investigation of the interactions of sodium with other nutrients-such
as potassium, calcium, chloride, magnesium, fatty acids, and fiber-in
influencing blood pressure.

0 Investigation of the role of specific dietary factors, including po-
tassium, calcium, fatty acids, fiber, amino acids, trace elements, and
alcohol, in the cause and potential prevention of hypertension and the
mechanisms for these effects.

o Investigation of the mechanism of obesity-associated hypertension
and determination of the ratio of fat to lean body mass that might
prevent development of hypertension.

166


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approaches to the control of high blood pressure. Hypertension lW44-67.

Subcommittee on Safety and Suitability of MSG and Other Substances in Baby Foods. 1970.
Safefy and suitability of salt for use in bnby foods. Washington, DC: National Research
Council, National Academy of Sciences.

Svetkey, L.P.; Yarger, W.E.; Feussner, J.R.; DeLong, E.; and Klotman, P.E. 1987. Double-
blind, placebo-controlled trial of potassium chloride in the treatment of mild hypertension.
Hypertension 9:444-50.

Tannen. R.L. 1983. Effect of potassium on blood pressure control. Annals of fnternal
Medicine 98(5 pt. 2k773-80.
Tyroler. H.A.; Heyden, S.; and Hames, C.G. 1975. Weight and hypertension: Evans County
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177-205. New York: Stratton.

174


High Blood Pressure 0

U.S., Congress, Iiouse, Subcommittee on Investigation and Oversight. Committee on Sci-
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USDA/DHHS. See U.S. Department of Agriculture and U.S. Department of Health and
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U.S. Department of Agriculture and U.S. Department of Health and Human Services. 1980.
Nutrition and your health: dietary guidelines for Americans. Home and Garden Bulletin No.
232. Washington, DC: U.S. Govemmenr Printing Office.

-. 1985. Nutrition and your health: dietary guidelines for Americans. 2d ed. Home and
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U.S. Department of Health, Education, and Welfare. 1979. Healthy people: the Surgeon
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79-55071. Washington. DC: U.S. Government Printing Office.

U.S. Department of Health and Human Services. 1980. Promoting health. preventing dis-
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Watkin, D.M.; Froeb. H.F.; Hatch, F.T.; and Gutman. A.B. 1950. Effects of diets in essential
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American Journal of Medicine 9:441-93.

Watt, G.C.; Edwards, C.; Hart, J.T.; Hart, M.; Walton. P.: and Foy. C.J.W. 1983. Dietary
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Williams, P.T.; Fortmann, S.P.; Terry, R.B.; Garay, S.C.; Vranizan. K.M.; Ellsworth, N.;
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Yamori, Y.; Horie, R.; Tanase, H.; Fujiwara, K.; Nara, Y.; and Lovenberg. W. 1984.
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Zoccali, C.; Mallamaci, F.: Define, D.; Ciccarelli, M.; Parlongo, S.; Iellamo, D.; Moscato,
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175


Chapter 4

Cancer

One should eat and drink in moderation (not
in excess, not at a rapid rate, foods not too
hot and not overly hard), maintain an even
temperament, eat a good diet and Ye Ge
(esophageal cancer) will not develop.
  Ancient Chinese aphorism of Yan,
quoted in O'Connor and Campbell ( 1986)

Introduction

Cancer, the second leading cause of death in the United States, is a group of
conditions of uncontrolled growth of cells originating from almost any
tissue of the body. The fundamental basis of cancer has been explained as
follows: "Every minute 10 million cells divide in the human body. Usually,
they divide in the right way and at the right time, governed by a complex set
of controls that have yet to be fully elucidated. When those controls fail,
cancer may arise. The carefully ordered pattern of cell growth, division,
and differentiation is lost" (Bishop 1984). This chapter reviews the scien-
tific evidence for the role of dietary factors in these processes.

Histwical Perspective

Although diet has been suspected as a cause of cancer since the disease was
recognized in the 1st century (Armstrong and Mann 1985). empirical evi-
dence was not reported until the early 20th century (Van Alstyne and Beebe
1913). The current era of research grows out of studies that were reported
more than 50 years ago. In one of the earliest investigations, dietary
information obtained from 462 cancer patients suggested protective effects
of whole meal bread, cruciferous vegetables, and fresh milk (Stocks and
Kay 1933). Records from insurance companies suggested that overweight
people were at higher risk for cancer than normal or underweight people
(Tannenbaum 194Ob).

This finding stimulated a series of animal experiments that demonstrated a
lower incidence of skin tumors, mammary tumors, sarcomas, hepatomas,
lung adenomas, and pituitary adenomas in severely underfed animals

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0 Nutrition and Health

(Tannenbaum 1940a; Tannenbaum and Silverstone 1957). Early rodent
studies showed that high-fat diets favored development of mammary tu-
mors (Silverstone and Tannenbaum 1950) and that vitamin A deficiency
was associated with gastric papillomas (Fujimaki 1926). These and other
early studies of diet and cancer causation have been reviewed (Armstrong
and Mann 1985; Carroll and Khor 1975).

Although research on the effects of dietary modification on induction of
cancer in rodents continued, there was little attempt to relate the results of
this research to humans. Interest in the role of nutrition in human carcino-
genesis renewed in the 19605 when a report from the World Health Organi-
zation examined lifestyle and environmental factors associated with cancer
risk and concluded "that the majority of human cancer is potentially
preventable" (WHO 1964). Since then, epidemiologic and experimental
research on the relationship between diet, nutrition, and cancer has ex-
panded rapidly. In 1980, the National Cancer Institute commissioned the
National Academy of Sciences (NAS) to review available information,
develop dietary recommendations for public distribution, and develop
recommendations for further research on diet, nutrition, and cancer (NRC
1982). This chapter reviews the evidence available at the time the recom-
mendations of the NAS report were developed as well as findings since that
time.

Significance for Public Health

Cancer accounted for 22 percent of all deaths in the United States in 1984. It
has been estimated that 965,000 new cases of cancer were diagnosed and
483,000 people died of cancer in the United States in 1987 (Silverberg and
Lubera 1987). An American born in- i98S has an approximately 30 percent
chance of eventually dying of cancer (Seidman et al. 1985). Although the
annual number of cancer cases has been steadily increasing as the popula-
tion grows, the age-adjusted total cancer incidence and mortality rates for
sites other than respiratory tract (cancers that are primarily due to cigarette
smoking) have as a whole remained stable during the past 30 to 40 years
(NRC 1982).

Incidence and mortality rates for cancer are significantly higher in black
than in white Americans or members of other minority groups. This differ-
ence is especially pronounced in males. Blacks also have the lowest surviv-
al rates for cancers at most sites. These differences in cancer experience
are more readily explained by social and environmental factors than by
biologic differences. Although their cancer rates vary greatly according to

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Cancer 13

disease site and specific tribal group, Native Americans have the lowest
overall cancer rates among the U.S. population (DHHS 1985).

The costs of this illness can be divided into those that are economic (direct
and indirect) and psychosocial (Hodgson and Meiners 1982). The direct
costs of cancer treatment in the United States were estimated to be $22
billion and the indirect costs $50 billion in 1985 (Sondik et al. 1987). Thus,
successful strategies to prevent cancer could have an enormous public
health impact on the saving of both lives and dollars.

Cancer may arise in any organ in the body, but tumors of the lung, colon and
rectum, breast, skin, and prostate occur most frequently. Cancers of 10
sites-lung, colon-rectum, breast, prostate, pancreas, leukemias. stom-
ach, ovary, bladder, and liver-biliary cancers-account for more than 73
percent of all cancer deaths in the United States (Silverberg and Lubera
1987) and are variably associated with dietary factors. Although the exact
proportion is unknown, several researchers have attempted to provide
quantitative estimates of the percentage of cancer in the United States
attributable at least in part to diet. One group estimated the proportion of
cancer deaths attributed to diet to be 40 percent in men and 60 percent in
women (Wynder and Gori 1977), and another estimated it to be 35 percent
overall, with a range of 10 to 70 percent (Doll and Peto 1981) (Table 4-l).

Scientific Background

Lifestyle Factors and Cancer Risk

In searching for the causes of cancer, considerable effort has been devoted
to studying both environmental and genetic factors on the incidence of
cancer. In the course of this research, it has become clear that many
cancers have external causes and, in principle, should therefore be prevent-
able. These conclusions are supported by several lines of evidence.

Comparisons of Incidence Rates Between Populations. Incidence rates of
specific cancers differ as much as IOO-fold among populations. These
variations are illustrated in Figure 4-1 for several types of cancer. Because
the incidence of cancer increases with age, rates are age adjusted for
comparison of populations with different age structures. Different groups
within the same country may also have distinctly different cancer incidence
rates. For example, a comparison of Mormons versus non-Mormons in
Utah in 1%7-1975 demonstrated overall cancer rates that were 28 percent
greater in the non-Mormons even after all smoking-associated cancers
were eliminated (Lyon, Gardner, and West 1980). Environmental and social
factors, including diet and nutrition, have been implicated as partial causes
of this variation.

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              Table 4-l
Proportions of Cancer Demths Attributed to Various Factorsa

Percent of All Cancer Deaths

                               Range of
                             Best      Acceptable
Factor or Class of Factors                Estimate      Estimates

Tobacco                         30         2540
Alcohol                           3          24
Diet                            35          lo-70
Food additives                           (-5b)-2
Reproductive and sexual behavior     :           1-13
Occupation                                    2-g
Pollution           ;          l-5
Industrial products                     1           l-2
Medicines and medical procedures            1         OS-3
Geophysical factors                    3          24
Infection                          lo?          I-?
Unknown                          ?           ?
alt should be understoo.i that these figures are speculative, and there is considerable
uncertainty associated with them.
Wome factors (e.g., food fortification) may be protective.

Source: Doll and Peto 1961.

Rates per 100,000

LungfBronch (M)  Stomach(M)    Breast(F)    Colon (M)    Prostate (M)
               Cancer Types

     m High incidence area    m Low incidence area
              Age-standardized incidence rates

Fiiure 4-l.  Range of incidence rate8 (internatiinal comparisons).

Source: Adapted from Howe 1986.
                       180


Cancer O

Variation in Rates Within a Population Over Time. Changes in cancer rates
in a stable population must be due to environmental rather than genetic
causes, but it is not always easy to distinguish between actual changes in
rates and those due to improvements in screening, diagnosing, and treating
as well as identifying cancer as a cause of death. Table 4-2 demonstrates
rate changes over time for stomach and lung cancer mortality, two cancers
for which death records are fairly reliable and survival is relatively short.
These data indicate that the rate of stomach cancer mortality in the United
States declined by 61 percent from 195&51 to 1975-the reasons for this
decline have not been established (Silverberg and Lubera 1987)-while the
rate of lung cancer increased 148 percent. The increase in rate of lung
cancer mortality is due primarily to increases in cigarette smoking.

Migrant Studies. Studies of migrants offer clear support for the roles of life
style and environment in cancer etiology because such populations have
"unwittingly performed etiological experiments on a large scale by migra-
tion from one environment to another" (Steiner 1954). Table 4-3 compares
cancer incidence rates among Filipinos in the Philippines (Manila), mi-
grants to Hawaii, and Hawaiian Caucasians and indicates a migration-
related decrease in cancers of the stomach, liver, and cervix, as well as an

Table 4-2

International Changes Since 1950 in Death Certification Rates for
        Cancers of Stomach and Lung

Country

Period

Stomach

Lung

Australia            195G51 to 1975       -53
Austria             1952-53 to 1976       -53
Chile              1950-51 to 1975       -56
Denmark            1952-53 to 1976       -62
England and Wales      1950-51 to 1975       -49
West Germany         1952-53 to 1975       -50
Ireland             1950-51 to 1975       -54
Israel              1950-51 to 1975       -49
Japan              1950-51 to 1976       -37
The Netherlands        1950-51 to 1976       -60
New Zealand         1950-51 to 1975       -54
Norway            1952-53 to 1975       -59
Scotland           19xb51 to 1975       -46
Switzerland          1952-53 to 1976       -64
United States         1950-51 to 1975       -61

+ 146
-a
+38
+87
+33
+36
+ 177
+58
+408
+a9
+ 137
+118
4-44
+72
+148

Average of male and female rates at ages 35 to 64, standardized for age.

Source: Doll and Peto 1981.

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O Nutrition and Health

                 Table 4-3
Cancer Incidence Rates in the Philippines and Among Filipinos and
             Caucasians in Hawaii

Cancer Site

Philippines            Hawaii

Manila    Filipinos   Filipinos   Caucasians
1977      1%2-65     1978-81     197841

Males
Stomach
Colon
Rectum
Liver
Lung
Thyroid
Prostate

10
5
6
20
29
ii

1:::        6.6       14.8
        18.8      33.6
12.4       16.2       17.5
7.5        4.1       5.6
15.9       27.3       75.3
5.0
14.0   3:::   6;::

Females
Colon
Lung
Thyroid
Breast
Cervix

4        6.4       11.6      26.7
9        17.3       16.3       36.4
5       22.4       17.4       6.3
31        18.2       36.2       92.9
16        16.6        7.5       10.2

Average annual incidence per 100,000 population, age-adjusted to the World Population
Standard.

aRate is based on fewer than 10 cases.

Source: Adapted from Kolonel, Hankin, and Nomura 1986.

increase in cancers of the colon, thyroid, prostate, and breast. Similar
trends have been noted for Japanese migrants (Doll and Peto 1981). Al-
though migrant studies suffer from variations in the source and quality of
data, these studies do imply that environmental conditions, rather than
genetics, are responsible for the changing incidence patterns (Modan 1980;
Haenszel 1982).

Carcinogenic Agents. Identification of carcinogenic agents through animal
assays may suggest sources of exposure through contamination of food or
water supplies. However, because of continuous monitoring of the food
supply and regulatory requirements that prevent the addition of or mini-
mize the concentration of food contaminants that have carcinogenic poten-
tial, this possible source of cancer risk has a nondetectable impact on
cancer incidence in the United States.

. Concepts of Carcinogenesis
The complex process of cancer development can work through multiple
paths. Figure 4-2 illustrates a current view of the steps that lead to cancer.
                       182


Cancer 13

DIRECT
CARCINOGEN         PROCARCINOGEN
\ /A&$!!:,
         ULTIMATE
        CARCINOGEN

           GENdHlC
              ALTERATION
REPAlR .-j CR:~lication
              FIXATION OF
            ALTEREDGENOME  J

  STAGE I
PROMOTION              DeditTerentiation
,,,F$;;; -j ~p$i;~i;tivarion
              CONVERSION

PROPAGATION

CANCER

Figure 4-2. CarcinogeneMs.

Initiation of carcinogenesis alters the genetic information (i.e., DNA) of
the cell. Promotion then leads to expression of genetic changes as malig-
nancy, which involves loss of control over cellular proliferation. Accord-
ing to this model, both events are required for malignant transformation,
and they must occur in this order. Many factors, including dietary factors,
may enhance or inhibit this process at certain stages. Recent advances in
molecular biology have revealed the presence of cancer-inducing genes
(oncogenes) within cells that can be activated under specific environmental
conditions (Bishop 1987). Current knowledge of initiation, promotion, and
regulation of oncogene expression is consistent with suggestions that most
cancers have external causes and therefore are likely preventable.

Carcinogenesis is complete when cells become neoplastic and are indepen-
dent of normal biologic controls. These tumor cells grow in number during
a silent interval, which may last 5 years or more, sometimes much more,
before a tumor can be detected clinically. This long latent period makes it
difficult to establish the time of onset of carcinogenesis and requires that
studies of dietary effects on cancer estimate dietary intake for times up to
20 or more years before diagnosis.

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O Nutrition and Health

Diet and Carcinogenesis

Several mechanisms have been proposed to account for observed associa-
tions between diet, digestive processes, and cancer. These include:
o Carcinogens in food that are present naturally, that are inadvertent
contaminants, or that form as products of cooking or preservation.
o Diet-induced metabolic activation or deactivation of carcinogens (Mil-
ler and Miller 1976). For example, formation of oxygen radicals and
  lipid peroxidation products can be retarded or blocked by normal
enzymatic processes or by the selenium or beta-carotene present in
  food (Ames 1983).

o Biologic formation of carcinogens in vim, as with conversion of bile
acids to tumor-promoting chemicals by normal colonic bacteria (Hill et
al. 1971). The bacteria that accomplish this conversion may be affected
by diet.

o Enhancement (e.g., by fats) or inhibition (e.g., by vitamin A) of
promotion (Doll and Peto 1981).

o Nutrient imbalance may impair immunity (Beisel 1984) and thus may
influence early rejection of malignant cells or the ability of cells to
repair damaged DNA (Wood and Watson 1984). This topic has been
reviewed extensively (Good 1981; Gershwin, Beach, and Hurley 1985:
Watson 1984).

Nutritional Support With Cancer Treatment
Severe losses of weight, digestive and absorptive ability, and cellular
immune competence are frequent consequences of cancer, and cancer
patients may exhibit classic signs of extreme malnutrition. This cachexia of
cancer has been attributed to reduced food intake due to anorexia, which
may be compounded by disorders of taste and smell; to gastrointestinal
malfunction caused by radiation, chemotherapy, or surgical therapy (Bren-
nan and Copeland 1981); and to metabolic abnormalities induced by the
tumor itself (Anonymous 1984).

The observation that some cancer patients show marked weight loss has
led to the idea that correction of malnutrition by diet or by tube or
intravenous feeding might improve the tolerance of patients to therapy as
well as improve the quality and length of life. Despite some inconsistencies
in results, numerous studies have demonstrated the ability of nutritional
support to restore body weight and other indices of nutritional status,
functional ability, and feelings of well-being in cachectic cancer patients
(Brennan 1981). On the other hand, although some studies have demon-

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Cancer O

strated improved ability of well-nourished patients to withstand therapy
with radiation (McArdle, Laplante, and Freeman 1986), many others have
not (Donaldson 1984). Most prospective clinical trials to determine the
effects of nutritional support on the survival of cancer patients have also
failed to demonstrate an improvement (Koretz 1984).

Suggestions that macrobiotic diets, high doses of vitamins, minerals, and
other nutritional supplements or other unorthodox nutritional methods
might cure cancer or delay its course have not been supported by con-
trolled scientific investigations (ACS 1984; Herbert 1986). The use of high-
dose (10 g/day) vitamin C, for example, has been used in attempts to
prolong the quality of life and the lifespan of terminally ill cancer patients
(Cameron and Pauling 1978), but controlled studies have found no differ-
ence in outcome among patients taking vitamin C or placebos (Creagan et
al. 1979; Moertel et al. 1985).

Methodological issues

Different types of studies provide different types of information, and no
studies are without limitations. An important consideration in reaching
conclusions is consistency of data. The conclusions reached must be based
on the relevance, quality, and the degree of concordance between the
epidemiologic data and laboratory evidence, as applicable.

Interpretation of the associations between diet and cancer depends upon a
critical evaluation of the study design and methods of analysis used to
reach conclusions. The following types of investigations have yielded
important information about diet-cancer relationships.

Epidemiologic Studies. Much of the evidence on diet and cancer risk
derives from epidemiology, "the study of the distribution and determinants
of health-related states and events in populations, and the application of
this study to control of health problems" (Last 1983). Epidemiology is a
relatively young science that has contributed to the expansion of knowl-
edge and improvement of public health (Feinstein 1987). Epidemiologic
studies are generally classified as correlation (ecologic), case-control (ret-
rospective), and cohort (retrospective or prospective) studies (for reviews
see NRC 1982; Byers and Funch 1984). Case-control and cohort studies
tend to be stronger scientifically than ecologic studies because they use
data from individuals, rather than population averages, to reach their
conclusions. However, they sometimes are limited by narrow ranges of
variation in exposure (e.g., to food groups or nutrients), which reduces the
opportunity to see a potentially true biologic association. The ability to

185


O Nutrition and Health

detect a meaningful level of association is determined by the range of
exposure as well as the size of the sample studied (Self et al. 1988).

Ecologic Studies. These studies permit analysis of a variety of diets,
especially in international comparisons, that might not be observable in
case-control or cohort studies. They can also assess changes over long
periods of time. In such studies, cancer rates among various populations
can be correlated with data on food disappearance, dietary surveys, or
blood chemistries. This type of study is most useful for generating hypoth-
eses about dietary factors related to cancer risk. An example is the high
correlation between dietary fat intake and death rate from breast cancer
illustrated in Figure 4-3. Ecologic studies can also relate metabolic or
biochemical changes in circulating hormones or fecal bile acids, for exam-
ple, to dietary intake and cancer incidence (Reddy et al. 1980). Such
comparisons usually rely on average population data rather than on indi-
vidual measures, and they tend to focus on cancer mortality rather than on
incidence. Their most serious weakness is the potential for an "ecologic
fallacy," which means that populations may differ with respect to two
associated variables (e.g., dietary fat, colon cancer) but that the individuals
who get the disease (i.e., colon cancer) may not necessarily be the ones
who had the exposure (e.g., high fat); variables other than the one of
interest, such as obesity, or caloric intake, may account for the observed
difference in disease incidence or mortality (Last 1983). Despite such
limitations, ecologic studies allow multiple comparisons and correlations
that permit relatively inexpensive rapid generation and examination of
hypotheses regarding the causes of disease (DHHS 1982).

Case-Control Studies. Case-control studies begin with selection of individ-
uals who have the disease of interest (the cases) and compare their present
or past exposure to potential risk factors to that of persons without the
disease (the controls). The greater the proportion of cases exposed to a
factor, the stronger is the hypothesis that the factor increases disease risk
Increased risk is often expressed as a relative odds, or odds ratio, which for
uncommon diseases like cancer expresses the risk of disease in person>
exposed to the factor as a ratio or multiple of the risk in persons noi
exposed. An important component of the study design is that cases ano
controls should be drawn from the same population so that the potentia
contribution of confounding variables can be minimized. Case-contra
studies are advantageous for studying rare cancers with long latent period:
because they require relatively few subjects and can be used to asses!
multiple hypotheses for causation. However, they can be affected b]
uncertainties regarding the representativeness of both cases and control:
and the validity of dietary measures. Statistical significance of such rela

186


Cancer O

Figure 4-3.  Dietary tat intake in relation to breast cancer-related death rate.

Source: Carroll, K.K., and Khor, H.T. 1975. Dietary fat in relation to tumorigenesis.
    Progress in Biochemical Pharmacology 10:308-53. Reprinted with permission
    from S. Karger AG, Basel.

tionships, however, does not guarantee a causal association, nor does lack
of statistical significance necessarily indicate a noncausal association
(Schlesselman 1982). Case-control studies may fail to confirm strong asso-
ciations observed in correlation studies of diet and disease. Whether this is
caused by the better control of confounding variables, by the inability of
studies on individuals to make sufficiently valid measurements of diets, by
insuffrcient variation of diets within a single population, or by a combina-
tion of these or other factors needs to be evaluated.

Several potential constraints must be addressed for a case-control study to
identify a relationship between a dietary pattern and a disease outcome. If,
for example, a population is homogeneous in intake of a food or nutrient, or
if amounts ingested by most members of the population are insufftcient to
observe an effect, one may find little difference in exposure between cases
and controls, even for dietary factors that show associations in other
studies. Case-control studies also depend on the sensitivity of the dietary
questionnaire or other instrument of measure. Cancer itself, or another

187


0 Nutrition and Health

preexisting condition, may lead to dietary changes and result in spurious
associations because the measured exposure at the time of disease onset
may be quite different from the exposure at the time the case is found.

Cohort Studies. Cohort studies solve some of these problems by comparing
groups that have and do not have the dietary patterns of interest. The main
difference in concept between cohort and case-control studies is that in
cohort studies, subjects were selected on the basis of exposure versus
nonexposure, while subjects are selected for case-control studies on the
basis of disease versus nondisease. Because prospective cohort studies
assess the risk of disease after a given exposure, they require more time and
resources than case-control studies. In such studies, there is no need to
attempt retrospective measures of diet and, therefore, less concern about
the possibility of biased recall. When the relationship of dietary exposure to
subsequent cancer risk is to be studied, a very large group must be followed
for many years because of the long latency period for a sufficient number of
incident cases to be collected. In such studies, a sufficient exposure
difference must also exist between the two groups for a potential effect to
be noticed, and diligent surveillance is required to ensure that no cases of
cancer are missed. The advantages of cohort studies are that exposure is
known at a given point in time, greater control over measurement tech-
niques is afforded, and exposure is known to occur before the onset of
disease. While good cohort studies can provide stronger scientific informa-
tion than case-control studies, they still suffer from the potential limited
range of dietary exposure and require many years for completion.

Clinical intervention Trials. Clinical trials provide the strongest research
design to test whether an intervention will have the hypothesized effect. A
specificity not possible in epidemiologic studies derives from the prospec-
tive nature and use of random assignment to a treatment (such as a diet) in
clinical trials. These trials may show whether animal studies are applicable
to people and whether people will adhere to the intervention for the
duration of the trial (Greenwald, Sondik, and Lynch 1986). In clinical trials,
a prospective cohort is randomly assigned to an intervention or to a control
groupfor example, assigning women at increased risk for breast cancer to
either a customary diet or a long-term intervention program to lower
dietary fat to less than 20 percent of daily calories. To achieve the statistical
power necessary to reach solid conclusions in the face of diseases of
multiple etiologies and widespread risk factor exposure may require trials
involving many thousands of participants and many millions of dollars. On
the other hand, the expense and effort are warranted if the results can be
expected to benefit a large share of the population.

188


Cancer 0

To facilitate the conduct of these clinical trials, methodological improve-
ments are needed. Present methods to determine the relationship between
diet and cancer risk require long waiting periods to identify end points. The
lack of sensitive and specific markers of carcinogenesis makes nutrient and
chemoprevention trials difficult, although advances in molecular biology
may improve this situation (Perera 1987). Finally, ethical issues may be
important in such trials-for example, withholding an intervention that
might benefit a group on one or several dimensions-and have been re-
viewed recently (Freedman 1987).

Animul Studies. Animal studies offer the advantage of confined popula-
tions and closer control of experimental variables, and they provide invalu-
able opportunities to study the mechanisms that underlie the relationship of
diet and cancer. The use of very high levels of a specific nutrient or food
type (e.g., vitamin C or wheat bran) to maximize efficiency and minimize
costs in these studies complicates extrapolation of results to humans. An
important weakness is that virtually all animal studies test single, genet-
ically uniform (inbred) strains of one or two nonhuman species under
highly uniform conditions of diet, temperature, stress, exposure to infec-
tious diseases, etc., so that there are often serious constraints in generaliza-
tion of results to a highly variable human population. However, animal
studies may complement human studies, and these two basic approaches
should be used in conjunction when possible (NRC 1982).

Association and Causation. When an epidemiologic study shows an asso-
ciation between a dietary factor and the risk of a specific cancer, other
studies may not necessarily show the same degree of association because
of variations in research design, length of observation, relevant nondietary
exposures, variation in human response, or chance associations. To dem-
onstrate a true association, it is necessary to rule out spurious correlations
due to artifacts or biases (problems of validity) that stem from systematic
errors in design or analysis (Lilienfeld and Lilienfeld 1980; Sackett 1979).
Even statistical associations between diet and disease do not guarantee
that a specific factor causes the disease; noncausal (confounding) associa-
tions may exist (Miettinen and Cook 1981). Statistical methods to identify
problems of bias and confounding can strengthen the interpretation of
study results (Kleinbaum, Kupper, and Morgenstem 1982) but cannot
solve all of the problems encountered in interpreting results and in isolating
"true" effects.

Dietary Interactions. Complex interrelationships and interactions among
nutrients are often not appropriately considered. For example, dietary fats
supply more than twice the calories per gram as protein or carbohydrates.

189


O Nutrition and Health

Although fat consumption would be expected to correlate with caloric
intake, few studies of the role of fat in colorectal cancer have taken this into
account. Distinctions between tightly linked nutrients may not always be
possible. Methods to control highly correlated variables, however, can
result in difficulty in interpreting results because control for the effect of
the confounding variable may also remove variance due to the "true"
effect. Thus, the statistical instability of highly correlated variables often
makes use and interpretation of multivariance analysis difficult if not
impossible (Pilch 1987).

Another type of interaction of nutrients and food components can result in
a synergistic effect, an effect greater than that expected from the sum of the
individual effects. The synergy between asbestos exposure and smoking in
causing lung cancer is a well-known example of a synergistic effect. It is
also possible to have factors that counterbalance each other. Nutrient
synergies in cancer etiology are not as well established, but a recent study
correlating cancer with low serum levels of selenium and alpha-tocopherol
(vitamin E) is illustrative. While the relative risk for cancer was 5.8 for low
selenium level and 1.6 for low alpha-tocopherol level, the interactive risk
was 11.4 for both occurring together (Salonen et al. 1985).

Detailed food diaries, the usual instruments for assessing diet (Sorenson
1982), are generally recorded only for days or weeks, whereas dietary
histories over several years may be most pertinent (Byers and Graham
1984). More recent dietary survey instruments may improve the validity
and efficiency of dietary assessment (Byers and Graham 1984; Willett and
MacMahon 1984a, 1984b).

These methodological problems, the limited understanding of cancer at the
molecular level, the variety of foods, and the complexity of the composi-
tion of foods in the diet have hindered our understanding of the relationship
among diet, nutrition, and cancer. Despite uncertainties, evidence sup-
ports a role for several dietary components in prevention or causation of
specific cancers. The most important of these reported associations are
summarized in Table 4-4 and discussed further below.

Dietary Guidelines for Cancer Prevention

Dietary changes beyond the minimum intakes required for preventing
nutritional deficiencies may decrease an individual's risk for cancer (EOC-
CPS 1986). Translation of research results into dietary guidelines has
always been controversial, but in 1979 the Director of the National Cancer
Institute proposed a series of recommendations (Upton 1979). Also in

190


Cancer 0

            Table 4-4
Reported Relationship Between Selected Dietary
     Components and Cancer

Selected cancer
sites in
descending order
of incidence
(Age-adjusted
incidence, SEER,
1984)
Lung       (55P
-_-----------_--------------

Breast      (51)
--------------------________

Colon      (36)
-_-------_-_---_-__-_______

Prostate     (34)
----------------------------

Bladder     (16)
--------------------________

Rectum     (15)
____________________________
Endometrium (13)
-------_--------------------
Oral Cavity   (11)
---__-__-____-______________
Stomach     (8)
------------------_---------
Kidney      (8)
---_________________________

Cervix      (5)
------_____________________
Thyroid      (4)
------______________________
Esophagus    (4)

                       Smoked,
   Body         Fruits        Salted,
   Weight        and           and
   and        Vege-         Pickled
Fat   Calories   Fiber  tables   Alcohol   Foods

                    -      +b


+      +              -       +



+      +       -      -



+      +              -



                    -

+                           +


+      +

-       +

-

+

+


+



+



                     +        +

Key: +  = Positive association; increased intake with increased cancer.
     -  = Negative association; increased intake with decreased cancer.

aRate per 100,000 population, age-adjusted incidence from United States, 1984, Sondik et
al. 1987.
bSynergistic with smoking.

191


O Nutrition and Health

1980, the National Cancer Institute commissioned the NAS to conduct a
comprehensive review of research findings on diet, nutrition, and cancer to
use as a basis for development of dietary guidelines and recommendations
for future investigation (NRC 1982). The most recent dietary guidelines
from the National Cancer Institute (Butrum, Clifford, and Lanza 1988) are
listed in Table 4-5.

As shown in Table 4-6 and discussed in the introductory chapter, dietary
guidelines have been issued by the National Cancer Institute, the Ameri-
can Cancer Society, the Federal Government (USDA and DHHS), and the
American Heart Association. They tend to be similar in making general
recommendations about maintenance of desirable weight, the importance
of a variety of wholesome foods, reduction of fat, adequate levels of fiber,
and, at most, moderate levels of alcohol intake. They vary, however, in the
development of quantitative guidelines and in the rationale used to indicate
a link between dietary intake and the risk for various diseases.

Key Scientific Issues

o Role of Dietary Fats in Cancer
o Role of Calories and Body Weight in Cancer
o Role of Dietary Fiber in Cancer
o Role of Vitamin A and Carotenoids in Cancer

o Role of Alcohol in Cancer
o Role of Other Dietary Constituents in Cancer

    Table 4-5
National Cancer Institute
Dietary Guidelines

1. Reduce fat intake to 30 percent or less of calories.
2. Increase fiber intake to 20 to 30 grams daily, with an upper limit of 35 grams.
3. Include a variety of vegetables and fruits in the daily diet.
4. Avoid obesity.
5. Consume alcoholic beverages in moderation, if at all.
6. Minimize consumption of salt-cured, salt-pickled, and smoked foods.

Source: ButNm, Clifford, and Lanza 1988.

192


              Table 4-6
Comparison of Dietary Guidelines for the American Public

NC1 Dietary

                       Fruits
                      and
Fat          Fiber       Vegetables     Obesity       Alcohol        Salt

Reduce fat intake Increase fiber in-  Include a variety

Guidelines _     to 30% or less of  take to 20 to 30 g,  of fruits and vege-
Butrum et al. 1988 calories       not to exceed 35 g tables in the daily
                                 diet

Avoid obesity

Consume alco-
holic beverages in
moderation, if at
all

Minimize consump-
tion of salt-cured,
salt-pickled, and
smoked foods

American Cancer  Cut down total fat Eat more high-
Society 1985     intake        fiber foods

5
  USDA/DHHS
  1985 Dietary
  Guidelines for
   Americans

American Heart
Association 1985

Avoid too much   Eat foods with
fat, saturated fat,  adequate starch
and cholesterol   and fiber

Total fat, 30% or
less of calories;
saturated fat, 10%
of calories; cho-
lesterol, 100
mg/l ,000 calo-
ries-not 300 mg/
day

Include breads,
cereals, pasta,
and starchy vege-
tables containing
natural complex
carbohydrates

Include foods rich
in vitamins A and
C; include cru-
ciferous vegeta-
bles

Eat a variety of
foods

Include at least 3
servings/day of
fruits and 3 serv-
ings/day of
vegetables

Avoid obesity

Keep alcohol con-
sumption moder-
ate if you do drink

Maintain desirable If you drink alco-
body weight    holic beverages,
           do so in modera-
           tion

Achieve and    If you drink, do
maintain desirable so in moderation
weight

Keep consumption
of salt-cured,
smoked, and nitrite-
cured foods moder-
ate

Avoid too much
sodium

Limit salt intake

Bource: Butrum, Cliiord, and Lanza 1988.


O Nutrition and Health

Role of Dietary Fats in Cancer

Despite some inconsistencies in the data relating dietary fat to cancer
causation, animal studies show an effect on carcinogenesis and support a
cancer-promoting role, and international epidemiologic studies have sug-
gested that differences in dietary fat intake may provide a meaningful key
to prevention of cancer. For example, substantial epidemiologic and ani-
mal evidence supports a relationship between dietary fat and the incidence
of both breast cancer (Kakar and Henderson 1985) and colon cancer
(Kolonel and Le Marchand 1986). Indeed, a comparison of populations
indicates that death rates for cancers of the breast, colon, and prostate are
directly proportional to estimated dietary fat intakes (Wynder et al. 1981;
Rose 1986). Other cancers that have been related to fat intake are those of
the rectum (Armstrong and Doll 197% ovaries (Rose, Boyar, and Wynder
1986). and endometrium (Mahboubi, Eyler, and Wynder 1982). Consider-
able uncertainties remain to be resolved about these relationships. For
example, the effects of different types of dietary fat (i.e., saturated vs.
unsaturated; animal vs. plant origin) have not been separated in most
human studies. But the weights of the studies to date are strongly sug-
gestive of the role for dietary fat in the etiology of some types of cancer.

Human Epidemiologic Studies

The risk for breast cancer is correlated with total fat consumption in
comparisons of countries (Armstrong and Doll 1975; Gray, Pike, and
Henderson 1979; Rose, Boyar, and Wynder 1986), districts in Japan
(Hirayama 1977), and ethnic groups in Hawaii (Kolonel, Hankin, et al.
1981). The risk for cancers of the colon and prostate is also correlated with
total fat consumption in international comparisons (Armstrong and Doll
1975; Knox 1977; Liu et al. 1979). A worldwide correlation between breast
and colon cancer mortality and total fat consumption has been demon-
strated (Carroll and Khor 1975) and is illustrated for breast cancer death
rates in Figure 4-3.

Although further epidemiologic study is needed to verify the association
between diet and breast cancer and to elucidate its biologic basis, the
consistency of the evidence derived from the epidemiologic and animal
studies suggests that the association may be causal (Miller 1986). Table 4-7
summarizes certain key (although Emited) dimensions of the human epi-
demiologic studies of diet and breast cancer. Correlation studies show the
strongest associations. Migrant studies often show that people who move
to a country with a higher incidence of breast cancer than their native
country tend to acquire the dietary habits of their new country of residence

194


Cancer 0

and may experience a cancer incidence that changes with the change in
dietary fat (Kolonel, Nomura, et al. 1981; Gori 1979). Case-control and
cohort studies relate the risk for breast cancer to total fat consumption in
some (Milleret al. 1978; Lubin, Wax, and Modan 1986) but not all (Graham
et al. 1982; Willett et al. 1987) studies. While methodological problems may
have obscured a true risk association in these negative studies (Willett et al.
1987; Hebert and Wynder 1987; Self et al. 1988), they reinforce the need for
cautious interpretation and additional study of diet and breast cancer risk.

A Canadian case-control study has related an elevated risk for colon cancer
with an increased intake of calories, total fat, and saturated fat (Jain et al.
1980). Fat consumption has been associated with colon cancer in American
blacks (Dales et al. 1978) and in Americans of Bohemian ancestry in
Nebraska (Pickle et al. 1984). Other studies have demonstrated no excess
risk for colon cancer, and a recent review has found the evidence to be
inconclusive (Kolonel 1987).

Some studies show associations between breast or colon cancer and meat
intake that are similar to those with fat intake (McKeown-Eyssen and
Bright-See 1985; Armstrong and Doll 1975; Lubin et al. 1981). At present,
these data do not establish meat and other animal protein intake as risk
factors independent of fat intake (Kolonel and Le Marchand 1986). In
postmenopausal breast cancer, the association of dietary fat may be related
to a higher intake of total calories during a high-fat diet, to obesity, or to a
lower intake of foods that provide protective micronutrients (Willett 1987).
In colon cancer, if various hypotheses hold true, the carcinogenesis-
enhancing effects of dietary fat may interact with the possibly protective
effects of dietary fiber (Jensen, MacLennan, and Wahrendorf 1982).

The effect of dietary cholesterol on cancer incidence is difficult to deter-
mine both because of the strong correlation of cholesterol with animal fat,
and therefore with protein intake, and because blood cholesterol levels
reflect more than dietary cholesterol levels. In one study, the correlation
with colon cancer incidence was stronger for dietary cholesterol than for
dietary fat (Liu et al. 1979). On the other hand, some studies that have
examined blood cholesterol correlations and cancer suggest that very low
blood cholesterol levels may be a risk factor for cancer (McMichael et al.
1984). Much more work is needed before firm conclusions can be drawn
about the relationship of either dietary or blood cholesterol levels to cancer.

195


0 Nutrition and Health

               Table 4-7
Summary of Epidemiologic Btudies Examining Dietary Fat and
             BreastCancer

Author(s)

Total Animal         Vegetable
Fat    Fat    Meat  Etsm   Fat

International Correlation
Lea 1964
Carroll et al. 1968
Hems 1970
Drasar & Irving 1973
Armstrong & Doll 1975
Carroll & Khor 1975
Hems 1978
Gray et al. 1979
Carroll 1980
Rose et al. 1986

Within-Country Correlation
Hirayama 1977
Enig et al. 1978
Nomma et al. 1978
Gaskill et al. 1979
Ingram 1981
Kolonel et al. 1981
Kinlen 1982

Case-Control Studies
Phillips 1975
Miller et al. 1978
Lubin et al. 1981
Graham et al. 1982
Talamini et al. 1984
Nomura et al. 1985
Le et al. 1986
Hislop et al. 1986
Katsouyanni et al. 1986
Lubin et al. 1986
Hirohata et al. 1987

+ (a)
+
+
+
+
+
+
+
+
+

+
+

+
+

+

0

0

064
0'

+

+
+

-

+ (4


+

+ (h)

+m
+ (4

+ @I

+ (4

+
h
0





+ (lx)

0

+ I - (i)
+/-(j) +(b)

+ W
o(b)

+






     0
     0






      +
      +
-

+ G-0

1%


Cancer 0

Table 4-7 (continued)

                  Total   Animal         Vegetable
Author(s)              Fat    Fat    Meat  Em   Fat

Cohort Studies
Hirayama 1978                          +
Phillips & Snowden 1983                0
Willett et al. 1987        0
Jones et al. 1987         0
Key: (a) = Fats and oils.
  (b) = Animal protein.
  (c) = Meat and animal protein.
  (d) = Meat, milk, and animal protein.
  (e) = Milk.
  (f) = Fried potatoes.
  (g) = Beef and pork.
  (h) = Dairy products.
   (i) = Positive for cheese and fat in milk. Negative for yogurt.
      No association for butter.
   (i) = Positive for gravy, beef, and pork. Negative for fish.

Animal Studies

Animals fed a high-fat diet often have higher rates of carcinogen-induced
cancers of the breast, colon, and pancreas than those fed low-fat diets
(Carroll 1986). Animal studies that indicate that dietary fat could influence
carcinogenesis date back more than half a century (Watson and Mellanby
1930), with experiments indicating that the incidence of skin tumors on
coal-tar-treated mice could be increased by more than 70 percent by
feeding them diets higher in saturated fat. Investigators studying mammary
tumors in mice found that the later a high-fat diet was begun, the lower the
incidence of tumors; that tumors occurred more frequently in obese mice
(Tannenbaum and Silverstone 1957); and that fat restriction inhibited mam-
mary tumorigenesis in normal mice (Tannenbaum 1942). Rats fed a low-fat
diet (2 percent linoleic acid) were noted to have markedly lower rates of
chemically induced (7,1Zdimethylbenz[a]anthracene (DMBA)) mammary
tumors than those fed high polyunsaturated (20 percent corn oil) or saturat-
ed (18 percent coconut oil, 2 percent linoleic acid) fats (McCay et al. 1980).

Various animal studies have also associated intestinal tumors with higher
levels of dietary fat. Rats fed 35 percent of total calories as beef fat were

197


O Nutrition and Health

noted to develop both more intestinal tumors and more metastases in
response to azoxymethane (AOM) than rats fed normal chow (Nigro et al.
1975). Rats given 1 ,Zdimethylhydrazine (DMH) for tumor induction were
noted to have more large bowel tumors on 30 percent lard diets than on low-
fat standard diets (Bansal, Rhoads, and Bansal 1978). The role of fat as a
tumor promoter, rather than inducer, is suggested by studies such as one
indicating that, relative to a 5 percent beef fat diet, a diet of 30 percent beef
fat increased the rate of intestinal tumors only when fed to rats after AOM
administration (Bull et al. 1979).

Some studies suggest that polyunsaturated fat has the greatest tumor-
enhancing effect for mammary (Cohen 1986), pancreatic (Birt and Roebuck
1986), and colon (Reddy 1986) cancers. High intakes of oleic (monounsatu-
rated) and linoleic (polyunsaturated) acids correlate with increased mam-
mary tumor incidence (Chart, Ferguson, and Dao 1983). In contrast, highly
unsaturated omega-3 fatty acids derived from fish oils may protect against
cancer (Braden and Carroll 1984) reduce tumor growth rates (Karmali,
Marsh, and Fuchs 1984), and minimize the incidence of tumors promoted
by high amounts of dietary corn oil (Ip, Ip, and Sylvester 1986). Hypotheses
regarding types of fat and cancer risk require additional study.

Biochemical Mechanisms

Although dietary fat generally exerts its maximum effect when fed after
carcinogen administration, it appears that sufficient duration of exposure to
high dietary fat levels before carcinogen administration might affect tumor
initiation as well; such an effect has been demonstrated for rat mammary
carcinogenesis (Dao and Chan 1983).

The effect of dietary fat may be direct or indirect (Cohen 1986). Fat directly
affects many cellular functions, including cell membrane fluidity, pros-
taglandin metabolism, and synthesis of potentially mutagenic lipid perox-
ide radicals (Welsch 1987). Direct effects also include changes in hormone
receptors (which might promote hormonally mediated tumor growth), cell
growth characteristics, and various intracellular chemicals. Fat-induced
changes in bile acid composition in the colon may promote bacterial
conversion of bile acids to tumor-promoting substances or may directly
damage the colonic mucosa (Kritchevsky 1982; Goldin 1986).

198


Cancer O

Role of Calories and Body Weight in Cancer

Animal studies and a few epidemiologic investigations support the hypoth-
esis that total caloric intake affects the risk of cancer. Some animal studies
compared normal controls with animals on diets severely restricted in
calories; others have compared normal and obese animals (Stunkard 1983).
Because accurate measures of caloric intake over long periods of time are
difficult, human studies usually focus on indirect measures such as body
weight, relative body weight, or body weight indices that are presumed to
correlate with increased caloric intake. Complicating these studies is the
question of energy expenditure in maintaining caloric balance. The rela-
tionship between caloric intake, body weight, and cancer was the subject
of a recent review (Albanes 1987) and a symposium (Pariza and Si-
mopoulos 1987). This symposium also contains several studies on the
association of exercise to cancer prevention.

Human Epidemiologic Studies

In international studies, a correlation between total per capita calories and
cancers of the breast, colon, rectum, uterus, and kidney has been reported
(Armstrong and Doll 1975). Case-control studies have found positive asso-
ciations between energy intake and breast cancer (Miller et al. 1978) and
energy intake and colorectal cancer (Jain et al. 1980; Lyon et al. 1987).

A positive association between increased body weight or body mass index
and an increased risk for cancer has been observed for several cancers,
including breast (de Waard and Baanders-van Halewijn 1974; Hirayama
1978; Mirra, Cole, and MacMahon 1971), kidney (Goodman, Morgenstem,
and Wynder 1986), endometrium (La Vecchia et al. 1984), and prostate
(Snowdon, Phillips, and Choi 1984). Other studies report no effect of body
weight on increased risk for cancers of the breast (Adami et al. 1977; Soini
1977), colon (Wynder et al. 1%9), and prostate (Greenwald et al. 1974).
Table 4-8 summarizes some of these and other retrospective human studies
of cancer and body weight.

In a large cohort study conducted by the American Cancer Society, the
lowest overall cancer mortality was observed in men whose body weights
ranged from 10 percent below to 20 percent above the average for their age
and height. The lowest risk overall for women was seen in those whose
weights ranged from 20 percent below to 10 percent above the average for
their age and height. Nonsmoking males (who usually weigh more than


O Nutrition and Health

        Table 4-8
Retrospective Human Studies Relating
   Body Weight and Cancer

First Author/
Year       Location      Comments

Breast

de Waard
1964

The Netherlands

Valaoras
1969

Mirra
1971

Greece


Brazil

Lin        Taiwan
1971 *

Adami
1977

Sweden

Soini
1977

Finland

Hirayama
1978

Japan

Choi
1978

Canada

Paffenbarger U.S.
1980

No statistical tests presented; 30% increased
risk for obesity, and 60% increased risk for
obesity plus hypertension; opposite trend in
premenstrual women.
Positive association with height, BW, and
BMI.

Associations observed among women 50
years old only; positive association with
height, BW, and BMI.
Increased effect among women 50 years old;
no effect for height; positive effect for
weight.

Nonsignificant case-control differences in
mean BW and BMI in postmenopausal
women. Opposite trend in premenopausal
women also not significant; no effect for
height; used measured BW for cases, self-
reported BW for controls.
Nonsignificant case-control differences for
BW or BMI. Nonsignificant positive
association with height; limited age range
(414 years), and no analysis by
menopausal status.

Increased risk for postmenopausal women
greater than for premenopausal.
Independent positive associations for both
BW and height.

Increased BW in postmenopausal cases.
Decreased BW in premenopausal cases.
Postmenopausal cases also taller.
Increased risk with BMI in postmenopausal
women. Decreased risk in premenopausal
women. Increased height in premenopausal
cases.

200


Cancer 0

Table 4-8 (continued)

First Authori
Year       Location
f?reast (continued)

Comments

Kelsey
1981

Brisson
1984

Kidney
Wynder
1974
McLaughlin
1984

Maclure
1985 (abstr)
Goodman
1986

Asal
1985 (abstr)
Yu
1986

Endometrium
Kelsey
1982

Henderson
1983

La Vecchia
1984

U.S.

U.S.

U.S.


U.S.

U.S.


U.S.


U.S.


U.S.

U.S.


U.S.


IdY

Increased risk with BW in postmenopausal
women. Decreased risk in premenopausal
women.

Increased risk with BW in pre- and
postmenopausal women; inverse association
with height.

Greater proportion cases with RBW > 125%
in females only.

Increased risk with BMI in females. Positive
association for weight gain since age 20 in
females.

Increased risk with BMI in men and women.

Increased risk with BMI in men and women.

Increased risk with BMI in men and women.

Increased risk with BMI in men and women
independent of tobacco and other risk
factors.

Increased risk with BW and similar trend for
BMI (not presented by authors).
Increased risk with BW and similar trends
for BMI and BW at age 20.
Increased risk with BMI greater for
premenopausal than for postmenopausal

201


O Nutrition and Health

Table 4-8 (continued)

First Author/
Year       Location       Comments

Prostate

Wynder
1971

Colorectal
Wynder
1%9

Thyroid
McTieman
1985 (abstr)

Meningioma
Bellur
1983

U.S.

No significant difference in RBW between
cases and controls with no significant
difference in height.

Japan

No significant difference in RBW between
cases and controls.

U.S.

Increased risk with BW in > = 60 vs.
< = 52 kg. Only women studied.

U.S.

Increased risk for "obese" women. No
significant difference among men.

Key: BW  = body weight.
  BMI = body mass index.
  RBW = relative body weight.
   P values for test for trend, unless otherwise indicated.

Source: Adapted from Albanes 1987.

smokers but have a lower cancer risk) showed a relationship between
relative body weight and cancer death that was nearly linear (Lew and
Garfinkel 1979). In the United States, individuals greater than 40 percent
overweight have mortality ratios (observed cancer deaths divided by ex-
pected cancer deaths) higher than average-weight individuals by 33 percent
for men and 55 percent for women (Garfinkel 1985). In men, this relation-
ship was statistically significant for cancer of the colon, rectum, and
prostate, and in women, for cancer of the breast, uterus (cervix and
endometrium), ovary, and gallbladder.

Animal Studies

Restriction of caloric intake reduces the incidence of many different can-
cers and increases the lifespan of laboratory animals (Tannenbaum 1940a;
Kritchevsky and Klurfeld 1987). Some of these suggest that the greatest
reduction in cancer incidence is associated with lifelong restriction of

202


Cancer O

calories, but caloric restriction begun in adulthood may also have a protec-
tive effect (Weindruch and Walford 1982).

Total caloric intake as well as calories derived from fat affect cancer risk,
but their relative importance may vary for different tumor types
(Kritchevsky, Weber, and Khnfeld 1984). One study that has attempted to
separate the effects of calories from those of fat suggested that tumor
incidence in rats depends on energy intake, energy retention, and body size
rather than on percent of fat calories in the diet (Boissonneault, Elson, and
Pariza 1986).

Biochemical Mechanisms

While no unifying principle to explain the relationship has emerged, cur-
rent investigations in animals support the idea that overnutrition increases
cancer risk (Pariza and Boutwell 1987). One hypothesis is that chemical
carcinogens may be stored in body fat for mobilization and transport to
target tissues. A second hypothesis is that the supply of available energy is
one factor that controls cell growth (Pardee et al. 1978; Scott, Wille, and
Wier 1984), and an excess of available energy may increase cell multiplica-
tion and affect the promotion phase of carcinogenesis. Excess energy
could also shorten the latent period. A third hypothesis involves the
influences of female hormones on breast, ovarian, and uterine cancers,
with metabolism of hormones in adipose tissue possibly playing a role in
tumor formation and growth. Androstenedione from the adrenal gland can
be converted to estrogen in adipose tissue and may stimulate cell division
in the target organs of obese individuals (Siiteri 1987). Thus, although
animal studies suggest that caloric restriction might reduce cancer inci-
dence, the results of human studies are not wholly consistent (see Table
4-8). To resolve these inconsistencies, additional studies are needed to
separate the individual effects of calories, fat, and obesity (Willett 1987).

Role of Dietary Fiber in Cancer

Dietary fiber includes components of plant materials that, when eaten,
resist the action of human digestive enzymes. Dietary fiber has diverse
chemical constituents, including carbohydrate and carbohydrate-like cel-
lulose, hemicelluloses, lignin, gums, and pectins. Major food sources of
fiber are fruits, vegetables, and whole grain cereals.

In some studies, particularly correlation studies, consumption of high-fiber
foods has been correlated with lower risk of colon cancer. An important

203


Ll Nutrition and Health'

issue in human studies is the lack of information about the specific compo-
nents of dietary fiber and how they may affect cancer risk. Although rodent
studies have provided conflicting results, they do suggest that the type of
fiber is important. In those studies that showed a protective effect, wheat
bran, a source of water-insoluble fiber, was more consistently associated
with lower risk of colon cancer than other fiber sources (Pilch 1987).

Human Epidemiologic Studies

The results from 44 epidemiologic studies conducted between 1973 and
1987 are summarized in Table 4-9. Numerous correlation studies have
suggested a protective effect of dietary fiber against colon cancer (Burkitt
1980; Reddy 1982; Greenwald, Lanza, and Eddy 1987). Of the 24 correla-
tion studies, 21 identified an inverse association of dietary fiber, fiber-rich
diets, or other measures of fiber consumption with occurrence of colon
cancer; 3 showed no association; and none reported a positive association.
One international study that found an inverse association with total dietary
fiber also found a protective effect of cereal fiber, even after adjustment for
intake of fat or meat (McKeown-Eyssen and Bright-See 1985).

In some studies, correlations with other nutrients were also observed.
Thus, while patterns of eating foods high in fiber show good correlation
with low colon cancer rates, other dietary components might also be
influencing this association. It must also be noted that international cor-
relation studies (seven studies) tend to derive their food data from similar
sources.

Several epidemiologic studies that include biochemical markers have cor-
related cancer rates to measures of stool weights, fecal bile acids, enzymes
from colonic bacteria, and fecal mutagens. Comparison of rural Finns (who
have low rates of colon cancer) to their urban counterparts shows that
intake of calories and fat is similar for both groups, but the rural Finns have
a higher intake of dietary fiber, a greater stool weight, and a lower level of
fecal bile acids than urban Finns (Englyst et al. 1982; Cummings and
Branch 1982; Jensen, MacLennan, and Wahrendorf 1982; Bingham et al.
1982).

The importance of these observations derives in part from the fact that
secondary bile acids, formed by bacterial degradation of primary bile acids
in the intestine, have been shown to promote tumors in animals (Wynder
and Reddy 1983), may be mutagenic (Wilpart et al. 1983), and are directly
correlated with population incidence of colon cancer (Hill 1983). Fecal
mutagens are also correlated with the incidence of colon cancer in popula-


Cancer 0

          Table 4-9
Summary of Epidemiologic Studies Examining
   Dietary Fiber and Colon Cancer

Authors            Year

         Vege-  High Fiber/
Fiber   Cereals   tables   Low Fat

International
Correlation Studies

Drasar & Irving
Irving & Drasar
Armstrong & Doll
Howell
Knox
Liu et al.
McKeown-Eyssen
& Bright-See

1973
1973
1975
1975
1977
1979

0
     - (a)
     - (a)

      -
- (a)

1985

Within-Country
Correlation Studies

Malhotra           1977
Lyon & Sorenson      1978
Enstrom            1980
Rozen et al.          1981
Maisto & Bremner      1981
Jensen             1983
Bingham et al.        1985

-(b)
0

-(b)
-09
-

Metabolic
Correlation Studies

MacLennan et al.       1978
Reddy et al.          1978
Reddy et al.         1980
Jensen et al.          1982
Reddy et al.          1983
Nair et al.           1984
Walker et al.          1986

0

Time Trend
Correlation Studies

McMichael et al.       1979   - (b)
Helms et al.          1982     -
Powles & Williams     1984        - (a)

-

-(b)

205


O Nutrition and Health

Table 4-9 (continued)

Authors            Year

Fiber

Cereals

Vege-  High Fiber/
tables   Low Fat

Case-Control Studies

Haenszel et al.        1973
Bjelke              1974a
Bjelke             1974b
Phillifis             1975
Modan et al.          1975
Graham et al.         1978
Dales et al.          1978
Moskowitz et al.        1979
Haenszel et al.        1980
Hunter et al.          1980
Jain et al.            1980
Martinez et al.        1981
Manousos et al.        1983
Pickle et al.          1984
Potter & McMichael     1986
Tuyns              1986
Macquar%-Moulin       1986
Lyon et al.          1987
Kune et al.         .I987

Cohort Studies

Hirayama

1981

0

-(b)
0
+

0
+ (a)

- (4
- (b>

+
        -

+ (a)
        -

Key: 0 = No association.

- = Inverse association (decreased risk).
+ = Direct association' (increased risk).
(a) = Adjustment for other food conlponents removes the association.
(b) = No test for significance or not statistically significant.

tions (Wilkins and Van Tassel1 1983), although no-such correlations have
been observed for individuals (Correa 1981). Recently, fecal mutagens
have been shown to be modulated by dietary fiber (Reddy et al. 1987). In
addition, fermehtation of fiber in the colon by intestinal bacteria results in
the release of short-chain fatty acids, which may directly influence colonic
mucosal cells (Reddy 1982). Further research is needed to elucidate the
role of fecal mutagens in colon cancer and the influence of v@ous dietary
fibers (Pilch 1987).                              .

Additional support for generating the fiber/cancer hypothesis comes from
time-trend correlation studies. Long-term trends in colon cancer for sev-
eral population groups also offer insights into the role of dietary fiber. In

206


Cancer 0

Denmark, the decrease in dietary fiber consumption from 1927 to 1977 has
been correlated to the rise in prevalence of colon cancer (Helms et al. 1982).
In seven other countries, changes in flour milling practices during World
War II led to increased consumption of total fiber, which correlated with a
reduced mortality of colon cancer in those countries 15 years later (Powles
and Williams 1984). Other wartime lifestyle changes, such as decreased fat
or meat consumption, however, could have also influenced mortality.

To date, 19 case-control studies have assessed the role of fiber-containing
foods in colon cancer: 3 of these studies found no effect (Moskowitz et al.
1979; Jain et al. 1980; Pickle et al. 1984). 3 found an increased risk
(Haenszel et al. 1973; Martinez et al. 1981; Potter and McMichael 19861,
and 13 observed a protective effect of fiber-containing foods, especially
vegetables. Protective effects have been found in two case-control studies
that examined the relative risk for a high-fat, low-fiber diet (Dales et al.
1978; Manousos et al. 1983). Overall, case-control studies present mixed
results. Some show fiber and fiber-containing foods to be protective: others
do not.

Animal Studies

Animal studies of dietary fiber and colon cancer have provided inconsistent
results due to a number of factors, including differences in the nature of the
carcinogen used, variations in composition of the diet, qualitative and
quantitative differences in the fibers fed, animal strain, or duration of the
experiment (Reddy 1986; Pilch 1987). In the past decade, a number of
studies have been conducted on laboratory rats fed diets of various fiber
sources and levels and exposed to certain known colonic carcinogens:
DMH, AOM, DMAB, and methylnitrosurea (MNU). When wheat bran was
used as the source of dietary fiber, a protective effect was seen in the
majority (Reddy 1982; Barbolt and Abraham 1978) but not all studies
(Bauer et al. 1979; Jacobs 1983). A protective effect against colon cancer
was found in studies of chemical carcinogens requiring microsomal activa-
tion (DMH, AOM, DMAB) but not in one study with MNU, a direct-acting
carcinogen. Other studies reported were less suggestive of protection.
Although two-thirds of studies showed that dietary cellulose was protective
for rats exposed to DMH and AOM, no effect was observed for the rest.
Studies of the effect of corn bran, rice bran, oat bran, pectin, and guar gum
must be considered indeterminant, with some showing a protective effect,
more showing an enhancing effect, and others showing no effect (Pilch
1987). The relevance of these animal models to human cancer needs to be
determined.

207


O Nutrition and Health

Biochemical Mechanisms

The means by which fiber may exert its protective action are not under-
stood. Several possibilities have been advanced: Fiber may act to reduce
transit time in the bowel and therefore decrease the time for exposure to
potential carcinogens; through its hydrophilic nature, it can dilute the
concentration of carcinogens in the colon; it can affect the production of
bile acids and other potential carcinogens in the stool; it can alter the nature
of fecal bile acids by virtue of its influence on the composition and meta-
bolic activity of fecal flora; and it can reduce colonic pH by increasing
fermentation and short-chain fatty acid production (NRC 1982; Eastwood,
McKay, and Brydon 1986).

Limited information is available on the types of dietary fiber that might
protect against cancer. Research will have to define the importance of
various fiber compounds relative to the risk for specific cancers. The term
fiber embraces a broad range of food components whose primary com-
monality is their relative indigestibility. Different types of fiber have very
different qualities. Some are classified as soluble, others insoluble. Some,
but not all, appear to affect gastric emptying. Some affect absorption of
certain nutrients, others do not. Animal studies suggest that different types
of fiber work differently with respect to the occurrence of colon cancer. As
noted earlier, wheat bran, which decreases gastrointestinal transit time and
increases stool weight, appears to more consistently reduce the frequency
of colon tumors in animals than other types of fiber (Pilch 1987). However,
until better methods for analyzing the fiber content of foods are developed,
the influence of fiber components such as pentosan fractions (Bingham et
al. 1979). uranic acids (pectins), or cellulose (Bingham, Williams, and
Cummings 1985) must be considered uncertain.

In humans, a sudden change from a low-fiber to a high-fiber diet may
provoke symptoms of gastrointestinal distress, although effects are not
generally seen with gradual increases. The most frequently suggested
adverse effect of high fiber intake is mineral imbalance. While the evidence
is mixed, a recent review suggested that consumption of diets containing
about 20 to 25 g of insoluble fiber from foods per day does not appear to
pose a problem relative to mineral availability (Pilch 1987). This amount
translates to approximately 30 to 35 g of total dietary fiber from a mixed
adult diet and is consistent with current recommendations of the National
Cancer Institute (20 to 30 g daily from a variety of food sources, including
vegetables, fruits, and whole grain cereals).

208


Cancer O

Role of Vitamin A and Carotenoids in Cancer

A large body of evidence suggests that foods high in vitamin A and car-
otenoids are protective against a variety of epithelial cancers (Mettlin 1984;
Kummet, Moon, and Meyskens 1983; Bertram, Kolonel, and Meyskens
1987; Palgi 1984).

Vitamin A in foods occurs in two forms: (1) preformed vitamin A (retinol
and retinol esters) from animal foods and (2) provitamin A (carotenoids that
the body can convert to vitamin A) from plant foods. Hundreds of other
carotenoid compounds in fruits and vegetables seem to have no vitamin A
activity. Beta-carotene-containing foods have been extensively studied in
cancer epidemiology (Peto et al. 1981). Although beta-carotene is most
efficiently converted (Linder 1985), it still has only one-sixth the biologic
activity of retinol. Many reports on the effects of vitamin A do not specify
whether they are studying preformed vitamin A, carotenoids in general,
retinoid analogs of vitamin A, or beta-carotene alone (NRC 1982). This
chapter uses the term vitamin A to include all of the above unless otherwise
specified.

Epidemiologic studies have used food intake records to analyze the intake
of beta-carotene, carotenoids, and retinol, or a "vitamin A index" that
combines these. A methodological difftculty is that foods such as green and
orange-yellow vegetables may contain protective factors in addition to
carotenoids (Mettlin 1984). Other complications are presented because
inverse correlations between blood levels of beta-carotene and retinol and
risk for cancer have been identified in some but not all studies (Willett and
MacMahon 1984a). Future studies that better distinguish the individual
effects of beta-carotene, carotenoids, retinol, and other food components
will require improved dietary assessment methods (Russell-Briefel, Cag-
giula, and Kuller 1985).

Human Epidemiologic Studies

Low levels of vitamin A (or retinol) in blood have been associated with an
increased risk for cancer in some (Wald, Idle, and Boreham 1980; Kark et
al. 1981) but not all (Wald et al. 1984; Willett et al. 1984; Nomuraet al. 1985;
Salonen et al. 1985) studies. Low levels of beta-carotene in stored blood
also have been associated with an increased risk for cancer in some
(Nomura et al. 1985; Stahelin et al. 1984) but not all (Willett et al. 1984;
Menkes and Comstock 1984) studies. There are problems, however, in
relating blood levels to cancer risk. Blood retinol remains unchanged
across a wide range of dietary intakes because of homeostatic mechanisms.


O Nutrition and Health

Thus, increased vitamin A is unlikely to result in increased serum retinol,
except during vitamin A depletion. Consequently, the association between
serum retinol and cancer may be due to factors that regulate serum retinol
rather than to dietary vitamin A itself. In contrast, serum carotenoids may
better reflect dietary carotenoids, and the relationship between dietary
carotenoids (or the foods that contain them) and cancer may be more direct
than that between serum retinol and cancer. A major weakness of these
studies is that blood levels of vitamin A or carotenoids observed at the time
of diagnosis may be different from those present when the disease began.

One prospective cohort study on the older population in Massachusetts has
shown that the risk for all cancers decreases with increasing intake of
carotenoid-containing vegetables (Colditz et al. 1985). Foods containing
vitamin A may be protective against cancer of the oropharynx (Ibrahim,
Jafarey, and Zuberi 1977), larynx (Graham et al. 1981), breast (Grahamet al.
1982), stomach (Stehr et al. 198% cervix (La Vecchia et'al. 1984), colon
(Modan, Cuckle, and Lubin 1981), and bladder (Mettlin, Graham, and
Swanson 1979). Results for cancer of the prostate have been mixed, how-
ever, with one study showing a protective effect (Schuman et al. 1982), two
studies showing the opposite (Graham et al. 1983; Heshmat et al. 1985), and
one showing no effect (Whelan, Walker, and Kelleher 1983).

Lung Cancer. The strongest evidence for the role of vitamin A in preven-
tion of human cancer comes from epidemiologic studies that correlate
consumption of carotenoid-containing vegetables or foods with a high
vitamin A index to protection against cancer of the lung (Shekelle et al.
1981; Kvale, Bjelke, and Gart 1983). These studies are summarized in
Table 4-10. The Western Electric Study of 1,984 middle-aged men, for
example, found a protective effect with provitamin A (beta-carotene) but
not preformed vitamin A (Shekelle et al. 1981). A case-control study of lung
cancer in white males in New Jersey showed a 30 percent greater risk of
cancer for men in the lowest quartile of carotenoid intake but no increased
risk for a low consumption of retinol or total vitamin A intake (Ziegler et al.
1986). The Western New York Diet Study showed a protective effect for
both total vitamin A and vitamin A from fruits and vegetables in men but
not in women (Byers et al. 1987).

An important question in each of these studies is whether the protective
effects attributed to vitamin A activity, as discussed above, are truly
attributable to vitamin A or whether they are due to some other factor that
may be present in the foods. For example, epidemiologic studies have
shown an inverse association between the consumption of cruciferous
vegetables such as cabbage, broccoli, Brussels sprouts, or cauliflower and

210


         Table 4-10
Dietary Vitamin A and Lung Cancer Risk:
  A Summary of Previous Studies

                    No. of                                    Findings
                   Cases:                                    (Approxi-
                   Controls                                         mate %
                       or                    No. of                Nutrient    of Study     Relative
   Reference (location)      Cohort Size     Sex        Foods    Nutrient       Level     Group)      Risk

   Cuse-Conrrol Studies

   MacLennan et al.       233:300       Males and     loo     Green, leafy     Low      (NW       2.2
    1978                        females           vegetables     High      (NW        I.0
   (Singapore)
   Mettlin et al. 1979       292:801        Males       33      Vitamin A      Low       (49)        1.7
N
E   (New York)                                                  Medium     (27)        I.5
                                                 High      (24)        I.0

   Gregor et al. 1980       78:llO        Males        IO      Vitamin A       Low      02)        2.5
   t England)                                                    Medium     (46)        2.8
                                                 High      (22)         I.0

    Hinds et al. 1984       364:627       Males and     85      Carotene       Lowest I    (25)         I.6
   (Hawaii)                       females                             2    125)        1.2
                                                                      3    (25)        I.1
                                                  Highest 4    (25)        I.0

   Ziegler et al. 1986       763900       Males        44      Carotene       Low      (25)        1.3
   (New Jersey)                                                   Medium     (SO)        1.3
                                                 High      cm         I.0

    &met et al. 1985        342: 546       Males and     55      Carotene       Low       (33)        I.5
   (New Mexico)       (Angles only)    females                          Medium     (33)        I.5
                                                 High      (33)         I.0

D
R
2

0


Table 4-10 (continued)

0
z

Wu et al. 1985
(Los Angeles)
Adenocarcinoma

Squamous cell

Byers et al. 1987
(New York)

   Prospective Studies
E   Bjelke 1975
   (Norway)
   Hirayama 1979
   (Japan)
   Shekelle et al. 1981
   (Chicago)

Kvale et al. 1983
(Norway)

149: 149        Females      21      Carotene

71:71


450902

Females


Males and
females

8,278


265.1 I8


3.102

Males


Males and
females

Males

16.713        Males and     50      Vitamin A

21


129

Carotene


Fat, vits.
A, C, E,
fiber,
protein

50


1


26

Vitamin A


Green-yellow
vegetables
Carotene

Lowest I    (25)
    2    (25)
     3    (25)
Highest 4    (25)

LOW      (50)
High      (50)

Lowest I    (2%
    2    (25)
    3    (25)
Highest 4    (23

Low      (32)
High      w
Lowa      (NP)
Highb      (NP)

Lowest I    (25)
    2    (25)
     3    (25)
Highest 4    (25)

Low      (35)
Medium     (2%
High      (36)

2.5
1.3
0.8
1.0

1.5
1.0

1.8
I.8
I.0

1.0
(fruits/vegs.)

2.6
1.0

1.8
1.0

7.2
5.5
3.0
1.0

1.4
1.2
1.0

BNP = Not presentea.

aFor Hirayama, low = not daily; high = daily.
Source: Byers, T.E.; Graham, S.; Haughey, B.P.; Marshall, JR.; and Swanson, M.K. 1987. Diet and lung cancer risk: findings from the Western New
  York Diet Study. American Journal of Epiderniobgy 125:351-63. Reprinted with permission.

E


Cancer 0

cancers of the alimentary tract (Hirayama 1977; Haenszel et al. 1976) and
large bowel (Graham et al. 1978). A study of lungcanceramong New Jersey
white males showed a protective effect for fruits and vegetables that was
greatest for dark yellow-orange and green vegetables, but no statistically
significant effect for retinol, carotenoids, or vitamin A activity (Zeigler et
al. 1986). The protective effect could have been due to unmeasured car-
otenoids, vitamin C, indoles, or other unknown components present in
these foods (Wattenberg and Loub 1978; NRC 1982). The lack of associa-
tion for vitamin A or carotenoids might also be due to problems in calculat-
ing vitamin A and carotenoid intake from food composition tables based on
dietary records (Beecher and Khachik 1984).

Animal Studies

Vitamin A and synthetic retinoids protect against epithelial cancers of the
skin, lung, bladder, and breast in animals (Spom 1980). High doses sup-
press induction of cancers of the cervix, vagina, colon, skin, forestomach,
tracheobronchi, pancreas, and liver (Welsch, Zile, and Cullum 1986).
Retinoids have also been shown to reverse the effects of carcinogens in
mouse prostate organ cultures (Lasnitzki and Goodman 1974). Although
beta-carotene is protective against skin cancer in animals, it has not re-
ceived as much attention as vitamin A or retinoids because beta-carotene is
poorly absorbed in animals. Synthetic analogs may have greater effects,
greater site specificity, and less toxicity than natural vitamin A (Spom and
Roberts 1984).

Biochemical Mechanisms

Because retinoids are required for normal cell differentiation, their de%
ciency leads to improper differentiation of stem cells in epithelial tissue. In
animals, retinoids may inhibit initiation and promotion stages of carcino-
genesis (Welsch, Zile, and Cullurn 1986). Retinoids may also have a role in
reversing cancerous changes, as has been demonstrated in mouse prostate
organ cultures @porn 1980).

Antioxidant chemicals are thought to protect against certain promoters of
carcinogenesis (Ames 1983). Foods containing vitamin A have been shown
to protect against the formation of oxygen radicals and lipid peroxidation
(Welsch, Zile, and Cullum 1986), and beta-carotene is a very efficient
neutralizer of oxygen radicals (Foote 1976). Vitamin A, along with vitamin
C, vitamin E, and selenium, may neutralize peroxidation effects and mini-
mize carcinogenesis (Ames 1983), although these hypotheses remain to be
confirmed.

213


O Nutrition and Health

Clinical Trials

Recurrence of urinary bladder cancer has been shown to decrease by about
half with synthetic retinoid treatment in two clinical trials (Studer et al.
1984; Alftlan et al. 1983). Micronucleus formation, a marker for cellular
genetic damage, has been reversed by beta-carotene treatment of people
who chew betel nuts and tobacco (Stich et al. 1984). Synthetic retinoid
treatment causes regression of bronchial dysplasia (Gouveia et al. 1982).
Clinical trials are now in progress to determine the efficacy of retinoids in
the prevention and treatment of cervical cancer, malignant melanoma, and
other cancers (Meyskens 1982). The National Cancer Institute is funding a
number of trials (Table 4-l 1) to determine the effects of beta-carotene and
other antioxidant nutrients on several cancer types. These will produce
results in the early 1990's.

Large amounts of retinoids in the blood or tissues, however, can be toxic
and may cause birth defects (Kamm 1982) and adverse effects on skin,
liver, and neurologic tissue (Olson 1983). Excessive intake of preformed
vitamin A or retinoid supplements should be avoided, especially by preg-
nant women. However, increased intake of carotenoids from foods alone is
unlikely to have any adverse effects, other than skin discoloration at very
large intakes.

Role of Alcohol in Cancer

Reviews of experimental and epidemiologic data suggest an association
between alcohol consumption and human cancer that is strongest for
certain head and neck cancers (Tuyns 1982; NRC 1982). Alcohol intake and
smoking act synergistically to increase the risk for cancer of the mouth,
larynx, and esophagus (Broitman, Vitale, and Gottlieb 1983). Although
alcohol has an effect independent of smoking in increasing cancer risk, it
remains uncertain whether the responsible agent is alcohol itself or any of
the more than 400 congeners (other chemicals) identified in alcoholic
beverages (Darby 1982). Consumption of excess alcohol is often accom-
panied by poor eating habits, but the effects of alcohol and nutrition can be
distinguished (see chapter on alcohol), and poor nutritional intake and
alcohol intake appear to have separate and multiplicative effects on the
risks of esophageal cancer (Ziegler et al. 1981). Chronic alcoholism, partic-
ularly in the marginally nourished individual, can deplete various essential
nutrients (Vitale, Broitman, and Gottlieb 1981). As discussed in the chap-
ter on infections and immunity, the nutritional deficiencies produced in
alcoholics could be associated with impaired immune function, permitting
increased carcinogenesis (Watson 1984).

2l4


Cancer O

         Table 4-11
NCI-Sponsored Prevention Clinical Trials
     Related to Vitamin A

Investigator/Cancer Site/Agent       Population Under Study

Hennekenslah sites/beta-carotene,
aspirin

Greenberg/skin/beta-carotene

Luande/skin!beta-carotene

Bowen/colonfbeta-carotene

KuIIerlIungJbeta-carotene

AIbaneslIunglbeta-carotene, alpha-
tocopherol
Safailskinlbeta-carotene, vitamins
CandE

Greenberg/colon/beta-carotene,
vitamins C and E

Moon/skin/retinal

Tangrea, PecWskin/l3-cis retinoic
acid

Meyskenslskinlretinol, 13-cis
retinoic acid

Taylorlesophagusibeta-carotene

Taylor/esophagus/beta-carotene,
multiple vitamins and/or minerals

Omennihmg/retinol, beta-carotene

U.S. male physicians, 40-84 years
old. No evidence of cancer, heart
disease, or stroke.

Males and females less than 85
years of age, basal or squamous
cell carcinoma within past year.
African albinos with epidermai
atrophy, dermal hypertrophy, or
stage III solar keratoses.
Males and females with prior
adenomatous colonic polyp.
Males, 55-70 years old, moderate
to heavy cigarette smokers.
Finnish males, S(M9 years old,
cigarette smokers.
Males and females, 40-80 years
old, 2 or more prior basal cell
carcinomas.

Males and females, less than 75
years old, prior neoplastic polyp.
Males and females, 21-85 years
old, more than 10 prior actinic
keratoses.

Males and females, 40-75 years
old, 2 or more prior basal cell
carcinomas.

Males and females, 40-85 years
old, 8 or more prior basal ceU or
squamous cell carcinomas.
Males and females, 40-69 years
old, severe esophageal dysplasia,
Linxian, China.

Males and females, 40-69 years
old, general population, Linxian,
China.

Males and females, minimum age
45 years, at least 20 years since
fust exposure to asbestos,
diagnosis of asbestosis.

215


O Nutrition and Health

Table 4-11 (continued)

Investigator/Cancer Site/Agent      Population Under Study

Goodman/Iung/retinoI, beta-
carotene

McLartyilunglretinoI, beta-carotene

Schatzkin/Iung/beta-carotene,
retinal, vitamin E, selenium

Surwitlcervixltrans-retinoic acid,
retinyl acetate

Males and females, 50-67 years
old, smoking history of 20 pack
years or greater, current smokers
or those who have quit smoking
less than 6 years previously.
Males and postmenopausal
females, former asbestos workers
verified by the Tyler Asbestos
Workers Program, University of
Texas Health Center patients with
moderate or severe sputum
cytology atypia.

Tin miners active and retired, more
than 40 years of age, at least 10
years of underground experience.
l&45 years old, moderate or
severe cervical dysplasia.

An international comparison shows a correlation between intake of beer
and the incidence of colorectal cancer (Vitale, Broitman, and Gottlieb
1981). A strong association between beer intake and rectal cancer and a
weak association between wine or whiskey and lung cancer have been
found in a prospective cohort study of Japanese men in Hawaii (Pollack et
al. 1984). These associations were seen only at high intakes, and no
increased risk was observed at moderate intakes. Case-control studies
have failed to show a consistent relationship between alcohol and colon or
rectal cancers, possibly due to confounding variables, including contami-
nants in alcoholic beverages. An increased incidence of liver cancer among
alcoholic patients appears to be due to increased exposure to hepatitis B
virus rather than to alcohol itself (Brechot et al. 1982).

Although it is difficult to determine true levels of alcohol consumption,
women with breast cancer are reported to consume more alcohol than
controls (Williams and Horm 1977). A slightly greater risk for breast cancer
in women has been associated with intake of as few as three alcoholic
drinks per week (Schatzkin et al. 1987). Another recent study found
increased risk associated with an average of one drink per day in a cohort of
89,538 U.S. women (Willett et al. 1987). Results of other analytical studies
are inconsistent.

216


Cancer O

Although the associations observed between alcohol and oral, esophageal,
and laryngeal cancers may be due in part to smoking, appropriate study
designs and analyses have demonstrated independent effects of alcohol
(Misslbeck and Campbell 1986). If the consumption of alcoholic beverages
is reduced, a sizeable decrease in the incidence of cancers of the buccal
cavity, pharynx, larynx, and esophagus should be possible (Tuyns 1982).

Role of Other Dietary Constituents in Cancer

Vitamin C

Vitamin C functions as a chemical-reducing agent and antioxidant. It is
synthesized in adequate amounts by most animals but not by some pri-
mates, fish, guinea pigs, and humans (Linder 1985).

Human studies have shown a protective association between foods that
contain vitamin C and cancers of the esophagus (Aoki et al. 1982; Acker-
man, Weinstein, and Kaplan 1978), stomach (Graham, Schotz, and Mar-
tino 1972; Higginson 1%7; Kolonel, Nomura, et al. 1981), and cervix
(Wassertheil-Smaller et al. 1981). Small-scale studies have indicated that
colonic polyps regress (DeCosse et al. 1975) or decrease in area (Bussey et
al. 1982) with vitamin C therapy. Recurrence of colonic polyps after
polypectomy was reduced among patients in the treatment group of a study
with 200 subjects (McKeown-Eyssen et al. 1987). Supplements of vitamins
C and E have been shown to reduce the formation of mutagens in the feces
in one study @ion et al. 1982) but not in another (Wilkins, Lederman, and
Van Tassel1 1981). While many studies support a role of vitamin C in
reducing cancer risk (Block and Menkes 1988), no wholly consistent pic-
ture of the role of vitamin C in human cancer has been defined.

Experimental animal studies have found that animals given both precursors
of carcinogenic nitrosamines and vitamin C develop fewer tumors than
animals given these precursors alone (Mirvish et al. 1976). Vitamin C
protects hamster lung cultures from the mutagenic effects of tobacco
smoke (Leuchtenberger and Leuchtenberger 1977) and has been shown to
reduce bladder tumors induced by one carcinogen (Pipkin et al. 1969) but
not by another (Soloway et al. 1975).

Biochemical studies suggest that vitamin C blocks the formation of carcino-
genic nitrosamines from nitrates and nitrites within the digestive tract
(Weisburger et al. 1980; Mirvish et al. 1975) and prevents oxidation of
certain chemicals to active carcinogenic forms (Pipkin et al. 1%9).


cl Nutrition and Health

Because most studies demonstrating a beneficial effect of vitamin C have
not quantified its actual intake levels, associations between vitamin C and
cancer prevention are subject to the same difficulties as those discussed for
vitamin A. Amounts of vitamin C in excess of the Recommended Dietary
Allowances @DA's) may cause rare adverse effects, including gastroin-
testinal disturbances, iron overload in susceptible individuals, altered me-
tabolism of certain drugs, precipitation of calcium oxalate kidney stones,
altered absorption (both positive and negative) of several minerals, and
interference with several laboratory tests (Sestili 1983). Despite limitations
in data, the American Cancer Society guidelines recommend "foods rich in
vitamins A and C" (ACS 1984), and the National Cancer Institute suggests
eating a variety of fruits and vegetables, thus ensuring an adequate supply
of vitamin C (Butt-urn, Clifford, and Lanza 1988). There is no adequate
evidence that larger amounts of vitamin C provide any additional benefits.

Vitamin E

Studies on vitamin E and the development of cancer are complicated by its
instability in stored blood serum, its wide prevalence in the food supply,
and its multiple chemical forms. Perhaps because of these problems, there
are relatively few studies on the role of vitamin E and cancer, but the role of
vitamin E as an antioxidant justifies its further consideration as a potential
preventive agent in cancer control (Willett and MacMahon 1984a).

In human studies, no relationship has been found between vitamin E levels
and the risk for cancer when incidence rates at all sites are combined in
either prospective (Willett et al. 1984; Stahelin et al. 1984) or case-control
analyses (Salonen et al. 1985; Nomura et al. 1985). In one case-control
analysis of prospective data, serum vitamin E had no statistically signifi-
cant independent association with cancer mortality, but low vitamin E
enhanced an independent risk observed for low serum selenium levels
(Salonen et al. 1985). A protective effect of serum vitamin E against cancer
of the breast has been found in one (Wald et al. 1984) but not a second
(Willett et al. 1984) study. In the positive study, an increased risk was
associated only with the lowest 20 percent of serum vitamin E levels. Low
vitamin E levels have also been correlated with an increased risk for lung
cancer (Menkes and Comstock 1984) and intestinal cancer (Gey, Bru-
bather, and Stahelin 1987), but a recent study found no such association
with ovarian cancer (Heinonen, Koskinen, and Tuimala 1985).

Variable results have also been observed in experimental animal studies.
Vitamin E was protective in carcinogen-induced tumor systems (Sham-
berger and Rudolph 1966; Bonmasser, Dallavalle, and Guiliani 1968) or

218


Cancer 0

when administered as a dietary supplement (Haber and Wissler 1%2), but
other studies have not observed this effect (Cook and McNamara 1980;
Epstein et al. 1967). A recent review states that the animal evidence is
inconsistent but suggests a protective effect of vitamin E in carcinogen-
induced tumor systems (Newbeme and Suphakam 1983).

Biochemical studies indicate that vitamin E functions as a lipid-soluble
antioxidant and free radical scavenger. Thus, the protective role tentatively
assigned to both carotenoids and vitamin C may also apply to vitamin E and
its derivatives. Vitamin E, like vitamin C, blocks the in vitro formation of
nitrosamines. The fact that vitamin E is lipid soluble permits this action in a
lipid environment, as opposed to the water-soluble vitamin C. Knowledge
of carcinogenic mechanisms from experimental and animal studies justifies
further exploration of the vitamin E and cancer prevention hypothesis.
Some concern has been expressed that reduced fat intake would compro-
mise availability of this fat-soluble vitamin, but it has been estimated that a
reduction in fat intake to 20 to 25 percent of daily calories should not result
in adverse effects from lowered vitamin E or other fat-soluble vitamin
intake (Judd, Kelsay, and Mertz 1983).

Selenium

Selenium is present in animal and plant foods as selenate, selenocystine,
selenomethionine, and other yet unidentified forms. A suggested daily
dietary intake for selenium has been established by extrapolation from
animal studies, but the range of 50 to 200 pg per person (NRC 1980) does
not imply greater benefit at the upper limit (Diplock 1987). Well over 90
percent of selenium intake is from cereal grains, fish, meat, and poultry (Lo
and Sandi 1980).

The average per capita consumption of dietary selenium in 27 countries
was inversely correlated with total cancer mortality as well as deaths from
leukemia and cancers of the colon, rectum, breast, ovary, and lung
(Schrauzer, White, and Schneider 1977). Inverse correlations between
local soil and crop levels of selenium and regional cancer incidence in the
United States (Shamberger and Willis 197 1) and between the average blood
selenium concentration of residents in different regions of the United
States and the incidence of cancer of the breast, colon, rectum, and lung in
these regions (Schrauzer, White, and Schneider 1977) have been reported.
These studies must be interpreted cautiously due to the mobility of both
food supply and population.

219


0 Nutrition and Health

In several case-control studies, persons with cancer had lower blood
selenium levels than controls (Shamberger et al. 1973; McConnell et al.
1980). These studies must also be interpreted cautiously because these low
levels of blood selenium may be a consequence of illness rather than its
cause (Helzlsouer 1983).

Prospective studies can show whether low serum levels precede cancer.
One prospective study showed that risk for cancer was increased in a group
with low serum levels of selenium and vitamins A and E (Willett et al.
1983). Two other prospective studies in Finland, where selenium intake is
half that of the United States, found an increased risk for cancer at all sites
among the population with low serum levels of selenium (Salonen et al.
1984; Salonen et al. 1985). All three ofthese prospective studies as well as a
subsequent case-control study (Kok et al. 1987) support the hypothesis
that serum selenium is a risk factor for cancer death in men but not in
women. These studies are summarized in Table 4-12.

Selenium inhibits neoplastic transformation in a variety of epithelial organs
in animals (Medina 1985). Studies have demonstrated protective effects
against cancer of the liver (Daoud and G&in 1978), breast (Ip 1981), colon
(Jacobs, Matney, and Griffin 1977), and skin (Shamberger 1970) from
selenite, selenate, or organic selenium. However, the dose giving this
protective effect in most experiments is similar to the dose that may be
toxic with long-term administration (Helzlsouer 1983).

Selenium is among the most toxic essential elements (Longnecker et al.
1987). Its effects in humans have been mostly limited to occupational
hazards (Buell1973) but toxic effects have been reported among individu-
als consuming excessive selenium supplements (CDC 1984). Selenium is
present in the active site of glutathione peroxidase, an enzyme that helps to
prevent perioxidative damage to the cells. Although the molecular basis for
the function of selenium as an inhibitor of neoplastic transformation is not
understood, its enzymatic role may explain this relationship. The docu-
mented toxicity and the narrow range of safe levels of intake of this nutrient
suggest that recommendations for increasing dietary intakes are not war-
ranted.

An association between protein consumption, especially animal protein,
and the incidence of certain cancers has been observed in several human
epidemiologic studies. However, the association of cancer and protein
intake is confounded by a high correlation of protein intake to many other

220


Findings

   Cancer Site


General

Inverse relationship between
cancer rates and selenium
exposure

._~-.-_
  No. of Studies  No. of Studies
  Showing the   Not Showing    Specific Nature of the
   Association   the Association       Association

     Correlution Studies
       4              Selenium in forage crops
                  I      Selenium in forage crops;

association a direct one for
some sites

Selenium in soil and water
Dietary selenium intake
Blood selenium levels
Selenium in water;

  Lower blood selenium levels
E  in cases than in controls

Colon-rectum


General

`           I

Case-Control Studies
I

2           1

Leukemias & Lymphomas      I

                                3
Mouth & Pharynx                      1

Breast
Skin

I
I

association a direct one

Gastrointestinal tract cancers
and Hodgkin's disease
Carcinoma only
Chronic lymphocytic
leukemia only

Plasma selenium increased in
cases, but RBC selenium
and glutathione peroxidase
levels decreased

Both basal and squamous cell
types                 n

Lower prediagnostic serum
selenium levels in cases than

General

in noncases

Cohort Studies
3             Association especially
             evident in males and

smokers

Source: Adapted from &tram, Kolonel, and Meyskens 1987.


u Nutrition and Health

nutrients, including fat. Thus, it has not been possible to define an indepen-
dent effect for protein (Kolonel and Le Marchand 1986; Palmer 1986). In
one international correlational study, for example, a positive association
was observed between total protein and animal protein and breast, colon,
prostate, renal, and endometrial cancers (Armstrong and Doll 1975). Simi-
larly, a migrant study indicated an association between meat consumption
and cancer of the breast and colon (Kolonell987). In a recent case-control
study of breast cancer, the greatest positive association was with a high-
protein, high-fat, and low-fiber diet, but when these three dietary compo-
nents were assessed independently, fat had the strongest association
(Lubin, Wax, and Modan 1986). A positive association between protein
and colon cancer has been found in another study, but again, the associa-
tion with fat was stronger (Jain et al. 1980). In an Australian case-control
study on large bowel cancer, the highest risk was assigned to a high-
protein, high-energy, low-fiber diet (Potter and McMichael 1986). Studies
have also found an association between breast cancer and meat intake
(Lubin et al. 1981) and an association of meat, especially beef, with large
bowel cancer among Japanese (Haenszel et al. 1973), although a subse-
quent study found a lower risk for all cancers among Japanese who con-
sumed a higher daily intake of meat (Hirayama 1981).

In animal studies, an excessive intake of protein is not consistently associ-
ated with an increased incidence of tumors at most sites. When animals
were fed ad l&turn diets with a protein content ranging from 10 to 51
percent of calories, the total incidence of tumors was not affected (Ross and
Bras 1973; Tannenbaum and Silverstone 1949), although certain tumors
such as bladder papillomas and mammary tumors are enhanced by in-
creased protein intake (NRC 1982). These same studies reported that high-
protein diets in early life increased the incidence of tumors (Ross and Bras
1973). Because very low-protein diets have a suboptimal nutritional value,
the decreased tumor risk at very low intake is not relevant for guidelines for
human diets.

Salt-Pickled, Salt-Cured, and Smoked Foods

Methods of storage and preparation of foods vary widely in different parts
of the world, and these differences may contribute to the large international
variation in some types of cancer. Smoked and charred foods acquire
polycyclic aromatic hydrocarbons (PAH`s), some of which are known to be
carcinogenic in animals (Chu and Malmgren 1965; Ames 1983). These and
other potential carcinogenic agents may be formed within foods during
cooking in amounts that may be related to the temperature and duration of
cooking at very high temperatures (Lijinsky and Shubik 1964; Lijinsky and
Ross 1967; Weisburger, Horn, and Barnes 1983). For example, high temper-

222


Cancer 0

ature grilling and broiling with open flames produces carcinogenic PAH's
on the charred surface of foods (Sugimura 1982). Burning amino acids with
sugars during cooking results in a variety of mutagenic chemicals, some of
which may be carcinogenic (Pourie et al. 1981). Salt-cured and salt-pickled
foods contain nitrates and nitrites that can form carcinogenic nitrosamines
in the mouth and stomach (Weisburger, Barnes, and Czemiak 1986). Salt-
cured and salt-pickled foods have been linked to gastric cancer, possibly
because of effects of salt on gastric mucosa (Joossens and Geboers 1985) or
conversion of nitrates to carcinogenic nitrosamines (Weisburger, Barnes,
and Czerniak 1986). Except for a few instances, however, potential
causative agents have not been identified in cured, pickled, or smoked
foods (Palmer and Bakshi 1983).

International epidemiologic evidence suggests that populations consuming
diets high in salt-cured, salt-pickled, and smoked foods have a higher
incidence of stomach and esophageal cancers. Stomach cancer has been
linked to pickled vegetables in Japan (Haenszel et al. 1972), salted fish in
Norway (Bjelke 1978), and smoked trout and mutton in northwestern
Iceland (Dungal 1961). Nitrates, nitrites, and N-nitroso compounds in food
and water (Weisburger, Barnes, and Czerniak 1986) and salted foods
(Geboers, Joossens, and Kesteloot 1985) have been associated with gastric
cancer in several epidemiologic studies. Salt-pickled and salt-cured foods
have been associated with an increased risk for cancers of the nasopharynx
(Sasco, Hubert, and De The 1985) and esophagus (Tttyns, Riboli, and
Doombos 1985). Esophageal cancer in China has been linked to the con-
sumption of pickled vegetables and nitroso compounds (Yang 1980). Most
international epidemiologic studies have linked smoked foods to gastric or
esophageal cancers (Bjelke 1978).

Esophageal (`luyns, Riboli, and Doombos 1985) and stomach cancers
(Geboers, Joossens, and Kesteloot 1985) have been associated with poor
nutrition. In fact, almost all diet and stomach cancer studies have found a
protective effect of vegetable and fruit intake (Cordle 1986), and even the in
vitro formation of N-nitroso compounds can be minimized by antioxidants
such as vitamins E and C (Weisburger, Barnes, and Czemiak 1986).

Nevertheless, the impact of risks from salt-cured, salt-pickled, and smoked
foods in the U.S. diet appear to be small, because rates of stomach and
esophageal cancers are low compared with those in other parts of the world
and because consumption of smoked, salt-cured, and salt-pickled foods
generally is not high.

223


O Nutrition and Health

Food and Color Additives

The FDA approves (or disapproves) all new food and color additives after
detailed review of the safety, purpose, and anticipated exposure. The FDA
also monitors the food supply for chemical contaminants such as
pesticides, environmental contaminants, and heavy metals through the
annual Total Diet Study, which has been conducted since the mid-MO's
(NRC 1982). Before substances are approved for marketing, they are
evaluated for safety on the basis of experimental studies in animals and
relevant clinical studies demonstrating their suitability for their intended
use. After marketing, if new evidence on the safety of the substance is
brought to light, such evidence is reviewed in depth to determine if there
should be a change in the regulatory status of the substance. This process
should protect the U.S. population against the presence of added sub-
stances in the food supply that could involve a risk to health, including
cancer.

Implications for Public Health Policy

Dietary Guidance

General Public

The dietary factors evaluated for the possible relationship to cancer risk are
fat, calories, fiber, foods high in vitamin A and carotenoids, and alcohol.
Roles for vitamin C, vitamin E, selenium, protein, and salt-cured, salt-
pickled, and smoked foods have been proposed.

Studies of carcinogen-induced tumorigenesis in experimental animals and
international epidemiologic comparisons have provided substantial but not
conclusive evidence that dietary fat increases the risk for cancers of the
breast, colon, rectum, endometrium, and prostate. The results of epi-
demiologic investigations within more homogeneous population groups,
however, are inconsistent. Because fat contains more than twice the calo-
ries per given quantity of protein or carbohydrate, high-fat diets are gener-
ally high in calories. Despite such complications, the animal and intema-
tional epidemiologic data suggest that a decrease in fat consumption by the
general public from the current 37 percent of total caloric intake might
reduce the risk for certain cancers.

Results from animal and human studies of obesity and cancer are not
wholly consistent, perhaps because of the difficulty of separating the
effects of calories, fat, and body weight. Furthermore, the level of caloric
restriction that seems effective in preventing cancer in most animal studies

224


Cancer O

is at a food intake level not advisable for most humans. Consistent with
other health recommendations, maintenance of desirable weight is recom-
mended and may potentially decrease the risk of breast, colon, prostate,
and endometrial cancers.

Correlational epidemiologic studies suggest an association between diets
low in fiber and increased risk for colon cancer, while results from case-
control studies are mixed. Studies in experimental animals indicate that
further research is needed on the effects of different types of fiber. While
inconclusive, evidence suggests that an overall increase in intake of foods
high in fiber might decrease the risk for colorectal cancer. Despite the need
for additional evidence, this recommendation is consistent with guidance
for reducing gastrointestinal disease.

Likewise, epidemiologic studies provide suggestive evidence that con-
sumption of foods containing carotenoids, including the beta-carotene
precursor of vitamin A, protects against development of epithelial cell
cancers such as those of the oral cavity, bladder, or lung. These studies
have generally shown lower rates of cancer among individuals consuming
the highest overall levels of vitamin A, carotenoids, or fruits and vegeta-
bles. These studies have not distinguished the specific form of vitamin A
associated with protection, nor have they ruled out the possibility of
protection from as yet unidentified components of fruits and vegetables.
Until the results of clinical trials examining these relationships become
available, an increase in consumption of fruits and vegetables might benefit
persons who now consume below-average amounts of these foods. There is
no evidence that vitamin A in amounts greater than the RDA is beneficial.

Despite some difficulties in distinguishing the cancer-producing effects of
excessive alcohol intake from those of cigarette smoking, evidence sug-
gests that a reduction in alcohol intake among the portion of a population
that drinks most heavily would help to reduce the prevalence of cancers of
the mouth, esophagus, pharynx, and perhaps other sites.

Excessive selenium intake is toxic. This fact and limitations in information
about selenium intake in the general population suggest that selenium
intake should not be increased above levels now in the average diet.

Although some epidemiologic studies suggest an association between di-
etary protein and cancer incidence, these studies are limited and not
consistently supported by animal evidence. Thus, the evidence does not
justify a recommendation to the general public to decrease protein on the
basis of its relationship to cancer.

225


             I





n

u Nutrition and Health

There is some suggestive but not conclusive evidence that correlates
consumption of salt-pickJed, salt-cured, and smoked foods with stomach
and esophageal cancers, indicating that the public should continue to limit
its intake of these foods to the current low levels of consumption.

Special Populations

Persons at high risk for diet-related cancers because of family history,
obesity, or excessive alcohol intake should receive counseling from
qualified health professionals to design approaches that could reduce their
elevated risk for cancer.

Patients with cancer should receive appropriate nutritional support and
dietary advice to maintain optimal nutritional status throughout medical,
surgical, or radiological therapy. There is no credible evidence that nutri-
tional changes specifically help in the cure of cancer patients.

Children and older persons are not currently targeted by the dietary guide-
lines relative to cancer risk due to limited data for these groups.

Nutrition Programs and Services

Food Labels

Evidence related to the role of dietary factors in cancer suggests that food
manufacturers should include on package labels information about nutri-
tional content of the food, especially for fat and carbohydrate components
(and including fiber components to the extent permitted by analytical
methods).

Food Services

Evidence related to the possible role of dietary factors in cancer suggests
that the public might benefit from increased availability of foods low in fat
and high in fiber.

Food Products

Evidence related to the role of dietary factors in cancer suggests that foods
low or reduced in calories and fat and high in fiber should be made
increasingly available by food manufacturers.

Special Populations

Persons with cancer should be provided with counseling and assistance in
the development of diets appropriate to their condition.

226


Cancer 0

Research and Suweillance

Research and surveillance issues of special priority related to the role of
diet in cancer should include investigations into:
o Molecular mechanisms of carcinogenesis and the ways in which ini-
tiating or promoting events may be affected by specific components of
dietary fat, fiber, protein, alcohol, vitamin A, carotenoids, and other
  vitamins or minerals.

o Quantitative relationships between food and nutrient intake and can-
cer incidence through chemoprevention and dietary clinical trials.
o The effect of specific components of dietary fat, fiber, vitamin A, and
carotenoids on cancer etiology.

o Interactions between dietary factors such as fat, fiber, calories, pro-
tein, and specific vitamins and minerals in cancer prevention and
causation.

o Development of biochemical markers of dietary intake to better
monitor effects of dietary intervention on cancer risk.
o Patterns of food intake best associated with cancer prevention.
o Development of national population data on food and nutrient con-
sumption patterns and specific cancer rates, including more accurate
assessment of intake of specific dietary factors within relatively homo-
geneous population groups.
o Levels of carcinogenic and mutagenic substances in the food supply.
o Dietary guidance methods that are most effective in helping people
improve patterns of food intake.
o The causes of wasting and malnutrition in cancer patients and the
effects of nutritional support on response to therapy and survival in
these patients.

227


0 Nutrition and Health

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Chapter 5

Diabetes

. . . urine wonderfully sweet, as if imbued
     with honey or sugar.
  Thomas Willis, physician to
   Charles II of England, 1670

Introduction

Diabetes mellitus (commonly called diabetes) is the name given to a spec-
trum of conditions found in 11 million Americans. Diabetes is charac-
terized by metabolic abnormalities (of which the most evident is hyper-
glycemia, an elevated concentration of glucose in blood) and by long-term
complications involving multiple organs, especially the eyes, kidneys,
nerves, and blood vessels. These complications result from a deficiency of
the hormone insulin, a reduction in the effectiveness of insulin, or other
less well understood metabolic disorders. There are two major forms of
diabetes mellitus: Type I, or insulin-dependent, and Type II, or noninsulin-
dependent. These types are distinguished by the need in Type I diabetes for
exogenous replacement of insulin, which is necessary for the metabolism
of glucose. The treatment goal for both types of diabetes is to prevent or
reduce the risk and severity of complications; generally this goal is best
achieved by maintaining normal or near-normal blood glucose and blood
lipid levels. In longstanding diabetes, certain other aims of treatment
assume great importance, including blood pressure control and reducing
protein load on the kidney (see the following section and the chapter on
kidney diseases).

Type I diabetes, or insulin-dependent diabetes mellitus (IDDM), formerly
known as juvenile-onset diabetes, accounts for about 10 percent of di-
abetes in the United States. It is characterized by an absolute deficiency of
insulin, caused by beta-cell destruction of the islets of Langerhans in the
pancreas. Genetic factors, including an autoimmune response (Eisenbarth
1986), affect the risk of beta-cell destruction as well as environmental
factors such as viral agents or cytotoxic chemicals (Arky 1983).

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Type I diabetes usually appears before age 40 and begins abruptly. Typical
symptoms are thirst, excessive urination, increased appetite, rapid weight
loss, breath that smells of acetone, and urine that is sweet because of its
high sugar concentration. Affected persons are usually of normal body
weight. Because their insulin levels are low, persons with Type I diabetes
require insulin for survival. Treatment usually includes administration of
insulin, diet coordinated with the insulin dosage schedule, and regular
physical exercise. At present, no method to prevent development of this
form of the disease has been identified (Browner 1986).

Type II diabetes, or noninsulin-dependent diabetes mellitus (NIDDM),
also known as adult- or maturity-onset diabetes, accounts for approximate-
ly 90 percent of all cases and affects at least 10 million Americans. It usually
appears in mid-life, most commonly among people who are overweight or
obese. Its onset is gradual, and many persons have a long history of mild
symptoms or display no symptoms at all. Often, the condition is first
diagnosed among individuals with no overt symptoms who display ele-
vated fasting blood glucose levels during a routine physical examination.
Genetic predisposition appears to play an important role in Type II as well
as in Type I diabetes.

Persons with Type II diabetes may display normal pancreatic histology,
secrete insulin in response to glucose ingestion, and have normal levels of
insulin in their blood. But because the body is less able to use this insulin,
or perhaps for some other as yet unknown reason (Feldberg, Pyke, and
Stubbs 1983, blood sugar levels are inappropriately high, and insulin levels
are insufficient. The three principal approaches to diabetes management
are diet, exercise, and treatment with oral antidiabetic agents or insulin.
Overweight persons able to lose weight can be managed by diet and
exercise alone. Some individuals unable to lose weight may respond to
treatment with sulfonylurea and other antidiabetic, hypoglycemic drugs
(agents that reduce blood sugar levels), but others will need insulin treat-
ment to control their diabetes.

Although it is generally believed that maintenance of normal blood glucose
levels will prevent or reduce the complications and premature mortality
associated with diabetes, this supposition has yet to be proved.

Historical Perspective

Since ancient times, diet has been recognized as a cornerstone of diabetes
management, yet ideas about the most effective dietary treatment have
varied widely throughout history (Bierman 1979). The uncertainty has

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Diabetes _I

been whether the sugar lost in the urine of persons with diabetes should be
replaced or whether carbohydrate intake should be restricted to prevent
further sugar loss. The fluctuations in recommendations for the relative
proportions of carbohydrate and fat in the diet of persons with diabetes are
outlined in Table 5-l.

In Egypt, the Ebers papyrus of 1550 B.C. described the use of wheat grains,
fresh grits, grapes, honey, berries, and sweet beer "to drive away the
passing of too much urine" (Wood and Bierman 1972). Around the time of
Christ, Aretaeus, a Cappadocian from a Roman province in East Asia
Minor, recommended a diet of milk, cereals and starch, fruits. and sweet
wines-another high-carbohydrate diet. Willis, in the 17th century, was the
first to describe in English medical literature the sweet taste of diabetic
urine. He believed that the lost sugar should be replaced and recommended
a diet rich in carbohydrates but limited to milk and barley water boiled with
bread.

Later, Rollo, a surgeon general of the Royal Artillery in the English Army,
deviated from the common diet of the time and recommended complete
avoidance of dietary carbohydrates. He advocated "animal food and con-

Table 5-l

  History of Dietary Composition (Relative Proportion of
Carbohydrate and Fat Calories) Used in Management of Diibetes

Date            Source

Carbohydrate

Fat

1550 B.C. (approx.)  Ebers papyrus @gwt)  High
1 A.D. (approx.)    Aretaeus (Asia Minor)   High
1675            Willis          High
1797            Rollo           Very low      High
1860-80          Bouchardat          Low        High
1900-20        Naunyn; Allen      Low (+ fasting)   Low
1900-20          von Noorden       High
1923          Geyelin
1929          Sansum     Efmal       Normal
1931            Rabinowitch         Moderate       LOW
1935           Himsworth       High
194040        Kempner; Ernest     High          Low
1940-70        ADAa (U.S.)        Limited        Moderate
1971 to date      ADA (U.S.)        increased       Reduced

V4DA = American Diabetes Association.

Source: Bierman, E.L 1979. Nutritional management of adult and juvenile diabetics. In
   Nutritional manegement of genetic diso&m, ed. M. Winick, pp. 107-17. New
   York: Wiley. Copyright 1979, John Wiley & Sons, Inc.. reprinted with permission.

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finement, with an entire abstinence from every kind of vegetable mat-
ter. . . ." (Wood and Bierman 1972). The noon meal prescribed by Rollo
consisted of "plain blood puddings, made of blood and suet, and dinners of
game or old meats which have been long kept, and as far as the stomach
may bear, fat and rancid old meats, as pork." Pile of the University of
Pennsylvania believed in Rollo's approach but found that while it met with
some success, ". . . unfortunately for the patient he soon becomes so
disgusted with this kind of diet as to refuse it altogether, and returns to his
old manner of living, which in no little while neutralizes all the efforts of
months of abstinence." In France, Bouchardat introduced green vegeta-
bles into the Rollo diet to decrease the monotony. Bouchardat, often
referred to as the most brilliant clinician in the history of diabetes, noted
that the urinary sugar levels of his patients with diabetes fell during the
German blockade of Paris in the France-Prussian war of 1870 to 1871, a
time of food shortages, and he developed the concept of caloric deprivation
for diabetes treatment (Wood and Bierman 1972).

Shortly before the discovery of insulin, the dietary treatment of diabetes
was based on the teaching of Naunyn, a German physician who believed in
limiting both protein and carbohydrates and, in the most severe cases, total
caloric intake. Allen of the Rockefeller Institute modified Naunyn's recom-
mendations, and in 1912 with the "Allen Starvation Treatment," he showed
that weight loss due to caloric restriction was beneficial to overweight
persons with diabetes. Although low-carbohydrate and low-calorie diets
predominated from the time of Roll0 to the advent of insulin, the carbohy-
drate "cures" also had followers. For example, von Noorden of Frankfurt
and Vienna found that patients showed marked improvement when placed
on oatmeal diets for the treatment of digestive disturbances.

The discovery of insulin in 1921 led to a reappraisal of the diabetic diet.
Geyelin of Columbia University was the first to try high-carbohydrate diets
in patients treated with insulin beginning in 1923. He expected an increase
in the need for insulin with the high-carbohydrate diets but found some
cases in which insulin requirements were actually lowered. In 1929, San-
sum, Gray, and Bowden recommended in their textbook that persons with
and without diabetes should have the same diet because it would be more
palatable; thus, people would follow it more consistently, and improved
physical and mental activity would result. At about the same time,
Rabinowitch of McGill University recommended that patients stay 5 to 10
lb under their average body weight and advocated the use of low-fat diets
(less than 50 g/day) for this purpose, noting that "if we could lower the
incidence of cardiovascular-renal disease . . . our diabetic death rate would
correspond to that of normal populations" (Wood and Bierman 1972). In

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Diabetes 0

1935, Himsworth of the University of London observed that the glucose
tolerance of normal subjects improved consistently as the percentage of
carbohydrate in the diet increased. Other workers, such as Kempner of
Duke University (using a rice diet providing 90 to 95 percent carbohydrate)
and Ernest and coworkers at the University of Goteborg (using a 72 percent
carbohydrate diet), noted improvements in both serum cholesterol levels
and diabetic symptoms. Despite the preponderance of this evidence, low-
carbohydrate, high-fat diets continued to be widely used.

Since the early 1970's, this trend has been reversed, based on new studies
demonstrating that high-carbohydrate intakes lead to improvement in
glucose tolerance and insulin sensitivity (Bierman et al. 1971; Brunzell et
al. 1971; Brunzell et al. 1974). The change to a higher carbohydrate diet was
intended to reduce total and saturated fat to levels associated with de-
creased risk of atherosclerotic heart disease (Bierman and Ross 1977). In
the present era, the availability of insulin has allowed clinicians to move
beyond short-term prevention of hyperglycemia and other metabolic abnor-
malities toward the prevention, delay, or reduction of long-term complica-
tions. Nevertheless, the question of how much carbohydrate should be in
the diabetic diet remains controversial (Reavan 1980; Jarrett 1981).

Throughout history, few physicians or researchers have agreed about the
best approach to nutritional therapy of diabetes. No specific dietary ap-
proach beyond caloric restriction and weight loss in the obese has proved
more advantageous than another. Even recent trends toward the use of
high-carbohydrate, low-fat, high-fiber diets (described later in this chapter)
need further validation. Clinicians must still make therapeutic decisions
about diet based on inadequate information, yet they are increasingly able
to attain treatment goals through individualized diets, self-monitoring of
blood glucose, and more physiologic provision of pharmacotherapy. Fu-
ture research may better define the optimal "diabetic diet" and quantify its
contributions to therapeutic goals.

Significance for Public Health

The substantial impact of diabetes on the health of Americans has been
documented extensively (NDDG 1985). Approximately 11 million people
in the United States are estimated to have diabetes, but almost halfare not
yet diagnosed (Harris et al. 1987; Kovar, Harris, and Hadden 1987). In
addition to Type I and Type II diabetes, gestational diabetes (impaired
glucose tolerance during pregnancy) occurs in 2 to 5 percent of all pregnan-
cies, placing both mother and baby at special risk, but in 98 percent of these
cases the condition is transient and the mother returns to normal after the
baby is born (NDDG 1985).

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O Nutrition and Health

Diabetes is directly responsible for nearly 36,000 deaths each year in the
United States, making it the seventh leading cause of death. It also contrib-
utes to nearly 95,000 additional deaths per year, 75 percent of which are
due to cardiovascular complications (Kovar, Harris, and Hadden 1987).
Mortality rates for white males and white females with Type I diabetes are
5 to 11 times greater, respectively, than for the general population. Type II
diabetes prevalence is 33 percent higher for blacks than for whites, and
mortality rates for blacks with this condition are twice those for whites.
American Indians and Alaskan Natives have mortality rates from Type II
diabetes 2.3 times that of the general population, with the highest world-
wide rate of diabetes occurring among the Pima Indians in the United
States (DHHS 1985).

Mortality rates increase with age. Twelve percent of patients with Type I
diabetes die within 20 years of onset, primarily from acute complications
below age 20 and from renal complications above this age. Type I diabetes
is especially serious at younger ages; half the diagnosed cases are in
children under age 20, and the condition is second only to cancer as a
chronic illness in this group. The survival of persons with Type II diabetes
is only 70 to 80 percent of that expected for the general population 25 years
after diagnosis (NDDG 1985).

Many of the adverse health effects of diabetes derive from its complica-
tions (see Table 5-2). Diabetic ketoacidosis is responsible for 2 to 14
percent of hospitalization for diabetes and is the underlying cause of 10
percent of diabetes deaths. Diabetes is the leading cause of new cases of
blindness among persons ages 20 to 74 and is responsible for one-fourth of
all new cases of end-stage renal disease and 40 to 45 percent of all non-
traumatic amputations in the United States. The risk of developing heart
disease is about twice as high among persons with diabetes as in the general
population, and ischemic heart disease is a factor in 50 to 60 percent of the
recorded deaths of adults with diabetes. Lipid abnormalities occur in a
substantial proportion of people with diabetes. Hypertension rates are also
twice as high among people with diabetes, and the risk of stroke increases
twofold to sixfold. Infants born to mothers with diabetes are at greater risk
for congenital anomalies, macrosomia, respiratory distress, jaundice, and
perinatal mortality (NDDG 1985). In addition, one-half of individuals with
diabetes suffer serious limitations of activity and one-third are unable to
work regularly. The economic cost of diabetes was estimated in 1985 to be
$13.8 billion per year, or about 3.6 percent of total health care costs in the
United States (NDDG 1985).

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Diabetes 0

Table 5-2

Clinical Complications of Diabetes

Deaths

o Each year, diabetes is the cause of about 36,000 deaths among Americans
and is a contributing cause in another 95.000 deaths.
Heart Disease and Stroke

o People with diabetes are two to four times more likely to have heart disease
and two to six times more likely to have a stroke than people who do not
have diabetes.

Kidney Disease

o Ten percent of all people with diabetes develop end-stage kidney disease
(where a person requires dialysis or a kidney transplant to live).
* Nearly 25 percent of all new patients with end-stage renal disease have di-
abetes.

Blindness

o Each year, 5,000 people lose their sight because of diabetes. Diabetic eye
disease is the number one cause of new blindness in people between the ages
of 20 and 74.

Amputations

o Diabetes causes about 45 percent of all nontraumatic leg and foot amputa-
tions in the United States.

Sources: American Diabetes Association 1996; Kovar 1987.

Key Scientific Issues

o Role of Obesity in Type II Diabetes
o Role of Specific Dietary Factors in Diabetes
0 Role of Dietary Therapy in Diabetes Management

Role of Obesii in Type II Diabetes

Obesity (see chapter on obesity) is strongly associated with the onset and
severity of Type II diabetes (O'Sullivan 1982). At least 80 percent of
persons with the Type II disease are more than 15 percent in excess of their
desirable body weight at the time of diagnosis. Some estimates suggest that
new cases of this condition could be reduced by nearly half by preventing
obesity in middle-aged adults (Wood and Bierman 1986). Much of the
increased risk of diabetes among black Americans and Pima Indians has
been attributed to high rates of obesity and its complications in these

255


0 Nutrition and Health

populations (DHHS 1985). The risk of diabetes increases with the degree of
obesity and its duration (NIH 1986) as well as by the specific distribution of
body fat; fat on the upper body is more associated with development of
Iype II diabetes than is lower body fat (Kissebah et al. 1982).

Type II diabetes is characterized by insulin resistance, which means that a
given amount of insulin does not work as efficiently as it does in non-
diabetic individuals. Obesity itself also can contribute to insulin resistance,
and insulin resistance can be profound when obesity is combined with Type
II diabetes. When this happens, the liver, skeletal muscle, adipose tissue,
and other target organs for insulin action do not respond appropriately,
perhaps because the number of insulin receptors has been reduced. As a
result, the pancreatic beta-cells secrete greater amounts of insulin. Thus,
an obese person with Type II diabetes may secrete normal to above-normal
amounts of insulin, but the hormone is relatively ineffective and blood
sugar levels remain high.

The specific cellular cause of the high blood glucose and other metabolic
abnormalities of Type II diabetes is still uncertain, although three defects
may be partially involved: a diminished pancreatic beta-cell response to
glucose, reduced synthesis or function of cellular receptors for insulin, and
an as yet uncharacterized defect in utilization of glucose following binding
to cellular receptors (Arky 1983).

Although the relationship of obesity to these defects remains to be estab-
lished, weight loss reduces insulin resistance as well as fasting and
postprandial blood glucose levels in overweight persons with diabetes
(Henry, Scheafer, and Olefsky 1985; Henry, Wallace, and Olefsky 1986;
Henry et al. 1986). Furthermore, significant caloric restriction lowers blood
glucose levels in these individuals even before weight loss occurs. Once
desirable weight is achieved, control of blood sugar levels can be accom-
plished by consuming just enough energy to maintain it. In general, the
more recent the onset of diabetes, the more responsive a person will be to
the beneficial effects of weight reduction. As weight falls to desirable
levels, improvements in cardiovascular disease risk factors-hypertension
and high blood lipid levels-also occur (Arky 1983).

While very low-calorie diets (fewer than 800 kcal) are usually reserved for
individuals with moderate to severe obesity (Stunkard 1982) diabetes and
other risk factors may demand that such measures be used under a doctor's
supervision. Although weight loss prescriptions are often difficult to imple-
ment (Wood and Bierman 1972), behavior modification to reduce calorie

256


Diabetes 0

intake and promote exercise can be effective and improves prospects for
persons with diabetes (Arky 1983; NIH 1986).

Role of Specific Dietary Factors in Diabetes

Carbohydrates

A diet containing 50 to 60 percent of total calories as carbohydrate is now
recommended for individuals with diabetes (ADA Task Force 1987), not
only because high-carbohydrate diets improve glucose tolerance and in-
sulin sensitivity (Bnmzel et al. 1971; Brunzel et al. 1974; Thompson,
Hayford, and Danney 1978), but also because the reduced fat-especially
saturated fat-intake that accompanies a high-carbohydrate diet lowers
cardiovascular risk. Still, some disagreement remains about the optimal
percentage of carbohydrate for persons with diabetes (Reaven 1980; Jarrett
1981). Furthermore, not all of the carbohydrate in a diet need be available
nutritionally; some of it can be in the form of fiber.

A more controversial issue is the relative proportion of simple and complex
carbohydrates that people with diabetes should consume. Blood glucose
and insulin levels sometimes respond differently to different types of
simple and complex carbohydrates in the diet (Crap0 1984). This response
can be expressed as a "glycemic index," which is the rise in blood glucose
following ingestion of a food as a percentage of the rise that follows
ingestion of a standard food. Food form, fiber type, digestibility of the
starch, and cooking and preparation procedures have been shown to affect
glycemic responses to foods. Even these responses may be altered when
foods are combined. Some studies have suggested that glycemic responses
to food combinations can be predicted from the glycemic index of the
carbohydrate components (Collier et al. 1986; Wolever et al. 198% where-
as others have failed to demonstrate predicted differences (Coulston and
Hollenbeck 1986; Laine, Thomas, and Bantle 1986). Although several
studies have suggested that positive clinical effects are produced when
persons consume diets containing low-glycemic-index foods (Kiehm, An-
derson, and Ward 1976; Simpson et al. 1981; Rivellese et al. 1980), these
suggestions are too preliminary to be considered a basis for therapy.
Because present knowledge of food composition and physiology does not
permit consistent prediction of glycemic responses, the use of glycemic
index tables is not currently recommended for people with diabetes (NIH
1986).

Some studies have been interpreted as supporting the idea that consuming
modest amounts of sucrose is acceptable in the diet of persons with

257


Ll Nutrition and Health

diabetes as long as they can maintain adequate metabolic control (ADA
1984; ADA Task Force 1987). For example, some investigators have found
no significant differences in blood sugar levels among persons with di-
abetes consuming sucrose or starch (Bantle, Laine, and Thomas 1986), and
others have reported that consumption of fructose-a constituent of
sucrose-leads to only a minimal rise in blood glucose levels (Arvidsson-
Lenner 1976; Bohannon, Karam, and Forsham 1978; Lamar 1959; Crapo,
Kolterman, and Olefsky 1980; Crapo, Kolterman, and Henry 1986). This
last observation has led to the idea that a level of up to 75 g/day of fructose in
the diabetic diet may be acceptable if it does not compromise nutritional
adequacy (Olefsky and Crap0 1980). In other studies, however, high-carbo-
hydrate diets, sucrose, and fructose have all been reported to increase
blood glucose, insulin, and lipid levels in persons with diabetes (Coulston
et al. 1987; Hallfrisch et al. 1983). These inconsistencies have yet to be
resolved. Thus, a recent consensus conference recommended that sucrose
intake be permitted only in persons who are not overweight and who do not
respond to sucrose intake by increasing blood lipid levels, and that in any
case, sucrose not exceed 5 percent of calorie intake from carbohydrate
(NIH 1986).

Fat

The traditional restriction of carbohydrate intake in persons with diabetes
leads to an increased fat intake (and, usually, saturated fat) because the
percent of protein in human diets typically does not vary much. This high
saturated fat consumption may have contributed to the frequent cardiovas-
cular complications seen in past years among persons with diabetes. Per-
sons with diabetes have higher plasma cholesterol and triglyceride levels
and lower levels of high density lipoproteins than nondiabetic control
populations. To help reduce this increased risk for coronary heart disease,
a diet low in total fat, saturated fat, and cholesterol has been recommended
(ADA Task Force 1987). Although these recommendations are consistent
with those of the American Heart Association (see chapter on coronary
heart disease), their effectiveness in reducing the incidence and the sever-
ity of cardiovascular complications in diabetics has not been firmly estab-
lished. This can be explained in part because persons with diabetes (like
those with other kinds of disease) are usually excluded from participation in
the major diet-heart disease intervention trials. However, because these
dietary recommendations are consistent with those recommended for
other adults with high blood cholesterol levels and with good nutritional
practices, the person with diabetes should know about them.

Some individuals with diabetes do not maintain normal plasma lipid levels
despite a fat-restricted diet, perhaps because of accompanying obesity,

258


Diabetes 0

uncontrolled hyperglycemia, or coexistence of a primary disorder of
lipoprotein metabolism. In such cases, the physician may need to prescribe
a more restrictive dietary regimen. If persons with diabetes exhibit poor
control of blood glucose levels accompanied by marked hypertriglyceride-
mia (plasma triglyceride levels over 1,000 mg/dl), they become at risk for
acute pancreatitis. This condition requires rapid treatment that may in-
clude restriction of dietary fat along with vigorous control of hyper-
glycemia through insulin or oral hypoglycemic agents.

Protein

The protein requirements of individuals with diabetes under good control
seem to be the same as those of healthy individuals: that is, a daily intake of
0.8 g/kg of body weight for adults and somewhat higher intakes for infants,
children, and pregnant or lactating women (NRC 1980). When insulin levels
are normal, protein is conserved in the body and the use of amino acids for
glucose synthesis is limited (Cahill 1970). In persons with poorly controlled
diabetes, dietary requirements may be increased because protein is used to
synthesize glucose.

Individuals with diabetes and concurrent renal insufficiency should avoid
excessive protein intake. Glomerular hyperfiltration (increased blood flow
and filtration across the renal glomerular capillary bed) leads to impaired
renal function in persons with diabetes, and increased protein intake may
exacerbate renal damage (see chapter on kidney diseases). Furthermore,
protein restriction slows the rate of decline in renal function in individuals
with diabetic nephropathy (Evanoff et al. 1987). Because past dietary
recommendations for persons with diabetes sometimes emphasized pro-
tein, and because the average American eats more protein than is necessary
to maintain health, current recommendations suggest that people with
diabetes should reduce protein intake below the level consumed by Ameri-
cans (ADA Task Force 1987).

Fiber

Recent studies have suggested that a higher intake of dietary fiber than is
typical for Americans might improve many clinical conditions, including
the abnormal glucose tolerance of diabetes (LSRO 1987). Some studies
have demonstrated that diets containing higher amounts of fiber (particu-
larly water-soluble fiber) and carbohydrate are associated with lower blood
glucose and serum lipid levels (Anderson 1980; Anderson and Chen 1979;
Wheeler 1982; Jenkins, Wolever, Jenkins, Lee, et al. 1983; Vahouny 1982).

259


0 Nutrition and Health

Inconsistencies in the results of studies of fiber and diabetes may be due to
differences in types and properties of fiber. As discussed in the gastroin-
testinal diseases chapter, the water-insoluble fibers, such as cellulose,
lignin, and most hemicelluloses, affect gastrointestinal transit time and
fecal bulk but have a limited impact on plasma glucose, insulin, or choles-
terol levels (McMurray and Baumgardner 1984; Hall, Bolton, and Hetengi
1980). However, the water-soluble fibers-pectins, gums, storage polysac-
chat-ides, and a few hemicelluloses-have little influence on fecal bulk but
reduce serum levels of glucose and insulin (Wheeler 1982; Anderson 1980;
Anderson and Chen 1979; Vahouny 1982).

Studies also indicate that blood glucose levels immediately following a meal
are more influenced by soluble than by insoluble fibers. Further study of
the effects of insoluble fibers on long-term baseline blood glucose levels is
needed (Cohen et al. 1980; Jenkins, Wolever, Bacon, et al. 1980; Jenkins,
Wolever, Taylor, et al. 1980; Jenkins et al. 1977; Jenkins et al. 1976; Miranda
and Horwitz 1978; Monnier et al. 1981). Several reports since 1976 suggest
that purified fiber supplements help to control blood glucose in individuals
with diabetes and that they decrease fasting serum glucose, reduce
glycosuria, decrease serum cholesterol, and lower fasting serum triglycer-
ide levels (Anderson and Tietyen-Clark 1986). Such supplements are most
effective when they are mixed with food (Williams, James, and Evan 1980;
Cohen et al. 1980) and when the total carbohydrate level in the diet is high
(Jenkins, Wolever, Bacon, et al. 1980).

Very high-carbohydrate, high-fiber diets, providing 70 percent of calories
as carbohydrate and 35 g of plant fiber per 1,000 calories, consistently
improve glucose tolerance, decrease fasting plasma glucose levels, lower
insulin needs, and decrease serum cholesterol concentrations. These re-
sults have been confirmed in longer term studies comparing a more moder-
ate diet that provides 5.5 to 60 percent of calories as carbohydrates and 25 g
of plant fiber per 1,000 calories (Anderson and Tietyen-Clark 1986; Ander-
son et al. 1987).

These benefits may be related more to the increased intake of complex
carbohydrate than to fiber. Some studies suggest that the fiber content is
not the major factor that determines, for example, the serum glucose
response to consumption of cereals (Jenkins, Wolever, Taylor, Barker, and
Fielden 1981; Jenkins, Wolever, Jenkins, Lee, et al. 1983). Nevertheless,
increasing the level of fiber in the diet of a person with diabetes, or in the
diet of someone at risk for diabetes, may help lower blood cholesterol and
triglyceride concentrations (Anderson and Chen 1979; Albrink, Newman,
and Davidson 1979).


Diabetes 0

The optimal amount and type of fiber that improve diabetes symptoms are
not well defined. If, as evidence suggests, at least 15 g of fiber per meal
(depending on total daily calorie intake) are necessary to achieve therapeu-
tic benefits for persons with diabetes, major changes in dietary patterns are
required. And the use of some of the viscous, soluble fibers is generally not
practical because of their unpalatability and gastrointestinal side effects.
High-fiber diets also may impair absorption of essential trace elements and
be inappropriate in persons with autonomic neuropathy, a neurologic dis-
ease (NIH 1986).

Alcohol

Abstinence from alcohol is not necessarily required for adults with di-
abetes, but some potential problems need attention. Alcoholic beverages
add calories without nutritional benefit and may need to be restricted in
overweight persons. In addition, excessive alcohol consumption by a per-
son who is fasting or undernourished may lead to hypoglycemia, which can
be a serious problem in persons taking insulin or oral hypoglycemic agents.
Intoxication itself may impair a person's adherence to a prescribed man-
agement plan. Finally, alcohol ingestion may raise fasting and postprandial
plasma triglyceride levels. Considering the increased risk for cardiovascu-
lar disease in persons with diabetes, alcohol consumption should probably
be avoided if the person has concomitant hypertriglyceridemia. When
alcohol is part of the meal plan, the person's fat intake should be reduced
accordingly to account for the calories (7 kcal/g of alcohol) (see chapter on
alcohol).

Alternative Sweeteners

Nutritive alternative sweeteners are sugars such as fructose and sorbitol
that can be used as sources of calories. Aspartame, strictly speaking, is a
nutritive sweetener, but it is used in such small quantities that its caloric
contribution is minimal. Non-nutritive alternative sweeteners, such as
saccharin and cyclamate, provide virtually no calories in relation to their
sweetness.

Alternative sweeteners may be useful for persons with diabetes consuming
sugar-restricted diets, both to provide sweetness without associated hyper-
glycemia and, in some cases, to help reduce caloric intake in overweight
individuals (Porikos, Booth, and Van ltallie 1977). The risks, benefits, and
effects of the different sweeteners in individuals with diabetes have not
been evaluated fully, however, and there is little general agreement about
the desirability, acceptability, or usefulness of these substances in diabetes

261


treatment. It is not known, for example, whether alternative sweeteners
contribute to better diabetes control or whether they are effective in weight
reduction programs in Type II diabetes. Because persons with diabetes are
likely to ingest greater quantities of alternative sweeteners than the general
population, issues of side effects, safety, and risk are especially important.
The American Diabetes Association's current position on use of nutritive
and non-nutritive sweeteners is that they are acceptable in management of
diabetes (ADA Task Force 1987).

Role of Dietary Therapy in Diabetes Management

Management Goals

Lifelong care is required to avoid or to reduce the risk factors and com-
plications of Type I and Type II diabetes. Because strategies to control
hyperglycemia are similar to those used to reduce excessive blood lipid
levels, blood pressure, and body weight and their associated cardiovascu-
lar risks, dietary therapy is considered the key to diabetes management
(ADA Task Force 1987). Maintaining blood glucose as close to physiologic
levels as possible will prevent hypoglycemia and its consequent damage to
the brain and nervous system; it will also improve the outcome of pregnan-
cy for women with diabetes (ADA Task Force 1987). Whether control of
hyperglycemia will prevent or delay the development of long-term cardio-
vascular, renal, retinal, or neurologic complications, however, has not been
established (Wood and Bierman 1986).

In persons with Type I diabetes, the goals of dietary management are to
maintain appropriate body weight and prevent hypoglycemia (as well as
hyperglycemia). These are accomplished by consuming meals with an
appropriate calorie content at regular intervals, coordinated with the times
of insulin injection and levels of physical activity. Because individuals with
this form of the disease are usually young and lean, caloric intake must be
adequate to support normal growth and development.

In contrast, 80 to 90 percent of individuals with Type II diabetes are
overweight, and the first goal of diet therapy for such persons is weight
loss. Hence, for most of these individuals, restriction of caloric intake and
increased physical activity leading to moderate weight loss may be suffi-
cient to control blood glucose levels and to avoid the need for insulin or
hypoglycemic medication (ADA Task Force 1987). Once desirable weight
is achieved, people with Type II diabetes must continue to adhere to the
recommended diet to maintain the reduced weight while consuming
amounts of nutrients necessary to maintain normal blood glucose levels.

262


Diabetes 0

For persons with either type of diabetes, dietary therapy is concerned with
(1) maintenance of proper nutrition, (2) the total number of calories in-
gested, (3) the distribution of caloric intake throughout the day, and (4) the
individual food sources that make up these calories. The American Di-
abetes Association has issued general dietary recommendations for per-
sons with diabetes, and these are summarized in Table 5-3. Issues related
to the American Diabetes Association guidelines-patient education strat-
egies, exchange lists, counseling-are discussed below. However, to en-
sure the most appropriate diet for any given person with diabetes, individu-
al diet plans should be developed with a trained dietitian or nutritionist
(Nuttal, Maryniuk, and Kaufman 1983).

Table 5-3

American Diabetes Association Dietary Recommendations
        for Persons With Diabetes

Dietary Factor

Calories

Carbohydrate

Protein

Fat

Cholesterol

Alternative sweeteners

Sodium

Recommendation

Should be prescribed to achieve and maintain a
desirable body weight.

Should comprise 55 to 60 percent of the calories with
the form and amount to be determined by individual
eating patterns and blood glucose and lipid responses.
Unrefined carbohydrates should be substituted for
retined carbohydrates to the extent possible. Modest
amounts of sugars may be acceptable as long as
metabolic control and desirable body weight are
maintained.

Should follow the Recommended Dietary Allowance
(NRC 1980) of 0.8 g/kg body weight for adults,
although more may be needed for older persons. Some
reduction in protein intake may prevent or delay the
onset of the kidney complications of diabetes.
Should comprise 30 percent or less of total calories,
and all components should be reduced
proportionately. Replacement of saturated with
polyunsaturated fat is desirable to reduce
cardiovascular risk.

Should be restricted to 300 mg/day or less to reduce
cardiovascular risk.

Both nutritive and non-nutritive sweeteners are
acceptable in diabetes management.
Should be restricted to 1,000 mg/l,O80 kcal, not to
exceed 3,000 mg/day, to minimize symptoms of
hypertension. Severe sodium restriction, however,

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0 Nutrition and Health

Table 5-3 (continued)

Sodium (continued)   may be harmful for persons whose diabetes is poorly
           controlled and for those with postural hypotension
           (low blood pressure and consequent dizziness when
           first standing up) or fluid imbalance.
Alcohol         Should be moderate and may need to be restricted
           entirely by persons with diabetes and insulin-induced
           hypoglycemia, neuropathy, or poor control of blood
           sugar, blood lipids, or obesity.
Vitamins and minerals  Should meet recommended levels for good health.
           Supplements are unnecessary for persons with
           diabetes except when caloric intake is exceptionally
           low or the variety of food intake is limited. Calcium
           supplements may be necessary under special
               circumstances.

Source: American Diabetes Association Task Force on Nutrition and Exchange Lists.
   1987. Nutritional recommendations and principles for individuals with diabetes
   mellitus: 1986. Diabetes Cam 10:126-32. Reproduced with pen&ion from the
    American Diabetes Association, Inc.

Education Strategies

Better management of diabetes reduces hospitalizations and other person-
al and economic costs. To achieve these benefits, persons with diabetes
must practice optimal self-care, which, in turn, depends on both knowl-
edge and support. Education of persons with diabetes is associated with
improved self-care skills, dietary adherence, and control of blood glucose
and blood lipid levels (Mazzuca et al. 1986; ADA 1986) and results in cost
savings greater than the costs of the education program (Davidson, Del-
cher, and Englund 1979). Although coordinated outpatient education pro-
grams are the preferred setting for education of persons with diabetes, the
lack of third-party reimbursement for such programs has impeded their
development (ADA 1986).

Use of Exchange Lists. Exchange lists categorize foods into groups with
similar energy, protein, carbohydrate, and fat content and indicate how
they can be used in meals. Because individuals with diabetes plan meals
that contain specific proportions of protein, fat, carbohydrates, and calo-
ries, the foods within each group-starch/bread, meat and substitutes,
vegetables, fruits, milk, and fat-can be freely substituted (exchanged) for
one another in the amounts designated. The exchange system is widely
used in diet counseling and meal planning for persons with diabetes.
Exchanges are not intended to be used as self-instructional materials and
generally require a trained nutritionist to explain their use, to help tailor the

264


Diabetes 0

diet to the individual's needs, and to assess the individual's understanding
of appropriate food intake (Slowie 1977).

In 1976, and again in 1986, the exchange system was revised to reflect
current scientific knowledge. The 1976 version reflected recommendations
to restrict intake of calories, cholesterol, and saturated fat. It identified
meat exchanges with high, medium, and low saturated fat content; it
included the cholesterol content of meat and fat exchanges; and it provided
the relative content of polyunsaturated and saturated fats (ADA and Amer-
ican Dietetic Association 1976). The 1986 revision retained these features
but changed the order of the exchanges to emphasize high carbohydrate
and high fiber intake and to update information about the nutrient content
of breads and fruits. Symbols were added to identify foods with high
sodium and fiber content, and lists of combination foods and foods recom-
mended for occasional use were added (Franz et al. 1987).

Dietary Counseling. Dietary counseling helps the person with diabetes
achieve good control of blood glucose and lipid levels by consuming
appropriate levels of calories and nutrients, maintaining consistency in the
timing of meals and snacks, and developing meal plans appropriate to
individual lifestyle and food preferences. Additional goals are to help
children and adolescents achieve normal growth and development rates
and to encourage adequate nutrition for the pregnant woman.

Despite the evident importance of dietary therapy, individuals with di-
abetes often fail to adhere to the recommended diet. This problem means
that patients and physicians must understand the importance of dietary
management goals and methods; in addition, practitioners must provide
detailed nutrition counseling (Hauenstein, Schiller, and Hurley 1987).
Although physicians have sometimes perceived dietary noncompliance as
the patient's fault, persons with diabetes have reported that dietary ad-
herence depends more on environmental factors (e.g., family, job, eco-
nomic status) or on physiologic factors (e.g., visual or ambulatory restric-
tions) that interfere with food purchase or preparation than on personal
control. Understanding these different perceptions can help individuals
with diabetes to assume greater responsibility for their own care (House,
Pendleton, and Parker 1986).

Meal planning for persons with diabetes can be based on several alternative
approaches: (1) dietary guidelines, such as the USDA/DHHS Dietary
Guidelines for Americans, supplemented with information specific to di-
abetes; (2) exchange lists (discussed above); (3) counting systems to
monitor total caloric and glucose consumption; and (4) sample menus

265


0 Nutrition and Health

tailored to the special needs of individuals (Green 1987). Any of these
methods may be appropriate for any given individual, but development of
an individual meal plan requires patient education both in principles of
good nutrition and in effective implementation of these principles. For the
most part, clinicians perform the initial examination, obtain a medical
history (including, perhaps, something about diet), outline an overall nutri-
tional plan, and refer the person with diabetes to a trained dietitian or
nutritionist for further counseling (Nuttall, Maryniuk, and Kaufman 1983).
The dietitian or nutritionist then obtains a detailed diet history, develops an
appropriate meal plan, and helps the person follow it by means of followup
contacts. The most effective approaches consider individual dietary, so-
ciocultural, economic, and lifestyle characteristics and involve the person
with diabetes in devising the diet plan (Nuttall, Maryniuk, and Kaufman
1983). Because behavior changes usually occur gradually, dietary counsel-
ing is also more effective when it presents information in small increments
that can be readily applied (Franz et al. 1987).

Nutrition information should be presented in stages to persons with di-
abetes. In the first stage, counselors should teach basic food selection skills
and develop simplified, individualized meal plans. In subsequent stages,
the counselor can provide more detailed information that extends and
reinforces existing knowledge and that helps the person to change dietary
behavior. Such information needs to be reinforced by continuing education
that reviews dietary management, evaluates adherence to the recom-
mended diet, provides further motivation to improve dietary behavior, and
incorporates the results of new information into the dietary management
program (Franz et al. 1986).

Implications for Public Health Policy

Dietary Guidance

General Public

Obesity greatly increases the risk for developing Type II diabetes, and
obesity is in turn related to caloric imbalance: excessive intake of energy
and/or insufficient energy expenditure. Because dietary fat contains more
than twice the calories of either protein or carbohydrate, a reduction in fat
intake should lead to a more favorable caloric balance, especially when this
dietary change is accompanied by appropriate levels of physical activity.
Controlling obesity by reducing dietary fat intake should help reduce the
prevalence of Type II diabetes and is also consistent with dietary recom-


Diabetes 0

mendations for the prevention of coronary heart disease, hypertension,
and some types of cancer.

Special Populations

Overweight persons with Type II diabetes benefit substantially from weight
loss and may accrue benefits when fat, salt, alcohol, and simple sugars are
reduced in combination with an appropriate increase in foods containing
complex carbohydrates and soluble fiber. Even moderate weight loss,
accomplished by reducing caloric intake and increasing energy expendi-

ture, reduces blood glucose and insulin toward normal levels.

Current research suggests that diets relatively low in fat and cholesterol,
salt, and protein can' reduce the risk of the long-term cardiovascular,
hypertensive, and renal complications of diabetes, respectively. Persons
with diabetes and concurrent insulin-induced hypoglycemia, neuropathy,.
or poor metabolic control should avoid alcohol. Although research has not
unequivocally established that complex carbohydrates and fiber improve
blood glucose and insulin levels in individuals with diabetes, diets higher in
these substances are generally lower in fat, cholesterol, and calories, and
they are associated with lower blood lipid levels and, therefore, lower risk
for coronary heart disease. Such diets can help reduce high blood choles-
terol levels and the risk for coronary heart disease.

Until similar uncertainties about the metabolic effects of sugar in persons
with diabetes are resolved, prudence dictates caution in the amount of its
use. Research on dietary management of Type I diabetes emphasizes the
`importance of weight maintenance, avoidance of hypoglycemia, and meta-
bolic control by coordinating caloric intake and expenditure with the
schedule of insulin administration. Information, counseling, and followup
on the appropriate application of these dietary principles and guidance for
dietary management should be provided to persons with diabetes by
qualified health professionals.

Nutrition Programs and Services

Food Labels

The food industry should be encouraged to provide nutrition information
on the labels of most food products. The information on calories, fat
(especially saturated fat), and other nutrient content will help the public to
control caloric intake and wiU help persons with diabetes to make the
necessary dietary modifications their physicians recommend.

261


0 Nutrition and Health

Food Services
Evidence related to the role of dietary factors in diabetes currently holds no
special implications for policy changes in food service programs.

Special Populations

Persons with diabetes of either type should be provided with counseling
and assistance with dietary changes to control their disease. This should be
coordinated with other aspects of their health care needs such as insulin
administration and levels of physical activity.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in diabetes should include investigations into:
o The role of calorie intake and physical activity, and subsequent weight
control, in the prevention of Type II diabetes.
a The metabolic consequences of obesity.
o The metabolic mechanisms of intestinal and hepatic processing of
dietary carbohydrate, and the effects of other nutrients and of fiber on
carbohydrate metabolism.

o The influence of dietary carbohydrates on glycemic responses in per-
sons with diabetes, and the effects of Such responses on development
of the cardiovascular, renal, retinal, and neurologic complications of
this condition.

o The influence of specific dietary factors-fat, cholesterol, sugar, pro-
tein, fiber-on development of the cardiovascular, renal, retinal, and
neurologic complications of diabetes.
o The long-term risks and benefits of non-nutritive sweeteners as aids to
adherence to dietary regimens.
o The behavioral and environmental factors that influence adherence to
weight loss and dietary regimens in persons with diabetes.
o The specific educational techniques that will improve acceptance of
and adherence to therapeutic regimens.

268


Diabetes O

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Life Sciences Research Otiice. 1987. Physiological effects and health consequences of dietary
fiber, pp. vii, 79-91. Bethesda, MD: Federation of American Societies for Experimental
Biology.

271


O Nutrition and Health

LSRO. See Life Sciences Research Office.

Mazzuca,S.A.;Moorman,N.H.;Wheeler,M.L.;Norton,J.A.;Fineberg,N.S.;Vinicor,E;
Cohen, S.J.; and Clark, C.M. 1986. The diabetes education study-a control trial ofthe effects
of diabetes patient education. Diabetes Core 9(l): l-10.
McMurray, J.F., and Baumgardner, B. 1984. A high-wheat bran diet in insulin-treated diabetes
mellitus: assessment with the art&&l pancreas. Diabetes Cure 7:211-14.
Miranda, PM., and Horwitz, D.L. 1978. High fiber diets in the treatment of diabetes mellitus.
Annals qflnternal Medicine 88482-86.

Monnier, L.H.; Blotman, N.J.; Colette, C.; Monnier, M.P ; and Mirouse, J. 1981. Effects of
dietary fibre supplementation in stable and labile insulin-independent diabetics. Diobetologio
20:12-17.

National Diabetes Data Group. 1985 August. Diabetes in America. NIH publication no.
85-1468. Washington, DC: U.S. Department of Health and Human Services.
National Institutes of Health. 1986. Diet and exercise in non-insulindependent diabetes
mellitus. Consensus Development Conference Statement, vol. 6, no. 8. December 19.
National Research Council. 1980. Recommended dietary olhwonces. Food and Nutrition
Board, National Academy of Sciences. Washington, DC: National Academy Press.
NDDG. See National Diabetes Data Group.

NIH. See National Institutes of Health.

NRC. See National Research Council.

Nuttall, F.Q.; Maryniuk, M.D.; and Kaufman, M. 1983. Individualized diets for diabetic
patients. Annals qflnternol Medicine 22:204-7.

Olefsky, J., and Crapo, P. 1980. Fructose, xylitol, and sorbitol. Diobetes Care 3:390-93.

O'Sullivan, LB. 1982. Body weight and subsequent diabetes mellitus. Journolofthe American
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Porikos, K.P.; Booth, G.; and Van Itallie, T.B. 1977. Effect of covert nutritive dilution on the
spontaneous food intake of obese individuals: a pilot study. American Journol of Clinical
Nutrition 30: 163844.

Reaven, G.M. 1980. How high the carbohydrate? Diubetologio 19:409-10.

Rivellese, A.; Riccardi, G.; Giacco, A.; Pacioni, D.; Genovese, S.; Mattioli, PL.; and
Manicini, M. 1980. Effect of dietary tibre on glucose control and serum lipoproteins in diabetic
patients. Luncet ii:447-50.

Simpson,H.C.R.;Lousley,S.;Geekie,M.;Simpson,R.W.;Carter.R.D.;Hockaday,T.D.;
and Man, J.I. 198 1. A high carbohydrate leguminous fiber diet improves all aspects of diabetic
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Slowie, L.A. 1977. Using the new exchange lists for instructing patients with diabetes.
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Stunkard, A. 1982. New development in the treatment of obesity in adults. Archives of
Neurology 39~736.
Thompson. R.G.; Hayford, J.T.; and Danney, M.M. 1978. Glucose and insulin responses to
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272


Diabetes 0

U.S. Department of Health and Human Services. 1985. Executive summary. Report qfthe
Secretary's Task Force on Block andMinor@ Health, p. 150. Washington, DC: U.S. Govem-
ment Printing CXfice.

Vahouny, G.V. 1982. Conclusions and recommendations ofthe symposium on "Dietary Fibers
in Health and Disease," Washington, D.C., 1981. American Journal of Clinical Nutrition
35: 152-56.

Wheeler, ML., 4. 1982. Fiber and the patient with diabetes mellitus: a summary and
annotated bibliography, p. 2. Chicago, IL: American Dietetic Association.

Wiiiams, D.R.R.; James, W.P.T.; and Evan. E.1. 1980. Dietary tibrc supplementation of a
"normal" breakfast administered to diabetics. Diubetologio l&379-83.

Wolever, T.M.S.; Nuttall, F.Q.; Lee, R.; Wang, G.S.; Josse, R.G.; Csima, A.; and Jenkins,
D.J.A. 1985. Redictionofthe relative blood glucose response ofmixed meals using the white
bread glycemic index. Diabetes Care 8:418-28.
Wood, EC., and Bierman, E.L. 1972. New concepts in diabetic dietetics. Nutrition Today
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-. 1986. Is diet the cornerstone in management of diabetes? New England Journal of
Medicine 315:122427.

273


Chapter 6
Obesity

They are as sick that surfeit with too much
  as they that starve with nothing.
  William Shakespeare (1X54-1616)
    Merchant of Venice, I.ii.

Introduction

Obesity is a condition of excess body fat. Because degree of fatness is a
continuum, any definition of obesity must be arbitrary and related to a
standard of normality. The standard of normality most commonly agreed
upon is the weight, adjusted for height, associated with longest survival.
Although the exact cutoff points for normality and the exact contribution of
obesity to illness and premature death are still under investigation, obesity
undoubtedly contributes to premature mortality, particularly when associ-
ated with elevated blood cholesterol levels, high blood pressure, or di-
abetes. Although poor health is not an inevitable consequence of obesity,
excess body fat poses health risks to many Americans. Despite rapid
advances in the definition and epidemiology of obesity, of adipose cell
metabolism, and of the causes and consequences of obesity, disagreements
still prevail on almost every key issue. Because the causes of obesity are not
well understood, knowledge about how to prevent and treat it is also
limited. This chapter outlines the current knowledge of the diagnosis, risks,
causes, and treatment of obesity, calls attention to areas of controversy,
and assesses the implications of this knowledge for public health policy.

Historical Perspective

Historians of obesity, finding few scientific records, have searched for
clues in linguistics, history, and art and have concluded that obesity as it is
now known did not occur in England, except in a few isolated instances,
until it began to appear in the English upper classes in the 18th and 19th
centuries (Trowel1 1975).

275


O Nutrition and Health

One hypothesis suggests the ability to store excess calories as fat in adipose
tissue was useful during prehistoric times as a protection against food
shortages. However, this ability later became a handicap in industrialized
societies. The industrial revolution allowed food to be available consis-
tently and reduced the physical effort needed to obtain, process, and
prepare it. Increased control of infectious diseases, modern transportation,
and increasingly sedentary patterns of work and recreation contributed to
the presence of the current high level of obesity in the United States.

Moderate obesity was considered a sign of health in this country until the
present century, and many societies still consider it healthy. The positive
attributes of body fat were extolled by early fertility symbols (e.g., the
Venus of Willendorffrom prehistoric times), by the ancient Greeks, and by
Shakespeare. On the other hand, Dickens described the association of
extreme obesity with poor health in the character of Mr. Pickwick, who
suffered from the cardiorespiratory syndrome that now bears his name.
These concerns eventually led life insurance companies to develop and use
rate structures based on tables of body weight-for-height (Rittenbaugh
1982).

Widespread interest in studying body fat (adipose tissue) was stimulated by
the publication in 1940 of "Adipose Tissue: A Neglected Subject" (Wells
1940). A subsequent prophetic observation correlated the distribution and
size of body fat cells with the development of atherosclerosis: fat cells
concentrated in the trunk region were more likely to be linked to heart
disease than were those on the arms or legs (Bjurulf 1959). In 1965, the
American Physiological Society published a large compendium of informa-
tion on adipose tissue that is still a good source of information (Renold and
Cahill 1965).

The first data using weight tables to predict life expectancy were collected
by the life insurance industry in 1913 (Association of Life Insurance
Medical Directors and Actuarial Society of America 1913), but tables of
ideal or desirable weight did not appear until the Metropolitan Life Insur-
ance Company published its first tables of ideal or desirable weight in the
1940's (Simopoulos and Van Itallie 1984). Concurrently, modern epi-
demiologic techniques began to identify obesity as a risk factor for some of
the major diseases of modem times: cardiovascular disease, diabetes,
hypertension, and cancer. The most recent epidemiologic data on obesity
as a health hazard were the subject of a national conference (NIH 1985) and
are reviewed in this chapter.

216


Obesity O

Significance for Public Health

Obesity is one of the most prevalent diet-related problems in the United
States. It affects about 34 million adults ages 20 to 74 (NCHS 1987), with
the highest rates observed among the poor and miriority groups (Van ltallie
1985; Van Itallie and Abraham 1985).

Population data for heights and weights (and, .therefore, obesity) among
Americans derive from three pational surveys: the National Health Exam-
ination Survey (NHES I) of 1960-62 (DHEW 1964), the first National
Health and Nutrition Examination Survey (NHANES I) of 1971,74.
(DHEW 1973), and NHANES II of-197&80 (McDowell et al. 1981; NCHS
1987). In addition-data are available from the Framingham Heart Study
(Hubert et al. 1983) and from the American Cancer Society Study of
1959-62 (Lew and Garfinkel 1979).

The 1971-74 NHANES found that 23.7 percent of men and 26.0 percent of
women ages 20 to 74 were overweight. These figures were based on a
definition of overweight that included persons whose weights met or
exceeded the 85th percentile of the body mass index, or BMI (weight in
kilograms divided by height in meters squared for men, and for women,
divided by height to the power 1.5) for individuals ages 20 to 29. The BMI is
discussed in more detail below, Because body weights increase with age,
population rates of overweight that have been reported for adults ages 25 to
74 (and age-adjusted) are higher-26.0 percent of men and 29.4 percent of
women (NCHS 1986).

NHANES II reported 25.6 percent of Americans ages 20 to 74 as over-
weight. Age-adjusted rates for blacks (36.6 percent) exceeded those for
whites (24.6 percent), and those for females of all races (26.7 percent)
exceeded those for males (24.4 percent). Although the rate for black males
(26.3 percent) was only slightly higher than that for white males (24.4
percent), the rate for black females of 45.1 percent was highest of all-
almost twice that of the 24.6 percent for white females (NCHS 1987). Rates
of obesity in the United States appear to be higher than those observed in
England, Canada, or Australia, at least among certain age groups (Bray
1985; Millar and Stephens 1987). The reasons for these differences have not
been established.

The peak overweight rates for men occur from ages 35 to 64, whereas rates
for women continue to increase throughout the ages in which they are

277


u Nutrition and Health

measured. The percent of adults classified as overweight increases from a
low of 5.5 percent among black males ages 20 to 24 to a high of 61.2 percent
among black women ages 45 to 54 (NCHS 1987).

NHANES II data also identified individuals at or above the 95th percentile
BMI for a reference population ages 20 to 29. By this criterion, 9.3 percent
of all Americans were classified as severely overweight, with the rate for
blacks (15.5 percent) almost twice that for whites (8.8 percent). Here too,
rates for females (10.6 percent) were higher than for males (8.0), with a
much higher prevalence among black females than among white females
(19.7 and 9.6 percent, respectively). The highest prevalence of severe
overweight was the 26.3 percent observed among black females ages 35 to
44; the lowest was the 3.4 percent rate seen in white females ages 20 to 24
(NCHS 1987). When adjustments were made for differences in age dis-
tribution among populations between surveys, the age-adjusted propor-
tions of men and women severely overweight (95th percentile by BMI) in
1976-80 significantly exceeded those in 1961-62 (Van Itallie and Abraham
1985).

The influence of poverty on the prevalence of overweight in women has
been established. For example, in the 45 to 54 age range, 54.1 percent of
poor women were overweight compared with 32.5 percent in the general
female population (Van Itallie 1985).

Severe overweight increases the risk for high blood cholesterol, high blood
pressure, and diabetes and, hence, for diseases for which these conditions
are risk factors (see chapters on diabetes, coronary heart disease, high
blood pressure, neurologic disorders, and kidney diseases). It also in-
creases the risk for gallbladder disease (see chapter on gastrointestinal
diseases) and for some types of cancer (see chapter on cancer). Its psycho-
social consequences are significant (see chapter on behavior). The great
prevalence of obesity and its physical and mental health consequences
suggest that its prevention should be a high public health priority.

Perhaps for these and other reasons, many Americans try to lose excess
weight. According to data from the 1985 National Health Interview Sur-
vey, 27 percent of males and 46 percent of females were trying to lose
weight by reducing caloric intake, increasing physical activity, or both
(Stephenson et al. 1987). The health consequences of these activities are
also of public health concern and are reviewed in this chapter.

278


Obesity O

Key Scientific Issues

o Definition of Obesity
o Health Consequences of Obesity
o Causes of Obesity
o Treatment of Obesity

Definition of Obesity

An ideal, health-oriented definition of obesity would be based on the
degree of excess body fat at which health risks to individuals begin to
increase. No such definition currently exists. Instead, the most commonly
used methods estimate body fat as a percentage of total body weight
(underwater weighing), establish an index of body fat level (skinfold thick-
ness or waist-to-hip circumference measurements), compare weight-for-
height measurements (height and weight tables), or compute an index of
body weight as a function of height (BMI) in reference to population
standards.

Much of the scientific disagreement about the level of body fat associated
with increased health risks to individuals or to populations can be at-
ributed to the difficulties in measuring body fat content and in defining
overweight and obesity. Even underwater weighing, which measures body
rat as a percent of total body weight and which is too cumbersome and
:xpensive to use in population studies, can produce inaccurate results
Barnes 1987). The easily available measurements of heights, weights, and
kinfold thicknesses, which are more frequently used in epidemiologic
<tudies for assessing obesity and its effects, can be even less accurate.

deference Body Weight Standards

4n ideal body weight-for-height based on minimal health risks has not yet
>een defined for either individuals or populations. Instead, weight-for-
reight is usually compared with standards based on survey populations.
The accuracy of such determinations, therefore, depends on the size and
ype of the reference population, as well as on the precision and appropri-
tteness of the measures used.

Yeight and Weight Tables. The reference standards most commonly used
o define obesity are those based on actuarial data from the Metropolitan

279


u Nutrition and Health

Life Insurance Company (MLIC), in which "desirable" or "ideal" weight is
the weight-for-height of insured persons with the longest lifespans. The
original 1949 tables were revised in 1959 (MLIC 1959) based on the Build
and Blood Pressure Study of 1959 (Society of Actuaries 1960), and again in
1983 (MLIC 1983) based on the Build Study of 1979 (Society of Actuaries
and Association of Life Insurance Medical Directors of America 1980).

Tables of heights and body weights derived from several studies are given in
Table 6-l. These tables present ranges of weight-for-height associated with
the lowest mortality rates. The midpoint of the range is usually used as the
standard for ideal or desirable weight. As seen in Table 6- 1, Metropolitan
desirable weights of 1983 are higher than those for 1959 in nearly all height
categories but especially in those that are shorter. Both sets of data present
as "desirable" body weights that are significantly lower than average
weights measured in population surveys.

Relative Weight. Relative weight refers to actual weight as a percent of the
desirable weight defined in the tables. A relative weight of 100 would thus
be a desirable weight. As commonly used, a relative weight of 120 percent
of that desirable is considered overweight, and relative weights of 140
percent or more are considered severely overweight (NIH 1985; Foster and
Burton 1985). The desirable weights were slightly more liberal in the 1983
Metropolitan tables than in the 1959 tables, particularly for persons of short
stature; weights for the shortest men in the 1983 table were heavier by 12 lb
and for the shortest women by 14 lb.

These tables are handicapped by major flaws in the data from the studies on
which they are based. For example, the tables present heights and weights
with shoes and clothing but whether heights and weights were obtained
with or without clothes and shoes was not consistent. The data for the
Metropolitan tables were drawn from persons who could afford life insur-
ance and were predominantly white and from middle-class males of young
and middle age; thus, they were not necessarily representative of other
groups. For these and other reasons, some experts believe that these tables
are limited in value (Knapp 1983).

Body Mass Index. Ratios of weight to height estimate total body mass
rather than fat mass, but they correlate highly with amount of body fat
(Revicki and Israel 1986). The most commonly used ratio is known as
Quetelet's index, or the BMI, and is usually defined as body weight in
kilograms divided by the square of the height in meters (wtiht*). A simple
nomogram to facilitate calculation of the BMI is given in Figure 6-l. In

280


Obesity O

population studies such as NHANES, this index is modified to reflect body
composition differences between men and women.

A great advantage of such an index is the capability to evaluate and
compare not only individuals but populations or subgroups within popula-
tions. Thus, various experts have recommended that the degree of obesity
be defined by the BMI and have established reference standards for its use.
These standards were derived from the same studies used to construct the
Metropolitan tables. The BMI equivalent to a relative weight of 100 was 22
kg/m* for men and 21.5 kg/m* for women (Simopoulos and Van Itallie
1984). Table 6-2 shows the equivalent body mass indices derived from the
three reference populations in common use: the 1959 and 1983 Metropoli-
tan tables of desirable weights (MLIC 1959, 1983) and the 1976-80
NHANES (NCHS 1987). The indices in Table 6-2 are translated from the
85th and the 95th percentile weight distribution of NHANES II and from
the 120 percent and 140 percent overweight cutoff points of the Metropoli-
tan tables of 1959 and 1983. These indices are in rather close agreement.
While some experts suggest that the body mass indices based on the 1959
Metropolitan tables, 26.4 for men and 25.8 for women, be considered the
upper limits of normal weight (NIH 1985), others favor the higher levels
derived from the more rigorous national probability sample of NHANES II
(NCHS 1987).

The term overweight rather than obesity is used in this discussion because,
although the BMI correlates highly with body fat, it does not distinguish
between body fat and lean body tissue. While excess fat tissue is generally
assumed to account for the additional weight and, therefore, the additional
mortality among overweight individuals, excess weight can also include
lean body mass (which weighs more than fatty tissue) (Van Itallie 1985;
Forbes and Welle 1983) or a larger body frame size (Simopoulos and Van
Itallie 1984). Such problems limit the use of the BMI as a standard for
health risk (Gam, Leonard, and Hawthorne 1986). Its clinical significance,
discussed below, has also been questioned (Callaway 1984).

Body Composition. Careful measurements of skinfold thickness made with
calipers generally correlate well with body fat content. The sums of the
scapular and triceps skinfolds that correspond to the 85th percentile of the
NHANES II population were 45.5 mm in men and 70.1 mm in women (Van
Itallie 1985). The lean body mass (or fat-free weight) can be calculated as
the difference between total body weight and the weight of adipose tissue
estimated from skinfold thickness or other methods. Elbow breadth and
wrist circumference may be useful indicators of body frame size (Si-
mopoulos and Van Itallie 1984).


                  Table 6-l
Comparison of Metropolitan Desirable Weights With Average Weights
            From U.S. Cohort Studies

   Average Weight for Age 40-49 y, kg (lb)
Insured Lives

3lood          American Cancer
t,Wh   Rnmild Ptnnrlv    .cnrietv .ctlldv

Metropolitan Tablesa (Medium
Frame), Weight in Kilograms   Build and I
(Pounds) (Without Clothing)   Pressure S.,,,   U..`." "LYYJ ""`.`LJ Y.....,
                      1959b       1979b        197%
  I959a        1983     (1935-1953)'   (1950-1971)e    ( 1959)=

                 c        -
Health and Nutrition     S
Examination Survey
(HANES I. 1979)d

(1971-1974)e '

Height (Without
Shoes), cm (ft
in)

156 (5 I)       50-55 (I I l-122)  57-62 (126-136)    60 (133)      61 (135)
159 (5 2)       52-57 (114-126)  58-63 (128-138)    62 (137)      63 (139)
162 (5 3)       53-59 (117429)  59-64 (130-140)    64 (141)     65 (144)
164 (5 4)       54-60 (120-132)  60-65 (132-143)    66 (145)      68 (149)
167 (5 5)       56-62 (123-136)  61-66 (134-146)    68 (149)      69 (153)
169 (5 6)       5844 (127-140)  62-68 (137-149)    70 (154)      72 (158)
172 (5 7)       59-66 (131-145)  64-69 (140-152)    72 (158)     73 (162)
174 (5 8)      61-68 (135-149)  65-70 (143-155)    73 (162)      76 (167)
177 (5 9)      63-69 (139-153)  66-72 (146-158)    76 (167)      78 (171)
179 (5 10)      65-72 (143-158)  68-73 (149-161)    78 (171)      80 (176)
182 (5 11)      67-74 (147-163)  69-75 (152-165)    80 (176)     82 (181)
185 (6 0)      68-76 (151-168)  70-77 (155-169)    82 (180)      85 (187)
187 (6 1)       70-78 (155-173)  72-78 (159-173)    84 (185)      87 (192)
190 (6 2)       73-81 (l-178)  73-80 (162-177)    86 (190)      90 (198)
192 (6 3)       75-83 (165-183)  75-83 (166-182)    89 (1%)     92 (203)

Men

67 (148)
68 (149)
69 (153)
71 (156)
73 (160)
74 (163)
77 (169)
78 (173)
80 (177)
83 (182)
85 (187)
87 (192)
90 (198)
92 (203)

  -
66 (145)f
68 (15O)f
73 (162)
72 (159)
75 (166)
78 (173)
79 (174)
79 (175)
83 (184)
85 (188)
88 (194)
92 (203)
92 (203)f
  -


146 (4 9)
149 (4 10)
151 (4 11)
154 (5 0)
156 (5 1)
159 (5 2)
162 (5 3)
164 (5 4)
167 (5 5)
169 (5 6)
172 (5 7)
174 (5 8)
177 (5 9)
179 (5 10)

43-48  (94-106)
4bI9 (97-109)
45-51 (100-l 12)
47-52 (103-l 15)
48-54 (106-l 18)
49-55 (109-122)
51-57 (112-126)
53-59 (116-131)
54-61 (120-135)
56-63 (126139)
58-65 (121143)
6&67 (132-147)
62-68 (136151)
6&70 (140-155)

48-54 (106-l 18)
48-54 (106-120)
5&56 (110-123)
51-57 (112-126)
52-59 (115-129)
54-60 (118-132)
55-61 (121-135)
56-63 (124-138)
58-64 (127-141)
59-65 (13tL144)
60-67 (133-147)
62-68 (136-150)
63-69 (139-153)
64-71 (142-156)

Women

54 (120)
56 (123)
57 (126)
59 (129)
60 (132)
62 (136)
63 (139)
65 (143)
67 (147)
68 (151)
70 (155)
73 (160)
75 (165)
77 (170)

52 (115)
54 (118)
54 (120)
56 (124)
57 (126)
59 (130)
60 (133)
62 (136)
64 (140)
65 (144)
67 (147)
70 (152)
70 (155)
72 (159)

  -
52 (115)
55 (121)
57 (126)
58 (128)
60 (132)
62 (136)
63 (139)
64 (142)
66 (146)
68 (150)
71 (156)
73 (161)
75 (165)

58 (127)f
59 (131)f
62 (136)
64 (141)
63 (138)
64 (141)
67 (148)
68 (151)
71 (156)
71 (156)
72 (158)
78 (172)
  -

-

,

aNot age specific: 1959 tables recommended for ages 25 and older; 1983 tables for ages 25 to 59 years.
bWithout shoes or clothing.
CValues are means for age groups 40 to 44 and 45 to 49. Self-reported heights without shoes and weights with indoor clothing.
dValues are means for age groups 35 to 44 and 45 to 54. Measured without shoes; clothing ranged from 0.20 to 0.62 lb (not deducted from
weights shown).
eYears when measurements taken.
rEstimated values obtained from linear regression equations.

Source; Manson, J.E.; Stampfer, M.J.; Hennakens, C.H.; and Willett, WC. 1987. Body weight and longevity. A reassessment. ./oumal of the
   American Medical Associatioh 257:353-58. Copyright 1987, American Medical Association, reprinted with permission.


u Nutrition and Health

Weight

kg lb

Body
Mass
Index
bWN21

Men

Obese

Height
cm in

Figure 6-l. A nomogram tar determining body mar index (SW). To
     usethiknomogram,placearulerorottwstraigMedge
     between the column for height ad the cotumn tar weight
   connecting an indiviiyfl'r numbers for those two variahlas.
     ReadttwBMlinkg/m wheretheatraightlinecros8esth0
   middle lines when the height aqj weight are connected.
   Overyelght: BMI ol W-30 kg/m ; obesityz BMI above 30
     kg/m . Heights and weights are without shoes or clothes.
Source: Bray, G.A. 1985. Obesity: definition. diagnoses and disadvantages.
    The Medical Journal of Australia 142:S2-58. Copyrlght 7988,
    The Medical Journal of Australia, reprinted with permlsslon.

284


I

Obesity 0

                Table 6-2
Body Mass Index (kg/m? Used to Define Desirable Weight and
    Overweight According to Three Different
       "Ideal" Reference Populations

BMI for "Ideal" Reference Population

"Ideal"
Reference

Mean

Overweight

Severe
Overweight

Studya      Population

Men Women Men Women Men Women

NHANES 11 20- to 29-
       year-olds      24.3   23.1   27.8   27.3   31.1   32.3
Metropolitan Desirable weight
1959      insured       22.0   21.5   26.4   25.8   30.8   30.1
Metropolitan Desirable weight
1983       insured       22.7   22.4   27.2   26.9   31.8   31.4
aThe NHANES II data define overweight as the 85th percentile or more of the distribution
of BMI for men and w'omen ages 20 to 29 and severely overweight as the 95th percentile
for that reference population (NCHS 1987). The Metropolitan 1959 data are taken from
the 1959 Metropolitan Llfe Insurance tables. Weights and heights were adjusted to ap-
proximate those without shoes or clothing (Simopoulos and Van ttallie 1984; NIH 1985).
The Metropolitan 1983 data are taken from the 1983 Metropolitan tables. Height and
weight were with shoes and light clothes (van ltatlie 1985; NIH 1985). For both the 1959
and the 1983 Metropolitan data, the weights for midpoint of medium-frame persons were
used, and for both studies overweight and severe overweight were defined as 20 percent
and 40 percent, respectively, over desirable weight.

Types of Obesity

Hyperplastic vs. Hypertrophic. Obesity is associated with too many
adipose cells (hyperplastic obesity), adipose cells that are too large (hyper-
trophic obesity), or both (Hirsch and Batcheloer 1976). Studies on differ-
ences and changes in fat cell sizes and numbers have led to the hypothesis
that while changes in the size of adipose cells may occur at any age, the
number of adult cells may be fixed and determined by weight gain during
certain periods of childhood development; fat cell number is established by
late adolescence (Knittle et al. 1979) and, once established, does not
decline. These suggestions have been interpreted to imply that the poten-
tial for sustained weight reduction in adulthood may depend, in part, on the
number of adipose cells present. That is, because people with excessive
numbers of fat cells may expect only limited success in weight reduction,
prevention of adult obesity should begin with limits on excessive weight
gain during childhood (Hirsch and Batcheloer 1976).

This hypothesis has received limited support. Although adult-onset
obesity is more commonly due to an increase in the size of a normal number

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of adipose cells than to an increase in their number (Krotkiewski et al.
1983), adipose cell number also increases in response to excessive weight
gain at any time throughout adult life (Sjostrom 1980). Some studies have
reported better treatment outcome among hypertrophic than hyperplastic
obese subjects (Bjomtorp et al. 1975), but others have not observed any
such difference (Strain et al. 1984), and the clinical significance of differ-
ences in fat cell size and number remains to be determined.

Upper Body vs. Lower Body. Women generally have been observed to have
more subcutaneous fat than men, but men appear to suffer a greater
cardiovascular risk from a given degree of fat than women (Bjomtorp 1983).
The distribution of body fat may be an indicator of this difference. More
men than women accumulate large fat cells in the abdominal region. This
distribution around the abdomen with increased waist-to-hip ratio, referred
to as upper body obesity, is associated with increased cardiovascular risk
factors such as hypertriglyceridemia and impaired glucose tolerance
(Krotkiewski et al. 1983). Lower body obesity is more typical of women,
who tend to accumulate fat in the hips, gluteal regions, and extremities, a
distribution that does not appear to be associated with increased cardiovas-
cular risk factors (Krotkiewski et al. 1983), perhaps because fat on the hips
is not well mobilized (Rebuffe-Strive et al. 1985). Adipose cells are insulin-
resistant in the abdominal region but usually are insulin-sensitive in the
gluteal region (Maugh 1982). Studies of siblings ranging in relationship from
identical twins to adoptive suggest that these differences in adipose cells
may be genetically determined (Bouchard et al. 1985). Accordingly, women
with upper body obesity with a waist-to-hip ratio similar to that of men are,
like men, at increased risk for hypertriglyceridemia, hyperinsulinemia,
diabetes, and cardiovascular disease (Krotkiewski et al. 1983).

Regardless of gender, a high waist-to-hip ratio predicts an increased risk for
cardiovascular disease and diabetes. Measurements made in 1%7 of waist-
to-hip circumference of 792 54-year-old men in Gothenberg were positively
correlated 13 years later with deaths from stroke and ischemic heart
disease (Larsson et al. 1984). Other indices of body fatness such as the
BMI, the sum of three skinfolds, or either waist or hip circumference alone
showed no such correlation. A 1Zyear study of 1,462 women found the
waist-to-hip ratio to be a better predictor of myocardial infarction, angina
pectoris, stroke, and death than any other anthropometric measurement
obtained (Lapidus et al. 1984). In both of these studies, persons whose
waist-to-hip ratio was in the top quintile of distribution (greater than 1 .O for
men or 0.8 for women) suffered the greatest incidence of cardiovascular
disease.

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Childhood Obesity. Obesity and extreme obesity in children have been
defined in several studies by a triceps or scapular skinfold thickness greater
than or equal to the 85th or 95th percentile, respectively, of children in the
same age group and sex between the baseline and a later year of measure-
ment in national surveys (Die& 1986). Increased weight-for-height above
the 85th percentile for a defined population has also been used and can be
deduced from standard growth charts (see chapter on maternal and child
nutrition). Obesity in children can cause psychosocial dysfunction, ortho-
pedic problems, abnormal glucose tolerance, hypertension, and elevated
cholesterol and triglycerides that may persist into adulthood (Dietz 1986;
Freedman et al. 1985). It also can increase the risk of obesity in adulthood
(Gam 1985a, 1985b; Shear et al. 1988; Sorensen and Sonne-Holm 1988).
According to a comparison of children studied in the NHES Cycle II and
Cycle III between 1%3 and 1970 and children studied later in NHANES I
and II from 1971 to 1980, obesity and extreme obesity in children appear to
be increasing by as much as 54 and 98 percent, respectively, in 6 to 1 l-year-
olds and by 39 and 64 percent, respectively, in 12- to 17-year-olds
(Gortmaker et al. 1987).

Health Consequences of Otbesity

Excess Mortality

Numerous studies have examined the effects of excessive body weight on
mortality. The best known studies include the Build and Blood Pressure
Studies of 1959 and 1979 (Society of Actuaries 1960; Society of Actuaries
and Association of Life Insurance Medical Directors of America 1980) and
the American Cancer Society Study (Lew and GarIinkell979; Lew 1985).
Several smaller studies include the Manitoba Study (Rabkin, Mathewson,
and Hsu 1977), the Chicago People's Gas Company (Dyer et al. 1975), the
Seven Countries Study (Keys 1980), the Longshoremen Study (Borhani,
Hechter, and Breslow 1%3), and the Provident Mutual Life Study (Blair
and Haines 1966). This subject has been reviewed extensively (Simopoulos
and Van Itallie 1984; NIH 1985; Manson et al. 1987).

In most of these studies, mortality increased with increasing weight. This
effect can be expressed as the mortality ratio, defined as the actual number
of deaths as a percent of expected deaths for the population as a whole. The
mortality ratio has been shown to increase with degree of obesity, and with
its duration, from 110 among persons 5 to 15 percent overweight to 227
among those 55 to 65 percent overweight (NIH 1985). Extreme (morbid)
obesity, defined in this instance as either 100 percent or 100 lb over

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desirable weight (Kral 1985), has been reported in one small series to be
associated with a mortality ratio of 1,200 percent (NIH 1985).

Although experts generally agree that excessive body weight is associated
with increased mortality (NIH 1985), the body weight associated with the
lowest mortality still lacks precise definition. Several important meth-
odologic issues contribute to this uncertainty. These include the failure to
control for cigarette smoking and inappropriate control for biologic effects
of overweight such as hypertension, hyperlipidemia, and hyperglycemia,
for weight loss due to subclinical disease (Manson et al. 1987), for weight
history, for body fatness, or for duration of the condition (Simopoulos and
Van ltallie 1984).

Several studies, for example, have reported a higher mortality at the lower
as well as the higher range of fatness. This J- or U-shaped curve was found
in the Build Study of 1979 (Society of Actuaries and Association of Life
Insurance Medical Directors of America 1980; Van Itallie and Abraham
1985), the Framingham Heart Study (Hubert et al. 1983; Garrison and
Castelli 1985), the American Cancer Society Study (Lew and Garfinkel
1979), and the Hawaiian Japanese Study (Rhoads and Kagan 1983). The
increased mortality at lower weights was related to several types of cancer
(Lew and Garfinkel 1979). The J-shaped curve was markedly reduced but
still observable when adjusted for smoking history (Garrison and Castelli
1985), as well as for serum cholesterol level, blood glucose level, and
systolic blood pressure (Harris et al. 1988).

In the Build and Blood Pressure Study of 1959 (Society of Actuaries 1960),
optimal weight for all ages, judged by survival, was close to that of 20- to
29-year-olds. Older cohorts were heavier, and the increase in relative
weight with increasing age was associated with increased mortality. Data
from the Framingham Heart Study confirm that being overweight in-
creases health risks for older people (Harris et al. 1988). Implicit in this
trend is the undesirable effect of weight gain beyond desirable weight after
maturity and the suggestion that weight gain acquired during adult life
might be more detrimental than the degree of overweight. In fact, one study
has reported the highest rates for cardiovascular and renal disease among
overweight adults who were below average weight as children but who
developed late-onset obesity (Abraham, Collins, and Nordsieck 1971).
However, in the Build Study of 1979, the effect of overweight on mortality
was more marked in obese men issued insurance policies between ages 15
and 39 than for equally obese men issued insurance policies between ages
40 and 69. A problem with both the 1959 and 1979 studies was the rather

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Obesity O

short average duration of time that policyholders were observed-6.6
years for the latter study. In the Build Study of 1979, the adverse effects of
underweight became evident in a relatively shorter time than the adverse
effects of overweight (Society of Actuaries and Association of Life Insur-
ance Medical Directors of America 1980).

The studies that do not show increased risk from obesity, such as the Seven
Countries Study and the Longshoremen Study, have limitations because
they were too short in duration, too small in sample size, or did not
consider the adverse effects of smoking or of preexisting illness (Si-
mopoulos and Van Itallie 1984; Van Itallie and Abraham 1985; Manson et
al. 1987). Under these circumstances, the adverse effects of overweight
would be obscured and of underweight exaggerated. Prospective data from
the Framingham Heart Study, in which a cohort was followed for 26 years,
clearly show the adverse effect on mortality of as little as 10 percent
overweight, using the 1959 Metropolitan tables (Hubert et al. 1983). Bear-
ing in mind data limitations, minimal mortality appears to occur at a weight
10 percent below the U.S. averages as shown in Table 6-l (Manson et al.
1987).

Other Health Consequences

Relative body weights above 100 to 109 percent of desirable are associated
with increased mortality as well as morbidity from heart disease, cancer,
diabetes, digestive diseases, and cardiovascular disease. The higher the
relative weight, the greater the risk for these conditions (Lew and Garfinkel
1979). From the NHANES II data, rates of hypertension and diabetes were
nearly tripled for persons 20 percent or more overweight, and hyper-
cholesterolemia was 50 percent more common (Van Itallie 1985). Obesity
is associated with reduced levels of high density lipoproteins but with
elevated levels of triglycerides and atherogenic lipoproteins (Albrink et al.
1980). The large American Cancer Society Study found mortality from
various causes to increase according to the degree of overweight. Data
from this study are shown in Table 6-3. Of all obesity-related diseases,
noninsulin-dependent diabetes is most clearly and strongly associated with
obesity. The details of these relationships are discussed in the chapter on
diabetes.

Many other serious conditions such as gallstones, sleep apnea, osteo-
arthritis, and other disabling disorders of locomotion bear a direct relation-
ship to obesity, although causality is not necessarily proved by these
associations.

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Table 6-3

Mortality Ratios for All Ages Combined in Relation to the Death
  Rate of Those 90 to 109 Percent of Average Weight

                  Weight Index
        Sex  <OS0  ONl-089  090-109  110-119  12&129  130-139  140+

Total deaths  M   1.25   1.05    1.00    1.15    1.27    1.46   1.87
         F   1.19   O.%    1.00    1.17    1.29    1.46   1.89
Coronary    M  0.88   0.90    1.00    1.23    1.32    1.55   1.95
heart       F   1.01   0.89    1.00    1.23    1.39    1.54   2.07
disease

Cancer,     M   1.33   1.13    1.00    1.02    1.09    1.14   1.33
all sites     F   O.%   0.92    1.00    1.10    1.19    1.23   1.55

Diabetes    M  0.88   0.84    1.00    1.65    2.56    3.51   5.19
         F   0.65   0.61    1.00    1.92    3.34    3.78   7.90
Digestive    M   1.39   1.28    1.00    1.45    1.88    2.89   3.99
diseases     F   1.58   0.92    1.00    1.66    1.61    2.19   2.29

Cerebral     M   1.21   1.09    1.00    1.15    1.17    1.54   2.27
vascular     F   1.33   0.98    1.00    1.09    1.16    1.40   1.52
disease
Source: Lew, E.A., and Gatfinkel, L. 1979. Variations in mortality by weight among
   750,000 men and women. Journal of Chronic Diseases 32:563-76. Copyright
   1979, Pergamon Press, Ltd., reprinted with permission.

Causes of Obesity

The causes of obesity are incompletely understood, so that effective treat-
ment is difficult. Obesity is the net result of an excess of energy consump-
tion over expenditure. Factors that must be considered as contributing to
causation are: (1) heredity, (2) primary overeating, (3) altered metabolism
of adipose tissue, (4) defective or decreased thermogenesis (the process by
which calories are converted into heat), (5) decreased physical activity
without an appropriate reduction in food intake, and (6) certain prescribed
medications. These potential causes can interact with one another. Of the
six factors, individuals may have some control of overeating and underac-
tivity.

Genetic Causes

Some studies of incidence of obesity among population groups, and among
individuals within population groups, suggest that the tendency for obesity
is inherited. On the other hand, separating genetic from cultural and
environmental contributions is difficult-a fact brought out by studies of
American Indians and blacks (Van Itallie and Abraham 1985; Van Itallie

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Obesity a

1985), two populations that display higher levels of obesity than other
groups. To explore the question of environment versus heredity, investiga-
tors have examined the weight characteristics of twins and adopted sib-
lings. In addition, studies of reduced energy expenditure in overweight
infants and adults, as reviewed later in this chapter, have provided evidence
in support of a genetig basis for obesity.

One study measured the body fatness of 871 biologic and adopted siblings
of French descent, including 87 pairs of monozygotic twins, and found that
the amount and distribution of fat were related to the closeness of the
genetic relationship. Similarities were not observed between adopted sib-
lings. The genetic effect was particularly noted in measurements of skin-
fold thicknesses and in lean body mass. At the same time, a substantial
environmental, or cultural, effect was also observed (Bouchard et al. 1985).
Aerobic capacity in response to submaximal exercise also appeared to be at
least partially genetically determined because similarities were greater
among twins than among siblings or adopted siblings (Bouchard et al.
1984). Although these findings do not entirely rule out effects of early
learned practices, they do make it tempting to speculate that for genetic
reasons, some persons are less able to benefit from exercise and are thus
more susceptible to obesity than others.

Another recent study provided even broader evidence for the genetic
determination of obesity. In a study of 4,071 pairs of twins, investigators
estimated that 80 percent of the contribution to obesity could be explained
by genetics (Stunkard, Foch, and Hrubec 1986). Evidence for a smaller but
still substantial genetic contribution was provided by investigations on 540
Danish adoptees (Stunkard et al. 1986). In this latter study, the BMI of the
adoptees correlated strongly with that of their biologic parents but not at all
with that of their adoptive parents, an observation that suggests that in this
Danish population, early family environment had apparently little influ-
ence in determining the degree of fatness.

Overeating

Overeating is clearly a prominent contributor to obesity. Yet, obese per-
sons do not necessarily consume more calories for their weight than lean
individuals. Nutrient intake, established by dietary interview of a probabil-
ity sample of 6,219 male and nonpregnant female adults selected from
NHANES I, did not correlate with the degree of obesity (Braitman, Adlin,
and Stanton 1985). Although underreporting of food intake by the obese
could not be ruled out, the authors suggested that factors other than
overeating, such as decreased levels of physical activity. be given increased
consideration in the etiology of obesity.

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Additional factors include complex controls of feeding behaviors at the
biologic and behavioral levels. At the biologic level, feeding behavior is
regulated in part by the brain hypothalamus (Dallman and Bray 1986) and
its interactions with brain neurotransmitters, nervous impulses from the
intestinal tract or from higher brain centers, circulating nutrients absorbed
from the intestinal tract, and certain hormones. While anatomic or bio-
chemical lesions in the brain can cause obesity, more frequent and likely
causes of overweight are improper signals coming to the brain, particularly
those from the adipose tissue and the intestinal tract @tricker 1984).

Feeding behavior occurs in response to hunger and to appetite induced by
the presence of food. Satiety and the resulting cessation of eating occur in
response to certain hormones, nervous impulses, and absorbed nutrients
signaling the brain (DaIlman and Bray 1986). Whether specific foods affect
feeding and satiety and, consequently, over- or undereating is uncertain.
Laboratory animals overeat and become obese if offered highly palatable
foods, especially those high in fat and sugar and low in fiber. The same may
be true of some humans (Herman and Polivy 1984). Foods low in fat and
high in naturally occurring fiber appear to induce satiety in humans at lower
levels of caloric intake than do high-fat, low-fiber foods (Heaton et al. 1983;
Duncan, Bacon, and Weinsier 1983).

Psychologic and behavioral factors also influence eating behavior, although
their precise role has been difficult to define. Suggestions that obese
persons were more dependent on external cues than internal signals of
physiologic hunger (Schachter 1971) or were more restrained (and, there-
fore, overcompensated) in their eating behavior (Herman and Polivy 1984)
have not proved as useful in diagnosis and treatment as was once thought
(Stunkard and Messick 1985). The effects of peer pressure (Herman 1978)
are also not well established.

Altered Adipose Cell Metabolism

Obesity might result from a metabolic error in energy balance in which an
unusually high proportion of available dietary calories is directed to
adipose tissue for storage. In humans and in many animals, adipose tissue
is not as active in fat synthesis as other tissues but instead depends largely
on circulating triglycerides for its fat content. These, in turn, originate from
chylomicrons derived from absorbed dietary fat or from very low density
lipoproteins synthesized by the liver from excess nutrients not immediately
needed as fuel.

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Obesity O

Lipoprotein Lipase. The removal of circulating triglyceride and its deposi-
tion in adipose tissue depends on lipoprotein lipase, an enzyme in adipose
tissue. In studies of genetically obese strains of experimental animals, the
observed increase in fat mass at the expense of lean body mass, even with
caloric restriction, has been attributed to an excess of adipose tissue
lipoprotein lipase (Greenwood and Vasselli 1981). Too much of this enzyme
appeared to "pull" triglyceride into the adipose tissue, cause deprivation of
other tissues (such as muscle), and lead to overeating. Thus. the over-
production of adipose tissue lipoprotein lipase might account for human
obesity. Increased synthesis of lipoprotein lipase has been observed in the
adipose tissue of obese persons who are losing weight, which could explain
the rapid regain of weight lost with dieting (Schwartz and Brunzell 1981).
However, other observers have reported no increase of adipose tissue
lipoprotein lipase activity in response to caloric restriction. Instead, they
report a decline in the enzyme with reduced calories and an increase with
return to higher caloric intake (Rebuffe-Strive, Basdevant, and Guy-Grand
1983). Until these inconsistencies can be resolved, the role of lipoprotein
lipase in human obesity remains uncertain.

Hormones. In times of caloric need, as in fasting or during exercise,
lipoprotein lipase is inactivated and adipose tissue is mobilized. Many
hormones stimulate lipolysis (breakdown of lipid), but epinephrine released
from the adrenal medulla and norepinephrine released from sympathetic
nerve endings are probably the chief activators of lipolysis during exercise
and stress, respectively. A genetic component to epinephrine-stimulated
lipolysis has been identified (Despres et al. 1982), which suggests that an
inherited impairment of epinephrine response during exercise could ac-
count for the observed failure of obese individuals to lose weight with
exercise (Ribeiro et al. 1984).

Insulin is another hormone that modifies energy balance and may contrib-
ute to obesity (Dallman and Bray 1986). Hyperinsulinemia and insulin
resistance, for example, can occur in all types of obesity and may be a link
between hypertension, obesity, and glucose intolerance (Modan et al.
1985). Plasma insulin, which increases in response to feeding, promotes
uptake of circulating triglycerides by adipose tissue and inhibits fat mobi-
lization, thereby favoring storage of excess calories as fat. These reactions
are reversed during fasting, when insulin levels are low. As discussed in the
diabetes and high blood pressure chapters, weight loss often is followed by
a correction of these abnormalities; when weight is regained, the problems
return.

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Whether human obesity is caused by a primary abnormality in adipose
tissue or in the hormones that regulate its deposition is unknown at this
time. However, adipocyte precursors obtained from massively obese sub-
jects release a factor that, when added to rat adipose cells in tissue culture,
causes cells to multiply (Lau, Roncari, and Hollenberg 1987). This finding
suggests that metabolic effects may indeed play a role.

Altered Thermogenesis

Ser Points. The weight of most people remains remarkably stable over the
adult years, despite large fluctuations in dietary intake. Experiments in
animals indicate that body weight is stabilized at a specific set point that is
maintained without conscious control by variations in metabolic rate in
response to food intake (Keesey 1986). A possible mechanism for such
stability is a change in body heat production, or thermogenesis, to compen-
sate for changes in energy intake (James 1983). Although human body
weight often appears to be regulated at a set point, its controlling mecha-
nism has not yet been demonstrated.

Heat production is an accurate measure of energy expenditure or metabolic
rate. Because measurement of actual heat production is cumbersome and
expensive, metabolic rate is usually determined by indirect calorimetry,
which converts meaSurements of oxygen consumption into calories,
ideally expressed per unit of lean body mass. Lean body mass is the body
compartment containing the most metabolically active tissues and ac-
counts for most energy expenditure. Thus, accurate methods for estimating
lean body mass are essential (Horton 1983) as are those for measuring the
degree of physical activity.

Metabolic date. The measure of the energy used for running the body's
essential metabolic machinery and for maintaining body temperature is the
resting metabolic rate (RMR), obtained when the subject is resting com-
fortably several hours after the last meal or physical activity. The basal
metabolic rate (BMR) is the energy the body needs when the subject is at
complete rest, before arising in the morning and 12 hours or more.after the
last meal (Horton and Danforth 1982). The RMR is much more convenient
to obtain, and although it is slightly higher than the BMR. it provides a
reasonable estimation of the BMR. At stable body weights, BMR and RMR
are higher in obese persons than in normal-weight persons because of the
increased body size. It is uncertain. however, whether the RMR of the
obese is the same (Himms-Hagen 1984; Blaza and Garrow 1983) or lower
(Danforth 1983) than that of normal-weight persons when it is expressed in
terms of lean-body weight.

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obesity 0

Diet-Induced Thermogenesis. The energy generated metabolically when
food is digested, called diet-induced thermogenesis, rises with increased
food ingestion. Adaptive thermogenesis is the increase in RMR that occurs
with increased food intake. Together, these forms of thermogenesis ac-
count for only about 10 percent of total energy expended. Failure to
increase thermogenesis with overeating could result in obesity, but
whether obese persons have defective thermogenesis has not been estab-
lished. In the Vermont Prison Study, thin prisoners required many more
calories to increase their body fat than could be calculated from the caloric
value of the food ingested (Sims et al. 1973). These results suggest that in
normal-weight individuals, extra calories are readily metabolized to heat
when they are not needed.

In persons of normal weight, thermogenesis increases following a meal and
is proportional to meal size (Rothwell and Stock 1986). The type of carbo-
hydrate consumed may affect heat production; sucrose appears to be more
thermogenic than glucose in normal-weight-but not obese-persons
(Sharief and Macdonald 1982). Other macronutrients may also be impor-
tant. The thermogenic effect of dietary protein, carbohydrate, and fat has
been estimated to be 25, 10, and 3 percent of calories ingested, respectively
(James and Trayhum 1981). The small amount of heat lost when fat is
processed may account for the importance of dietary fat as an inducer of
obesity. Despite these findings, other investigators found a very small
increase in total heat output with overfeeding and have concluded that any
such adaptation to carbohydrate (but not fat) intake is very small (James
1983).

Effect of Weight Loss. In studies using continuous indirect calorimetry.
reduced glucose-induced thermogenesis was found after obese subjects
lost 9 to 33 kg (compared with controls), suggesting that defective ther-
mogenesis is one of the factors causing relapse of obesity after weight loss
(Schutz et al. 1984). In another study, energy expenditure was measured in
a respiration chamber before and during weight reduction in obese sub-
jects, and it declined as fat was lost; results were based on lean body mas>
(Ravussin et al. 1985). Other investigators analyzed the caloric content of
measured liquid formula diets fed to obese and lean (never obese) patient4
during long-term hospital stays of many months' duration under metabolic
ward conditions. They found that obese and lean subjects required similar
amounts of energy per square meter of surface area per day. After weight
loss and stabilization to a lower body weight, the obese subjects showed ;I
28 percent decrease in calories required to maintain body weight at the ne\\
level (Leibel and Hirsch 1984).

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13 Nutrition and Health

Other researchers, however, have identified problems with methodology or
experimental design in such studies of defective thermogenesis in the obese
(James 1983). For example, measurement of thermogenesis over periods of
time longer than a few hours is only feasible where calorimetry chambers
are available. Although people can reside in such chambers and move about
freely for days at a time, activity is far from normal. Moreover, the need to
express oxygen consumption in terms of lean body mass presupposes
accuracy of methods of measuring body composition. Changes in heat
production when dieting subjects are re-fed also complicate these studies.
Although some evidence favors the hypothesis that adaptive ther-
mogenesis occurs with weight change and is mediated by thyroid activity
and the sympathetic nervous system (Danforth 1983; Landsberg and Young
1983; Horton 1983), the effect appears to be small and the role of ther-
mogenesis in weight loss must be considered unsettled.

Lack of Exercise

Various studies have shown that physical inactivity in adult life shortens life
expectancy (Paffenbarger et al. 1986), perhaps because underactivity with-
out concomitant decrease in food intake can result in obesity. The very
large difference in caloric expenditure between the most inactive and most
active occupations, 2,300 to 4,400 kcal daily (Joint FAO/WHO Ad Hoc
Expert Committee 1973), suggests that exercise could help manage and
prevent obesity. Obesity may be a disease of inactivity, but that hypothesis
has been difficult to prove (Stern 1984). Direct methods of measurement of
daily physical activity are lacking, and current methodology for evaluating
activity at home cannot detect whether inactivity contributes to obesity
(Garrow 1978). Most studies that have compared the activity patterns of
lean and obese subjects are based on questionnaires.

Epidemiologic data from the Lipid Research Clinics Prevalence Study
show relatively low energy intakes to be coupled with increasing body
weight, particularly in women (Dennis et al. 1985). Other epidemiologic
data support this finding (Braitman, Adlin. and Stanton 1985). These and
other investigators attribute the finding to decreased activity level. In
another study, persons who participated in vigorous weekend activity were
leaner than those who did not (Morris et al. 1980). A correlation also has
been reported in young adolescents between degree of obesity and number
of hours of television watched per week (Dietz and Gortmaker 1985).

Another interesting, but as yet unvalidated, aspect of the relationship
between physical activity and body weight is involuntary movement-
spontaneous fidgeting or moving, which varies widely from individual to

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Obesity O

individual. In one study, for example, that measured energy expenditure in
unselected subjects, very large individual differences in energy-100 to 800
kcal/day-were attributed to differences in spontaneous activity (Ravussin
et al. 1986). Among infants, energy expenditure at age 3 months was more
than 20 percent lower in those who became overweight than in infants
whose weight remains normal (Roberts et al. 1988). A reduced 24-hour
energy expenditure in adults correlated strongly with subsequent weight
gain in southwestern American Indians with a high prevalence of obesity
(Ravussin et al. 1988). Much is still to be learned about the relationship
among physical movement, caloric expenditure, and body weight, but the
cumulative effects of physical activity over time could be important in
preventing or correcting obesity (Black 1983).

Prescribed Medicatiocs

Many drugs prescribed fo;-clinical conditions other than obesity may cause
weight gain. Such drugs include propranolol, clonidine, and related medi-
cations prescribed for hypertension and other cardiovascular diseases that
may change metabolic rates and decrease levels of energy expenditure.
Adrenal steroids such as prednisone, prescribed as anti-inflammatory
agents, cause hypertrophic obesity. Some people experience weight gain
with tranquilizers such as amitriptyline and diazepam, certain anti-
histamines such as cyproheptadine, and birth control pills. These and other
issues related to medications are reviewed in the chapter on drug-nutrient
interactions.

Treatment of Obesity

To lose weight. one must decrease caloric intake, increase caloric expendi-
ture. or do both. Thus. the chief approaches to weight reduction involve
behavior change related to diet and exercise, drugs to decrease hunger or
increase satiety. and surgical or mechanical intervention designed to re-
duce food intake. To date. none of these methods has proved to be entirely
effective. and none is without risk.

Weight loss reduces health risks in the obese. In theory, it should be
accomplished easily. but in practice. traditional diet therapy has not been
very successful: people who lose weight tend to gain it back (Stunkard
1986). Thus. a combination of diet and exercise seems the most sensible
approach 10 treatment (Wicker 1984). Because obesity is a condition
requiring continuous attention. any behavior changes required to maintain
weight 1~44 mu\t be lifelong.


0 Nutrition and Health

Behavior Modification

Behavior changes to induce weight loss were based initially on the theory
that faulty eating behavior caused obesity and could be corrected by a
programDf record keeping, stimulus control, and reinforcement of appro-
priate behaviors. The early programs focused on the importance of eating
behavior and introduced specified behavioral procedures to change eating
patterns. Weight losses, however, were modest, and behavior therapy is
now used as part of broader programs that include nutrition education,
exercise, and cognitive restructuring (Stunkard 1987). Such programs form
the basis of many commercial efforts that treat a substantial number of
mildly obese people in this country (Brownell 1986). Current approaches
are trying to increase the amount and duration of weight loss by combining
various behavior modification techniques with low-calorie diets (Wadden,
Stunkard, and Brownell 1983). The results have not been evaluated from a
long-term perspective.

Drugs and Surgical Methods

Thus far, no drug therapy has induced long-term weight loss. Drugs are
aimed at decreasing hunger or increasing satiety, usually by mimicking
certain neurotransmitters or hormones that play a physiologic role in
feeding behavior (Sullivan and Triscari 1985). One problem is that weight
lost with drug therapy is more often regained than with other methods,
suggesting that appetite-suppressant drugs lower the set point level at
which body weight is regulated and only secondarily suppress appetite
(Stunkard 1982). Regardless, weight loss would be expected to occur only
during the period of drug therapy, suggesting the need for chronic treat-
ment.

Surgical intervention appears appropriate only for selected persons with
massive obesity or with its severe complications who have not responded
to more conservative treatment. Jejunoileal bypass has been largely aban-
doned because of unfavorable side effects. Other procedures such as
gastric balloons and gastric surgery, which reportedly cause substantial
weight loss-although rarely to ideal weight-in morbidly obese persons
(Kral 1985), require further study before their long-term effects are known.

Dangers of Dieting

Extremely low-calorie diets, 300 or 400 kcal per day, have resulted in deaths
due, at least in part, to the effects of dietary deficiencies on the heart
muscle (Van Itallie and Abraham 1985). Short-term studies indicate that the
same problems are less likely to occur with diets higher in calories (range of

29%


Obesity O

800 kcal) and with better quality protein (Wadden, Stunkard, and Brownell
1983). Nevertheless, such higher calorie diets still require careful medical
supervision.

Another possible risk of dieting is the effect of repeated attempts on long-
term prospects for weight less. One study of rats has suggested that cyclic
weight reduction may increase the difficulty of losing weight. Obese rats
subjected to two repeated episodes of weight reduction and weight gain lost
less weight during the second cycle and regained it more easily and with a
lower food intake (Brownell et al. 1986). Whether similar effects occur in
humans is as yet uncertain.

Fad weight loss regimens of unscientific merit have been estimated to cost
consumers $5 billion annually (Herbert 1981). While such diets attract
many people's attention they may be dangerous, especially when they
provide less than the full complement of essential nutrients (Dwyer 1985).
This danger is discussed in greater detail in the chapter on dietary fads and
frauds.

Depression brought on by dieting is a serious condition affecting many
obese persons (Stunkard and Rush 1974). Preoccupation with being thin
may lead to two related and often serious eating disorders, anorexia ner-
vosa and bulimia, that occur most commonly in adolescent girls (Herzog
and Copeland 1985). Anorexia nervosa is characterized by an extreme fear
of becoming obese, with severe diet restriction and weight loss sometimes
to the point of cachexia and death. Bulimia is a syndrome of secretive binge
eating followed by self-induced vomiting or purging. These conditions are
discussed in detail in the chapter on behavior.

Implications for Public Health Policy

Dietary Guidance

General Public

Excess weight or overweight occurs when too few calories are expended
and too many consumed for individual metabolic requirements. The ex-
traordinarily high prevalence of obesity in the United States-one-fourth of
American adults are overweight and nearly one-tenth are severely over-
weight-coupled with its role as a risk factor for diabetes. hypertension,
coronary artery disease and stroke. gallbladder disease. and some types of
cancer, suggests that a reduction in the average weight of the general

299


0 Nutrition and Health

population would improve the Nation's health. Americans, in general,
would benefit from a lifestyle that includes more physical activity and a diet
containing fewer calories.

Because fat contains more than twice the caloric value per gram of either
protein or carbohydrate, the general public would benefit from reduced fat
intake. In addition, it may be difficult to meet essential vitamin and mineral
requirements on low-calorie diets. Because sugar and alcohol provide
calories from carbohydrate but no other nutrients, individuals seeking to
attain and maintain desirable body weight should use these substances
sparingly.

Evidence indicates that exercise bums calories, increases the proportion of
lean to fat body mass, and, therefore, raises the metabolic rate. Therefore,
increased levels of physical activity are important for attaining desirable
body weights among the general population.

Special Populations

Qualified health professionals should evaluate overweight persons for the
presence of chronic disease risk factors-especially elevated blood choles-
terol, blood glucose, or blood pressure. Such evaluation is important for
individuals whose excess body fat is distributed mainly on the abdomen.
This pattern is more typical for men than for women, and it increases risks
for diabetes, high blood pressure, hyperlipidemia, and heart attacks.

Health professionals should work with obese persons to restrict caloric
intake and to increase caloric expenditure. Such advice should also be
provided to overweight persons, with or without other significant risk
factors, to help reduce their risk for heart disease, stroke, some kinds of
cancers, and many other diseases and to prevent or reduce psychosocial
complications of obesity. Professional guidance is recommended because
many popular means to reduce weight may themselves pose risks to health
and because unsupervised efforts to control obesity usually fail over the
long term. Although excess body fat is difficult to lose, current research
suggests that long-term individual or group programs that facilitate behav-
ioral changes in diet and exercise are most likely to be effective. The
intensity of these programs and the precise goal for weight loss should
depend on the patient's degree and distribution of overweight, weight
history, chronic disease risk factors, health status, and personal choices,

Current evidence is insufftcient to recommend similar programs for over-
weight children. Obesity in infancy and childhood increases the risk for

300


Obesity 0

adult obesity. but most overweight children will not become obese. Be-
cause no method now exists to predict which children will develop obesity
as adults, because research has not yet identified effective methods to
prevent adult obesity, and because children require adequate energy and
nutrients to develop and grow normally, low-calorie diets should not be
generally recommended for this group. Instead, they should be reserved for
children with.elevated risk factors for chronic disease. For most overweight
children and their families, qualified health professionals should provide
counseling and assistance in developing diets that contain adequate. but
not excessive, calories and social and physical activities in which the child
enjoys participating.

Nutrition Programs and Services

Food Labels

Evidence related to the role ofdiet in obesity indicates that calorie informa-
tion should be provided on most food product labels.

Food Services

Evidence related to the role of diet in obesity suggests that service pro-
grams should include a variety of foods low in calories in their menus.

Food Products

Evidence related to the role of diet in obesity suggests that the food
industry should continue to develop food products low in calories and with
adequate nutrient content.

Special Populations

Overweight patients should be provided with counseling and assistance in
the development of diets low in calories and high in essential nutrients, as
well as lifestyle modifications that include high levels of physical activity to
achieve appropriate weight goals.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
nutrition and exercise in obesity and weight management should include
investigations into:

o Determination of ideal or desirable body weights for individuals or for
the population of various ages.

301


0 Nutrition and Health

o Determination of the health risks associated with various degrees of
overweight in children and adults.
o Identification of an effective means to measure total body fat and its
regional distribution in individuals and in the population.
o Identification of the types of obesity most associated with increased
chronic disease risk.

o The contribution of genetic and metabolic factors to obesity, including
the molecular and genetic basis of energy metabolism and the nature of
genetic aberrations in human obesity.
o The effects of diet, exercise, and weight loss on metabolism and
thermogenesis.

o The effects of physical activity on maintenance of desirable body
weight.

o The identification of dietary, behavioral, environmental, or genetic
factors that predict development of obesity or the ability to lose weight
successfully.

o Identification of the dietary, behavioral, environmental, social, or
genetic factors that increase the risk of overweight in high-risk popula-
tion groups.

o The health consequences of repeated cycles of weight gain and loss.
o The most effective individual, group, and community intervention
strategies for weight management.
0 The most effective intervention strategies for use with high-risk
groups.

o The most effective means by which to educate individuals and the
public about the factors predisposing to weight gain and loss.
o The most effective ways in which to promote increased physical activi-
ty in the population.
0 The long-term effectiveness of existing weight control programs.

302


_ Obesity 0

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Stunkard, A.J.; Foch,T.T.; andHrubec, Z. 1986. A twin study ofhumanobesity. Journalofthe
American Medical Association 25651-54.

Stunkard, A.J.; Sorensen, T.I.A.; Hanis, C.; Teasdale, T.W.; Chakraborty, R.; Schull, W.J.;
and Schulsinger, E 1986. An adoption study of human obesity. New England Journal of
Medicine 314: 193-98.

Sullivan, A.C., and Triscari, 1. 1985. Pharmacologic approaches to the regulation of metabo-
lism and obesity. In Recent advances in obesity research IV, ed. J. Hirsch and T.B. Van Itallie,
pp. M-207. London: Libbey.

Trowell, H. 1975. Obesity in the Western world. Plant Foods for Man 1:157-68.

U.S. Department of Health, Education, and Welfare. 1964. Cycle I of the health examination
survey: sample and response, United States, l%O-1%2. Vital andHealth Statisrics, series 1 I,
no. 1. DHEW publication no. (PHS) 1000.

-. 1973. Plan and operation of the health and nutrition examination survey, United
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no. (HSM) 73-1310.

Van ItaUie, T.B. 1985. Health implications of overweight and obesity in the United States.
Annals of Internal Medicine 103983-88.

Van Itallie, T.B.. and Abraham, S. 1985. Some hamrdsofobesity and its treatment. InRecent
advances in obesity research IV, ed. J. Hirsch and T.B. Van Itallie, pp. I-19. London: Libbey.

Wadden, T.A.; Stunkard, A.J.; and Brownell, K.D. 1983. Very low calorie diets: their efficacy,
safety, and future. Annals of Internal Medicine 99:675-N.

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Chapter 7

Skeletal Diseases

For the women of this city do not possess sut!IIcient devotion to look after
everything as the purely Greek women do. If nobody looks after the movements
of the infants the limbs of the majority become distorted, as the whole body
  rests on the legs . . . [when] the bones have not yet become strong.
         Childrearing advice to the women of
            Rome, Soranus of Ephesus
         in second century A.D. (Ternkin 1956)

Introduction

Histori~l Pempecth

Major skeletal diseases influenced by nutrition include rickets, osteo-
malacia, and osteoporosis. Among all the nutritionally related skeletal
diseases, rickets, the "softening'* of bones in children, is probably the most
well known. Rickets and its adult form, osteomalacia, traditionally viewed
as urban diseases, have been largely eradicated in the industrialized world
by milk fortification, enrichment of infant foods with vitamin D, the use of
vitamin D supplements by children, and improved environmental condi-
tions that promote adequate exposure to sunlight. Rickets is still prevalent
in the developing world and is occasionally found elsewhere, especially
where rapid urbanization has created conditions similar to the Industrial
Revolution when social conditions and air pollution prevented adequate
exposure to sunlight.

Hippocrates was the fast to describe rickets. In the frfh century B.C., he
observed children whose ". . . legs and arms attain full size, but the body
will not grow correspondingly at the spine." Not until 1645 was the first
formal description of the condition published; the classic study De
Rachitide by Glisson, who traced its origin to the Greek word rachitis, or
spinal disease, followed soon after (Guggenheim 1981).

The incidence of rickets increased with the Industrial Revolution. Rickets
became known as the "English Disease," although it was prevalent
throughout Northern Europe, where overcrowding and substandard living

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conditions had become the norm. The disease was astonishingly wide-
spread. For example, in 1907, half of the children between ages 6 months
and 3 years admitted to Paris hospitals were reported to suffer from rickets,
and in 1921, perhaps three of every four infants in New York City were
affected.

Understanding developed slowly about the relationship between vitamin D
deficiency and rickets. Cod liver oil was prescribed as treatment as early as
1807, but it was only in the late 1800's that rachitic lion and bear cubs at the
London Zoo were cured when fed bone meal, milk, and cod liver oil
(Todhunter 1973). The preventive powers of sunlight were observed in
1890.

It was not until this century that researchers untangled the complex inter-
actions among vitamin D, sunlight, social conditions, and the disease. The
isolation of vitamin D from fats and oils and the understanding of its
activation in skin by ultraviolet radiation finally provided the keys to
rational public health prevention of rickets and osteomalacia.

Today, osteoporosis-loss of bone mass-has become the most important
bone disease in Western countries. The studies of early skeletons by
Trotter and international comparisons by Nordin established that bone loss
in aging persons occurs in every population. Such studies, coupled with
population-based evidence suggesting a dietary contribution, stimulated
current work on the role of diet in the prevention of age-related bone
disease (Nordin 1984).

Significance for Public Health

Osteoporosis

The major skeletal disease in which nutrition may play a role is os-
teoporosis, characterized by a decrease in the amount of bone often so
severe that it leads to fractures after even minimal trauma. Osteoporosis
may be classified into primary and secondary forms. Primary osteoporosis,
specifically involutional osteoporosis, may occur in two types: Type I
(postmenopausal) osteoporosis (accelerated decrease in bone mass that
occurs when estrogen levels decline after menopause), and Type II (age-
related) osteoporosis, the inevitable loss of bone mass with age that occurs
in both men and women (Riggs and Melton 1986). Secondary osteoporosis
may develop at any age as a consequence of endocrinologic and gastroin-
testinal conditions or metabolic disorders, as well as prolonged bedrest and
states of weightlessness, that result in bone demineralization.

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Osteoporosis afflicts 15 to 20 million Americans, causing each year an
estimated 1.3 million fractures of the vertebrae, hips, forearms, and other
bones in those 45 years of age and older (Consensus Development Panel
1984). The risk of hip fractures is about twice as great in women as in men.
Because women live longer than men, the absolute incidence is even
higher. One-third of women 65 years and older have vertebral fractures,
the most common break caused by osteoporosis. By age 90, one-third of
women and one-sixth of men will have suffered hip fractures, leading to
death in 12 to 20 percent of these cases and to long-term nursing home care
for many of those who survive (Riggs and Melton 1986). Millions of other
older Americans find their mobility restricted and the quality of their lives
diminished by the consequences of osteoporosis. The total direct and
indirect costs of osteoporosis to the U.S. economy were estimated to be
between $7 and 10 billion in 1986 (Peck, Riggs, and Bell 1987).

Without effective measures to prevent the development of this disease, the
costs of osteoporosis to the United States will increase because of the rapid
increase in the number of older Americans. Prevention of osteoporosis is
especially important, not only because of the costs of the disease, but also
because treatment of osteoporosis, once fractures have occurred, is rela-
tively ineffective and the functional limitations and deformities that devel-
op are often irreversible. Precisely why certain individuals develop os-
teoporosis and others do not is incompletely understood. Aging itself, the
loss of sex hormones at menopause, and genetics all play a role. To date,
estrogen-replacement therapy is the best documented method of prevent-
ing osteoporosis in postmenopausal women. Although this treatment has
been associated with increased risk of developing endometrial and other
cancers, this association may not be significant especially at lower doses of
estrogen (Ettinger, Genant, and Cam 1987). Table 7-1 lists factors that
increase or decrease the risk for developing osteoporosis. Although much
is yet to be learned about how diet can affect the development of this
disease, suliicient scientific evidence now exists to make nutrition a focus
of programs to prevent or to treat osteoporosis.

Rickets and Ostaomalacia

Two other important diet-related bone diseases are rickets, which affects
growing children, and osteomalacia, which affects adults. Both are charac-
terized by an inadequate mineralization of bone. In osteoporosis, both the
mineral and protein components of bone are lost; the remaining bone is
thinner but normal in composition. In rickets and osteomalacia, the protein
matrix is poorly mineralized, so the bone that remains is rubbery or soft.

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0 Nutrition and Health

      Table 7-1
Scientific Valiii of Risk Factors

WeIl Established        Moderate Evidence
Obesity ( - )         Alcohol ( + )
Black ethuicity ( - )     Cigarette smoking (+)
Age (+I          Heavy exercise ( - )
Premenopausal       Low dietary
oophorectomy ( + )      calcium ( + )
Consumption of
corticosteroids (+ )
Estrogen use (- )
Extreme immobility ( + )
(+) = increased risk; (-) = decreased risk.

Inconclusive or
Inadequate Evidence
Moderate physical
activity
Asian ethnicity
parity
Diabetes
Thiazide diuretic use
Progestin use
Drinking water fluoride
Caffeine use

Source: Peck, WA; Riggs, 6.L; Sell, N.H.; Wallace, R.B.; Johnston, C.C., Jr.; Gordon,
    S.L; and Shulman, L.E. 1988. Research directions in osteoporosis. American
   &wne/ of Medicine S&275-82. Copyright 1988, American Joumal of Medicine,
    reprinted with permission.

Although clinical cases of rickets and osteomalacia are relatively uncom-
mon in the United States today, they are important for public health
consideration because they can be prevented or treated.

Scientific Background-Bone Physiology

Bone is a spongy protein matrix in which crystals of calcium and phos-
phorus salts are embedded. From birth until death, bone tissue is con-
tinually being formed, broken down, and reformed in a process called
remodeling. The cells that break down bone are called osteoclasts, and
those that build bone are called osteoblasts.

From infancy through young adulthood, the activity of the osteoblasts
normally predominates over that of the osteoclasts, resulting in the steady
accumulation of bone mass. By the fourth decade, this process levels off
and the amount of bone mass achieved at this time is called peak bone
mass. Men develop a peak bone mass 30 percent more dense than that of
women, and blacks about 10 percent more dense than that of whites
(Consensus Development Panel 1984). Hence, although all individuals lose
bone as they get older, women are more susceptible to osteoporosis than
men, and whites more than blacks. Men in general and blacks as a group
can sustain a greater loss of bone before the onset of fracture because they
have a greater bone mass at skeletal maturity. However, differences in

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bone mass do not fully explain the differences in osteoporosis rates be-
tween the sexes and races. Differences in bone architecture and structure
must also be important.

Usually between the ages of 30 and 40, the balance of bone remodeling
activity then swings over to the osteoclasts and adults begin to slowly lose
bone mass. Mineral is lost more readily from trabecular bones, found in the
vertebrae and pelvis, than from the cortical bones that form the limbs. The
decline in estrogen production after menopause is associated with the
period of most rapid bone loss in women.

The nutritional controls of bone mineralization have yet to be identified
fully. At present, the only established nutritional determinants of miner-
alization are calcium, phosphate, and vitamin D.

Several recent reviews summarize present knowledge of nutrition and bone
metabolism (Aloia et al. 1985; Chan and Alon 1985; Chart, Alon, and
Hirschman 1985; Favus 1985; Heaney 1986; Heaney et al. 1982; LSRO
1981; Marcus 1982; Parfitt et al. 1982; Peck, Riggs, and Bell 1987; Raisz
1982,1988; Raisz and Kream 1983; Riggs and Melton 1986; Riggs, Seeman,
et al. 1982; Riggs, Wahner, et al. 1982). The following sections cite only a
few key articles and recent studies that are not included in these reviews.

Key Scientific Issues

a Role of Calcium in Skeletal Disease
o Role of Vitamin D in Skeletal Disease
o Role of Phosphate in Skeletal Disease
o Role of Calories and Protein in Skeletal Disease
o Role of Alcohol in Skeletal Disease
o Role of Other Minerals in Skeletal Disease
o Role of Other Vitamins in Skeletal Disease
o Role of Exercise in Skeletal Disease

Role of Calcium in Skeletal Disease

Ninety-nine percent of the body's calcium is found in the bones and teeth,
where it is essential for their formation and maintenance; the remaining 1
percent in fluids and soft tissue is critical for proper functioning of every

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nerve and muscle cell. Because of calcium's importance throughout the
body, constant skeletal remodeling most likely evolved to provide a contin-
uous supply of calcium.

Despite the evident physiologic importance of calcium, remarkatly few
studies have documented the effects of dietary calcium on peak bone mass
reached by different populations, and none explains how different levels of
dietary calcium affect age-related bone loss.

Such studies are complicated by the difficulties of studying large groups of
people over long periods of time. In the United States, variations by age,
sex, and season in calcium intake are thought to reflect the consumption of
dairy products, which are also major sources of protein and phosphate,
nutrients that may affect calcium metabolism. Moreover, the availability of
calcium for building and maintaining the skeleton is determined not only by
the amount of calcium in the diet but also by how much of that calcium is
absorbed and how much is retained by the body.

Calcium Absorption

Calcium absorption is determined by (1) the amount of dietary calcium that
goes into solution, (2) the interaction of calcium with other dietary sub-
stances within the small intestine, and (3) the level of activity of active and
passive transport systems that move calcium across the intestinal wall and
into the body. The amount of calcium in solution in the intestinal tract is
influenced by the physical and chemical form of calcium consumed (Reck-
er 1985; Reeker and Heaney 1985). Calcium salts in food or supplements are
usually soluble in the stomach's acidic environment. Persons who cannot
produce gastric acid may absorb calcium poorly (Reeker 1985) and may
require calcium supplements (e.g., calcium carbonate, calcium gluconate,
calcium citrate), which should be ingested with meals.

Calcium is a cation, a positively charged molecule, that can react with
negatively charged molecules, called anions, to form complexes. Some of
these calcium complexes are insoluble and cannot be absorbed. For exam-
ple, the anion oxalate, which is found in spinach, rhubarb, and other plant
foods, reacts with calcium to form calcium oxalate, which is quite insolu-
ble. Other food anions, particularly polyphosphates, can also impair ab-
sorption.

Calcium is transported across the intestine principally by calcium-binding
proteins, whose concentration is regulated by the active hormonal form of
vitamin D. Factors that diminish the availability and metabolism of vitamin

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Skeletal Diseases cl

D also diminish the absorption of calcium from the small intestine. Many
drugs- can interfere with calcium absorption. Examples incmde tetracy-
clines, which bind with calcium to form insoluble complexes, and anti-
epileptic drugs that impair intestinal transport of calcium and inhibit activa-
tion of vitamin D.

Calcium Retention

Calcium is lost from the body primarily in the urine and in the feces. Renal
excretion, an important determinant of calcium balance, is regulated by
hormones and is influenced by dietary protein intake. Increasing the level
of protein in the diet seems to increase the amount of calcium lost in the
urine (Margen et al. 1974; Allen, Oddoye, and Margen 1979), and epi-
demiologic data shoti .that hip fractures and protein intake are positively
correlated (Hegsted 1986). Secretion of calcium into the intestine, on the
other hand, is probably not regulated by hormones but reflects the rate of
production of intestinal juice in the digestive process, all of which can be
infhrenced by diet.

Calcium and Peak Bone Mass

Peak bone mass is determined by several factors. Calcium deficiency does
not ordinarily cause selective impairment of mineralization. Instead, there
is increased bone resorption or breakdown due to excessive parathyroid
hormone (PTH) secretion (secondary hyperparathyroidism) and decreased
bone formation. A rickets-like syndrome has been reported in infants on
extremely low calcium intakes (Kooh et al. 1977), but it differs somewhat
from the rickets produced by vitamin D and phosphate deficiency.

Genetic determinants of peak-bone mass are important (Farmer et al. 1984).
For example, the larger bone mass in blacks than in whites in the United
States can be detected in the fetus and may be due to differences in the
vitamin D endocrine system (Bell, Greene, et al. 1985). On the other hand,
lactase deficiency, which is more common in blacks, has been associated
with a decreased calcium intake and an increased likelihood of developing
osteoporosis in whites (Newcomer et al. 1978). This inconsistency suggests
a strong role for genetic factors in the incidence of osteoporosis, although
current observations need to be evaluated with a closer assessment of the
magnitude of individual variations within a given group.

The role of dietary calcium in determining peak bone mass is uncertain.
Populations of similar ethnic backgrounds have been observed in which
there are differences in calcium intake but no difference in bone mass. For

317


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example, one study reported that Guatemalans and Panamanians have
similar peak cortical bone mass, although calcium intake is thought to be
considerably higher in Guatemalans (Gam et al. 1969).

Other population studies, however, suggest that calcium intake does affect
peak bone mass. In two regions of Yugoslavia, where dairy product intakes
differ, average bone mass was higher in the area with the higher calcium
intake. Because dairy products also contain substantial amounts of phos-
phate and protein, calcium may not have been the only determinant of this
difference. Nevertheless, the difference in peak bone mass seems to affect
skeletal disease; the incidence of hip fractures was substantially lower in
the group consuming more dairy products (Matkovic et al. 1979). One
investigator in the United States has reported that women with a greater
calcium intake because of a high calcium concentration in the water supply
also had a greater bone mass, but only if they also had an adequate intake of
vitamin D (Sowers, Wallace, and Lemke 1985).

These data are not entirely consistent, but they suggest the importance of
peak bone mass in skeletal health and the need for further research on the
nutritional determinants that affect the skeleton up to age 35. Presumably,
persons with greater bone mass in early adulthood are able to resist the
effects of age-related bone loss.

One reason for uncertainty about the influence of dietary calcium intake on
bone mass is that young individuals can adjust to a decreasing calcium
intake by an increased efficiency of calcium absorption. This compensa-
tion is mediated by calcitriol (1,25dihydroxyvitamin D), the active hor-
monal form of vitamin D. However, this compensatory response is blunted
with age.

Nevertheless, a low calcium intake could interfere with the adolescent
growth spurt and could compromise the subsequent consolidation of skel-
etal mass that occurs up to the age of 35. From 1976 to 1980, the median
calcium intake for boys ages 12 to 14 was 1,024 mg, which is close to the
Recommended Dietary Allowance (RDA) of 1,200 mg for that age group. In
contrast, median calcium intake of 793 mg for girls in that age group was
below the RDA (Carroll, Abraham, and Dresser 1983). More recent data on
the calcium intakes of men and women 19 to 50 years of age indicate that
while calcium intakes have increased slightly from 1977 to 1985 and are
above the RDA of 800 mg for men, they fall below the RDA of 800 mg for
women (Marston and Raper 1987). Thus, the influence of this level of intake
on peak bone mass in women is of great interest.

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Skeletal Diseases O

Calcium and Age-Related Bone Loss

At present, studies of the effect of calcium supplementation on age-related
bone loss are inconclusive. Some reports indicate that a sufficiently high
calcium intake can reverse a negative calcium balance and thereby sup-
press bone loss (Horsman et al. 1977; Reeker, Saville, and Heaney 1977).
Other studies have found that daily calcium supplementation as high as
2,000 mg/day is of little or no help in preventing bone loss in
postmenopausal women (NW et al. 1985; Riis, Thomsen, and Chris-
tiansen 1987). However, it should be noted that the Danish women in this
study were consuming an average of 950 mg/day before entry into the study
(Riis, Thomsen, and Christiansen 1987). This intake is well above the RDA
for calcium of 800 mg/day, making it difficult to extrapolate these results to
American women, many of whom consume less than 500 mg/day in their
diet.

Understanding the influence of calcium intake on age-related bone loss is
complicated in that age itself may influence both the intestinal absorption of
calcium and the skeleton's subsequent utilization of calcium. It is not clear
when age-related decreases in calcium absorption first begin. Decreases in
absorptive ability may begin as early as age 30 or as late as age 60 (Heaney
et al. 1982). Decreased absorption may result from the kidney's decreased
ability to synthesize calcitriol (the active form of vitamin D) and decreased
intrinsic absorptive capacity. Treatment of older individuals with calcitriol
regularly increases calcium absorption (Gallagher et al. 1982), but whether
this means that osteoporosis could be caused by an inadequate supply of
vitamin D is debatable. Osteoporotic persons have somewhat lower cal-
citriol levels in their blood. Although older people may have a reduced
ability to synthesize calcitriol in response to PTH, one study has found no
difference between postmenopausal women with osteoporosis and age-
matched healthy postmenopausal women in response to PTH (Riggs,
Ham&a, and DeLuca 1981). Differences in calcitriol synthetic ability in
response to PTH stimulation may explain differences in the underlying
pathologies of 5pe I and 5pe II osteoporosis. A recent study reported
impaired calcitriol synthesis in aging women with age-related osteoporosis
(Tsai et al. 1984), while others (Riggs, Hamstra, and DeLuca 1981) reported
no differences in postmenopausal osteoporotics relative to their age-
matched controls. Trials with calcitriol have failed to demonstrate its safety
and efficacy for treatment of osteoporosis (Ott and Chesnut 1987; Falch et
al. 1987; Aloia et al. 1988).

At least two possible mechanisms might explain why calcitriol synthesis
and intestinal absorption both decrease with age. One mechanism may be

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O Nutritidn and Health

important to the pathogenesis of `Qpe I (postmenopausal) osteoporosis,
while the other may be more important in the pathogenesis of `Qpe II (age-
related) osteoporosis (Riggs and Melton 1986). In the first, the reduced
inhibition of estrogen on bone resorption at menopause increases the
supply of calcium released from bone into the blood and reduces FTH
secretion, which in turn reduces calcitriol synthesis in the kidney, and, as a
result, decreases calcium absorption in the intestine. The failure to respond
to decreased calcium intake could then be attributed to an unregulated
increase in bone resorption and loss.

This sequence does not explain the age-related bone loss associated with an
increasing FTH level that occurs in both men and women. Although the
increasing level of immunoreactive PTH might be due to impaired renal
excretion of inactive metabolites of this hormone, measures of PTH biolog-
ic activity also show an age-related increase. These findings were con-
firmed in several recent studies that reported an increase in the biologically
active form of the hormone with age (Forero et al. 1987; Young et al. 1987).
Hence, a second hypothesis explains age-related bone loss in both sexes in
terms of the kidney's decreased ability to synthesize calcitriol (Tsai et al.
1984) and (probably) the intestine's decreased intrinsic ability to transport
calcium (Francis et al. 1984). These two conditions would result in second-
ary hyperparathyroidism, but because of the renal abnormality, there
would be blunted or minimal increase in calcitriol synthesis, persistent
impairment of calcium absorption, and negative calcium balance.

Both hypotheses may be true in different individuals or in the same individ-
ual under different circumstances, but whichever mechanism holds, cal-
cium supplementation could theoretically decrease bone loss. If bone
resorption increases because of decreased estrogen, the effect of increased
calcium should be inhibition of bone resorption, but only to the extent that
calcium supplementation either decreases PTH secretion or increases
calcitonin secretion. If the primary event is decreased calcitriol synthesis,
then calcium loading should be effective only to the extent that it increases
passive absorption.

Whatever the role of calcium in achieving and maintaining skeletal mass,
calcium intake is superimposed on genetic and age-related changes in bone
cell function. Calcium may also affect bone formation directly by increas-
ing either the replication or differentiation of bone cells. Even when caI-
cium supplies are adequate, an age-related decrease in osteoblastic bone
formation may occur. This change is demonstrated by the fact that the
packets of new bone formed on remodeling surfaces are thinner or smaller
in older individuals (Courpron 1981).

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Calcium Toxicity

Excessive calcium intake can cause inappropriate mineralization, particu-
larly in the soft tissues. Many years ago, large amounts of calcium carbon-
ate were regularly prescribed for patients with peptic ulcer. A small propor-
tion of them developed milk-alkali syndrome, characterized by hyper-
calcemia, deposits of calcium in the kidneys, and progressive impairment
of renal function. This disorder is now rare (Carroll and Clark 1983).
Moreover, the prescribed doses were much larger than the 1 to 2 g of
calcium per day that have been suggested for women in the general popula-
tion.

Nevertheless, some people who have a defective intestinal barrier to
calcium absorption may absorb too much calcium and develop soft tissue
calcifications or renal stones (see chapter on kidney diseases). Therefore,
when calcium supplements are recommended to pre-or postmenopausal
women who are at high risk for development of renal stones, they should be
screened for excessive urinary concentrations of calcium to determine the
appropriate dose. A high fluid intake (i.e., at least 2 liters of water per day)
should be encouraged when calcium supplements are used. High calcium
intakes may also cause constipation in some individuals.

Role of mmin D in Skeletal Disease

The role of vitamin D in preventing rickets and osteom.alacia is well
established (Jacobs 1979). Subtle abnormalities in vitamin D metabolism
can affect the development and maintenance of bone mass in the absence of
these two diseases.

Vitamin D is synthesized in the skin in response to sunlight. In the body, the
vitamin is transformed first by the liver to 25-hydroxyvitamin D and then
by the kidneys into its active hormonal form, called 1,25-dibydroxyvitamin
D or calcitriol. This active form helps to increase the absorption of calcium
by stimulating intestinal formation of the calcium-binding proteins that
transport calcium across the intestinal wall into the body. Vitamin D also
acts directly on bone: in low doses it stimulates deposition of new bone, but
at high doses it stimulates resorption of bone.

The supply of vitamin D can easily be limited or its activation to calcitriol
impaired. Although only a few minutes of exposure to sunlight produces
the daily requirement of vitamin D in the skin, many people do not receive
this exposure, particularly in the winter. This deficiency can be overcome
by consuming foods fortified with vitamin D; however, some individuals

321


O Nutrition and Health

who are on vegetarian diets that limit dairy products and who have limited
intake of these foods may not obtain enough vitamin D from their diets
(Hellebostad, Markestad, and Halvorsen 1985).

Various diseases may impair the conversion of vitamin D to calcitriol.
Hepatic disease, for example, may lead to decreased synthesis of the
intermediate 25-hydroxyvitamin D. Impairment of intestinal mucosal func-
tion decreases absorption of vitamin D and calcium. Too rapid intestinal
transit and impaired fat absorption also decrease calcium and vitamin D
absorption. Loss of vitamin D metabolites through enterohepatic circula-
tion may be less important because there is no clear evidence that conju-
gated vitamin D metabolites excreted in the bile are conserved by reabsorp-
tion (Amaud 1982). Although gastrointestinal disorders might be expected
to lead to impaired bone mineralization, most persons with gastrointestinal
disease and decreased bone mass have osteoporosis rather than osteo-
malacia. Moreover, diminished bone mass in persons with gastrointestinal
disease often fails to respond to treatment with vitamin D in any form
(Amaud 1982). Other nutritional elements such as protein, and other fac-
tors from the liver and intestine such as somatomedin or insulin-like growth
factors and enteroglucagon, may be as important as, or more important
than, vitamin D in the bone loss that accompanies gastrointestinal disease.

Osteoporosis

Perhaps the most important question concerning vitamin D supplementa-
tion is its use in the prevention and treatment of postmenopausal and age-
related osteoporosis. Ten to fifteen years ago, patients with osteoporosis
were given vitamin D supplements in doses of 50,000 to 150,000 IU a week
in addition to other forms of therapy such as calcium, estrogen, and
fluoride supplements. Retrospective analysis of these studies indicates that
large doses of vitamin D have no significant effect on the incidence of
vertebral compression fractures (Riggs, Seeman, et al. 1982). Thus, current
recommendations are that vitamin D intake be adequate400 to 1,000 IU/
day-but not increased.

The possibility that impaired activation of vitamin D into 1,25-dihydroxy-
vitamin D or calcitriol, rather than vitamin D supply, is the limiting factor in
older persons and in people with osteoporosis has inspired several experi-
ments with calcitriol supplementation. Calcitriol supplements can increase
calcium absorption and may increase the body's stores of calcium, but
effects on bone mass and the incidence of bone fractures are as yet
unknown. Some studies argue that calcitriol supplementation actually
decreases bone mass (Jensen et al. 1985), a finding that is consistent with

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Skeletal Diseases O

previous observations that excessive I ,25-dihydroxyvitamin D has a direct
catabolic effect on bone. On the other hand, those studies were done in
embryonic bone cultures and may have limited in viva application. Because
most of these studies do not show an increase in bone mass, yet some
suggest that the incidence of fractures decreases (Gallagher et al. 1982),
calcitriol supplementation may improve the quality rather than the quantity
of bone.

Some data suggest that a decreased availability of 25-hydroxyvitamin D
also could be important in osteoporosis, particularly in the older popula-
tion. Before vitamin D is converted to calcitriol in the kidneys, it is
transformed to 25-hydroxyvitamin D in the liver. An inadequate amount of
the liver precursor could lead to an insufficient amount of calcitriol formed
in the kidneys. Blood levels of 25-hydroxyvitamin D are reduced in older
subjects, particularly in those who have limited exposure to the sun (Lam-
berg-Allardt 1984). These individuals are at especially high risk for develop-
ing hip fractures. Many patients with hip fractures also have low levels of
25-hydroxyvitamin D.

Maintaining an adequate supply of vitamin D, either through exposure to
sunlight or from dietary sources, may help to reduce the incidence of hip
fractures in older persons, but it is difficult to judge how great that effect
might be.

Rickets and Osteomalacia

Vitamin D deficiency rarely causes rickets and osteomalacia in the United
States because most Americans get enough sunlight and ingest sufftcient
amounts of vitamin D available in fortified foods and dietary supplements.
Nevertheless, rickets and osteomalacia due to vitamin D deficiency do
occur and need to be prevented.

Rickets occurs most often in children who stay indoors and who are
breastfed and not given vitamin D supplements (Edidin et al. 1980). The
incidence may be somewhat higher in black children, who make less
vitamin D for a given amount of sun exposure than do white children.
Socioeconomic factors may also be important. Children with vitamin D-
deficiency rickets often do not have adequate health care, or they are
affected by unusual practices that limit sun exposure or vitamin D intake.

The most common cause of osteomalacia in the United States is an inher-
ited or acquired defect in the metabolism of vitamin D (Jacobs 1979).
Formation of 25-hydroxyvitamin D in the liver is usually not the problem,

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because only a relatively small amount of hepatic tissue is required to
supply adequate amounts. A failure to form 1,25dihydroxyvitamin D in
the kidney is a much more serious problem. As indicated above, ihis
problem may occur in a subtle form with aging.

Deficient absorption of vitamin D also causes rickets and osteomalacia in
the United States. Gastrointestinal disease impairs absorption, but it is
more likely to cause osteoporosis than osteomalacia, probably because
general nutritional deficits decrease bone formation, increase bone resorp-
tion, and deplete the protein matrix. Causes of deficient absorption include
pancreatic insufficiency, nontropical sprue, or intestinal bypass surgery
(Passmore and Eastwood 1986). In patients with these conditions, vitamin
D as well as calcium and other nutrients may be poorly absorbed. Vitamin
D metabolism may also be abnormal after gastrectomy (Nilas, Chris-
tiansen, and Christiansen 1985). Clear-cut osteomalacia due to vitamin D
deficiency is also rare, but it occurs occasionally in older individuals who
remain indoors and eat inadequate diets.

In renal failure, impaired vitamin D hydroxylation to the biologically active
form may lead to marked impairment of mineralization (see chapter on
kidney diseases). Most patients in the United States with renal failure do
not develop typical osteomalacia, but instead develop osteitis fibrosis
cystica, a condition characterized by resorption of bone due to marked
secondary hyperparathyroidism (Dunstan et al. 1985), failure to form 1,25-
dihydroxyvitamin D, and impaired intestinal absorption of calcium. In
chronic renal failure, however, sufficient calcium may be obtained through
dialysis or from increased resorption of bone to maintain mineralization _
even though dietary sources are reduced.       

In renal osteodystrophy, some observations suggest that 1,25-dihydroxyvi-
tamin D is not always sufficient to produce mineralization in patients with
osteomalacia. Although it has been suggested that the lack of 24,25-di-
hydroxyvitamin D, another renal metabolite, causes this condition, admin-
istration of this metabolite does not consistently cure osteomalacia. The
role of other substances s.uch as aluminum and magnesium is also uncer-
tain.

Osteomalacia can also result from prolonged ingestion of anticonvulsant
medication, particularly phenytoin, perhaps due to impaired formation of
25-hydroxyvitamin D in the liver or to a direct effect on intestinal calcium
transport. This problem is usually associated with marginal intakes of
vitamin D or limited sun exposure and can be overcome by moderate
vitamin supplementation (Mosekilde et al. 1977).

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Skeletal Diseases O

Finally, osteomalacia can occur in renal tubular acidosis associated with
such disorders as the Fanconi syndrome (Chan and Alon 1985). Other
defects, including impaired vitamin D hydroxylation to the biologically
active form and low tubular reabsorption of phosphate, may be present as
well. It is not clear that acidosis by itself impairs mineralization, although it
certainly decreases skeletal mass and impairs bone growth.

Inherited or acquired defects in vitamin D metabolism produce some forms
of rickets. In vitamin D-dependent rickets, for example, 1,25-dihydroxyvi-
tamin D does not form in the kidney. This defect can be treated effectively
by replacement doses of calcitriol. Other kinds of rickets resist treatment
with large doses of vitamin D because of defects in the function of cellular
receptors for 1,25-dihydroxyvitamin D.

Other vitamin D metabolites may play a role in mineralization. In several
experiments, 25-hydroxyvitamin D or 24,25dihydroxyvitamin D has been
used successfully to treat certain patients who failed to respond to cal-
citriol. These compounds are bound more tightly to vitamin D-binding
protein than is calcitriol and retain activity for longer time periods. In
animal studies and in vitro, some evidence indicates that 24,25-dihydrox-
yvitamin D can stimulate cartilage growth. On the other hand, none of the
vitamin D metabolites is essential to rats for normal growth and mineraliza-
tion of the skeleton when adequate calcium and phosphate are supplied by
dietary manipulations or by continuous subcutaneous infusion (Under-
wood and DeLuca 1984). At present, it is uncertain whether 25-hydrox-
yvitamin D or 24,25dihydroxyvitamin D has a specific role in maintaining
skeletal mineralization (Brommage and DeLuca 1985). Thus, the major role
of vitamin D in mineralization appears to be its effect on the intestine and,
perhaps, on renal tubular reabsorption of phosphate in the kidney.

Vitamin D Toxicity

Excessive amounts of vitamin D are potentially toxic and can cause bone
loss by increasing resorption or breakdown and by impairing bone growth
and mineralization (Cobum and Brautbar 1980; Holmes and Kummerow
1983), although the moderate increases in intake that occur through dietary
supplementation seem unlikely to have such adverse effects.

Role of Phosphorus in Skeletal Disease

Phosphorus is the second most abundant mineral in the body, exceeded
only by calcium. About 85 percent of the body's phosphorus is in bone as
bone mineral, principally hydroxyapatite crystals containing about two

325


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atoms of phosphorus for every three atoms of calcium. All plant and animal
foods are rich in phosphorus, and except for the prematurely born infant
who is fed human milk, nutritional deficiencies of phosphorus are rare.
Human breast milk contains enough phosphorus to nourish a full-term
infant but not, apparently, to support the growth requirements of preterm
infants.

Phosphate is important in mineralization both in animal models and in
clinical disease. In rats, rickets occurs only with a combined deficiency of
vitamin D and phosphate relative to calcium, but in people, rickets can be
produced by phosphate deficiency even in the presence of a high con-
centration of 1,25dihydroxyvitamin D (Rowe et al. 1979). Phosphate's role
in mineralization is obvious in persons with phosphaturic osteomalacia or
vitamin D-resistant rickets. In these persons, a combination of frequent
administration of phosphate plus large doses of vitamin D restores bone
growth and mineralization to an extent that cannot be achieved by either
agent alone. Even with the use of calcitriol, phosphate supplementation is
needed to mineralize bone in this condition (Chan, Alon, and Hirschman
1985).

Some forms of phosphate, such as plant phytates, are poorly absorbed and
can also bind calcium, increasing calcium excretion in the feces. Increased
phytate in the diet may contribute to osteomalacia but does not necessarily
influence bone mass. When large amounts of aluminum hydroxide antacid
gels are ingested, phosphate depletion can also occur because of the
formation of aluminum phosphate, which is insoluble and unabsorbable.
The clinical significance of these interactions has not been established.

Many studies indicate that phosphate regulates bone formation and resorp-
tion (Raisz and Kream 1983). In vitro studies have shown that increasing
phosphate concentration beyond the physiologic range can inhibit bone
resorption (Lorenzo, Holtrop, and Raisz 1984). Although osteoclast activi-
ty may decrease, morphologic studies suggest that the osteoclasts are less
effective rather than inactivated.

Increasing the phosphate concentration in cultures of bone-forming cells
increases both collagen synthesis and deposition of mineral. In vitro miner-
alization may require the addition of an organic phosphate compound such
as beta-glycerol phosphate. Organic phosphate may provide a constant
delivery of phosphate that does not precipitate, or it may provide more
effective organic forms because they are hydrolyzed locally in the matrix.

326


Skeletal Diseases 0

The enzyme alkaline phosphatase can cleave organic phosphate com-
pounds in bone, thus raising the local concentration of inorganic phosphate
and promoting mineralization. Although the precise role of alkaline phos-
phatase is uncertain, mineralization is impaired when this enzyme is defi-
cient, as in the disease familial hypophosphatasia.

Some in vivo studies also indicate that phosphate promotes bone growth.
The rate of bone formation across animal species is generally proportional
to their serum phosphate concentration. For example, rats with high serum
phosphate levels also have high rates of skeletal growth. Within species,
serum phosphate levels are also higher at times of rapid bone formation, as
in early infancy and puberty in humans. Hormones may be more likely than
nutrition to control these changes in serum phosphate concentration. An
inadequate intake of phosphorus could, in theory, impair skeletal growth as
well as soft tissue growth, but phosphates are so abundant in foods that a
seriously deficient intake would probably indicate decreased intake of
other nutrients.

While phosphate deficiency can lead to decreased bone mass, excessive
phosphate intake can also harm the skeleton. The adverse effects of high
phosphate intake have been studied extensively in animals (LSRO 1981;
Jowsey, Reiss, and Canterbury 1974). Excessive dietary intake of phos-
phate produced bone disease in animals, particularly ifthe diet was also low
in calcium. The current American diet is quite rich in phosphorus; this
imbalance might affect bone health adversely, but that hypothesis has not
been proved.

Recent studies suggest that the adverse effects of excessive phosphate are
largely mediated through secondary hormonal responses or through toxic
effects of phosphate deposition in soft tissues. Excessive phosphate intake
reduces serum calcium concentration, particularly when the calcium in-
take is low, because some of the phosphate carries calcium with it into soft
tissue. The resulting hypocalcemia stimulates PTH secretion, which leads
to increased bone resorption and increased phosphate excretion in the
urine. Because the effect of PTH on the kidney continues after the phos-
phates have been absorbed, fasting hypophosphatemia is common in per-
sons consuming large amounts of phosphate, presumably due to secondary
hyperparathyroidism (Herbert et al. 1966; Reiss et al. 1970; Sherwood et al.
1968). High phosphate intakes can also decrease calcitriol production in the
kidneys, impairing calcium absorption and producing further secondary
hyperparathyroidism (Portale, Halloran, and Morris 1987).

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0 Nutrition and Health

The aforementioned sequence of events occurs in experiments and may
also occur in persons with renal failure who cannot excrete phosphate
efficiently; whether nutritional phosphate excesses in American diets pro-
duce similar changes in the healthy population is in question. Bone mass
may be lower in people who consume diets that contain a relatively high
ratio of phosphorus to calcium as compared with vegetarians, for whom
this ratio is substantially lower (Marsh et al. 1980). The difference is small,
however, and many other uncontrolled variables may be involved. Some
young adults have elevated FTH activity with a high phosphorus intake
(Bell et al. 1977). More recently, direct measurement of increased FTH
level and action with high phosphorus intake was reported in young adults
consuming ordinary foods (Calvo, Kumar, and Heath 1988).

Role of Calories and Protein in Skeletal Disease

An adequate intake of calories and protein is essential for the growth and
maintenance of a healthy skeleton. Calories support the synthesis of bone
tissue and also "spare" the body from using for energy the protein that is
needed to form bone matrix. In children, insufficient calorie or protein
consumption inhibits skeletal growth. Adults who consume insufficient
calories or protein may also lose bone mass and become susceptible to
bone fractures-.

Changes in calorie consumption may affect hormone production. In chil-
dren, the decreased skeletal growth associated with malnutrition is.proba-
bly mediated, at least in part, by decreased production of qomatomedin or
insulin-like growth factors. In adolescents and adults, calories may also
affect the production of sex hormones (Cuttler et al. 1985), as'demonstrated
in adolescent women (whose growth spurt is associated with menarche).
The onset of menses may depend on a certain body weight or level of fat
stores, that, in turn, depends on adequate nutrition, including calories.
Healthy-women who lose large amounts of weight may stop menstruating,
although factors other than calories may also be involved. In persons with
anorexia nervosa, menstrual disorders may occur earlier than can be
accounted for simply by weight loss (J3rossman, Ontjes, and Heizer 1985).

The combination of decreased intake of calories, calcium, and other nu-
trients and decreased production of estrogen may be responsible for re-
duced density of bone mass in persons with anorexia nervosa (Rigotti et al.
1984). Female athletes, particularly runners and ballet dancers, who have


Skeletal Diseases O

very low body fat content, a low intake of calories and calcium, and
amenorrhea also have decreased bone mass (Drinkwater et al. 1984; Mar-
cus et al. 1985).

Low body fat, which presumably reflects a low calorie intake, may also
cause reduced bone mass in postmenopausal women (Dequeker, Goris,
and Uyterhoeven et al. 1983). One hypothesis suggests that after meno-
pause, body fat provides a continued source of estrogen that retards bone
loss in obese women. Another possibility is that women who weigh more
put more stress on the skeleton and stimulate bone mass to increase,
perhaps through an effect on the vitamin D-endocrine system (Bell, Ep-
stein, et al. 1985). Cigarette smoking seems to affect bone mass adversely,
but this finding may be related to the lower caloric intake and decreased
estrogen production observed in women who smoke (Rundgren and
Mellstrom 1984).

Protein

Adequate dietary protein is essential for bone growth; the skeleton is
second only to muscle in terms of total body protein content. Abnormal
protein nutrition may cause osteoporosis, and a decreased protein intake
could contribute to the decline in bone mass observed in alcoholics,
although nutritional factors other than the direct effects of alcohol may also
be involved.

High protein intake may also cause bone loss. In young individuals, in-
creasing dietary protein intake increases calcium excretion in urine and
produces a negative calcium balance (Heaney et al. 1982; Hegsted 1986).

,  Under ordinary circumstances, increased phosphate intake accompanies
increased protein intake; high-protein foods are often high in phosphate as
well. If dairy products are the source of protein, calcium intake may also
rise. Thus, whether moderately high-protein diets have an adverse effect
on bone mineralization has not yet been established (Heaney and Reeker
  1982).

Why calcium loss results from high protein intakes is also uncertain. The
acid content of the diet may be a major factor because much of the calcium
loss from a high-protein diet can be reproduced by administering the sulfur-
containing amino acids that were in that diet (Tschope and Ritz 1985).
Increased acidity induces calcium loss by increasing renal excretion di-
rectly as well as by increasing the dissolution of mineral from the skeleton
and impairing mineral deposition.


0 Nutrition and Health

Role of Alcohol in Skeletal Disease

Excessive alcohol intake is a risk factor for osteoporosis (see Table 7-l),
but the basis for this relationship has not been established (Consensus
Development Panel 1984). In women, the incidence of hip fractures has
been observed to increase with increasing alcohol consumption (Paganini-
Hill et al. 1981). The association between alcohol and bone loss was first
described more than 20 years ago in a population of young male alcoholics
(Saville 1%5). More recent radiographic evidence has confirmed extensive
bone loss among alcoholic patients ranging in age from 24 to 62 (Spencer et
al. 1986). Other studies have reported significant bone loss, decreased
bone density, increased bone resorption, and increased fracture incidence
among alcoholics (Nordin 1984).

Why alcohol induces bone loss is uncertain. The main hypotheses include
poor nutrition, alcohol-induced calcium diuresis, secondary effects of liver
disease, and induction of excessive PTH secretion. Malabsorption of
calcium has been observed in some studies (Nordin 1984) but not in others
(Spencer et al. 1986). The current lack of information on mechanism of
action, the effects of excessive alcohol intake on bone loss in women of
different ages, and the effects of moderate alcohol intake on bone metabo-
lism suggest a need for further research.

Role of Other Minerals in Skeletal Disease

The skeleton is a storehouse for relatively large amounts of sodium,
magnesium, copper, silicon, and other minerals, whose intake may affect
mineralization of the skeleton.

Fluoride

The effects of fluoride on bones and teeth have been observed and studied
for nearly 100 years. Fluoride is incorporated into tooth enamel, and its
beneficial effect in reducing the incidence of caries is well established (see
chapter on dental diseases).

Fluoride could be a possible treatment for osteoporosis because it is rapidly
and extensively accumulated into bone mineral. It stimulates osteoblast
activity and new bone growth, particularly that of trabecular bone, the type
most susceptible to fracture. Animal studies have not produced consistent
data about the effect of fluoride on experimentally induced osteoporosis
(Bikle 1983). Human epidemiologic studies show that subjects living in
areas where water is fluoridated have greater bone densities than those

330


Skeletal Diseases 0

living in low-fluoride areas (Bernstein et al. 1966; Simonen and Laitinen
1985); however, other epidemiologic studies suggest that small amounts of
fluoride have no consistent effect on fracture incidence (Kanis and Meunier
1984). Nevertheless, human clinical studies have demonstrated an im-
proved calcium balance with short-term administration of large doses of
fluoride, increased bone mass when fluoride was administered for at least a
year, and an increased volume of trabecular bone and a decreased inci-
dence of fractures in groups treated with fluoride for at least 2 years (Bikle
1983).

Consequently, fluoride in relatively high doses of 50 to 100 mg of sodium
fluoride daily has been used to treat osteoporosis. These doses increase
bone mass in a substantial proportion of persons and may decrease frac-
tures (Riggs, Seeman, et al. 1982). Such high intakes of fluoride, however,
produce skeletal abnormalities such as osteophytes (bony overgrowths)
and stimulate bone matrix formation at inappropriate sites. Fluoride thera-
py without supplemental calcium and vitamin D may produce os-
teomalacia, and gastrointestinal and rheumatic side effects have also been
reported (Bikle 1983). Controlled prospective trials of fluoride in the treat-
ment of osteoporosis are currently under way in the United States.

Aluminum

The effect of consuming large amounts of aluminum hydroxide in antacids
was mentioned earlier in the phosphates section. Aluminum hydroxide's
role in impairing bone growth and mineralization is complex because it
affects phosphate absorption, osteoblast function, and mineral deposition
itself. Whether aluminum causes impaired mineralization in renal os-
teodystrophy or whether it accumulates as a result of this condition is
uncertain (Quarles et al. 1985).

Magnesium

Bone recycling may be impaired by the direct effects of magnesium on bone
cells (Johannesson and Raisz 1983) as well as by the decreased production
of PTH and hypocalcemia that develop in severe magnesium deficiency
(Rude et al. 1978). The high levels of circulating magnesium observed in
renal failure are associated with impaired mineralization in vitro and can
slow the formation of hydroxyapatite. Changes in dietary magnesium,
however, do not significantly affect the regulation of bone metabolism.

Sodium
High sodium intakes can cause increased loss of calcium in the urine and
could affect age-related bone loss (Breslau et al. 1982; Goulding 1983). The

331


0 Nutrition and Health

issue of sodium in the diet is discussed in the chapter on high blood
pressure.

Trace Elements

Other ions may affect mineral metabolism. Zinc and silicon, which are
deposited in bone, are important factors in bone mineralization (Calhoun,
Smith, and Becker 1974; Carlisle 1981). Circadian variations in serum zinc
concentration parallel serum calcium changes (Markowitz, Rosen, and
Mizruchi 1985). Copper has been shown to inhibit bone resorption (Wilson,
Katz, and Gray 1981). Low boron intake may also be a risk factor for
osteoporosis (Nielsen et al. 1987). The clinical importance of these sub-
stances in bone metabolism is unknown.

Role of Other Vitamins in Skeletal Disease

Vitamin A deficiency can alter bone remodeling in animals but is not a
major cause of bone disease in humans. Excessive levels of vitamin A,
obtained from animal foods or supplements (but not as beta-carotene from
plants), can produce hypercalcemia and skeletal abnormalities, with thin-
ning of the cortex and fractures in some areas and overproduction of bone
in other areas.

Vitamin C deficiency is associated with osteoporosis but is not a major
factor in the disease in the United States (Lynch et al. 1967). There is no
evidence that megadoses of vitamin C adversely affect the skeleton.

Vitamin K-dependent proteins, particularly osteocalcin, have recently
been identified in bone. At present, their metabolic roles are not clearly
defined. Their current importance as clinical indicators for bone turnover
is difftcult to assess (Delmas et al. 1983; Slovik et al. 1984; Cole and
Gundberg 1985; Price, Parthemore, and Deftos 1980). Depressed circulat-
ing levels of vitamin K have been reported recently in patients with
osteoporosis (Hart et al. 1985), and vitamin K deficiency produces hyper-
calcemia in rats (Robert et al. 1985). Warfarin, an anti-coagulant that
blocks the action of vitamin K, can reduce bone mineral in vitamin D-
treated rats (Price and Sloper 1983). Further investigations are needed to
explain this interaction between vitamin K and bone mineralization.

Role of Exercise in Skeletal Disease

Although not strictly a nutritional issue, the role of exercise in skeletal
disease is important. That physical activity affects maintenance of skeletal

332


Skeletal Diseases 0

mass was first noted in spinal injury patients (Freedman 1949) and has since
been confirmed in patients who require bed rest, in normal volunteers who
stay in bed for long periods of time, and in astronauts who work in gravity-
free environments (Anonymous 1983).

Whether exercise prevents osteoporosis has not yet been established.
Although the evidence from cross-sectional and prospective studies sug-
gests that physical exercise may increase the peak bone mass achieved at
maturity and may also reduce losses of bone mass after maturity, many of
these studies have methodological flaws (Block et al. 1987). Nevertheless,
until better information becomes available, 3 to 4 hours of weight-bearing
exercise per week is potentially beneficial to the skeleton and could repre-
sent a safe, low-cost method for maintaining bone mass.

Implications for Public Health Policy

Dietary Guidance

General Public

The prevalence, health consequences, and expense of osteoporosis among
Americans make it a compelling public health priority. Dietary factors of
particular concern are calcium, phosphate, vitamin D (and its hormonally
active form calcittiol), protein, sodium, calories, and alcohol. How these
factors affect peak bone mass development is important and requires
further investigation. Other lifestyle factors that may decrease the risk for
osteoporosis include increased exercise and decreased cigarette smoking.
In postmenopausal women, estrogen-replacement therapy has been the
best documented method of preventing osteoporosis.

The dietary factors associated with bone mass, the universality of bone
loss with age, the interaction of diet and lifestyle with genetic factors, and
the difficulties in measuring bone loss in populations make defining the
relationship between diet and osteoporosis difficult. However, evidence
suggests that, particularly during the first three to four decades of life,
ingesting adequate calcium, maintaining appropriate body weight, exercis-
ing, restricting alcohol, and avoiding cigarette smoking are appropriate
public health strategies for prevention of osteoporosis.

Most interest in the dietary control of osteoporosis focuses on calcium.
Although current epidemiologic and clinical evidence is uncertain, chronic
low calcium intake may decrease peak bone mass, especially during ado-
lescence. Surveys indicate that dietary calcium intake of adolescent girls is

333


O Nutrition and Health

one-third or more below the 1,200 n&day recommended for this popula-
tion and that adult women of reproductive ages also consume less than the
recommended 800 mg/day. Although the ideal level of calcium intake for
development of peak bone mass is unknown, and although it has not yet
been established whether increased calcium intake will prevent os-
teoporosis, females, particularly adolescents and young adults, in the
United States should increase food sources of calcium. The public should
also be educated about the calcium content of various foods, particularly
low-fat dairy products, and should maintain adequate calcium intake at all
ages.

Additional study of the epidemiologic association between diets high in
protein and increased prevalence of osteoporosis is required to make
further conclusions.

Special Populations

Children, pregnant and lactating women, and older people have special
needs for calcium based on, respectively, the extra skeletal demands of
growth, milk production, or the age-related decrease in absorption of
calcium. Older Americans consume amounts of calcium that average as
much as 40 percent below current recommendations of 800 mg/day.
Postmenopausal women should receive counseling on supplemental use of
estrogen, and all groups should receive information about calcium-rich
foods. People who take calcium supplements also need education on
appropriate use, side effects, the forms in which they are best absorbed,
and interactions with other medications.

Nutrition Programs and Services

Food Labels

Present evidence on the role of dietary factors in skeletal disease has no
special implications for change in policy related to food labeling. However,
nutrition labeling, which lists calcium and other nutrient content, should'be
encouraged on most food products.

Food Services

Aside from the special populations noted below, evidence related to the role
of dietary factors in skeletal diseases currently holds no special implica-
tions for change in policy related to food service programs.

334


Skeletal Diseases tl

Food Products

Foods abundant in calcium are widely available in the United States.
However, the diversity of U.S. dietary patterns suggests the possibility of
calcium fortification of a limited nuhber of foods. These additions should
be carefully selected to avoid excessive calcium in the food supply. For-
tification should be chosen based on the frequency of consumption of a
food by the targeted populations, and the calcium should be in a phys-
iologically available form. It is important to continue fortification of suit-
able foods with vitamin D because this has been instrumental in reducing
the prevalence of rickets and osteomalacia in the United States.

Special Populations

Food services offered to children, adolescents, and young adults should
provide diets with sufficient calcium to enhance achievement of peak bone
mass. Persons who are unable to convert vitamin D to its active form may
require supplementation with calcitriol. Those with chronic malabsorption
syndromes may require supplementation with calcium or calcitriol.

Whether calcium, vitamin D, or calcitriol should be provided to older
women to prevent or delay postmenopausal bone loss is as yet uncertain.
Although evidence for the precise role of physical activity in prevention of
osteoporosis is still emerging, it seems reasonable to include exercise as a
component of any program to enhance the skeletal integrity of older
Americans. Older persons should be encouraged to maintain regular activi-
ties such as walking and other weight-bearing exercise.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in skeletal diseases should include investigations into:
0 Changes in calcium and phosphate requirements throughout life.
0 The effects of altering proportions of phosphate and protein on calcium
  requirements and bone mineralization.
o The effects of increased calcium intake on peak bone mass and on
prevention of postmenopausal bone loss.
0 Potential toxicities of high-dose supplements of calcium.
o The development of calcium sources with improved bioavailability.
o Safe and adequate levels of vitamin D added to the food supply.

335


0 Nutrition and Health

a The relationship of vitamin D and its metabolites to calcium in the
development of peak bone mass and prevention of bone loss.
a The levels of vitamin D and its metabolites, fluoride, and calcium that
are safe and adequate for the treatment of osteoporosis.
a The effects of moderate and excessive alcohol intake on bone mineral
metabolism.
a The effects of various levels of physical activity on loss of bone mass.
a The relationship of other vitamins and minerals to peak bone mass and
to prevention of bone loss.

336


Skeletal Diseases cl

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Journal of Pediatrics 106:533-44.

Cobum, J.W., and Brautbar, N. 1980. Disease states in man related to vitamin D. In Vitamin D:
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Cole, D.E.C., and Gundberg, CM. 1985. Changes in osteocalcin associated with parathyroid
hormone infusion with X-linked hypophosphatemic rickets. Chica Chimica Acra 151: l-7.

Consensus Development Panel. 1984. Osteoporosis. Journal of the American Medical Asso-
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Courpron, P 1981. Bone tissue mechanisms underlying osteoporosis. Orthopedic C'bnics of
North America 12:513-45.

Cuttler, L.; Van Vleit, G.; Conte. EA.; Kaplan, S.L.; and Grumbach, M.M. 1985.
Somatomedin-C levels in children and adolescents with gonadal dysgenesis: differences from
age-matched normal females and effect of chronic estrogen replacement therapy. Journal of
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Delmas, PD.; Wahner, H.W.; Mann, K.G.; and Riggs, B.L. 1983. Assessment of bone
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Dequeker, J.; Goris, P.; and Uyterhoeven, R. 1983. Osteoporosis and osteoarthritis (os-
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Drinkwater, B.L.; Nilson, K.; Chestnut, C.H., III; Bremner, W.J.; Shainholtz, S.; and
Southworth, M.B. 1984. Bone mineral content of amenorrheic and eumenorrheic athletes.
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Drossman, D.A.; Ontjes, D.A.; and Heizer, W.D. 1985. Anorexia nervosa. Gastroenterology
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Dunstan,C.R.;Hills,E.;Norman.A.W.;Bishop,J.E.;Mayer,E.;Wong.S.Y.;Johnson,J.R.;
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1985. The pathogenesis of renal osteodystrophy: role of vitamin D, aluminum, parathyroid
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Edidin, D.V.; Levitsky, L.L.; Schey, W.; Dumbovic, N.; and Campos, A. 1980. Resurgence of
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Ettinger, E.; Genant, H.K.; and Cam, C.E. 1987. Postmenopausal bone loss is prevented by
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Falch. J.A.; Odegaad, O.R.; Finnanger, A.N.; and Matheson, I. 1987. Postmenopausal os-
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Favus, M.J.; 1985. Factors that influence absorption and secretion of calcium in the small
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Forero, M.S.; Klein, R.F.; Nissenson, R.A.; Nelson, K.; Heath, H.; Arnaud, C.D.; and
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338


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Francis, R.M.; Peacock, M.; Taylor, G.A.; Storer, J.H.; and Nordin. B.E.C. 1984. Calcium
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0 Nutrition and Health

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Markowitz. M.E.; Rosen, J.F.; and Mizruchi, M. 1985. Circadian variations in serum zinc (Zn)
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Matkovic. V.; Kostial. K.; Simonovic, I.; Buzina, R.; Brodarec. A.; and Nordin, B.E.C. 1979.
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Mosekilde, L.; Christiansen, M.S.; Lund, B.; Helmer, 0.; Sorenson, S.; and Melsen, F. 1977.
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Newcomer, A.D.; Hodgson, SE.; McGill, D.B.; and Thomas, RJ. 1978. Lactase deficiency:
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340


Skeletal Diseases Cl

Nielsen, F.H.; Hunt, C.D.; Mullen, L.M.; and Hunt. J.R. 1987. Effect of dietary boron on
mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB Journal
1:394-97.

Nilas, L.; Christiansen, C.; and Christiansen, J. 1985. Regulation of vitamin-D and calcium
metabolism after gastrectomy. Gut 26:252-57.

Nilas, L.; Borg, A.; Gotfredsen. A.; and Christiansen. C. 1985. Comparison of single- and
dual-photon absorptiometry in postmenopausal bone mineral loss. Journul ofNac/enr Medi-
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Nordin. B.E.C., ed. 1984. Metabolic bone and stone disease. New York: Churchill
Livingstone.

Ott, S.M., and Chesnut, C.H. 1987. Calcitriol treatment does not increase bone mass in
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Paganini-Hill, A.; Ross, R.K.; Gerkins, V.R.: Henderson. B.E. ; Arthur. M.: and Mack. T.M.
1981. Menopausal estrogen therapy and hip fractures. Annuls of Intemul Medicine 95:28-31.

Parfitt, A.M.; Gallagher, J.C.; Heaney, R.P.; Johnston, C.C.: Neer. R.: and Whedon. G.D.
1982. Vitamin D and bone health in the elderly. American Journal of Clinical Ntttririon
36:1014-31.

Passmore, R., and Eastwood, M.A. 1986. Davidson and Passmorc humnn nutrition and
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Shulman, L.E. 1988. Research directions in osteoporosis. Americnn Journal of Medicine
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Price, PA.; Parthemore, J.G.; and Deftos. L.J. 1980. New biochemical marker for bone
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Raisz, L.C., and Kream, B.E. 1983. The regulation of bone formation. Nenf England Journal
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Reeker, R.R. 1985. Calcium absorption and achlorhydria. New, England Journal of Medicine
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bone metabolism and calcium balance. American Journal of Clinical Nutrition 41:254-63.

341


u Nutrition and Health

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Reiss, E.; Canterbury, J.M.; Borovitz, M.A.; and Kaplan, E.L. 1970. The role of phosphate in
the secretion of parathyroid hormone in man. Journal of Clinical Investigation 49:214649.

Riggs, B.L., and Melton, L.J. 1986. Involutional osteoporosis. New England Journal of
Medicine 314: 167-6.

Riggs, B.L.; Hamstra, A.; and DeLuca, H.F. 1981. Assessment of 25-hydroxyvitamin D,-
hydroxylase reserve in postmenopausal osteoporosis by administration of parathyroid ex-
tract. Journal of Clinical Endocrinology and Metabolism 53:833-35.

Riggs, B.L.: Seeman, E.; Hodgson, S.F.; Taves, D.R.; and Fallon, W.M. 1982. Effect of
fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis.
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Riggs,B.L.;Wahner,H.W.;Seeman,E.;Offord,K.P.;Dunn,W.L.;Mazess.R.B.;Johnson,
K.A.; and Melton, L.J.. III. 1982. Changes in bone mineral density of the proximal femur and
spine with aging: differences between the postmenopausal and senile osteoporosis syn-
dromes. Journal of Clinical Investigntion 70:716-23.

Rigotti, N.A.; Nussbaum, S.R.; Herzog, D.B.; and Neer, R.M. 1984. Osteoporosis in women
with anorexia nervosa. New England Journal of Medicine 311:1601~.

Riis, B.; Thomsen, K.; and Christiansen, C. 1987. Does calcium supplementation prevent
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Robert, D.; Jorgetti, V.; Lacour, B.; Leclerq. M.; Coumot-Witmer, G.; Ulmann, A.: and
Drueke, T. 1985. Hypercalcemia during experimental vitamin K deficiency in the rat. Cal-
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Rowe, J.C.; Wood, D.H.; Rowe, D.W.; and Raisz, L.G. 1979. Nutritional hypophosphatemic
rickets in a premature infant fed breast milk. New England Journal of Medicine 300:293-%.

Rude, R.K.; Oldham, S.B.; Sharp, C.F.; and Singer, ER. 1978. Parathyroid hormone secre-
tion in magnesium deficiency. Journal of Clinical Endocrinology und Metabolism 47:800-806.

Rundgren. A., and Mellstrom, D. 1984. The effect of tobacco smoking on the bone mineral
content of the aging skeleton. Mechanisms of Aging and Development 28:273-77.

Saville. PD. l%S. Changes in bone mass with age and alcoholism. Journal ofBone and Joint
Surgep 47A:492-99.

Sherwood. L.M.; Mayer, G.P.; Bamberg, C.F.; Kronfeld, D.S.: Hurback. G.D.; and Potts,
J.T. 1%8. Regulation of parathyroid hormone secretion: proportional control by calcium, lack
of effect of phosphate. Endocrinology 83: 1043-5 1.

Simonen. 0.. and Laitinen, 0. 1985. Does fluoridation of water prevent bone fragility and
osteoporosis. Lancer ii:432-34.

Slovik. D.M.: Gundberg, C.M.; Neer. R.M.; and Lian, J.B. 1984. Clinical evaluation ofbone
turnover by serum osteocalcin measurements in a hospital setting. Journnl of Clinical Endo-
crinology and Metabolism 59:228-30.

Sowers, M.F.R.; Wallace, R.B.; and Lemke. J.H. 1985. Correlates of mid-radius bone density
among postmenopausal women: a community study. American Journal of Clinical Nutririon
41:1045-53.

Spencer, H.; Rubio, N.; Rubio, E.; Indreika, M.; and Seitam. A. 1986. Chronic alcoholism:
frequently overlooked cause of osteoporosis in men. American Journal of Medicine
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Skeletal Diseases 0

Temkin, O.N., ed. and transl. 1956. Soranus, Gynecology, pp. I U-16. Baltimore. MD: Johns
Hopkins Univ. Press.

fodhunter, E. 1973. Some aspects of the history of dietetics. World Review of Nutrition and
Dietetics 18: 12-13.

T'sai, K.S.; Heath, H.. III; Kumar. R.; and Riggs, B.L. 1984. Impaired vitamin D metabolism
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rschope. W., and Ritz, E. 1985. Sulfur-containing amino acids are a major determinant of
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343


Chapter 8

Dental Diseases

Sweet things are bad for the teeth.
      Jonathan Swift
Polite Conversation, Dialogue II (1738)

Introduction

Historical Perspective

Descriptions of the oral manifestations of scurvy and various single and
multiple B-complex deficiencies in humans were among the earliest contri-
butions to nutrition knowledge (Jolliffe 1962). Recognition of the oral signs
of nutrient deficiency was facilitated by the pain associated with pathology
in the mouth and the easy access to the mouth for examination.

Early research on oral pathology was controversial because of diverse
results from laboratory research and the lack of basic knowledge about the
complexity of nutrition and the interrelationships among nutrients. Experi-
mental diets were crude by today's standards and often resulted in multiple
nutrient deficiencies. Moreover, pure nutrients were not available for
supplementation of deficient diets, and dietary supplements rarely con-
tained the full complement of essential nutrients. Early experimental de-
sign also differed significantly from naturally occurring conditions that
might predispose to nutritional disorders.

Controversy especially centered on dental caries (tooth decay) observed in
rats in early studies. Two schools of thought developed, with one empha-
sizing that decay was a result of environmental influences on the tooth
surface and the other maintaining that lesions were evidence of systemic
nutritional deficiencies. Neither perspective considered the role of micro-
organisms in decay processes until much later (Shaw 1952).

345


0 Nutrition and Health

Role of Sugars

The relationship between sweet foods and tooth decay was observed by the
ancient Greeks. Aristotle, for example, associated rotted teeth with con-
sumption of soft figs. In the 15th century, Arculanus recommended avoid-
ance of sweet and sticky foods to prevent tooth loss. The experimental
demonstration of tooth demineralization in the presence of carbohydrates
(but not meat) mixed with saliva occurred in 1890 (Newbrun 1982). These
studies foreshadowed the many animal and human studies of sugar and
caries incidence that have led to our current understanding of the etiology
of this condition.

Role of Fluoride

One of the first descriptions of mottled enamel appeared near the turn of
this century when the tooth enamel of immigrants to America from Naples
was observed to be speckled with white areas or to be mottled, pitted, or
discolored (Eager 1901). This condition, called denti di Chiaie, was thought
to result from local geologic conditions, and a change in the source of water
was suggested as the reason for the lower incidence of this abnormality
among the children of these immigrants.

A similar phenomenon was observed in children living in Colorado Springs
(Black and McKay 1916; McKay and Black 1916) and other locations by
investigators who noted that the mottled teeth of these children, although
apparently inadequately mineralized, were more resistant to dental caries
than normally calcified teeth (McKay 1929). Studies in the 1930's demon-
strated the relationship of water-borne fluoride to the prevention of tooth
decay (Smith, Lantz, and Smith 1931; Dean 1938) and led to early sugges-
tions that dental caries might be controlled by increasing the fluoride
concentration of drinking water. More conclusive evidence of the inverse
relationship between fluoride in the water supply and dental caries was
provided by early surveys (Dean, Arnold, and Elvove 1942) that were later
confirmed (Russell and Evolve 1951; Englander and Wallace 1962; Adler
1970).

Results of the epidemiologic surveys of the 1930's established the fluoride
concentrations in natural water that provided near maximal caries protec-
tion without producing objectionable mottling of teeth (fluorosis). The first
clinical trial to add fluoride to communal water supplies began in Grand
Rapids, Michigan, in 1945, where fluoride concentration was adjusted to 1
part per million (ppm). After 6.5 years of fluoridation, caries prevalence in
4- to 6-year-old children in Grand Rapids was about 50 percent of that in the
nonfluoridated (less than 0.2 ppm) neighboring community of Muskegon.

346


Dental Diseases O

After 15 years of fluoridation, children 12 to 14 years of age, born- and
raised in Grand Rapids, had about 55 percent lower caries scores than
children of the same age prior to fluoridation (Arnold et al. 1%2). Many
other studies demonstrated that controlled fluoride supplementation of
community water supplies could reduce dental caries without causing
undesirable side effects (Galagan and Vermillion 1957; Dean et al. 1950;
Ast and Chase 1953; Knutson 1970; Hutton, Linscott. and Williams 1956;
Connor 1970).

Significance for Public Health

Dental caries and periodontal disease are important and widespread public
health problems in the United States. They are rarely life threatening but
can cause substantial expense, pain, restriction of activity, and work loss
(Corbin, Kleinman, and Lane 1985). Although dental caries among chil-
dren, as well as some forms of adult periodontal disease, appear to be
declining, the overall prevalence of these conditions imposes a substantial
burden on Americans. Of the 13 leading health problems in the United
States, dental disorders rank second in direct costs (Carter Center Health
Policy Task Force 1984). Dental care cost $21.3 billion in 1985 (U.S.
Department of Commerce 1986).

Dental Caries

Dental caries, or tooth decay, is caused by a progressive dissolution of
mineral from tooth surfaces by acid produced by oral bacteria. Advanced
disease can result in tooth loss. The National Health and Nutrition Exam-
ination Survey (NHANES) of 1971-74 reported that Americans ages 1 to 74
years had an average of 1.3 decayed, 5.3 missing, and 6.4 filled teeth.
Because people normally have a total of 28 to 32 permanent teeth (depend-
ing on the presence of the four wisdom teeth), nearly half of the teeth in the
average American mouth were filled, missing, or decayed at that time
(NCHS 1979). A more recent survey (NIDR 1987) summarized the preva-
lence of coronal caries by the mean number `of decayed and filled perma-
nent surfaces (DFS). As shown in Figure 8-1, the mean DFS (which does
not include missing teeth) for age 18-19 is 12, and for employed adults over
age 40, the mean DFS is 29. The average for all ages was 23 DFS out of 128
possible surfaces. Comparing mean decayed and tilled teeth (DFT) in the
recent National Institute of Dental Research survey (NIDR 1987) with the
National Center for Health Statistics (NCHS) household survey
(NHANES I) conducted in 1971-74, the employed persons in the recent
NIDR survey had a lower mean DFT through age 34. Beyond that age,
tooth loss prevents any meaningful comparisons with earlier data.

347


0 Nutrition and Health

Age Range

Figure 8-l.  The dbtribution of maan dacayad and filled coronal
      surfaces (DFS) by age as determined from the NIDR
     survey of employed adults and seniors.
Source: National Institute of Dental Research 1987.

The mean number of root surface lesions by age is shown in Figure 8-2.
Decay of tooth roots (root caries) was three times higher in persons 65
years and older than in employed adults, 63 percent as opposed to 21
percent, and only half of such lesions had been filled. The higher preva-
lence in older persons results from increased exposure of root surfaces due
to age-related gum recession or periodontal disease.

The number of decayed, missing, and filled permanent teeth increases
steadily with age. In 1980, the average child had at least 1 carious lesion in a
permanent tooth by age 8,4 by age 12, and 11 by age 17 (NIH 1981). In the
1971-74 NHANES, the number increased from an average of 1.7 in chil-
dren 6 to 11 years to 22.2 in adults 65 to 74 years (NCHS 1979). The number
does not differ by sex, but blacks overall tend to have fewer decayed,
missing, and filled teeth during adulthood.

Within the past two decades, the incidence of dental caries in children has
been declining, perhaps by as much as 30 to 50 percent. This decline has
been attributed largely to increased intake of fluoride from drinking water,
food, toothpastes, mouth rinses, and topical application, although de-
creased intake of cariogenic foods and improved dental hygiene and care
have also been suggested as contributory factors (Leveille and Coccodrilli
1982; Navia 1985; Corbin et al. 1987).

348


Dental Diseases 13

Figure 8-2.  The diitribution of meOn decayed and filled root surfaces
     (DFS) by age as determined from the NIDR survey of
     employed adults and seniors.

Source: National Institute of Dental Research 1987.

Both the benefits and the safety of water fluoridation have been carefully
examined and endorsed by many professional and scientific organizations
and by U.S. Surgeons General since the mid-1940's. More than 120 million
people in 8,000 U.S. communities currently are provided with optimally
adjusted fluoridated water. An additional 10.7 million people in 3,000
communities drink water with naturally occurring fluoride (Center for
Prevention Services 1985; Ismail et al. 1987). Nevertheless, despite the
proven benefits of fluoride, only 61 percent of the U.S. population on
public water supplies now receive fluoridated water (Liie 1986).

Periodontal Disease

Periodontal disease includes a spectrum of pathologic conditions ranging
from minor gum inflammation (gingivitis) to severe loss of the bone struc-
ture supporting the teeth (periodontitis). Advanced disease results in
loosening of and eventual loss of teeth. In national surveys of the early
1970's, 23 percent of children ages 6 to 17 years had gingivitis (NCHS
1979). Subsequent statewide surveys have reported rates varying from 19
to 44 percent in this group (Corbin, Kleinman, and Lane 1985).

National surveys of adult periodontal disease found little change in preva-
lence of periodontitis between 1960-62 and 1971-74. The National Adult
Dental Health Survey of 1985-86 reported gingival bleeding in 43 percent of
employed adults and 47 percent of persons over age 65. Seventy-seven

349


0 Nutrition and Health

percent of all adults, and 95 percent of older persons, had at least one site in
the mouth with periodontal attachment loss of 2 mm or more. More severe
periodontal destruction, 4 mm or more attachment loss, was observed in 24
percent of adults and 68 percent of older persons. The percent of persons
by severity of loss of attachment and age group is shown in Figure 8-3. For
both working adults and older persons, the severity of periodontal disease
increases with age, and it is more prevalent among males than among
females (NIDR 1987). Periodontal disease is a major cause of tooth loss,
and efforts to prevent this condition are desirable (Rank et al. 1983).

Loss of Teeth

The two major causes of tooth loss are dental caries and periodontal
disease. Toothlessness limits individual selection of foods to those that
require little biting or chewing, therefore influencing the nutritional intake
of affected individuals.

In the 1971-74 NHANES, about 15 percent of the adult population ages 18
to 74 years had lost all permanent teeth. Another 9 percent had lost all of
their upper or their lower permanent teeth, and by the ages of 65 to 74,46
percent of Americans were edentulous (NCHS 1979). Nevertheless, these
figures represent a significant decline from surveys taken in 1960-62 (Isma-
il et al. 1987).

This favorable trend for decreased tooth loss has continued. The 1985-86
survey of employed adults showed that toothlessness has almost been
eliminated in this group; only 4 percent were missing all theirteeth, and half
had lost none or at the most one tooth. However, as shown in Figure 8-4,
toothlessness increases with age and remains a major problem among older
Americans. The survey indicated that 42 percent of Americans over age 65
were edentulous and that only 2 percent have retained all 28 permanent
teeth. Comparing the prevalence of tooth loss in the recent survey to that
reported by the NCHS survey in 1960-62, the current sample had less tooth
loss at every age interval.

Scientific Background

Normal Tooth Development

The tooth is a very specialized structure important for the proper initial
processing of solid foods. A schematic cross-section of a tooth is presented
in Figure 8-5. People normally develop two sets of teeth, 20 deciduous, or
primary, teeth and 32 permanent, or secondary, teeth. Each tooth develops
from a tooth bud that forms in the area of the jaw. Each tooth bud contains a


Dental Diseases 0

Figure 8-3. Percent ol persons by severe loss of periodontal
     attachment (pocket depths measuring 4 mm or more)
     and age soups as determined tram the NIDR survey
     of employed adults and seniors.

Source: National Institute of Dental Research 1987.

Age Group
(Years)

Fiiure 8-4. Comparison ot tha percent of edenhhus parsons in the
     lfB5-88 NIDR survey to that reported from the NCHS
      survey of 1960-82.

Source: National Institute of Dental Research 1987.

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0 Nutrition and Health

Crown (Enamel)

Dentinal tubules

Alveolar hone

Blood vessel in

(De

Win)

Figure 8-5.  Schematic cross-section of a typical mandibular tooth. The
     gums recede with age, exposing the cementum of the tooth
        root.

dental organ that produces the tooth enamel and a dental papilla that
produces the tooth pulp and the dentin. Cells from the dental follicle form
the cementum and periodontal ligament after the tooth has formed.

The deciduous teeth begin forming at about 6 weeks in ufero, when cells in
the primitive oral cavity differentiate to form the dental lamina-the site of
development of the tooth buds. The dental lamina is active from the second
month of embryonic development, when the first buds for the deciduous
teeth are formed, until about the age of 5 years, when the buds for the last
permanent molars are initiated.

The formation of the tooth crown begins with the secretion of a dentin
matrix containing collagen fibrils. Mineral ions then enter the matrix to
form small crystals on or between the fibrils. Successive layers of dentin
are formed. Enamel formation begins as soon as the first dentin layer has
been laid down. Cells of the enamel organ secrete successive layers of a
matrix that is chemically different from dentin matrix. Mineral crystals
appear in each layer as it is secreted and grow larger as more mineral enters
the tissue; matrix proteins and water are removed. This so-called matura-
tion of the enamel continues after the full thickness of enamel matrix has

352


Dental Diseases 0

been laid down. These events occur at different times for the various
deciduous and permanent teeth, beginning from a few months before birth
until late adolescence.

As the tooth erupts into the mouth, it loses the layers of cells and blood
vessels that covered the enamel. The enamel, however. continues to
mature during the period immediately after tooth eruption and to incorpo-
rate minerals (including fluoride) into its structure from saliva, food, and
drinking fluids. Otherwise, the enamel of fully erupted teeth is not known
to have any metabolic dependence upon nutrients consumed in the diet.
The inner surface of dentin adjacent to the pulp remains lined with the cells
that formed it, and these cells continue to form secondary dentin at a very
slow rate throughout the life of the tooth.

Thus, there are different periods in the developmental history of the tooth.
During the preeruptive period when the crowns are forming in the jaws
(which, for the wisdom teeth, continues into late adolescence), the devel-
oping enamel and dentin of the crowns are subject to nutritional deficien-
cies or imbalances in the same way as other tissues. In fact, in the enamel
the preeruptive period can be divided into two phases, the secretory and
the maturation stage. Nutritional deficiencies or excesses may affect either
stage separately or both. Hypoplastic lesions in the enamel reflect distur-
bances affecting the secretory process. Hypomineralized defects, such as
the white spot lesions of fluorosed enamel, give evidence of interference
with the maturation process. After eruption, when the crown of the tooth
has emerged from the jaw and the enamel is bathed instead by the saliva as
well as exposed to micro-organisms and their byproducts, sloughed cells,
and food debris, nutritional deficiencies or excesses and dietary habits may
affect teeth in a totally different manner.

The development and maintenance of the soft tissues and bone that anchor
and support the teeth (the periodontium) are also subject to nutritional
deficiencies. The periodontium comprises the gingiva (the tissue that cov-
ers the alveolar bone process and surrounds the top of the tooth), the
periodontal ligament (the soft connective tissue that surrounds the roots of
the teeth and joins the root cementum and the alveolar bone), the root
cementurn (a specialized calcified tissue that covers the tooth root), and the
alveolar bone (the bone that forms and supports the sockets of the teeth).
The bony tissue of the alveolar process is dependent on the presence of
teeth. The alveolar bone grows in response to dental eruption, is modified
by dental changes, and resorbs when the teeth are lost as a result of

353


O Nutrition and Health

advanced dental caries and/or periodontal disease. The resorption of al-
veolar bone ridges (residual ridge resorption) has been described as an oral
disease entity (Atwood 1971).

Throughout life, the oral soft tissues undergo rapid rates of turnover and
repair, and the continued presence of optimum levels of nutrients is neces-
sary to maintain proper oral health and to resist disease.

Dental Caries

Once a tooth is fully erupted, it becomes subject to the influence of
chewing, acids in the mouth, and bacterial plaque. Dental caries begins
with dissolution of the mineral surface of the tooth by acid produced from
fermentable carbohydrate (e.g., sugar) by dental plaque bacteria. Next, the
dissolution advances further into the enamel, first appearing as a white
spot, and subsequently into the dentin and eventually into the pulp. If left
untreated, the result is destruction of the crown and root system, tooth
loss, and resorption of the surrounding bone (Newbrun 1978). The decay
that begins in pits and fissures, on the smooth surfaces, or on exposed roots
of the teeth is invariably due to the combined effects of bacterial infection
and host and dietary factors over time (Wei, Fomon, and Anderson 1977;
Shaw 1978, 1987). Patients with reduced salivary flow are also at increased
risk (Mandel 1983).

Of the many bacteria found in tooth plaque, Streptococcus mutans is
considered the primary etiologic agent in coronal caries (Loesche 1986;
Shaw 1987). This bacterium is unique in that it produces enzymes that
convert table sugar (sucrose) into long sticky polysaccharides. The poly-
saccharides promote firm attachment and accumulatibn of the bacteria in
dental plaque (Gibbons and van Houte 1978). If not removed, the bacteria
metabolize sugars (including sucrose) and produce acids that dissolve
minerals from the teeth and begin the decay process. Root caries, decay of
tooth root cementum following recession of gum tissues, has been regarded
as an independent type of caries (Nikiforuk 1985). However, a relationship
between root caries and coronal caries has been reported recently (Vehk-
alahti 1987). Decay also occurs around restorations where plaque is diffl-
cult to remove.

Whereas sugais facilitate the action of cariogenic bacteria, saliva is a major
impediment to the pathogenesis of these bacteria (Vogel 1985; Mandel
1986). This fluid, secreted by the major and minor salivary glands, coats the
tissues of the mouth and provides protection against bacteria that cause
disease. The saliva contains molecules that when adsorbed to the tooth can
influence attachment of bacteria to this surface and, when present in the

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Dental Diseases Cl

fluid, can clump bacteria together such that they cannot attach to the teeth
but rather are cleared from the mouth by swallowing. Saliva also contains
enzymes and proteins with antibacterial activity that inhibit bacterial
growth or kill bacteria. In addition to these defense mechanisms, saliva can
contain antibodies that attack specific kinds of bacteria. Another important
function of saliva is that it supplies the calcium and phosphorus. minerals
important in the remineralization of tooth surfaces that have lost mineral
due to acid attack.

Several types of interventions might prevent tooth decay. The most impor-
tant diet-related interventions are fluoridation of drinking water and con-
trol of sugar intake, but other approaches such as oral hygiene, application
of plastic sealants, use of topical fluorides, and various chemotherapeutic
agents have also been shown to be effective (Navia 1985). The eficacy of a
caries vaccine that would prevent infection by cariogenic bacteria is under
investigation (Navia 1985; Krasse, Elmilson, and Gahnberg 1987).

Periodontal Disease

Periodontal disease encompasses pathologic changes of the gingiva, peri-
odontal ligament, cementurn, and alveolar bone that make up the attach-
ment and supporting tissues of the teeth (Lindhe 1983). The destruction of
these tissues (the periodontium) results in the loosening and loss of the
teeth. The etiology of this disease, like that of dental caries, is multifac-
torial, involving bacterial infection, host factors, diet, and duration of
infection. The accumulation of bacterial plaque near the gum line can cause
a nondestructive inflammation of the gingival tissue (gingivitis). Early
studies (L6e, Theilade, and Jensen 1965; Theilade et al. 1966) showed that
dental placfue caused clinical gingivitis and that when the plaque was
removed the disease was reversed or prevented. If the inflammation per-
sists, the disease can progress and destroy the gingival connective tissue
and underlying tissues to form a subgingival or periodontal pocket. As the
pocket depth increases, the alveolar bone (bone supporting the tooth) is
resorbed and the tooth is lost. The primary etiologic agents for periodontal
disease are subgingival bacteria (Socransky 1977).

The bacteria make and release toxic substances, destructive enzymes, and
antigenic molecules that cooperate in the destruction of periodontal
tissues. Large amounts of bacterial products can directly damage tissues or
can cause overstimulation of the immune system with resulting tissue
damage; under normal oral conditions, the immune system is protective
against bacterial challenge (Nisengard 1977; Seymour 1987). Other factors
that can decrease host defense mechanisms and, therefore, promote peri-
odontal disease are immunologic defects. metabolic problems, endocrine

35.5


0 Nutrition and Health

dysfunctions, and nutritional deficiencies. Reduced salivary flow is also a
risk factor (Mandel 1983).

Key Scientific Issues

o Role of Diet in Tooth Decay
0 Role of Diet in Periodontal Disease

o Role of Diet in Other Dental Conditions
o Effect of Tooth Loss on Nutritional Status

Role of Diet in Tooth Decay

Although diet is indicated as one of the main direct determinants of dental
caries, it is also linked to each of the other determinants of causation,
prevention, and treatment. Dietary factors are important for the host's
normal tooth development, host resistance, and salivary composition; for
selection and maintenance of the microbial population; and for the amount
of time teeth are in contact with sugars and their acid byproducts (Alfano
1980). Sugars are the most important dietary factors in the causation of
dental caries; fluoride is most important in its prevention. The role of other
dietary components such as fats, protein, and minerals in modulating these
effects is also of much current interest.

Role of Sugars

Despite the complex etiology of dental caries, the causative role of dietary
sugar-especially sucrose-is well established (Keyes and Jordan 1963).
Caries-producing bacteria have a rather high need for a range of simple
sugars (glucose, fructose, lactose, maltose, and sucrose) that they readily
metabolize into acids that demineralize teeth. The unique role of sucrose,
however, depends on its ability to be converted by mouth bacteria into
extracellular polymers of glucose or fructose that adhere firmly to the tooth
surfaces (Gibbons and van Houte 1978; Doyle and Ciardi 1983). Together
with the micro-organisms that secrete them, these extracellular products
facilitate the further attachment to teeth and proliferation of bacteria.

Food sugars, such as glucose and fructose that diffuse into this plaque,
nourish the micro-organisms. Food starches are converted to a limited
extent by salivary enzymes to soluble glucose that can be used by plaque
bacteria. Although saliva readily neutralizes organic acids, it has limited
access to the acids generated at the tooth surface beneath the plaque.


Dental Diseases 0

Recent reviews of extensive animal studies and human epidemiologic and
clinical observations during the past 30 years have thoroughly documented
the role of sucrose and other sugars in tooth decay (Newbrun 1982; Glins-
mann, Irausquin, and Park 1986). Studies in rats, for example, have dem-
onstrated a direct relationship between the amount of sucrose in the diet
and caries incidence that reaches a plateau when the sucrose concentration
is 8 to 40 percent by weight. Such studies have also demonstrated the
importance of the consistency and composition of the diet. Sucrose has
been shown to have a greater cariogenic effect than glucose, fructose, or
other simple sugars. Caries incidence increases directly with the frequency
of sugar consumption (Bowen et al. 1983).

Despite methodological difficulties in assessing population-wide sugar
intake, human epidemiologic studies have generally indicated an associa-
tion between sugar intake and tooth decay (Sreebny 1982) as well as
increasing rates of tooth decay among populations whose sugar intake is
increasing (Burt and Ismail 1986). Human clinical studies have demon-
strated a virtual absence of tooth decay and much lower concentrations of
cariogenic bacteria in the mouths of children with inherited metabolic
disorders (e.g., fructose intolerance) that prevent sucrose consumption
(Newbnm 1982).

Other clinical studies show the importance of frequency of sugar consump-
tion and the form in which it is consumed. Sugars in solution are more
readily cleared from the mouth than sugars in solid foods and, therefore,
are more likely to have only a transient influence on plaque acidity. Foods
that adhere to the teeth are more cariogenic than those that wash off
quickly (Gustafsson et al. 1954). In addition, people eat foods in different
ways. It appears that any increase in the length of time food remains in the
mouth is likely to increase the initiation and progression of caries (New-
brun 1978).

Metabolism of sugars by mouth bacteria results in acid production con-
comitant with a pH drop in dental plaque from a level near neutral to about
5. This effect lasts 20 to 30 minutes until buffering agents in saliva restore
the normal pH. Recurrent exposures to such episodes for extended time
periods lead to dissolution of the enamel. The presence of calcium, phos-
phate, fluoride, and other minerals in the saliva permits remineralization
when the pH is neutral. Thus, the tooth is exposed to alternating cycles of
dissolution and remineralization. If the balance favors dissolution, clinical
carious lesions occur, and if it favors remineralization, early lesions are
repaired and advanced caries does not develop.

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O Nutrition and Health

Research into the cause of caries has not entirely overcome problems in
measurement of sugar intake, the confounding effects of other dietary
components, and secular trends in dental hygiene and fluoride consump-
tion. Evidence exists that sugars as they are consumed in the average
American diet contribute to the development of dental caries. Current
average daily intake levels in the United States are 62 to 143 g, or 18 to 32
percent of total caloric intake (Glinsmann, Irausquin, and Park 1986).
Reduction of dietary sugar would be expected to reduce levels of tooth
decay in the population, in particular at the time of tooth eruption (Loesche
1985).

Nursing Bottle Caries

A special example of the importance of the duration of contact between
fermentable sugars and teeth is nursing bottle caries (Gardner, Norwood,
and Eisenson 1977; Ripa 1978; Dilley, Dilley, and Machen 1980; Kelly and
Bruerd 1987). This unique pattern of dental caries, where the upper in-
cisors become badly decayed, has been described in young children. In
severe cases, the chewing surfaces of the molars become affected, but the
lower incisors rarely develop lesions. The lesions on the upper incisors
begin as a generalized demineralization on the third of the crown next to the
gums and progress so that the tooth is encircled by a ring of decay that may
become so deep that the crown breaks off just above the gum.

This condition occurs when children are put to bed with a bottle of milk,
formula, juice, or sweetened beverages. These practices allow sugars in
milk or other fluids to remain in contact with the tooth surfaces for
extended periods. The position of the upper incisors makes them especially
vulnerable, while the lower incisors are usually protected by the tongue.
These carbohydrates are metabolized to acids by the oral micro-organisms
that are always present on tooth surfaces, and this action is compounded
by the infrequent swallowing and reduced salivary flow that occur during
sleep.

Role of Fluoride

The efficacy of fluoride in the prevention of tooth decay is well established.
It is generally assumed to prevent caries by decreasing the solubility of
tooth enamel, promoting remineralization of the enamel surface, modify-
ing the chemical interactions in plaque, or inhibiting lactic acid production
by cariogenic bacteria (Navia 1985).

Since 1945, when fluoride was first added to community water supplies,
more than 35,000 published scientific papers have attested to the efficacy,

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Dental Diseases O

safety, and cost-effectiveness of fluorides in prevention of tooth decay
(Richmond 1985). Many of these studies demonstrate reductions in dental
caries of 50 percent or more when fluoride is added to a community water
SUPPlY.

One focus ofresearch in the 1930's and 1940's was to determine the optimal
level of fluoride in drinking water. This concentration is about 1 ppm for
temperate regions. Current recommendations for optimum fluoride con-
centrations vary from 0.7 to 1.2 ppm, depending on regional variation in
prevailing air temperature because the amount of water consumed tends to
be less in colder climates. Caries incidence increases when drinking water
contains less than the optimum level of fluoride, but mild forms of fluorosis
(the mottling of tooth surface) can begin to occur at about twice the
optimum level. Fluorosis occurs only when developing teeth are exposed
to excess fluoride, generally over a period of months; once a tooth is fully
formed, continuing fluoride exposure may promote the remineralization
process.

For children living in areas with inadequate concentrations of fluoride in
the water, dental authorities recommend fluoride supplements at dosages
that depend on the natural fluoride content of the local water supply and the
age of the child. The dosages currently recommended by the Council on
Dental Therapeutics of the American Dental Association and the American
Academy of Pediatrics are provided in Table 8-l. The effectiveness of
prenatal fluoride supplementation, however, is uncertain because clinical
studies of its effects on subsequent caries incidence have been equivocal
(Driscoll 1981).

          Table 8-l
Suppiemental Fluoride Dosage Schedrjled
   (in mg F/d*) According to
Fluoride Concentrations of Drinking Water

                     Concentration of
                 Fluoride in Water (ppm)
               LeSS                    Greater
Age (years)         than 0.3       0.3 to 0.7       than 0.7

Birth to 2           0.25    :25           0
2 to 3             0.50                       0
3to13             1.00      030           0
a2.2 mg of sodium fluoride contain 1 mg of fluoride.

Source: Council on Dental Therapeutics 1984.


O Nutrition and Health

Another area of uncertainty concerns current levels of fluoride intake.
When the optimal level of about 1 ppm was originally established, the
primary source of fluoride for human consumption was the water supply.
Today, fluoride is also available from toothpastes, mouth rinses, and soft
drinks and foods prepared with fluoridated water. These sources have
increased the availability of fluoride beyond that originally envisioned,
perhaps to levels that might induce fluorosis (Horowitz et al. 1984). Several
recent studies have observed an increased incidence of mild (barely notice-
able) tooth mottling among children taking fluoride supplements or living in
communities where water is fluoridated. Although there is no evidence that
this condition is harmful, these observations have led some authorities to
suggest reevaluation of previously accepted standards for optimal fluoride
use (Navia 1985; Leverett 1982).

Controversy about water fluoridation is not new. Despite the preponder-
ance of community studies conclusively demonstrating the effectiveness of
both naturally occurring and purposefully supplemented fluoride in drink-
ing water, opposition has been raised on grounds of effectiveness, safety,
and individual rights (Taves 1979; Watson and Schrotenboer 1983). How-
ever, studies have failed to show any relationship between fluoride and
increased risk for heart disease, brain lesions, liver disease, allergies,
kidney disease, mental retardation, cancer, or mutagenicity (Richmond
1985). Indeed, studies of one chronic disease, osteoporosis, suggest a
protective effect for fluoride (Simonen and Laitinen 1985; see chapter on
skeletal diseases). Based on the scientific evidence, the courts have consis-
tently ruled that States and municipalities have the right to implement
fluoridation as a public health procedure (Block 1986; Lee 1986).

Role of Other Dietary Factors

Protein. Experimental data show certain critical periods in the develop
ment of the teeth of young rats, during which a marginal protein deficiency
exerts striking effects (Nakamoto, Mallek, and Miller 1979a, 1979b). When
low-protein diets were fed to rats at any time throughout pregnancy and
lactation, the molars of their offspring were altered in shape and were
significantly smaller than the molars of offspring from control rats (Shaw
and Grifftths 1963; Holloway, Shaw, and Sweeney 1961). Although the
change in tooth size occurred without a reduction in enamel thickness,
minor cusps of the third molars of the offspring from these protein-deficient
females frequently did not develop, suggesting that nutritional deficiencies
can prevent normal tooth development. Caries incidence was higher in the
offspring of protein-deficient females than in control offspring when both
were fed the same caries-producing diet after weaning. The offspring from

360


Dental Diseases 0

protein-depleted females had abnormalities of the salivary glands (de-
creased DNA, RNA, and protein concentrations, and decreased net
weight) and the saliva (greatly reduced salivary flow and small increase in
salivary protein concentration), which may partially explain their increased
caries incidence (Menaker and Navia 1973a, 1973b, 1974).

Supplementing the diet of pregnant and lactating rats with 1 percent DL-
methionine (the limiting amino acid of casein) prevented almost all of the
abnormalities, but supplementation begun at weaning was ineffective
(Shaw and Griffiths 1963). That the deficient nutrient was protein, but not
calories or other nutrients, was demonstrated when protein supplements
alone prevented these abnormalities (Menaker and Navia 1973a, 1973b,
1974).

In humans, protein-energy malnutrition is often associated with poor den-
tal health. Delayed tooth eruption and impaired tooth development are
common findings among children in developing countries where protein,
calories, and other nutrients are inadequate (Steggerda and Hill 1942;
Sweeney 1946). Abnormal lesions on the teeth of younger children in less
developed nations have been reported to be highly susceptible to tooth
decay even when children consume lesser amounts of sugar-containing
foods and consume foods less frequently than children in more highly
developed nations (Sweeney et al. 1969; Sweeney, Saflir, and de Leon
1971). Nevertheless, the permanent teeth in older children and adults in
developing countries are not more susceptible to caries than those in older
children and adults in industrialized countries (Russell 1966). At present,
there is no evidence to indicate that an increase in caries incidence accom-
panies delayed tooth eruption. Little information on the influence of pro-
tein deficiency on the rate of salivary flow or on saliva composition in
humans is available (Vogel 1985).

Fur. In animal studies, increasing the concentration of fat in a diet with the
carbohydrate concentration held constant reduces the caries-producing
potential of the diet (Shaw 1950). This may have to do with the sequence in
which foods are eaten. When dietary sugar is followed by a food such as
cheese (which is high in fat), the usual acid-forming response is blunted and
less acid is present in plaque (Edgar 1981; Edgar et al. 1982; Schachtele and
Jensen 1983). The significance of these observations for human tooth
decay, however, has not yet been established.

Vifnmin A. Studies of the continuously erupting incisor of the rat showed
that a severe deficiency of vitamin A impairs tooth formation (Wolbach and

361


O Nutrition and Health

Howe 1925, 1933; Boyle and Bessey 1941; Schour, Hoffman, and Smith
1941). The observed changes resembled the effects of vitamin A deficiency
on tissues of ectodermal origin elsewhere in the body. Bones formed
entirely during a period of vitamin A deficiency contain reduced amounts
of calcium, suggesting an effect on bone mineralization and the resulting
bone structure. A deficiency of vitamin A for a limited time before tooth
eruption has been shown to increase the susceptibility of rat molars to
caries (Harris and Navia 1980; Navia and Harris 1980). Other studies, in
which the third molars of rats were cultured, showed that vitamin A
deficiency delays tooth formation and interferes with mineralization of
both enamel and dentin (Navia et al. 1984). Vitamin A deficiency has also
been observed to disrupt normal differentiation of rat tooth-forming cells
and to alter the distribution of certain molecular components of dentin and
pulp (Bunyasingh et al. 1984).

Vitamin D and Calcium. In early studies of rickets, deficiencies of a fat-
soluble vitamin, later identified as vitamin D, resulted in the softening and
discoloration of the enamel of developing teeth, delayed tooth eruption,
and an irregular tooth arrangement in the jaw (Mellanby 1918; Mellanby
1919). These defects were also seen in the offspring of pregnant animals
given a vitamin D-deficient (rickets-producing) diet but not in animals that
received daily supplements of cod liver oil (Mellanby 1928). Calcium de%
ciency resulted in less severe defects in the enamel and dentin, but deficien-
cies of both calcium and vitamin D resulted in very poorly formed enamel
and dentin (Mellanby 1923). These early studies indicated the need during
tooth development for adequate dietary intake of calcium and vitamin D.

In a series of clinical trials in England in which children received vitamin D
supplements to their regular diet, modest reductions in dental caries were
observed both for secondary teeth that had erupted before the trials began
and for teeth that erupted during the trial (Committee for the Investigation
of Dental Disease 1936). Despite evidence for a beneficial role of vitamin D
in tooth development, clinical trials to determine whether vitamin D sup-
plements reduce dental caries have yielded varied results (Shaw 1952), and
this area remains uncertain.

A long-term study of dental abnormalities in children showed that the
inherited conditions of vitamin D-dependent rickets or hypoparathyroid
syndrome, both of which reduce levels of plasma calcium, are associated
with abnormal lesions in tooth enamel but normal dentin. Children with low
plasma levels of phosphorus but normal levels of plasma calcium developed
normal enamel but abnormal dentin. Those with low plasma levels of both

362


Dental Diseases O

calcium and phosphorus developed abnormalities in both enamel and
dentin (Nikiforuk and Fraser 1979). The implications of these observations
for dietary intake in normal children are unknown.

Phosphate. An increasing amount of phosphate in the diet reduces experi-
mental caries incidence in rats (Nizel and Harris 1964). but supplementa-
tion of the diet of children with phosphate has not been shown to produce
benefits (Stralfors 1964; Ship and Mickelsen 1964; Averill and Bibby 1964).
Phosphate supplementation of chewing gum is reported to produce a reduc-
tion in caries incidence (Baron and Bilotti 1979; Finn et al. 1978; Jamison
1979; Richardson 1979).

Trace Elements. Certain epidemiologic surveys and experimental animal
studies have suggested that some trace elements such as molybdenum,
vanadium, strontium, and iron can inhibit caries development and that
other elements such as selenium, magnesium, and cadmium can accelerate
caries development. None of these studies has demonstrated either an
independent action of these elements or an action that either augments or
decreases the influence of fluoride (Curzon 1983; Navia 1970).

Other Food Components. Foods containing salts or acids can stimulate
salivary flow, alter its buffering capacity, or decrease microbial acid pro-
duction. Food components such as lectins (Gibbons and Dankers 1981,
1982), tannins (Kashket, Paolino, and van Houte 1985), and other less well-
characterized substances (Madsen 1970) can inactivate bacteria or influ-
ence their metabolism and reproductive ability and, in these ways, may
affect caries incidence.

Alternative Sweeteners. Sucrose and other simple carbohydrates can be
replaced by polyols or non-nutritive sweeteners in many kinds of foods.
The benefits of such products must take into account the quantities of
cariogemc sweeteners that must be replaced to achieve significant caries
reduction, the relationship of a food's overall chemical composition and
physical properties to its cariogenicity, and the possibility of other nutri-
tional or health effects (Hoskins 1978).

Role of Diet in Periodontal Disease

Periodontal disease is an infection of the gums and supporting structures
caused mainly by the microbial flora that adhere to dental plaque. Like
dental caries, the etiology of this disease includes specific microbiologic,
environmental, and systemic components. The gingival sulcus (the space

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0 Nutrition and Health

between the gums and the teeth) harbors bacteria that directly and indi-
rectly affect the formation of periodontal lesions and the later destruction
of periodontal tissues and their cellular components. Environmental infht-
ences on the gums include dietary sugars and other factors that promote the
formation of plaque on tooth surfaces, entrapment of food in periodontal
lesions, and poor dental hygiene. Systemic influences on the initiation and
progression of periodontal lesions are less well defined and more difficult to
investigate, although there is considerable evidence that persons who are
diabetic, immunosuppressed, or genetically susceptible are especially
prone to periodontal disease. In general, only severe nutritional deficien-
cies or extreme endocrinologic imbalances appear to adversely affect the
resistance of the gums. Diet may influence periodontal disease not only
through its effects on plaque formation, but also through stimulation of
salivary flow, antigenic stimulation of immune mechanisms, and enhance-
ment of host repair and defense mechanisms (Alfano 1976; Navia 1985);
however, its precise role is as yet undefined.

Role of Calcium

Calcium is a necessary mineral in the formation of all calcilied tissues,
including those of the periodontium. In adult dogs, a low-calcium diet
produces radiologic evidence of loss ofalveolar bone within 2 months and a
periodontal syndrome within 1 year (Hemikson 1968). When the diet was
supplemented with calcium, the periodontal disease reversed within 6
months.

It has been proposed that periodontal disease is caused by internal resorp-
tion of bone due to an imbalance of dietary calcium-to-phosphorus ratio
(Krook et al..1972). A more recent study (Svanberg et al. 1973) using similar
conditions failed to confirm those results.. Most scientists believe that
periodontal disease is initiated by subgingival bacterial infection. Addition-
al studies are necessary before the role of calcium in the etiology of
periodontal disease can be ascertained.

Role of Vitamin C

A diet deficient in vitamin C (ascorbic acid) causes scurvy in humans.
Advanced disease produces gingival changes and loosening of the teeth.
Scurvy.and some types of periodontal disease in humans are similar to
experimental scurvy in the guinea pig and in both Old and New World
monkeys, with bleeding `of the gingiva, destruction of the periodontal
membranes, and loosening and ultimate loss of teeth (Alvares et al. 1981;
Boyle and Bessey 1941; Glickman 1948). There is ample evidence that
ascorbic acid, which is required for the formation of collagen in connective

364


Dental Diseases O

tissues, is necessary for the repair and maintenance of periodontal tissues.
Only severe deficiencies result in aggravating periodontal disease.

Role of Folate

Folate is a member of the vitamin-B complex necessary for the normal
production of red blood cells. Folate deficiency is a common type of
hypovitaminosis in humans. In experimental gingivitis studies in humans,
folate supplementation resulted in significantly less inflammation of gum
tissues (Vogel and Alvares 1985). Its role in gingivitis and periodontal
disease is under investigation.

Role of Other Nutrients

Various periodontal abnormalities have been produced in experimental
animals as a result of nutritional deficiencies of protein (Chawla and Glick-
man 1951), tryptophan (Bavetta and Bemick 1956), calcium (Becks and
Weber 1931), magnesium (Klein, Orent, and McCollum 1935), vitamin A
(King 1940), vitamin D (Becks and Weber 1931), and B-complex vitamins
(Becks, Wainwright, and Morgan 1943; Tomlinson 1939). However, in these
studies, only severe deficiencies resulted in periodontal destruction, and
most of these experiments were carried out in grown animals.

On the basis of current knowledge, nutritional deficiencies or imbalances
do not seem likely to exert major influences on the prevalence or severity of
periodontal disease in the general population. However, the ability of
individuals with nutritional abnormalities to resist the progression of peri-
odontal lesions initiated by microbiologic and environmental influences
may be reduced. Severe protein malnutrition might alter the immunologic
system in such a way as to render the host unusually susceptible to
infection.

Role of Diet in Other Dental Conditions

Residual Ridge Resorption

The alveolar ridge (the bony ridge in which teeth are positioned) is vulner-
able to the resorption or loss of mineral subsequent to tooth loss. This
process results in a progressive change in the shape and a reduction in the
size of the ridge that greatly affects the stability and retention of dentures
(Atwood 1971,1979; Tallgren 1972). While some patients adapt to ill-fitting
dentures and contend that they can eat anything, many patients adapt by
changing their diet (Yurkstas and Emerson 1964).

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0 Nutrition and Health

Resorption of the residual ridge results from an imbalance of bone resorp-
tion and bone formation, as does osteoporosis, leading to speculation about
a possible relationship between these conditions. The role of calcium in the
prevention and treatment of osteoporosis, either alone or in combination
with vitamin D, estrogen, or fluoride, has received much attention, and
calcium deficiency has been reported to be a factor in both osteoporosis
and residual ridge resorption (Barzel 1979; Menczel et al. 1982). A study of
44 toothless patients found a relationship between a history of reduced
dietary calcium intake and severe accumulated ridge reduction (Wical and
Swoope 1974). Denture patients who were given daily supplements of
calcium and vitamin D in a l-year double-blind controlled study had 36
percent less bone loss than the group that received a placebo (Wical and
Brussee 1979). However, the wide overlap of bone loss in the treatment and
control groups suggested considerable individual variation and the need for
further research in this area. Approaches available to minimize residual
ridge resorption or restore lost bone are the following: use of implants,
bone rebuilding with calcium phosphate preparations, and prevention of
tooth loss.

Oral Cancer

In its earliest stages, oral cancer is painless and may present no overt
symptoms. Because dentists see many people regularly, and because den-
tists have access to the oral cavity, they are in a unique position to provide
early identification of suspicious lesions and signs of tobacco habits that put
people at risk for oral and other diseases.

Although alcohol and chewing tobacco are known to increase risk, the role
of nutrition in oral cancer in humans is less well established (see cancer
chapter). In part, this is because epidemiologic studies on the relationship
of nutrients to cancers elsewhere in the body have not been extended to
include oral lesions. However, animal models have been developed for the
experimental production of oral cancer that take advantage of the easy
accessibility of the tongue and the mucosa of the oral pouch of the hamster
for the application of suspected carcinogens and for later observation of
their effects (Marefat and Shklar 1977; Shklar 1972).

These models permit the evaluation of nutritional influences in cancer
formation. In several studies, animals whose diets were supplemented with
derivatives of vitamin A developed oral tumors that were fewer, smaller,
and later in appearance on exposure to the carcinogen 9,lO dimethyl-1,2
benzanthracene (DMBA) than those in animals that had not received the
supplement (Shklar, Marefat, et al. 1980; Shklar, Schwartz, et al. 1980;

366


Dental Diseases O

Burge-Bottenbley and Shklar 1983). A similar test of vitamin E (DL-L-
tocopherol) produced fewer and smaller tumors in the animals that re-
ceived it (Shklar 1982; Schwartz et al. 1985; Odukoya. Hawach. and Shklar
1984). More study of these issues is needed. Similarly, results from small
studies on the influence of nutrients on the course of head and neck cancer
suggest the need for further investigation (Dwyer et al. 1986).

Effects of Tooth Loss on Nutritional Status

The loss of teeth in adulthood should not be considered a normal or an
inevitable event, but a pathologic result of disease or trauma that affects the
normal physiologic process of the jaws, teeth. muscles. and nerves of the
mouth.

Chewing Ability

The loss of natural teeth as a result of dental caries, periodontal disease, or
trauma significantly reduces the ability to chew foods, as demonstrated by
a variety of chewing-efficiency tests (Manly and Vinton 1951; Yurkstas,
Fridley, and Manly 1951; Kapur, Soman, and Yurkstas 1974; Rissin et al.
1978; Kapur and Garrett 1984; Perez, Kapur, and Garrett 1985). Other
studies suggest that tooth loss leads to reduced force in chewing such foods
as carrots, meats, raw vegetables, and peanuts; markedly lower chewing
performance (Manly and Vinton 195 1; Kapur and Garrett 1984); and avoid-
ance of certain hard-to-chew foods (Yurkstas and Emerson 1964). Patients
with reduced salivary flow may be unable to wear removable dental pros-
theses due to lack of lubrication (VA 1986).

Swallowing Ability

Dentures can cause a loss of sensation in the mouth that can lead to
problems in swallowing. In a study of 584 individuals who had to have a
foreign object remaved from the esophagus, the absence of natural teeth
was considered a major factor (Ray and Vinson 1958). Dentists are urged to
warn all patients provided with partial or complete dentures about this
hazard and about the need for care in the preparation and chewing of food.
Of 16 patients seen during 1 year because of impaction of a foreign body in
the throat, only 3 had normal teeth (Wengraf 1969).

Choking on food was reported to be the sixth most common cause of
accidental death in the United States in 1979, with 700 of 2,900 fatalities
occurring among people 75 years or older (NSC 1979). Studies of choking
victims have found that many have poor dental status (Haugen 1963;

367


0 Nutrition and Health

Anderson 1977), and poorly fitting dentures are frequently suspected to be
a factor in the blockage of airways with inadequately chewed and swal-
lowed food.

Effect on Food Selection

In addition to reduced chewing efficiency, various studies have demon-
strated that loss of natural teeth, even when replaced with dentures, can
cause the following impairments: diminished ability to discriminate food
particle size and texture, such as ability to differentiate between soggy and
crisp wafers (Kapur and Collister 1970); increased flow of stimulated
salivary gland secretion (Kapur, Collister, and Fischer 1967; Kapur and
Garrett 1984); and diminished ability to perceive subtle differences in the
sweet taste of certain solid foods (Giddon et al. 1964).

Effect on Nutritional Status

Some early studies reported that inadequate dental function as a result of
toothlessness or inadequate prosthetic devices contributed to the estab-
lishment and maintenance of nutritional deficiencies (Mann, Mann, and
Spies 1945; Greene, Dreizen, and Spies 1947; Ruikka, Sourander, and
Kasanen 1967; Makila 1%8, 1%9a, 1969b). However, dietary intake can be
adequate in an individual with reduced chewing provided that food is
selected carefully and prepared appropriately (Geissler and Bates 1984).

Implications for Public Health Policy

Dietary Guidance

General Public

Dietary factors of principal interest in dental diseases are sugars and
fluoride. Frequent consumption of sugars, especially sucrose, promotes
formation of dental plaque, the key predisposing cause of both caries and
periodontal disease. In the United States, the daily intake of sugars ranges
on average from 62 to 143 g, or 18 to 32 percent of total caloric intake.
Evidence exists that sugars as they are consumed in the average American
diet contribute to the development of de ital caries, suggesting that the
general public should reduce its sugar consumption.

The role of fluoride in prevention of tooth decay is also well established
from animal studies and from human epidemiology and clinical trials.
Although fluoride is present in foods, the most efficient source of this
nutrient for the general public is community drinking water that naturally

368


Dental Diseases 0

contains fluoride at an optimal level or to which fluoride is added to achieve
the optimal level. Most, but not all, water supplies can be fluoridated, and
current recommendations for optimum fluoride concentrations vary from
0.7 to 1.2 ppm depending on regional variation according to prevailing air
temperature. Conclusive evidence shows that such levels of fluoride are
safe.

Although other nutrients such as vitamin A, vitamin C, calcium, and
phosphate may also be associated with prevention of dental diseases,
evidence is insufftcient at this time to recommend changes in dietary
patterns on the basis of their relationship to these conditions for the general
public.

Special Populations

Persons with diminished salivary flow are at special risk for caries and
periodontal disease. They also may be unable to wear removable dental
prostheses due to the lack of lubrication by saliva. Artificial saliva prepara-
tions containing fluoride and topical fluoride gels help to prevent tooth
decay in such persons and can be recommended as an adjunct to sugar-
restricted diets and appropriate dietary counseling. Children over the age
of 6 months are at risk for nursing bottle caries, and their parents and
caregivers should receive guidance in dietary and behavioral approaches to
prevent this condition. Evidence related to the benefits of fluoride con-
sumption by pregnant women on subsequent tooth development of the
fetus and caries in the offspring is insufficient to recommend fluoride
supplementation during pregnancy. Individuals with diabetes are especial-
ly prone to periodontal infections and should take special care to use
available dietary and therapeutic means to control disease.

Nutrition Programs and Sewices

Food Labels

The presence and relative amount of added sugars, especially sucrose,
contained in processed foods, as indicated by ingredient lists on food
labels, should continue to play an important role in identifying dietary
factors associated with dental disease.

Food Services

Evidence related to the role of dietary factors in dental disease suggests
that food service programs should provide optimally fluoridated drinking
water and promote noncariogenic foods, especially in programs for popula-
tions at high risk for dental diseases.

369


O Nutrition and Health

Special Populations

Persons with an active history of dental caries or with reduced salivary flow
and parents of young children should be provided with counseling and
assistance in developing diets low in cariogenic foods and in accessing
appropriate sources of fluoride. Persons with diabetes are especially prone
to periodontal infections and should take special care to use available
dietary and therapeutic means to control their disease (see chapter on
diabetes).

Research and Sunreillance

Research and surveillance issues of priority related to the role of diet in
dental diseases should include investigations into:
o The definition of critical periods of development of dental tissues that
may be sensitive to nutrient intake.
o The role of nutritional factors in the maintenance and repair of the
periodontium and oral tissues.

o The relationship between nutritional imbalances during tooth develop-
ment and the formation of tooth lesions or defects that may increase
caries susceptibility in children.

o The role of nutrition and nutritional status in the etiology and patho-
genesis of dental diseases in older persons and other high-risk popula-
tions.

o The relationship between nutrition and both the immune and the
nonspecific defense mechanisms of oral tissues and fluids.
o The most effective means to educate the public on the role of water
fluoridation, diet, and dental care in preventing dental diseases.
o The mechanisms of fluoride action in the prevention of dental disease
or osteoporosis.

o The effect of dietary factors such as vitamin A, vitamin E, and alcohol
on the initiation and progression of oral cancers.
o Epidemiologic methods to determine the correlation between mal-
nutrition and dental caries and/or periodontal disease.
o The role of calcium in the etiology and/or prevention of residual ridge
resorption and periodontal disease.
o Estimation of the levels of fluoride from all sources in the diets of
children.

o Estimation of the extent of dental fluorosis in the population.

370


Dental Diseases O

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0 Nutrition and Health

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Chapter 9

Kidney Diseases

Bones can break, muscles can atrophy,
glands can loaf, even the brain can go to
sleep, without immediately endangering our
survival; but should the kidneys fail . . .
neither bone, muscle, gland, nor brain could
          carry on.
   Homer W. Smith (1895-1%2)
  From Fish to Philosopher, Ch. I

Introduction

Histokal Perspective

For centuries, it has been known that dietary intake affects the composition
of urine (see, for example, the discussion in the chapter on diabetes) and
must, therefore, have an effect on kidney function. The idea that protein
restriction might prevent further loss of kidney function in people with
chronic renal insufficiency emerged during the first half of the 20th century
(Addis 1948). Early studies in experimental animals suggested that excre-
tion of urea by the kidney required "renal work." This idea received
support from studies demonstrating that animals fed high-protein diets for
prolonged time periods have enlarged kidneys as well as increased urea
excretion. Early investigations also revealed significant increases in renal
blood flow and glomerular filtration rates when meat was substituted for
dietary carbohydrate or when extra protein was added to the diet (Brenner,
Meyer, and Hostetter 1982).

These studies suggested that high-protein diets might stress the kidney
workload to the point of failure. They also suggested that protein restriction
might minimize the work required of kidneys that were already diseased
and, thereby, prevent futher functional losses (Addis 1948). Additional
research indicated that protein restriction could retard the progression of
renal failure (Blatherwick and Medlar 1937; Farr and Smadel 1939; Addis
1948). However, the data supporting these observations were derived from
rats. the study design was often faulty, and the applicability of these
findings to humans-while of great interest-was uncertain.

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O Nutrition and Health

In later decades, the development of kidney dialysis and transplantation
techniques focused attention on methods-including manipulation of
diet-to treat renal disease rather than to prevent it. Today, as more is
learned about the progression of chronic renal disease, the role of diet in the
etiology of this condition has become increasingly apparent.

Significance for Public Health

End-stage renal disease (ESRD) occurs when the kidneys are chronically
unable to function sufficiently on their own, so that dialysis or kidney
transplantation becomes necessary to maintain life. ESRD occurs in about
19,000 people each year in the United States (Schmidt, Blumenkrantz, and
Wiegman 1983), and blacks are disproportionately affected as a result of
hypertension-induced ESRD. Currently, about 80,000 persons undergo
maintenance hemodialysis two or three times a week and another 11,000
persons undergo continuous ambulatory peritoneal dialysis (HCFA 1984).
Approximately 9,000 kidney transplants were performed in 1986.

The estimated annual cost for maintenance hemodialysis and peritoneal
dialysis treatment in the United States, including the expenses incurred by
Medicare, State and private insurers, and Veterans Administration, mili-
tary, and public health hospitals, is well over $2 billion (HCFA 1984). This
estimate does not include the costs for pensions and from lost income, nor
does it include the expenses for ancillary hospitalization, which is a fre-
quent occurrence. A maintenance dialysis patient spends an average of
approximately 15 to 16 days a year in the hospital (Blagg, Wahl, and Lamers
1983; Carlson et al. 1984). In addition to ;he financial costs of ESRD
treatment, the patient and the patient's family often endure great physical
and emotional suffering from the ravages of chronic renal failure, the
frequent superimposed illnesses, and the burden of the treatment reg-
imens.

Nutrition may affect persons who have, or are at risk for developing, ESRD
in two ways. First, evidence shows that the intake of certain nutrients may
influence the rate of progression of renal failure in persons with underlying
renal disease. Second, individuals with advanced renal failure and those
who undergo maintenance dialysis treatment often suffer from malnutri-
tion and other nutritional disorders. It is possible, but not proved, that
these nutrition-related complications may contribute to the debility, high
incidence of superimposed illnesses, and poor rehabilitation typical of this
condition.


Kidney Diseases 0

Scientific Background

Functioning kidneys regulate the composition and volume.of body fluids
within very narrow limits. They do so by balancing intake and excretion of
body fluids and the waste products derived from metabolic processes. If
the kidneys fail to maintain homeostasis, a wide range of potentially lethal
metabolic disorders can develop throughout the body.

Each human kidney contains about 1.2 million separate functional units
called nephrons (Tisher and Madsen 1986), each with a glomerulus that
removes ("clears") unwanted salts, waste products, and other chemicals
from plasma along with the water in which they are dissolved. Normally,
very little protein is removed. These -substances are excreted from the
kidney through a tubule that is connected to each glomerulus. The tubule
can reabsorb back into the circulation most of the filtered water and some of
the chemical substances, and it can actively remove other chemicals from
blood. The fluids and chemicals that are not reabsorbed by the tubules
drain into collecting ducts, flow through the ureter, and are stored in the
bladder for eventual excretion as urine. The rate at which the glomeruli
clear the blood of waste products is called the glomerular filtration rate
(GFR).

Kidney Stones

When the concentration of certain salts in urine exceeds the limits of
solubility, the salts can crystallize and form stones within the kidney or
other parts of the urinary tract. The substances found most frequently in
kidney stones include calcium, oxalate, phosphate, uric acid, and cystine
(Smith, Van den Berg, and Wilson 1979). Although these substances derive
from foods, oxalate and urate are also synthesized endogenously, and
excessive dietary intake has not been shown to cause stone formation in
healthy people. Instead, the supersaturated concentration of these sub-
stances in urine is the critical factor that set the stage for stone formation
together with inadequate production of crystallization inhibitors (Kok,
Papapoulos, and Bijvoet 1986) or inborn errors of metabolism that produce
large amounts of the relevant metabolites.

Treatment of these conditions by diet or drugs is aimed at reducing the
concentration of stone-forming substances in urine. The principal means to
this end is to increase urine production to at least 2,500 ml per 24 hours by
encouraging patients to drink water throughout the day unless on a low-
fluid regimen (Smith, Van den Berg, and Wilson 1979).

383


O Nutrition and Health

Additional dietary measures to treat patients with chronic stone-forming
conditions depend on the composition of the stones as well as on the
genetic defect. For example, some persons who excrete excessive amounts
of calcium in their urine reduce these levels in response to a low-calcium
diet (Coe 1984); other persons increase calcium excretion, apparently
because they compensate by synthesizing greater amounts of 1,25-di-
hydroxyvitamin D, absorbing more calcium, and increasing the release of
calcium from bone (Broadus et al. 1984).

Dietary measures to reduce oxalate excretion include restriction of oxa-
late-rich foods, such as rhubarb, spinach, chocolate, and tea, and restric-
tion of excessive intake of ascorbic acid (vitamin C), which is metabolized
to oxalate. Uric acid stones have been treated with diets low in purine-rich
foods, such as organ meats, fish, shellfish, and legumes. Persons with
cystine-containing stones have responded successfully to low-protein diets
(Sherrard 1983). Calcium phosphate stones have been treated successfully,
if paradoxically, with high-phosphate diets that increase urinary excretion
of pyrophosphate, an inhibitor of calcium crystallization (Smith, Van den
Berg, and Wilson 1979). Reports that low-carbohydrate, low-protein, high-
fiber, or vegetarian diets prevent stone formation have not been confirmed
(Anonymous 1983).

Chronic Renal Failure

Chronic renal failure is permanent kidney damage with an associated
depression of the GFR; it results in retention of waste products, abnormal
plasma biochemistry, and symptoms ranging from lassitude to convulsions
to death. Chronic renal failure is the consequence of longstanding and
progressive renal damage and is usually irreversible. It may result from
chronic glomerular disease (e.g., glomerulonephritis), chronic infections,
polycystic kidneys or other congenital anomalies, vascular diseases,
obstructive processes such as kidney stones, certain systemic or endocrine
diseases, drug reactions, or hypertension.

The early stage of renal insufficiency occurs when the GFR falls to about 40
to 70 ml/min from a normal level of about 80 to 130 ml/min. Studies in
animals with renal injury indicate that when the loss of kidney function
causes renal insufficiency, the remaining functioning nephrons enlarge and
the GFR increases (Deen et al. 1974; Hostetter et al. 1981). As a result of
these adaptive changes, the loss of kidney function is proportionately less
than might be expected from the loss of nephrons. In the injured or diseased
kidney, increases in capillary blood flow and in the blood pressure gradient
across the capillary wall have been reported (Hostetter, Troy, and Brenner

384


Kidney Diseases O

1981). Also, the chemical, electrical, and physical barriers to the movement
of plasma proteins across the glomerulus into the renal tubule may be
impaired (Olson et al. 1979, 1982).

For many years researchers have known that chronic renal disease often
progresses to ESRD (Mitch et al. 1976; Rutherford et al. 1977; Adler and
Kopple 1983; Klahr, Buerkert, and F'urkerson 1983). Furthermore. the
progressive loss of renal function occurs even in persons in whom the
underlying cause of the renal disease has disappeared or abated-for
example, in persons who have had relief of urinary tract obstruction,
control of hypertension, or partial recovery from certain types of acute
renal failure (McCormack et al. 1958; Kleinknecht et al. 1973; Rodriguez-
Iturbe et al. 1976; Senekjian et al. 1979; Torres et al. 1980). Although the
rate of progression of renal failure varies greatly among individuals, the
decline in kidney function is constant in many individuals so that remaining
function declines in approximately linear fashion (Mitch et al. 1976;
Rutherford et al. 1977; Barsotti et al. 1981). It is not known in what
percentage of persons with renal insufficiency will progress to renal failure,
but the suspicion is that most people who lose more than 50 percent of their
GFR will experience continued progression of the disease.

Chronic renal failure causes pervasive disorders in appetite as well as in the
body's absorption, excretion, and metabolism of many nutrients. Conse-
quently, nutritional therapy is essential in managing this condition. These
disorders include: the accumulation in blood of urea and other waste
products of protein metabolism and the clinical consequences of this ac-
cumulation (nausea, vomiting, and weakness leading to convulsions and
coma) (Kopple 1978); a decreased ability of the kidney to either excrete a
large salt load or to conserve salt when dietary sodium is restricted (Gonick
et al. 1966); impaired ability to excrete water, potassium, magnesium,
acids, and other compounds (David et al. 1972); a tendency to retain
phosphorus (Bricker 1972; Cobum et al. 1977); decreased intestinal ab-
sorption of calcium (Cobum et al. 1977) and possibly iron (Lawson et al.
t 97 1) ; and a high risk for developing certain vitamin deficiencies-particu-
larly vitamin B,, vitamin C, folic acid, and the active form of vitamin D,
t-25-dihydroxycholecalciferol, which is synthesized by the kidney (Kopple
and Swendseid 1975).

The chronic renal failure patient is also likely to accumulate certain poten-
tially toxic chemicals that normally are ingested in small amounts and
excreted in the urine. Aluminum is such a toxin; it can cause severe bone
disease, dementia, muscle weakness, and anemia in persons with kidney

385


0 Nutrition and Health

failure (Elliott, MacDougall, and Fell 1978; Drueke 1980; Kaiser et al. 1984;
Polinsky and Gruskin 1984). Currently, common sources of aluminum are
the antacids aluminum hydroxide and aluminum carbonate, which persons
with kidney disease frequently ingest to reduce intestinal absorption of
phosphorus. Formerly, hemodialysis solutions contaminated with alumi-
num often caused aluminum toxicity, but such contamination has now been
eliminated.

Acute Renal Failure

Acute renal failure is a general term used to describe a sudden decrease in
the GFR, often to less than 2 percent of normal. Its early signs result from
the accumulation of urea and other nitrogenous wastes. Electrolyte imbal-
ance, metabolic acidosis, and other severe effects follow, as the person
becomes increasingly uremic and other body systems are disrupted. Its
most common causes are shock, severe infection, trauma, drugs, obstruc-
tion, and certain types of glomerulonephritis. In most instances, the condi-
tion is reversible if the person survives the underlying disease (Mitch and
Wilmore 1988).

Despite the many advances in medical care during the past few decades,
morbidity and mortality from acute renal failure remain high (Brezis,
Rosen, and Epstein 1986). When associated with obstetrical complications,
the mortality rate is about 17 percent; acute renal failure associated with
surgery or trauma has a mortality of 51 to 53 percent (Brezis, Rosen, and
Epstein 1986; Mitch and Wilmore 1988), and that caused by shock or sepsis
accompanied by inadequate nutrition has a mortality rate of about 85
percent (Feinstein et al. 1981; Feinstein et al. 1983).

Protein-Energy Malnutrition in Renal Disease

One of the most prevalent nutritional complications of chronic renal failure
is wasting, or protein-energy malnutrition (Kopple 1978, 1984). There are
many causes for this wasting. Dietary intake, particularly of calories, is
often inadequate (Kluthe et al. 1978; Kopple 1978; Salusky et al. 1983;
Wolfson et al. 1984) because of loss of appetite due to the accumulation of
toxins in kidney failure, the unappealing diets prescribed in renal failure,
emotional depression, the debilitating effects of chronic illnesses, and the
effects of acute superimposed illnesses on the patient's ability to eat or to
accept intestinal tube feeding. The high incidence of superimposed ill-
nesses can cause protein breakdown and wasting (Blagg, Wahl, and Lamers
1983; Carlson et al. 1984; Kopple 1984), as can the dialysis procedure itself.
During dialysis, many biologically valuable nutrients may be lost (Kopple
1978), including amino acids, peptides, proteins (with peritoneal dialysis),


Kidney Diseases O

glucose (during hemodialysis with glucose-free dialysate), and certain
water-soluble vitamins. The hemodialysis procedure also seems to increase
net protein breakdown by unknown mechanisms (Borah et al. 1978; Farrell
and Hone 1980). Renal failure patients sustain blood losses from frequent
laboratory testing, occult gastrointestinal bleeding (very common in renal
failure patients), and the sequestration of blood in the hemodialysis equip-
ment (Linton et al. 1977). Because blood is rich in protein, these losses may
cause serious protein depletion.

Patients with acute renal failure also demonstrate varying degrees of pro-
tein wasting. In some individuals, the net rate of protein breakdown (i.e.,
the difference between the total rate of protein degradation and protein
synthesis in the body) may be very low-as little as 25 to 30 g/day, but in
others, it may be as high as 240 g/day (Feinstein et al. 1981; Feinstein et al.
1983). For comparison, the total protein mass in a typical male is only about
6,000 g, excluding coilagenous, or structural. fibrous protein (Cahill 1970).
Patients with acute renal failure are often unwilling or unable to eat because
of uremic poisoning or underlying illnesses such as abdominal infection,
trauma, and surgical wounds. Thus, starvation often accompanies acute
renal failure unless specific steps are inaugurated to nourish the patient.

In the United States, dialysis treatment is readily available for most pa-
tients with acute renal failure. Hence, patients with this condition do not
often die from uremic poisoning; rather, death comes from complications
such as infection associated with failure to heal wounds. Because, as
discussed in the chapter on infections and immunity, protein-energy mal-
nutrition may reduce the body's resistance to infection and impair wound
healing, the profound wasting typical of acute renal failure may contribute
to the high morbidity and mortality of this condition.

Dietary Management of Renal Failure

Diseased kidneys cannot clear metabolic waste products from the blood,
maintain fluid and electrolyte balance, or convert vitamin D to its active
form. The resulting elevated levels of nitrogenous wastes, electrolytes, and
other metabolites can depress appetite and impair absorption of essential
nutrients, thus establishing conditions that lead to uremia and malnutrition.
Moreover, treatment of renal disease may demand severe dietary restric-
tions or induce nutrient losses. Dietary management of this condition,
therefore, must provide protein, energy, and other essential nutrients in
amounts adequate to avoid deficiencies but sufficiently restricted to avoid
stressing the diminished excretory capacity of the diseased kidney. The
goals of nutritional therapy for both acute and chronic renal failure are to


O Nutrition and Health

maintain optimal nutritional status, to minimize the toxic effects of excess
urea in blood, to prevent loss of lean body mass, to promote patient well-
being, to retard the progression of renal failure, and to postpone initiation
of dialysis (Burton and Hirschman 1983; Abel 1983). In children, an addi-
tional goal is to maintain growth rates as close to normal as possible
(Holliday 1983).

These goals are accomplished by the methods listed below.

Restricting Fluid Intake. Energy, protein, and other essential nutrients are
provided in as small a fluid volume as is possible to maintain water balance.

Restricting Protein. Nitrogen balance must be maintained without any
unnecessary accumulation of urea or other toxic nitrogenous waste prod-
ucts. The degree of protein restriction depends on the severity of renal
damage as assessed by the use of GFR determinations. To enhance incor-
poration of amino acids into body protein and to reduce protein breakdown
in more severely ill persons, dietary protein or supplements of high biologic
value (containing a high proportion of essential amino acids) are often
recommended (Burton and Hirschman 1983).

Increasing Energy Intake. The higher the energy intake, the less dietary
protein is required to maintain nitrogen balance. Increasing the carbohy-
drate and fat content of the diet provides calories that do not stress the
compromised excretory capacity of the kidney. This energy is protein-
sparing; it improves nitrogen balance and prevents catabolism of body
proteins. Patients with acute renal failure, however, are often unable to
tolerate high carbohydrate loads and may require insulin administration
(Abel 1983).

Regulating Phosphate, Calcium, and Magnesium Intake. Intake of certain
nutrients must be monitored carefully to ensure that they do not accumu-
late in blood and cause problems. Phosphate restriction is necessary to
prevent the metabolic bone disease that often accompanies renal failure;
phosphate levels can also be regulated with phosphate-binding agents that
cause dietary phosphate to be excreted rather than absorbed. Calcium may
be administered as a supplement as needed. Excessive magnesium levels
are not usually present unless magnesium-containing antacids are used;
avoiding them or using magnesium-binding agents prevents toxic ac-
cumulation of this substance.

388


Kidney Diseases O

Supplementing Vitamins and Trace Elements. Supplemental water-soluble
vitamins and trace elements are usually provided to compensate for inade-
quate intake and losses in dialysis.

Using Enteral and Parenteral Methods of Nutritional Support. Intravenous
administration of nutrients and energy may be necessary for patients with
acute renal failure who are unable to take food by mouth (Abel 1983).
Administration of supplemental nutrients by mouth or tube has also proved
helpful in certain cases.

Providing Appropriate Counseling and Support. Diets for renal patients
are based on contradictory principles (meet nutritional needs but restrict
protein and phosphorus), are especially restrictive, and require careful
monitoring of the patient's nutritional status. Thus, trained nutrition pro-
fessionals are usually essential for dietary management. Long-term nutri-
tion counseling of patient and family is especially necessary for children
with renal disease to promote growth without increasing the kidneys'
excretory load (Holliday 1983).

Key Scientific Issues

o Role of Protein in Renal Disease
0 Role of Phosphate in Renal Disease
o Role of Lipids in Renal Disease

Role of Protein in Renal Disease

Chronic Renal Failure

Renal function begins to decline in normal humans after about the fourth
decade of life (Rowe et al. 1976), and it has been postulated that high-protein
diets may contribute to this decline. Typical protein intake among Ameri-
cans is considerably higher than the Recommended Dietary Allowance
(RDA) for dietary protein (NRC 1980), and in healthy young men and
women, a high protein intake has been noted to increase renal blood flow
and the GFR (Pullman et al. 1954; Wiseman et al. 1987). There are also
similarities between the type of scarring that occurs in normal aging human
kidneys and the kidneys of rats fed high-protein diets. In adults who have
had a congenital absence, failure of development, or surgical removal of
one kidney during childhood, an abnormally high incidence of spontaneous

389


O Nutrition and Health

glomerular scarring occurs in the remaining kidney (Kiprov, Colvin, and
McCluskey 1982). Although the precise cause is not known, one theory is
that increased glomerular capillary blood flow and pressure associated with
high-protein diets may contribute to progressive renal injury in certain
individuals.

In rats, a high-protein diet stimulates an increase in glomerular filtration
rate, capillary blood flow, capillary blood pressure gradients, and enlarge-
ment of individual nephrons, whereas a low-protein diet will blunt or
prevent these responses (Hostetter et al. 1981). Normal rats fed high-
protein diets throughout life have a higher incidence of renal disease in old
age (Striker et al. 1969; Lalich, Faith, and Harding 1970; Everitt, Porter,
and Wyndham 1982; Zucchelli et al. 1983). When fed a high-protein diet,
rats with renal injury develop progressive renal failure. When such animals
are fed a low$rotein diet, the progression of renal failure is retarded or
arrested (Blatherwick and Medlar 1937; Farr and Smadel 1939). One cur-
rent hypothesis is that a high-protein intake causes filtration and excretion
of protein and, thus, causes progressive injury to the glomerulus, including
its basement membrane (filtering wall), by increasing both glomerular
capillary blood flow and intracapillary blood -pressure (Hostetter et al.
1981; Brenner, Meyer, and Hostetter 1982). This hypothesis further holds
that a low-protein diet retards or stops progressive renal damage by pre-
venting these high pressures and flow rates.

Traditionally, dietary protein restriction has been used to minimize the
toxicity that occurs in renal failure (Kopple et al. 1%8). Many of the waste
products that accumulate in kidney~failure are products of amino acid and
protein metabolism. Current evidence suggests that some of these waste
products cause toxic symptoms.

Recent studies in rats and humans have demonstrated that dietary control
can retard the rate of progression of renal failure in a variety of renal _
diseases (Mitch et al. 1984). In rats, several models of renal insufficiency
have been studied, including surgical removal of renal tissue, ligation of the
arteries to the kidney, and experimental glomerulonephritis (Ibels et al.
1978; Karlinsky et al. 1980; Haut et al. 1980; Laouari et al. 1983; Kenner et
al. 1985). In these animals, diets low in protein or phosphorus retarded or
prevented progression of renal failure.

In humans with renal insufficiency, virtually all recent studies indicate that
a diet low in protein or phosphorus retards the progression of renal failure
(Maschio et al. 1982; Alvestrand, Ahlberg, and Bergstrom 1983; Barsotti et
al. 1983; Barsotti et al. 1984; Gretz, Korb, and Strauch 1983; Mitch et al.

390


Kidney Diseases O

1984; Rosman et al. 1984). Each of these studies, however, has limitations
inherent in experimental design related to the retrospective nature of many
of the studies, an insufficient number of patients studied, the lack of control
groups, poor documentation of patients' actual intake, and the paucity or
absence of data that indicate whether these restrictive diets induce mal-
nutrition. Adequate controls are especially important because not all per-
sons with renal insufficiency progress to advanced renal failure, and the
rate of progression can vary markedly from individual to individual.

In assessing protein restriction in renal failure management, some investi-
gators have used a modifled low-protein diet supplemented with the nine
essential amino acids or with mixtures of some essential amino acids and
ketoacid or hydroxyacid analogs of other essential amino acids (Walser
1975; Alvestrand, Ahlberg, and Bergstrom 1983; Barsotti et al. 1983;
Gretz, Korb, and Strauch 1983; Mitch et al. 1984). The ketoacid or hydrox-
yacid analog is structurally identical to its corresponding essential amino
acid, except that the amino group attached to the second (alpha) carbon of
the amino acid is replaced with a keto group or hydroxy group, respectively
(Figure 9-l).

          NH,
           I -
Amino Acid  R-Y -cooH
             H

Keroacid  R-!-COO"

             OH
           I
Hydroxyacid    R -C- COOH


               H

Fbun S-1. Ths comparative structures of amino acids, katoacids, and
     hydroxyacids.TheRsymbolreferstothesidech8inofthese
     chamiils, which Is dtfhwent for each indiiidual compound.

391


O Nutrition and Health

Acute Renal Failure

Several studies in rats also indicate that a high amino acid intake by
infusion may predispose to acute renal failure caused by loss of blood flow
to the kidney (Zager and Venkatachalam 1983; Zager et al. 1983). The
amino acid intake that predisposes to acute renal failure, when expressed
per kilogram body weight, is not substantially greater than the quantity that
might be consumed by humans. The reason for this effect is not known.

For unexplained reasons, acute renal failure causes a metabolic reorgani-
zation that promotes breakdown of muscle proteins and reduces the ability
of the body to utilize amino acids to prevent wasting and to rebuild tissues
(Clark and Mitch 1983). Although some studies in rats or humans support
the benefits of nutritional therapy to prevent loss of body weight and
protein mass in acute renal failure (Wilmore and Dudrick 1969; Toback
1977), most studies have not confirmed these observations. At the present
time, no nutritional regimen prevents protein wasting in severely ill pa-
tients with this condition (Leonard, Luke, and Siegel 1975; Oken et al.
1980; Feinstein et al. 1981; Feinstein et al. 1983).

Merely increasing the protein intake does not stop acute wasting in many
patients with acute renal failure (Feinstein et al. 1983). Giving large
amounts of amino acids engenders formation of more urea with little or no
evidence for increased accrual of body protein (Frohlich et al. 1974; Fein-
stein et al. 1981; Feinstein et al. 1983). Moreover, if greater quantities of
nutrients are infused intravenously, an enhanced accumulation of water,
minerals, and metabolic waste products may increase uremic poisoning or
promote the need for more dialysis treatments. The inadequacies of current
treatment methods for acute renal failure emphasize the importance of
developing effective methods to prevent this condition.

Role of Phosphate in Renal Disease

Because the phosphate content of the diet is usually proportional to the
protein content, it has been difficult to separate the effects of these nu-
trients on the progression of renal disease. Nevertheless, as mentioned
above, diets low in phosphorus have been shown to retard the progression
of renal failure in laboratory rats and in humans. One possible explanation
is that a low phosphorus intake prevents the deposition of calcium phos-
phate in kidney tissue, which may cause further renal damage (Ibels et al.
1981; Alfrey and Tomford 1982). Whether low-phosphate diets prevent the
onset of renal damage in humans has yet to be determined.

392


Kidney Diseases 0

Role of Lipids in Renal Disease

Whether lipids and their metabolic products affect the development of
progressive renal injury is still under investigation. Arachidonic acid is a
fatty acid found in meat, fish, and certain plant foods; it is synthesized in
the liver from linoleic acid and metabolized in the kidney into a family of
eicosanoid compounds that include prostaglandins, thromboxanes, pros-
tacyclins, leukotrienes (Dunn 1983). Prostaglandins affect blood flow and
blood pressure inside the glomerulus, platelet aggregation, and the inflam-
matory process. Certain eicosanoids increase glomerular blood flow and
pressure inside the glomerulus and may impair platelet clotting, while
others have the opposite effect. In renal failure, there is an increased
elaboration of certain eicosanoids in the kidney (Suzuki et al. 1980; Bar-
celli, Weiss, and Pollak 1982) that may delay further deterioration of kidney
function (Klahr, Buerkert, and Purkerson 1983; Dunn 1983). The adminis-
tration of prostaglandins also appears to affect the progression of chronic
renal disease in animals (Zurier et al. 1977; Kelley, Winkelstein, and Izui
1979; McLeish et al. 1980).

Thus, reduced progression of renal injury and maintenance of a more
normal GFR have been demonstrated in experiments in which rats and
mice with impaired renal function were given fatty acid precursors of
prostaglandins (Barcelli, Weiss, and Pollak 1982), injections of certain
prostaglandins (Zurier et al. 1977; Kelley, Winkelstein, and Izui 1979),
drugs that inhibit synthesis of prostaglandins that cause platelet clotting
(Purkerson et al. 1985), or anticoagulants that inhibit platelet clotting
(Purkerson et al. 1982).

These studies have been used to raise the hypothesis that renal disease may
stimulate the glomerulus to synthesize eicosanoids that cause platelet
clotting, intlammation, and replication of cells in the glomerulus, which, in
turn, promote further renal injury (Purkerson et al. 1985). At the same time,
inhibiting the synthesis of certain other eicosanoids in the glomerulus may
protect the diseased kidney from continuing injury and from progressive
loss of function. Because some eicosanoids appear to promote renal injury
while others protect the diseased kidney from further damage, the dietary
significance of these observations is as yet uncertain.

393


0 Nutrition and Health

Implications for Public Health Policy

Dietary Guidance

General Public

Nutrients of particular interest in the occurrence of renal disease are
protein, phosphate, and certain fatty acids. Although there is evidence in
animals and humans that protein restriction can retard the progression of
end-stage renal disease, there is no evidence that current protein intakes by
the American population adversely affect the prevalence of renal disease.

Dietary phosphate restrictions have been noted to retard the progression of
renal disease, but there is not sufficient evidence to indicate a role in the
prevention of this condition. Nor may any implications be drawn for the
general public on the relationship of dietary fatty acids intake to renal
disease. Suggestions that certain lipids may increase the progression of
renal disease have yielded conflicting research results.

Special Populations

Protein restriction is a therapeutic measure prescribed for patients with
advanced renal disease, and end-stage renal disease patients on dialysis
must follow a protein-, potassium-, and phosphate-restricted maintenance
diet. A qualified health professional should provide information to such
patients on using these diets appropriately.

Nutrition Programs and Services

Food Labels

Evidence related to the role of dietary factors in renal disease currently
holds no special implications for change in policy related to food labeling.

Food Services

Evidence related to the role of dietary factors in renal disease currently
holds no special implications for policy changes in food service programs.

Special Populations

Patients with renal disease should receive counseling and assistance in
developing diets low in protein and low in phosphate. Those with renal
stones should receive advice on diets that reduce excretion of stone-
promoting factors (purines and excessive calcium) and should receive
recommendations for a high daily fluid intake in excess of two liters.

394


Kidney Diseases 0

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in renal disease should include investigations into:
o The ability of low-protein diets to retard the decline of renal function in
normal aging.

o The mechanisms by which dietary protein affects renal function.
o The relationship of the role of dietary protein to that of phosphate in its
effect on kidney function.

o The mechanisms by which other nutrients such as fatty acids or amino
acids might affect renal function.
o The use of various diets-such as those low in protein or phosphate-
to retard the rate of progression of renal failure.
o The relative merits of specialized formula diets, pharmacologic thera-
py, and traditional low-protein diets in treating progressive renal
failure.

0 The causes of wasting, malnutrition, and other nutritional disorders
that occur in renal failure.

0 The treatment-with calories, amino acids, or drugs-of wasting, mal-
nutrition, and other nutritional disorders that occur in renal failure.
0 The interplay of dietary factors (such as calcium, vitamin D, phos-
phate, protein, and oxalate) in the etiology of renal stones.
o The effect of omega-3 fatty acids in preventing the immune inflam-
matory response in chronic renal disease.
o The regulatory mechanisms in the utilization and metabolism of keto-
acids in humans.

o The impact of reduced protein/amino acid intake on the quantitative
dynamic status of protein and specific amino acid metabolism in organs
and the entire body.

o Lipid metabolism as affected by reduced protein and amino acid
intake.

o The role of lipids in the progression of chronic renal disease: lipid
turnover by renal cells, effect on tubular growth and function, relation-
ship of hyperlipidemia to renal injury, and effect of drugs in the
treatment of hyperlipidemia.
o Control of renal growth and impact of nutrition on renal mass.

395


O Nutrition and Health

o Mechanisms that produce toxicity of uremia and consequences of
uremic symptoms.

o Effect of protein restriction, as opposed to total calorie restriction, on
renal injury.

396


Kidney Diseases O

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end-stage kidneys. American Journal of Medicine 7 1~33-37.

Kaiser, L.; Schwartz, K.A.; Bumatowska-Hledin, M.A.; and Mayor. G.H. 1984. Microcytic
anemia secondary to intraperitoneal aluminum in normal and uremic rats. Kidney Internafion-
al 26~269-74.

Karllnsky, M.L.; Haut, L.: Buddington. B.; Schrier. N.A.; and Alfrey. A.C. 1980. Preserva-
tion of renal function in experimental glomerulonephritis. Kidney fnrernational
17(3):293-302.

Kelley, V.E.; Winkelstein, A.;and Izui, S. 1979. Effect ofprostaglandin Eon immune complex
nephritis in NZB/W mice. Laboratory Investigation 41:531-37.

Kenner, C.H.; Evan, A.P. ; Blomgren, P.; Aronoff, G.R.: and Luft. EC. 1985. Effect of protein
intake on renal function and structure in partially nephrectomized rats. Kidney Inrernarional
271739-50.

Kiprov. D.D.; Cob/in, R.B.; and McCluskey. R.T. 1982. Focal and segmental glomeruloscler-
osis and proteinuria associated with unilateral renal agenesis. Laboratory Investigafion
46:27581.

Klahr, S.; Buerkert, J.; and Purkerson, M.L. 1983. Roleofdietary factors in the progressionof
chronic renal disease. Kidney International 241579-87.

Kleinknecht, C.; Grunfeld, J.P.; Gomez, PC.; Moreau, J.F.; and Garciatos. R. 1973. Diagnos-
tic procedures and long-term prognosis in bilateral renal cortical necrosis. Kidney Interna-
lional 4:3W.

Kluthe, R.; Luttgen, EM.; Capetianu, T.; Heinze, V.; Katz, N.; and Sudhoff. A. 1978. Protein
requirements in maintenance hemodialysis. American Journal of Clinical Nlrtrition
31:1812-20.

Kok. D.J.; Papapoulos, S.E.; and Bijvoet, O.L.M. 1986. Excessive crystal agglomeration with
low citrate excretion in recurent stone-fotmers. Lancet i: 1056-58.

Kopple, J.D. 1978. Abnormal amino acid and protein metabolism in uremia. Kidney Interna-
tional 14:34&48.


O Nutrition and Health

-. 1984. Nutrition in renal failure. Causes of catabolism and wasting in acute or chronic
renal failure. In Nephrology. Proceedings of the IXth International Congress of Nephrology,
vol. II, ed. R.R. Robinson, pp. 1498-1515. New York: Springer-Verlag.

Kopple, J.D., and Swendseid, M.E. 1975. Vitamin nutrition in patients undergoing mainte-
nance hemodialysis. Kidney International 7:S79.

Kopple, J.D.; Shinaberger, J.H.; Cobum, J.W.; and Rubini, M.E. 1968. Protein nutrition in
uremia: a review. American Journal of Clinical Nutrition 21:50&15.

Lalich, J.J.; Faith, G.C.; and Harding, G.E. 1970. Protein overload nephropathy in rats
subjected to unilateral nephrectomy. Archives of Pathology 89:548-59.

Laouari, D.; Kleinknecht, C.; Gubler, M.C.; and Broyer, M. 1983. Adverse effect of proteins
on remnant kidney: dissociation from that of other nutrients. Kidney International 24(suppl.
16):S248-53.

Lawson, D.H.; Boddy, K.; King, PC.; Linton, A.L.; and Will, G. 1971. Iron metabolism in
patients with chronic renal failure on regular dialysis treatment. Clinical Science 41:345.
Leonard, C.D.; Luke, R.G.: and Siegel, R.R. 1975. Parenteral essential amino acids in acute
renal failure. Urology VI(2): 154-57.

Linton, A.L.; Clark, W.F.; Dreidger, A.A.; Werb, R.; and Lindsay, R.M. 1977. Correctable
factors contributing to the anemia of dialysis patients. Nephron 19:95.

Maschio, G.; Oldrizzi, L.; Tessitore, N.; D' Angelo, A.; Valvo, E.; Lupo, A.; Loschiavo, C.;
Fabris, A.: Gammaro, L.; Rugiu. C.; and Panzetta, G. 1982. Effects of dietary protein and
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McCormack, L.J.; Beland, J.E.; Schnekloth, R.E.; and Corcoran, A.C. 1958. Effects of
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McLeish. K.R.; Gohara, A.F.: Gunning, W.T., III; and Senitzer, D. 1980. Prostaglandin Et
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%:47O-79.

Mitch. W.E.. and Wilmore. D.W. 1988. Metabolic and nutritional factors in the treatment of
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Mitch. W.E.; Walser. M.; Buffington, G.A.; and Lemann, J., Jr. 1976. A simple method of
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Olson, J.L.: Hostetter. T.H.: Rennke. H.G.; Brenner, B.M.; and Venkatachalam, M.A. 1979.
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400


Kidney Diseases Cl

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Rosman, J.B.; Meijer, S.; Sluiter, W.J.; Terwee, P.M.; Piercbec. T.P.; and Danker. A.J. 1984.
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Rutherford, W.E.; Blondin, J.; Miller, J.P; and Greenwalas, V. 1977. Chronic progressive
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Samsky, I.B.; Fine, R.N.; Nelson, P.; Blumenkrantz, M.J.; and Kopple, J.D. 1983. Nutritional
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Schmidt, R.W.; Blumenkrantz, M.; and Wiegmann, T.B. 1983. The dilemmas of patient
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Senekjian, H.O.; Stinebaugh, B.J.; Mattioli, C.A.; and Suki, W.N. 1979. Irreversible renal
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Smith, L.H.; Van den Berg, C.J.; and Wilson, D.M. 1978. Current concepts in nutrition:
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Sk Kidney International 12:193-98.

401


R

u Nutrition and Health

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The progression of vesicoureteral reflux nephropathy. Annals oflnterna/Medicine 92:776-W.

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Nutrition 37~547-55.

Zager. R.A., and Venkatachaiam. M.A. 1983. Potentiation of ischemic renal injury by amino
acid infusion. Kidney International 24:62CL25.

Zager, R.A.; Johannes, G.; Tuttle, S.E.; and Sharma, H.M. 1983. Acute amino acid
nephrotoxicity. Journal of Laboratory Clinical Medicine 101:130-40.

Zucchelli, P.; Cagnoli, L.; Casanova, S.; Donini. U.; and Pasquali, S. 1983. Focal
glomerulosclerosis in patients with unilateral nephrectomy. Kidney International 24:64%55.

Zurier, R.B.; Damjanov, I.; Sayadoff, D.M.; and Rothtield, N.F. 1977. Prostaglandin El
treatment of NZB/NZW Fi hybrid mice. II. Prevention of glomerulonephritis. Arthritis and
Rheumatology 20: 1449-56.

402


Chapter 10

Gastrointestinal Diseases

Now good digestions wait on appetite, and
       health on both.
     William Shakespeare
   Macbeth, III.iv. (1605-1606)

Introduction

The gastrointestinal system extracts nutrient- and energy-yielding mole-
cules from plant and animal foods and digests them to smaller subunits that
can be absorbed. Here also, indigestible food wastes are prepared for
excretion. The full complement of essential nutrients is required for normal
gastrointestinal function, as for any other bodily system, and malnutrition
can adversely affect nutrient digestion and absorption. Similarly, infectious
and other diseases that impair gastrointestinal function can impair nutri-
tional status. These interrelationships are important in infant malnutrition
as well as in the adult conditions reviewed in this chapter.

Historical Perspective

The history of digestive physiology is remarkable both for the early under-
standing of its importance to nutrition and health and for the imaginative
research experiments that elucidated its function. This early history was
reviewed by McCollum (1957).

Hippocrates (460-370 B.C.) believed that although there were many differ-
ent kinds of foods, there was only one aliment. As early as the second
century A.D., Galen (130-200) studied digestion in swine and concluded
that the function of the stomach was to convert food into particles small
enough to be absorbed.

In the 18th century, de Reaumer (1683-1757) investigated digestion in birds.
He inserted food into metal tubes closed at the ends by screens and placed

403


O Nutrition and Health

the tubes in the stomach of a predatory bird. When the bird regurgitated the
tubes, he was able to observe the dissolution of bones and the partial
dissolution of meat in a fluid that tasted salty and bitter. Later, he performed
similar experiments in dogs. Similar studies were conducted by Stevens in
1777 using as a subject a man who had earned his living for the past 20 years
by swallowing stones. Stevens placed foods in perforated silver containers,
and the man swallowed them. By the time the containers were recovered in
stool, all foods except seeds were observed to be completely dissolved.

Perhaps the best known human digestive experiments were conducted by
Beaumont (1785-1853) on a patient, Alexis St. Martin, who had a perma-
nent opening from his stomach to the outside of his body (a fistula) as a
result of a gunshot wound. Beaumont had easy access to and from St.
Martin's stomach through the fistula and was able to observe gastric action
on many types of foods.

Modem digestive physiology began in the 20th.century with the identifica-
tion of digestive enzymes. Although the basic principles of digestive phys-
iology have been known for decades, the complex neuroendocrine interac-
tions between the brain, digestive tract, and other tissues that control and
regulate gastrointestinal function are as yet incompletely understood and
are the subject of much current investigation (Nicholl, Polak, and Bloom
1985).

Significance for Public Health

Data from several national surveys provide evidence that these gastroin-
testinal conditions are extremely prevalent and cause considerable impair-
ment of health and functional ability in the American population. In 1984,
the incidence of digestive diseases and conditions that required medical
attention or restricted normal activities was 7.6 per 100 persons per year.
The incidence rate was highest for infants, children, and young adults (10.3
to 11.9 per 100) and lowest for adults ages 45 to 64 (4.7 per 1.00). Gastroin-
testinal conditions were responsible for an average of 32 days per 100
persons per year of limited activity among people of all ages, but among
adults over age 65, the rate of restricted activity was 63 days per 100
persons per year (NCHS 1986).

Also in 1984, diseases of the digestive system accounted for a total of over 4
million hospitalizations at an average length of stay of 6.3 days. For patients
under age 15, the leading gastrointestinal causes of hospitalization were

404


Gastrointestinal Diseases 0

appendicitis, noninfectious gastroenteritis. and colitis. For patients ages 15
to 44, gastroenteritis and colitis were the leading causes. For adults ages 45
to 64, ulcers and gallstones predominated, and for adults over age 65,
cancer, diverticula, and gallstones were the most important causes (NCHS
1987b). The total direct medical cost for gastrointestinal diseases in the
United States is estimated at $17 billion per year (Klurfeld 1987).

Mouth, pancreas, colon, and rectal cancers were responsible for about 20
percent of all cancer deaths in 1986. There were 245,000 new cases of
cancers of the mouth and digestive tract, and these diseases caused 125,000
deaths that year. Cancers of the colon and rectum are the second leading
cause of new cancer cases in men and the third leading cause in women (see
chapter on cancer). In 1986, 60,000 Americans died of colon and rectal
cancers (Silverberg and Lubera 1987).

The interaction between infectious diarrhea1 diseases and malnutrition is
the primary cause of infant and child mortality and morbidity worldwide
(see chapter on infections and immunity), accounting for about 1.5 billion
diarrhea1 episodes annually (Chen and Scrimshaw 1983). In the United
States, these conditions are relatively rare but still were estimated to be
responsible for about 5 percent of all infant deaths in 1985 (Wegman 1986).

Because most persons with diverticular disease are asymptomatic, the true
prevalence of this condition is unknown. Diverticular disease is common in
industrialized countries but extremely rare among rural populations in
developing countries. Its frequency ranges from about 5 to 40 percent of
subjects in Westernized nations (Painter 1985). Among Americans sur-
veyed, 8.4 out of every 1,000 persons reported having diverticula (NCHS
1986). Frequency increases with age, and up to 70 percent of people from
age 40 to 70 may be affected (Taylor and Duthie 1976). In 1980, diver-
ticulosis caused 200,000 hospitalizations, incurring health care costs that
exceeded $300 million dollars (Almy and Howell 1980). For hospitaliza-
tions recorded in 1984, the average hospital stay for such disorders was 8
days (NCHS 1987b).

Data from the National Hospital Discharge Survey, conducted by the
National Center for Health Statistics, indicate that gallstones were respon-
sible for 488,000 operations annually in the United States; the average
hospital stay for this condition was 7.6 days in 1984 (NCHS 1987b). Nearly
3,000 Americans died of complications of gallbladder disease in 1986
(NCHS 1987a).

405


u Nutrition and Health

The estimated incidence of inflammatory bowel diseases increased from
1.9 cases per 100,000 population in the period 1935 to 1954 to 6.6 cases per
100,000 in 1965 to 1975. Projections based on incidence rates suggested that
20,000 to 25,000 new cases of this condition were admitted to hospitals in
the United States in 1980 (Kirsner and Shorter 1982). The National Center
for Health Statistics reported that 9.6 of every 1,000 Americans surveyed
stated that they had enteritis or colitis (NCHS 1986).

Chronic liver disease and cirrhosis are the ninth leading cause of total
deaths and the seventh cause of disease in the United States. They caused
the death of more than 26,000 Americans in 1986 (NCHS 1987a). These
conditions are discussed in more detail in the chapter on alcohol.

Scientific Background: The Digestive System

The primary functions of the digestive system are to ingest, digest, absorb,
transport, and excrete food components. It accomplishes these tasks by
means of the various digestive organs of the body and the enzymes listed in
Table 10-1, as well as by response to the numerous regulatory neu-
rochemical and hormonal substances produced by the brain, organs of the
digestive system, and other tissues that are summarized in Table 10-2. This
complex system extracts essential vitamins and minerals from diverse
plant and animal foods and breaks down the carbohydrate, protein, and fat
molecules in these foods to common subunits that can be absorbed. Once
absorbed, these subunits are used as building blocks for the molecules that
make up body tissues or for energy production. The structure and function
of the digestive system, its response to disease, and the relationship
between gastrointestinal function and nutritional status have been re-
viewed extensively (Floch 1981; Green and Greene 1984; LSRO 1987;
Martin, Mayes, and Rodwell 1985; Trowell, Burkitt, and Heaton 1985).

The cellular lining of the digestive tract has a very large surface area and is
readily exposed to potential mechanical, thermal, and microbial damage.
Its anatomic location, gastric acidity, and elements of the immune system
protect it from damage (Cole and Kagnoff 1985; Kagnoff 1983). This topic is
reviewed in the chapter on infections and immunity.

Mouth

The physical and chemical breakdown of food begins in the mouth with the
physical action of chewing and the enzymatic action of saliva. The parotid
and submaxillary salivary glands produce fluids and enzymes that convert
smaller carbohydrates and proteins to sugars and amino acids. Fats, how-
ever, are not generally altered in the mouth. Secretion of salivary fluid

406


                             Table 10-l
                 Summary of Digestive Processes

                            Method of Activation and
Source of Secretion and              Optimal Conditions                   End Products
Stimulus for Secretion      Enzyme        for Activity          Substrate        or Action
Salivary glands: Secrete sali-  Salivary amylase   Chloride ion necessary. pH   Starch        Maltose plus I :6
va in reflex response to                 6.6-6.8.           Glycogen      glucosides (oligosac-
presence of food in oral                                    charides) plus malto-
cavity.                                                    triose.
Liial glands        Lingual lipase    pH range 2.0-7.5; optimal,   Short-chain primary  Fatty acids plus 1,2-
                              4.0-U.             ester link at sn-3   diacylglycerols.
Stomach glands: Chief cells  Pepsin A (fundus)   Pepsinogen converted to    Protein       Peptides.
and parietal cells secrete   Pepsin B (pylorus)  active pepsin by HCI. pH
gastric juice in response to             1 J-2.0.
reflex stimulation and     Rennin       Calcium necessary for     Casein of milk    Coagulates milk.
action of gastrin.                activity. pH 4.0.
Pancrew Presence of acid   Trypsin       Trypsinogen converted to    Protein       Polypeptides.
thyme from the stomach            active trypsin by enteroki-   Peptides       Dipeptides.      F
activates duodenum to              nase of intestine at pH                                        %
produce (I) secretin, which           5.2-6.0. Autocatalytic at pH                     3.
hormonally stimulates flow              7.9.                                           2
of pancreatic juice; (2)                                                            cl
              Chymotrypsin    Secreted as chymotrypsino-   Protein       Same as trypsin.
cholecystokinin, which                                           g
                       gen and converted to active  Peptides       More coagulating
stimulates the production                                                                 5
of enzymes.                  form by trypsin. pH 8.0.             power for milk.        tl
                                                                           C'
                 Elastase       Secreted as proelastase and   Protein        Polypeptides.       3
                        converted to active form by  Peptides       Dipeptides.
                        trypsin.           b


                     Table 10-l (continued)                    0

                              Method of Activation and               2
Source of Secretion and               Optimal Conditions                   End Products     g:
Stimulus for Secretion      Enzyme         for Activity          Substrate        or Action      s

Pancreas (continued)     Carboxypeptidase   Secreted as procarboxypepti-  Polypeptides at the  Lower peptides.      5
                        dase. activated by trypsin.   free carboxyl end of  Free amino acids.
                                                  the chain           :
                                                                iz
              Pancreatic amylase pH 7.1.              Starch        Maltose plus 1:6     3
                                       Glycogen       glucosides (oligosac-
                                                 chat-ides) plus
                                                           maltotriose.
              Lipase        Activated by bile salts,     Primary ester     Fatty acids, mono-
                        phospholipids, colipase. pH  linkages of triacyl-
                              8.0.                        acyiglycerols, di-
                                       glycerol       acylglycerols,
                                                  glycerol.
                  Ribonuclease                       Ribonucleic acid    Nucleotides.
              Deoxyribonuclease                 Deoxyribonucleic   Nucleotides.
                                                acids

               Cholesteryl ester   Activated by bile salts.     Cholesteryl esters   Free cholesterol
              hydrolase                               plus fatty acids.
             Phospholipase A,   Secreted as proenzyme,    Phospholipids     Fatty acids, lyso-
                        activated by trypsin and
                              Ca2+.                      phospholipids.


Liver and gallbladder: Cho-
lecystokinin, a hormone
from the intestinal
mucosa-and possibly also
gastrin and secretit+
stimulate the gallbladder
and secretion of bile by the
liver.

Small intestine: Secretions of
Brunner's glands of the
duodenum and glands of
Lieberkuhn.

(Bile salts and alkali)

Fats-also
neutralize acid
thyme

Aminopeptidase

Polypeptides at the
free amino end of
the chain

Dipeptidases                   Dipeptides

Fatty acid-bile salt
conjugates and
finely emulsified
neutral fat-bile salt
micelles and
liposomes.

Lower peptides.
Free amino acids.

Amino acids.

                Sucrase       pH S&7.0.            Sucrose        Fructose, glucose.

                 Maltase       pH 5.8-6.2.            Maltose         Glucose.

                 Lactase       pH 5.4-6.0.            Lactose       Glucose, galactose.

                Trehalase                          Trehalose        Glucose.

             Phosphatase     pH 8.6.           Organic phosphates Free phosphate.   2
                Isomaltase or 1:6                 1:6 glucosides     Glucose.
             glucosidase                           3.
                                                                   E
                                                                           co
             Polynucleotidase                     Nucleic acid      Nucleotides.           z
                                                                           e.

                Nucleosidases                 Purine or pyrimidine Purine or pyrimidine   EL
              (nucleoside                        nucleosides      bases, pentose        u
             phosphorylases)                             phosphate.            &'


Source: Murray, R.K.; Granner, D.K.; Mayea, P.A.; and Rodwell, V.W. 1998. Harper's Biochemistry. pp. 554-55.21 st ad. San Mateo, CA: Appleton 8   !ii
   Lange. Copyright Appleton EL Lange 1985, reprinted with permission.


0 Nutrition and Health

    Table 10-2
Gastrointestinal Hormones

Hormone

Localization

Major Action

Gastrin

Cholecystokinin (CCK)


Secretin

Gastric inhibitory
peptide


Vasoactive intestinal
polypeWe


Motilin

Somatostatin

Pancreatic polypeptide

Enkepbabns

Substance P

Bombesin-like
immunoreactivity
Enteroglucagon

Gastrin antrum,
duodenum
Duodenum,
jejunum
Duodenum,
jejunum
SmaIl bowel

Pancreas

Small bowel

Stomach,
duodenum,
pancreas
Pancreas

Stomach,
duodenum,
gallbladder
Entire gastroin-
testinal tract

Inhibits pancreatic bicarbonate
and protein secretion
Opiate-like actions

Uncertain

Stomach,     Stimulates release of gastrin and
duodenum     CCK

Pancreas, small
intestine

Unknown

Gastric acid and pepsin secretion

Pancreatic amylase secretion

Pancreatic bicarbonate secretion

Enhances glucose-mediated
insulin release. Inhibits gastric acid
secretion
Smooth muscle relaxation;
stimulates pancreatic bicarbonate
secretion
Initiates interdigestive intestinal
motility
Numerous inhibitory effects

Source: Adapted from Martin, Mayes, and Rodwell 1985.

depends on neuroendocrine regulation and is affected by the sight, smell,
taste, and thought of food. The role of salivary secretions is discussed
further in the chapter on dental diseases.

Esophagus
Swallowed food enters the esophagus and travels through it to the stomach.
At the esophagogasttic junction, the lower esophageal sphincter muscle

410


Gastrointestinal Diseases 0

normally prevents gastric fluids from flowing into the body of the
esophagus. Neurohormonal mechanisms control the pressure of this
sphincter and, as discussed below, may be affected by digestion of certain
foods in the small intestine (Pope 1983).

Stomach

in the stomach, food is broken down into increasingly smaller particles and
compounds by mechanical, chemical, and enzymatic means. The acidic
gastric secretions contain the enzyme pepsin, which converts proteins into
short chains of amino acids, and gastric lipases, which, along with lingual
lipase, initiate triglyceride digestion. The movement of the stomach emp-
ties liquids into the duodenum continuously while food solids are reduced
to the consistency of paste. The selective rates of discharge of substances
into the duodenum may be related to their caloric density (Brener, Hendrix,
and McHugh 1983), to effects of neuropeptides (Morley 1982), or other
hormones that control gastrointestinal function.

Small Intestine

Most digestion and absorption take place in the small intestine, as do
modulation of fluid balance, orderly advancement of food residues into the
colon, reabsorption of bile salts, and absorption of vitamin B,,. The spe-
cialized absorbing cells, enterocytes, are distinguished by numerous mi-
crovilli that greatly increase the absorptive surface area. This surface
epithelium contains enzymes that split carbohydrates and small peptides.
These cells also convey nutrients to the circulatory and lymphatic systems,
which distribute them to the rest of the body. Digestion is primarily accom-
plished by enzymes secreted by the pancreas and delivered to the small
intestine: amylase, which converts starch to sugar; lipase, which splits
triglycerides into fatty acids and monoglycerides; and trypsin and chymo-
trypsin, which split proteins into amino acids and small peptides. Other
substances such as secretin, which is produced by the cells of the duo-
denum, and pancreatic polypeptide help to control the level of intestinal
acidity.

The absorption of sugars, peptides, amino acids, and fatty acids proceeds
in the upper part of the small intestine (iejunum), whereas bile salts and
vitamin B,, are absorbed in the distal portion or the ileum. By the time food
residues pass the ileum, most usable food molecules have been digested
and absorbed, so that only small amounts of carbohydrates (Levine and
Levitt 1981), other macronutrients, and fiber are delivered to the colon.

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Liver and Mary Tract

The liver, the largest body organ, synthesizes proteins, oxidizes fat, regu-
lates the release of glucose from glycogen, and detoxifies drugs, hormones,
and other potentially deleterious substances. It also converts cholesterol
into bile acids and secretes hepatic bile, which is concentrated in the
gallbladder before delivery into the duodenum.

Pancreas

The pancreas has both exocrine and endocrine functions that influence
digestion and nutrient metabolism. It secretes hormones such as glucagon
and insulin into the blood, and digestive enzymes, principally amylase,
lipase, and proteases, into the digestive tract.

Colon

The principal functions of the large intestine are to concentrate, store, and
excrete food wastes. The colon contains large numbers of bacteria, which
produce enzymes that act on the remaining food residues, fiber, and cells
and mucus sloughed from the upper intestinal tract. The products of this
bacterial digestion and fermentation include short-chain fatty acids (e.g.,
propionic, butyric); gases such as carbon dioxide, methane, and hydrogen;
and other volatile substances (Cummings 1983). The ascending colon has a
thinner muscle wall, a greater luminal volume, and a much larger popula-
tion of bacteria than does the more muscular descending colon, which
slows the movement of feces until they are partially dehydrated, concen-
trated, and ready to be expelled through the anus.

Key Scientific Issues

o Effects of Dietary Factors on Gastrointestinal Function
o Role of Dietary Factors in Intestinal Disorders
o Role of Dietary Factors in Gallbladder Disease
o Role of Dietary Factors in Other Digestive Disorders

Effects of Dietary Factors on Gastrointestinal Function

The diet must provide sufficient nutrients and energy to synthesize the
rapidly renewing cells that line the gastrointestinal tract, the enzymes that
digest and transport nutrients across the intestinal wall, and the regulatory
neuropeptides and other hormones that control these processes. Digestive
function can be seriously disrupted by inadequate nutrition ;IS well as by

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Gastrointestinal Diseases O

infections, toxic substances, and chronic disease. The composition of the
diet can influence the rate of reproduction of bacteria in the intestine and,
thus, can affect nutrient absorption. Dietary components affect the mor-
phology and synthesis of the cells that line the digestive tract as well as fecal
composition and elimination.

Malnutrition

Nutritional inadequacies can cause abnormalities of the mucous mem-
branes of the mouth, tongue, and digestive tract. Frequent consequences of
starvation and protein-energy malnutrition are an inability to absorb or
digest food molecules and decreased pancreatic function (Kerndt et al.
1982). As discussed in the chapter on infections and immunity, cellular
immune functions are depressed in malnutrition and starvation. Because
the cells that line the digestive tract are renewed every few days, nutrient
deficiencies can be reflected in ulceration, hemorrhage, or loss of resis-
tance to micro-organisms that are usually not pathogenic.

Atrophy of the gastric and intestinal mucosa is an especially serious
consequence of malnutrition. The microvilli flatten and lose much of their
absorptive surface and no longer produce adequate digestive or absorptive
enzymes. Food passes undigested and unabsorbed into the colon, where
bacterial action induces gas production and the influx of water, inducing
diarrhea and further damage to the digestive tract. These effects are most
severe in young children and cause a characteristic cycle of malnutrition,
infectious disease, malabsorption, and diarrhea that is common throughout
the developing world (Chandra 1983; Hamilton 1985; see chapter on infec-
tions and immunity). They also occur among patients with chronic diseases
that interfere with adequate nutrition, anorexia nervosa, impaired immuno-
logic responses to certain food substances (Floch 1981), or severe micro-
bial infections of the gastrointestinal tract (DuPont 1984).

Once the microvilli are reduced, recovery of gastrointestinal function
occurs only slowly, if at all. Because food intake induces diarrhea, enteral
and parenteral feeding methods that bypass the digestive tract must be
employed along with immediate efforts to prevent dehydration, edema,
vitamin and mineral deficiencies, and excessive accumulation of body fat
( Roediger 1986).

In various conditions in which the bowel mucosa are compromised by
disease, macromolecules that are normally excluded may be absorbed.
These, especially protein molecules, may alter systemic immune functions
(see chapter on infections and immunity).

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u Nutrition and Health

Effects of Fiber

Most studies of the relationship of diet to gastrointestinal function have
focused on the role of dietary fiber. Physiologic responses to dietary fiber
occur within the entire length of the gastrointestinal tract. Dietary fibers
from different plant sources have diverse chemical constituents; some are
soluble and some are insoluble. The major constituents of dietary fiber are
cellulose, hemicelluloses, pectins, mucilages, gums, algal polysaccha-
rides, and lignin. Fibers from different foods have different effects on
water-holding capacity, viscosity, ion-exchange capacity, binding of miner-
als and organic compounds, bacterial fermentation, and transit time. Food
processing can alter these effects. In general, dietary fibers from many
sources increase the flow of saliva, improve feelings of satiety, delay
digestion and absorption, bind intestinal bile acids, increase the mass of
intestinal bacteria, decrease the time stools take to pass through the bowel,
and increase stool weights and frequency of elimination (Trowell, Burkitt,
and Heaton 1985). Although animal studies demonstrate that fiber intake
increases the length of the intestine and causes greater proliferation of
mucosal cells, these effects cannot be readily distinguished from those of
other dietary factors, and their applicability to humans is uncertain (LSRO
1987).

Some potential adverse effects have also been observed very infrequently
with diets high in fiber, including intestinal obstruction (primarily due to
gel-forming fiber); interference with absorption of calcium, magnesium,
zinc, manganese, and iron; inflammation of the bowel mucosa (with certain
gums); and colonic volvulus (Klurfeld 1987).

Role of Dietary Factors in Intestinal Disorders

Diseases of the gastrointestinal tract affect food consumption, digestion,
absorption, and excretion. Although one might expect dietary factors to be
important in preventing and treating such conditions, research in this area
has not been extensive, and present understanding is limited. The dietary
factors most frequently associated with gastrointestinal illnesses are alco-
hol (liver disease and cancer); inadequate fiber (constipation, hemor-
rhoids, diverticular disease, and possibly some types of cancer); fat (gall-
bladder disease and possibly some types ofcancer); and substances such as
gluten in wheat (celiac disease in genetically predisposed individuals).

Cancer

The effects of dietary risk factors such as alcohol, fat, and food mutagens
and carcinogens on the causation of cancers of the gastrointestinal tract,

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Gastrointestinal Diseases 0

and the effects of substances such as fiber or vitamin A in their prevention,
are reviewed in the chapter on cancer.

Celiac Disease

This genetic-immunologic disorder, also known as nontropical sprue or
gluten-induced enteropathy, results from an immunologic reaction to the
gluten fraction of proteins from wheat, rye. or oats (Chandra and Sahni
1981). Its symptoms may be silent and its prevalence is uncertain. but it is
thought to affect about 1 in 2,500 persons in the United States (Gluten
Intolerance Group 1982). When patients with this disorder ingest gluten.
the cells that line the small intestine undergo atrophy, causing malnutrition,
stunting of growth, and anemia. Although strict removal of gluten from the
diet alleviates symptoms and restores the integrity of the intestinal mucosa.
some immunologic abnormalities may persist. Neither the fundamental
defect nor the genetic basis of celiac disease is understood (Cole and
Kagnoff 1985).

Constipation

The National Center for Health Statistics has reported that more than 20 of
every 1,000 persons surveyed state that they suffer from frequent constipa-
tion (NCHS 1986). Although constipation, defined as three or fewer bowel
movements per week, can be caused by diabetes, hypothyroidism, uremia,
neurogenic bowel disorders, abnormalities in the structure of the colon,
rectum, or anus, and by various medications, most constipation cannot be
attributed to an underlying disease. Instead, dietary intake patterns are
widely presumed to cause this condition, in particular, inadequate con-
sumption of fiber and, especially in the older person, insufficient fluid
intake. The effect may vary with coarseness of bran or degree of cooking
(Klurfeld 1987), but numerous studies have demonstrated that increased
intake of wheat bran and other sources of insoluble fiber prevents constipa-
tion and relieves its symptoms (LSRO 1987).

Diverticular Disease

Diverticulosis occurs when diverticula, abnormal outpocketings of the
intestinal wall, form in the colon and cause pain in the left lower abdomen
without fever. Although diverticula may occur over extensive areas of the
colon, they do not usually produce demonstrable muscle thickening,
changes in intraluminal pressures, or other noticeable symptoms
(Fleischner, Ming, and Henken 1964; Weinreich and Andersen 1976). A
closely related disease, diverticulitis, which occurs when the outpocket-
ings become infected, causes constipation and diarrhea, flatulence, ab-
dominal pain, fever, and mucus and blood in the stools (Almy and Howell
1980).

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u Nutrition and Health

Some experts believe that diverticula occur as a result of increased colonic
intraluminal pressure needed to eliminate small, hard stools that form as a
result of low-fiber diets (Burkitt, Walker, and Painter 1974). The idea that
diverticular disease might result from inadequate intake of dietary fiber is
supported by animal studies (Cello 1981); by measurement,s in humans of
intestinal transit times, bowel motility, stool weights, and intraluminal
pressures (Burkitt, Walker, and Painter 1974; Painter 1985); and by intema-
tional comparisons of fiber intake and disease prevalence rates (Mendeloff
1986). Numerous dietary intervention trials have reported beneficial ef-
fects of bran and other fiber sources on pain, constipation, and other
symptoms as well as on intraluminal pressures (Painter 1985; LSRO 1987).
Despite concerns that these studies have not always employed adequate
control groups, and despite the needs for further research to define the role
of other nutrients such as fat (Manousos et al. 1985) and to identify the most
effective sources and types of fiber, fiber supplements are now often used
successfully in clinical management of uncomplicated diverticular disease
(LSRO 1987).

Inflammatory Bowel Disease

Nonspecific inflammatory bowel disease includes two diseases of the di-
gestive tract: (1) ulcerative colitis, characterized by rectal bleeding, diar-
rhea, abdominal cramping and pain, loss of appetite, and weight loss, and
(2) Crohn's disease, a chronic inflammation anywhere throughout the
length of the digestive tract that may induce similar symptoms along with
tistulas and narrowing of the bowel (Kirsner and Shorter 1982). Their
etiology and pathogenesis is unknown. Patients with these conditions can
become severely malnourished. Active cases are usually treated with low-
residue diets and caloric supplements (Harries et al. 1983) elemental
enteral formulas (Neidich, Schussel, and Sharp 1985). or total parenteral
nutrition with complete bowel rest (Ostro, Greenberg, and Jeejeebhoy
1985).

Potential food allergens, such as carrageenan thickeners and cow milk, and
low-fiber diets have been suggested as possible dietary factors aggravating
these diseases, but evidence to support such inferences is limited (Kirsner
and Shorter 1982). Studies of the relationship of low-fiber diets to etiology
or treatment of Crohn's disease (Jones et al. 1985) have yielded equivocal
results, and the role of diet in inflammatory bowel disease is uncertain at
this time (LSRO 1987).

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Gastrointestinal Diseases O

Irritable Bowel Syndrome

This condition of pain, abdominal distension, and alteration in bowel habits
is thought to be due to an inappropriate reaction of the intestinal wall to
stress (Eastwood and Passmore 1983), motility disturbances, diet (Harvey
1985), or food hypersensitivity reactions (Bentley, Pearson. and Rix 1983).
Dietary fiber has been used to treat irritable bowel syndrome with demon-
strable improvements in constipation (Fielding 1985; Harvey 1985). but its
effects on other symptoms have been equivocal (LSRO 1987).

Lactose Intolerance

An insufftciency of lactase, the enzyme responsible for breakdown of
lactose (milk sugar) in the small intestine, can cause lactose intolerance,
characterized by abdominal discomfort, pain, and diarrhea as a result of
bacterial action on undigested lactose in the colon (Newcomer and McGill
1984). Lactose intolerance is not an inevitable consequence of lactase
deficiency. Many lactase-deficient individuals can consume modest
amounts of lactose-containing foods with little difficulty. Modification of
milk and milk products by addition of lactase, or the use of fermented
products such as cheese or yogurt, permits consumption of milk products
by such individuals with minimal symptoms (Kolars et al. 1984; Barillas
and Solomons 1987).

Genetic absence of lactase beyond the age of 5 or 6 occurs among remark-
ably high proportions of Asians (85 to 95 percent), Africans (50 to 99
percent), American Indians (85 to 95 percent), and American blacks (70 to
75 percent), as well as among a signiticant percentage of healthy Caucasians
(Gray 1983). Acquired deficiencies can occur as a result of malnutrition
(Kemdt et al. 1982) or disease. Reports that lactase activity is lost with
aging have not been confirmed (Rosenberg and Bowman 1984).

Role of Dietary Factors in Gallbladder Disease

Cholesterol, precipitated from supersaturated bile, is the principal compo-
nent of most gallstones in patients from industrialized countries. Dietary
and diet-related risk factors for this condition include diabetes, obesity
(Diehl et al. 1987), and excess intake of calories and dietary fat (Heaton
1985). Many of these are also risk factors for coronary heart disease.

Low-fiber diets are associated with gallstone formation. In primates, the
action of fiber and other substances that bind cholesterol in the intestine is

417


O Nutrition and Health

thought to stimulate the liver to increase production of bile acids, thereby
increasing cholesterol solubility (Strasberg, Petrunka, and Ilson 1976).
Although cellulose, hemicellulose, lignin, and other insoluble fiber compo-
nents have little effect on blood cholesterol levels, soluble components
such as pectin and guar appear to reduce cholesterol levels by 10 to 15
percent (LSRO 1987). Dietary fiber has also been shown to increase the
pool of bile acids in laboratory animals (Usuga et al. 1976).

In humans, large doses of wheat bran have been reported to increase bile
cholesterol solubility (Pomare et al. 1976). One study has indicated that a
fiber-rich diet decreases the cholesterol saturation index of bile signifi-
cantly (Thornton et al. 1983). Human epidemiologic investigations, how-
ever, have not been able to distinguish associations of gallstone formation
with varying levels of fiber from associations with other dietary factors
such as sugar, alcohol, or other macronutrients (Smith and Gee 1979;
Scragg, McMichael, and Baghurst 1984).

Role of Dietary Factors in Other Disorders of the Digestive System

Cirrhosis

The only digestive system disorder besides cancers in the 10 leading causes
of death for Americans is cirrhosis (with other chronic liver diseases), and
its most powerful dietary correlate is alcohol consumption. This issue is
addressed in the chapter on alcohol.

Appendicitis

Studies based on epidemiologic comparisons between industrialized na-
tions and less developed regions have associated low-fiber diets with in-
creased prevalence of appendicitis (Segal 1985; Walker and Burkitt 1985).
However, Western trends in fiber intake are not consistent with the decline
in appendicitis rates during the past few decades, and not all studies have
shown that patients with appendicitis consume less fiber than control
subjects (Cove-Smith and Langman 1975). Nondietary factors may be more
important (Barker et al. 1986). Nevertheless, reports that children 7 to 18
years of age whose fiber intake is in the upper 50th percentile have a 50
percent lower risk of appendicitis (Brender et al. 1985) warrant further
investigation.

Reflux Esophagitis

This disorder, an inflammation of the lower esophagus (heartburn) caused
by the backflow of stomach acids, can occur when the lower esophageal
sphincter does not contract properly. Alcohol, dietary fat, and both regular

418


Gastrointestinal Diseases O

and decaffeinated coffee (Cohen 1980; Feldman et al. 1981) have been
demonstrated to reduce sphincter pressure and to increase reflux. Spices
and tomato and orange juices also may affect some persons.

Ulcers

Gastric and duodenal ulcers are local erosions of the mucosa that result
from excessive production of gastric acid and pepsin or from decreased
mucosal resistance to these substances. They may result from defects in
control of secretion and motility or in synthesis of prostaglandins that
either inhibit gastric acid secretion or promote secretion of bicarbonate
(Johannson and Bergstrom 1982). The role of nutritional factors in the
etiology of ulcers is uncertain. Speculation that refined foods reduce the
buffering capacity of stomach secretions (Cleave 1975) has not been con-
firmed, nor is evidence sufficient to define a causal relationship for linoleic
acid, prostaglandins, or peppers in peptic ulcers. The geographic distribu-
tion of duodenal ulcers is not consistently associated with fiber consump-
tion (Tovey 1985), nor have clinical studies reported consistent effects of
fiber on treatment (LSRO 1987). The observation that increased dietary
fiber intake reduces rates of recurrence (Rydning et al. 1982) requires
further confirmation.

The bland milk-and-cream-based Sippy diet, used in former years, is no
longer recommended as treatment; it has not been demonstrated to jm-
prove symptoms better than any other method, is atherogenic, and is
deficient in essential vitamins and minerals (Zucker and Clayman 1983).
Today, ulcer patients typically are encouraged to consume a varied and
balanced diet, taken slowly in four or five small meals a day, but limited in
alcohol, coffee, and other substances that lead to discomfort and pain.
Patients should avoid late evening snacking that stimulates nocturnal acid
secretion (Floch 1981). Patients are also advised to avoid cigarette smok-
ing, which accentuates symptoms and retards healing, and aspirin, which
irritates the gastrointestinal mucosa and can cause mucosal hemorrhages.
It should be noted that there are many current, very effective phar-
macologic therapies for the management of ulcer disease.

Implications for Public Health Policy

Dietary Guidance

General Public
Dietary fat, fiber, and alcohol are significant factors associated with gas-
trointestinal diseases, although the great variety of these conditions makes

419


u Nutrition and Health

generalizations difficult. Because diets that contain a large proportion of
calories from fat may be low in fiber, it is often difficult to separate the
effects of these substances on gastrointestinal disease. Thus, current evi-
dence on whether dietary fiber helps prevent diverticulosis is not con-
clusive. Similarly, whether dietary fiber helps prevent inflammatory or
irritable bowel disease is uncertain. Nevertheless, evidence that dietary
fiber helps treat and prevent constipation and manage chronic diverticular
disease suggests the prudence of consuming diets higher in fiber and lower
in fat.

The strong cause-and-effect association between excessive alcohol con-
sumption and the development of chronic liver disease and cirrhosis (as
reviewed in the chapter on alcohol) emphasizes that persons who consume
alcoholic beverages should do so in moderation. Epidemiologic associa-
tions between diet and some types of gastrointestinal cancer (as reviewed in
the chapter on cancer) suggest-but do not yet prove-that consuming less
fat and alcohol and more fiber would help reduce the risk for these cancers.

Evidence on the role of dietary factors in the development of gastric or
duodenal ulcers or reflux esophagitis is insufftcient to make recommenda-
tions at this time.

Special Populations

Higher intakes of dietary fiber can prevent or relieve symptoms of constipa-
tion and chronic diverticular disease. Qualified health professionals should
inform persons with these conditions about foods with relatively high fiber
contents. Individuals with celiac disease should be provided with informa-
tion on foods free of wheat gluten. Those with inflammatory bowel disease,
irritable bowel syndrome, lactose intolerance, gallbladder disease, heart-
bum, and ulcers should be provided with guidance on diets appropriate to
their conditions.

Nutrition Programs and Services

Food Labels

Evidence related to the role of dietary factors in gastrointestinal disease
suggests that food manufacturers should include on package labels infor-
mation about nutritional content of the food, especially for fat and carbohy-
drate components (and including fiber components to the extent permitted
by analytical methods).

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Gastrointestinal Diseases 0

Food Services

Evidence related to the role of dietary factors in gastrointestinal diseases
suggests that food services should include provisions for adequate intake of
high-fiber and low-fat foods.

Food Products

Evidence related to the role of dietary factors in gastrointestinal diseases
suggests that the public would benefit from additional products that are low
in fat and calories and higher in fiber.

Special Populations

Persons with gastrointestinal diseases should receive counseling and assis-
tance in developing appropriate diets for their particular condition.
Qualified health professionals should provide appropriate training and
enteral or parenteral nutritional support to persons with conditions that
prevent food ingestion, cause malabsorption, or impair bowel function.

Research and Surveillance

Research and surveillance issues of special priority related to dietary
factors affecting gastrointestinal function and diseases of the gastroin-
testinal tract should include investigations into:
0 The prevalence of gastrointestinal diseases among the population.
o The influence of dietary factors such as specific dietary fibers, fat, and
calories on development and function of the digestive tract.
0 The influence of dietary factors on the development and release of
enzymes and hormones that affect gastrointestinal function.
o The role of intestinal flora on nutrient bioavailability.
0 The most effective nutrient-related interventions to improve the recov-
ery of intestinal function following episodes of malnutrition or disease.
o The mechanisms by which dietary fiber may WC rk in the prevention
and treatment of bowel cancer, appendicitis, diverticular disease, gall-
bladder disease, and other gastrointestinal conditions.
o The identification of specific dietary factors that might influence the
causation, prevention, and treatment of celiac disease, inflammatory
and irritable bowel syndromes, ulcers, and other gastrointestinal disor-
  ders.

o The most effective means to achieve dietary counseling to help allevi-
ate gastrointestinal disorders.

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0 Nutrition and Health

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Neidich, G.; Schussed. K.; and Sharp, H.L. 1985. Noninvasive outpatient nutritional therapy
in inflammatory bowel disease. Journal of Parenteral and Enteral Nutrition 9:350-52.

Newcomer, A.D., and McGill, D.B. 1984. Clinical consequences of lactase deficiency.
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Ostro, M.J.; Greenberg, G.R.; and Jeejeebhoy, K.N. 1985. Total parenteral nutrition and
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Painter, N. 1985. Diverticular disease of the colon. In Dieraryfibre,fibre-depletedfoods und
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Chapter 11

Infections and Immunity

There are sure to be two prescriptions
diametrically opposite. Stuff a cold and
  starve a cold are but two ways.
   Henry David Thoreau
       (1817-1862)
A Week on the Concord and Merrimuck
    Rivers, "Wednesday"

Introduction

Interactions among nutrition, infections, and immune disorders have im-
portant implications for individual, public, and economic health in this
Nation and around the world. In the past decade, substantial advances in
scientific knowledge have occurred in the study of malnutrition, the deter-
minants of infection, and the components and functions of the immune
system. Nevertheless, many details of this complex three-way interaction
remain unclear. This chapter reviews the physiologic and immunologic
mechanisms that protect people against illness, nutrition's role in the
proper function of these mechanisms, malnutrition's negative effects on
immune function, infectious illnesses and their detrimental effects on an
individual's reserves, food allergies that cause adverse reactions, and the
problems of food-associated illnesses and other diseases.

Historical Perspective

Famine and pestilence have been closely associated throughout recorded
history. Ancient scriptures in India noted the apparent relation of diet and
the ability to resist disease (Chandra 1983). Episodes of plagues, for exam-
ple, have been recorded throughout history, although the influence of
malnutrition on these outbreaks is not certain. During wars, dysentery,
typhus, and smallpox were leading causes of death; malaria, diarrhea1
diseases, typhoid, measles, and pneumonia also caused many deaths. Poor
nutrition and contaminated food invariably accompanied episodes of infec-
tious disease. Although the impact of malnutrition on such infections is
difficult to determine, malnutrition may predispose to or alter the severity
of infection, and most infections aggravate malnutrition (Beisel et al. 1977;
Alexander and Stinnett 1983).

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Modem public health concepts concerning sanitation, water purification,
good nutrition, and immunization have helped eliminate many infectious
diseases in the United States. By the early 1900's, the importance of
adequate nutrition and vitamins was recognized. For many years before
specific antimicrobial therapy became available, a combination of bedrest
and wholesome foods was commonly used with varying effectiveness to
treat subacute and chronic infections such as tuberculosis. The introduc-
tion of antibiotics in the 1940's led to the control of many infectious
illnesses, especially those caused by bacteria.

Vaccines have now made possible the control or elimination of many
infectious diseases. For example, live-virus vaccines against measles,
mumps, and rubella, first available in the 1%0's, have dramatically im-
proved the control of these diseases. Other once commonplace infections,
such as cholera, typhoid fever, tetanus, rabies, poliomyelitis, diphtheria,
and pertussis, have been virtually eliminated in the United States or
drastically reduced by immunization programs and improved environmen-
tal and social conditions (Braude 1985). Smallpox was the first communica-
ble disease to be eradicated worldwide, with the last known indigenous
case occurring in October 1977 in Somalia (Chin 1980). Nonetheless,
nutritional status can affect the immune response stimulated by vaccina-
tion; hence, especially in developing countries, nutritional and vaccination
programs are essential components of infectious disease control strategies.

Food-borne microbial illness is a significant issue in infections. Since the
1906 enactment of the Wiley Act, the first pure food and drug law, much
legislation has been passed to protect the food supply from infectious
micro-organisms. Federal and State governments conduct or promote
many activities to prevent food-borne diseases from threatening the Na-
tion's health: they establish safety standards, inspect food establishments
serving the public, train food handlers and food sanitarians, certify milk
and shellfish shipped interstate, inspect meat and poultry, monitor out-
breaks of disease, and act to eliminate the sources of food-borne microbial
illness (Hartman, Porter, and Withnell 1981). To minimize or eliminate
micro-organisms from the commercial food supply, the food industry uses
a variety of processing methods and preservatives. Occasionally, a serious
breach of safety in a commercial plant or process has resulted in a serious
outbreak of food poisoning.

Today, and in the past, many infections occur with greater severity and
some infections occur more frequently in malnourished persons than in
well-nourished people. Yet, as will be discussed, many aspects of the
relationships of malnutrition to immune responses and to susceptibility to

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Infections and Immunity 0

infection are still poorly understood. Although malnutrition due to pro-
longed food deprivation may increase the risk for infection, malnutrition is
more likely to be a result than a cause of an infectious or other serious
disease. During the prolonged starvation suffered by inhabitants of the
Jewish ghetto in Warsaw during World War II, for example, almost 500
deaths were attributed solely to simple starvation, but many more deaths
occurred because of malnutrition in combination with tuberculosis, ty-
phus, or other infectious diseases. Not surprisingly, most of the population
showed clinical evidence of poor immune function (Winick 1979).

Even now, despite many medical advances, the combined effects of infec-
tion and malnutrition constitute the most common cause of death among
children throughout the developing world (Chen 1983) and they remain as
major problems among premature and low birth weight infants-and
among severely ill hospitalized patients-in the United States (Chandra
1983; Keusch 1984).

The history of food allergies and intolerances is less well known. Hippocra-
tes (460-370 B.C.) and Galen (131-210 A.D.) reported a relationship be-
tween consumption of specific foods and allergic digestive and skin symp-
toms, specifically describing reactions to ingestion of cow and goat milks,
respectively. Systematic observations of food allergies began to appear in
the 20th century, and recently, the literature in this field has grown rapidly
(AAAI 1984). Diet may also cause disease by transmitting infectious micro-
organisms or toxic substances that enter or are contained within the natural
foods.

Significance for Public Health

Tremendous progress has been made in infectious disease control during
the past century, yet, except for smallpox, infectious diseases remain a
serious public health problem. In 1982, for example, over 25,500 tuber-
culosis cases were reported, along with hundreds of thousands of salmonel-
losis and hepatitis cases and millions of cases of sexually transmitted
diseases, hospital-acquired infections, influenza, and other acute respira-
tory illnesses (CDC 1983). In the past decade, new varieties of infectious
disease (e.g., legionnaires' disease, toxic shock syndrome, AIDS, viral
diarrheas) have emerged, often with fearsome consequences. The ultimate
conquest of infectious diseases, therefore, is far from over.

In the developing world, where food and water supplies are often contami-
nated with micro-organisms, food-borne diseases take their highest toll. In
1980, more than 1 billion cases of diarrhea1 diseases were estimated to

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occur in children under age 5 (Chen 1983). Contaminated food and water
were largely responsible for the high rates of infant and childhood mortality
recorded among developing populations.

Despite high standards of sanitation in the United States, the incidence and
costs of food-associated disease are considerable (although assessments of
the magnitude of the problem vary widely due to difftculties with data
collection and case reporting). In the United States in 1982, only 656
outbreaks of food-borne disease were reported to the Centers for Disease
Control (CDC 1983). However, published estimates range from 24 to 81
million cases per year of gastroint :stinal illness due to contaminated food
or person-to-person spread (Archer and Kvenberg 1985). In cases in which
the causes were confirmed, bacterial pathogens accounted for approxi-
mately two-thirds of the outbreaks and chemical agents for about one-fifth.
Parasitic and viral outbreaks occur more infrequently in the United States.
Although an outbreak is defined as an incident in which two or more
persons experience a similar illness after eating a common food or in which
epidemiologic analysis implicates food as a source of illness, a single case
of botulism or chemical poisoning also constitutes an outbreak (CDC 1985).
The discrepancies in estimates are due to limitations in the available data.
The economic costs of food-associated illness have been estimated to range
from $1 billion to $10 billion annually for direct medical costs, lost wages,
and reduced industrial productivity (Todd 1984). A more recent analysis
has placed the economic costs as high as $23 billion, excluding costs to
industry (Archer and Kvenberg 1985).

Because gastrointestinal, skin, and respiratory symptoms of food allergies
and intolerances resemble those caused by many other conditions, the true
incidence of these food-related problems has been difficult to establish.
Unexplained symptoms are often attributed to food allergies when no other
reason can be found or when the symptoms improve after the offending
food is removed from the diet. The percent of food allergy cases confirmed
in double-blind food challenges is usually quite low. Estimates of the
incidence of cow milk allergy have ranged from 0.3 to 7.5 percent, with
higher rates reported for infants than for adults. Rates as high as 25 percent
have been reported in individuals who had eczema as infants or asthma in
childhood. The percentage of the population that reacts adversely to foods
or food components is unknown (AAAI 1984).

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Sciintific Background

Effects of Malnutrition

Simply defined, malnutrition means poor nutrition, but malnutrition may
take many forms, including excesses as well as deficiencies of body nu-
trients. Both deficits and excesses may be generalized, involving multiple
nutrients, or they may be limited to one, or only a few, of the many nutrients
the body needs to maintain normal health and body composition. Most
forms of malnutrition appear to make the human body more susceptible to
infectious diseases. Obesity has been linked with increased susceptibility
to infection only rarely. Malnutrition is a far more common association
(Edelman 1981).

Many forms of malnutrition also have detrimental effects on immune
system function (Suskind 1977; Stinnett 1983). These adverse influences of
malnutrition depend, to a large degree, on the severity of the nutritional
deficiency (Scrimshaw and Wray 1980). Most reported examples of the
interaction between malnutrition and infection deal with severe gener-
alized malnutrition, which is also called cachexia. Dry (nonedematous)
cachexia has also been termed marasmus, whereas wet (edematous)
cachexia is known as kwashiorkor. The terms protein-calorie or protein-
energy malnutrition are widely used in medical literature to denote gener-
alized undernutrition, but these terms fail to indicate that most clinical
forms of generalized malnutrition involves multiple nutrient deficiencies as
well as protein and other sources of metabolizable energy. In contrast to
severe generalized malnutrition, far less is known about the effect of single
nutrient deficiency (e.g., vitamins, minerals, trace elements, amino acids,
and unsaturated fatty acids) on the immune system function and other host
defensive mechanisms (Beisel et al. 1981; Beisel 1982a; Chandra 1988).

Effects of Infectious Disease

Infectious agents include a wide variety of micro-organisms such as bac-
teria, viruses, rickettsia, fungi, and parasites. When an infectious agent
invades a host, the results can range from no disease to an acute or chronic
illness. Whether a clinically apparent infection develops depends on the
virulence (ability to cause serious illness) and dose of the invading micro-
organism, the route by which the micro-organism enters the body, and the

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host's ability to resist infection. This ability is influenced by age, sex,
heredity, previously acquired immunity, the presence or absence of other
disease processes, and overall nutritional status. Depending on its severity,
generalized or single nutrient malnutrition can adversely affect the struc-
ture and function of various body cells and tissues. These deficiencies can
secondarily impair the adequacy of many non-specific host defense mecha-
nisms (Suskind 1977). The weakening of immunologic and nonspecific
defenses can lead, in turn, to a more severe illness (Scrimshaw et al. 1986).
Infectious diseases and immune functions are intimately linked to each
other as well as to nutritional status, and each of these variables are
interactive (Beisel 1982b, 1984; Chandra 1983). Although each species of
virulent bacteria, virus, parasite, or other disease-causing micro-organism
produces a different, but characteristic, illness in humans, the nutritional
consequences of most acute infectious diseases are quite similar. These
consequences occur as a result of fever, loss of appetite, vomiting and
diarrhea, and other symptoms of generalized infection. The overall in-
crease in body metabolic rates and the reprioritization of many biochemical
pathways during acute infections combine to increase the body's require-
ments for nutrients as well as simultaneously to increase body losses of
nutrients (Beisel 1985). These nutritional costs of infection occur at a time
when food intake is reduced by anorexia. Thus, the magnitude of nutrient
depletion often depends more on the severity and duration of illness than on
the species of infecting organism.

Most infections stimulate protective immune responses; however, some
responses are harmful. Examples are kidney inflammation (Bright's dis-
ease) or rheumatic fever after some streptococcal infections and heart or
thyroid inflammation after certain viral infections. Abnormal function of
the immune system increases the chance for infections that lead to mal-
nutrition. As will be discussed later, malnutrition depresses the immune
system and makes infected people more susceptible to still other infections
(Scrimshaw, Taylor, and Gordon 1968). Malnutrition, depressed immunity,
and infection thus interact in a cyclical downhill spiral that can eventually
lead to death (Mata 1975; Keusch 1984).

Nonspecific Host Defense Mechanisms

Nonspecific defenses include both active and passive components. Passive
mechanisms (such as normal microbial flora, skin and mucous membranes,
and body surface secretions) help prevent micro-organisms from entering
body tissues. For example, surface secretions and coughing cleanse the
lungs and prevent microbial entry, as does the production of mucus in the
intestine and normal intestinal motion. Many of these passive components
are impaired by inflammation and in severely malnourished patients.

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The more active forms of nonspecific host defenses include the ability of
body cells to kill micro-organisms or to release substances that aid in
eliminating them. These defenses are also impaired during malnutrition
(Beisell985; Kauffman, Jones, and Kluger 1986). For example, whenever
an infection begins, acute-phase responses are triggered by the release of
interleukin-1 (IL-l) and other substances from body cells (Kluger, Op-
penheim, and Powanda 1985; Dinarcllo 1988; Movat et al. 1987). IL-l is a
hormone-like mediator produced by activated blood monocytes and tissue
macrophages. In addition to its ability to stimulate the immune system
through its action on lymphocytes, IL-l initiates numerous metabolic and
physiologic changes that make up the nonspecific but active host defense
mechanisms known as acute-phase responses. IL-l acts on the brain
(Breder, Dinarello, and Saper 1988) and on the liver, islet of Langerhans
cells in the pancreas, bone marrow, contractile cells of skeletal muscle,
circulating blood granulocytes, vascular endothelium, intestinal mucosa,
and adipocytes of fat depots (Beisell985; Dinarello 1988). Another defense
mechanism is the complement system, which includes about 20 proteins
that circulate in inactive forms in the blood. When an infection occurs,
these proteins are activated to produce inflammatory responses, mem-
brane lysis, and other effects that cause bacterial death (Claman 1987).
These nonspecific defense responses are also impaired by malnutrition, as
will be discussed later in this chapter.

Cellular and Humoral Immunity

The immune system protects the body against infection by producing
specific substances in response to foreign materials called antigens. Immu-
nity to specific antigens occurs through the cooperative interactions of two
subsets of blood cells, T lymphocytes and B lymphocytes, that give rise to
cell-mediated (cellular) and antibody-mediated (humoral) immunity, re-
spectively (Claman 1987).

Cell-mediated immunity is provided largely by thymus-dependent T lym-
phocytes. There are several subtypes of T lymphocytes, each with specific
functions. Helper and suppressor T lymphocytes regulate the quantities of
antibodies produced, while killer T lymphocytes, which respond selec-
tively to foreign material, can search and destroy internally infected,
transplanted, or malignant body cells. Each T lymphocyte class responds
to different types of infection or to different forms of malnutrition (Beisel
1982a, 1984). Mature lymphocytes in blood can be classified by their
function and by unique marker molecules on their surfaces.

Bumoral immunity is provided by antibodies, which are specific immu-
noglobulin (Ig) proteins produced by B lymphocytes in response to specific

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0 Nutrition and Health

antigens. Antibodies of various classes, such as IgM, IgG, or IgA, are of
major importance in preventing or terminating infections of many different
types, and they also neutralize toxins of bacterial origin, such as those
produced by diphtheria or tetanus bacilli (Braude 1985). This protection
can be long term. Exposure to a specific antigen, either through an infec-
tion or vaccination, stimulates the immune system to produce antibodies.

Preformed, concentrated antibodies against specific antigens and con-
tained in serum (e.g., antiserum or antitoxin) can be administered thera-
peutically or prophylactically to provide direct immediate short-term pas-
sive immune protection. For example, antitoxin is used to treat botulinism,
and hyperimmune globulin is given to help prevent hepatitis. In addition to
these protective functions, harmful immune responses sometimes can
occur as a consequence of circulating antibodies, as in allergies or autoim-
mune diseases.

Methodological Issues

Despite recent advances in immunologic methodology that permit identifi-
cation of pathogens and various subsets of lymphocytes, clinical assess-
ment of immune function is still quite difficult and uncertain, especially
under field conditions. Immunologic responses to antigens may take
months to develop. Skin testing for immediate and delayed reactions to
antigens is not specific enough to accurately assess infection or immuno-
logic function in all situations (Miller 1978). Adequate methods to evaluate
the immunologic status of body surface secretions, especially within the
gastrointestinal tract, have not yet been developed. Although the func-
tional capabilities of various types of immune system cells can now be
evaluated in specialized laboratories, these studies require exacting tech-
niques to transport the blood sample, to isolate the cells, and to maintain
them in culture throughout the testing. As a result of these difficulties, few
reliable data have been obtained in human subjects on the influence of
individual essential nutrients on specific immune system functions or on
the mechanisms of interaction between nutrition and immunity (Chandra
1981; Solomons and Keusch 1981). In addition, as with other studies in diet
and health, the use of animal models for the study of infection and malnutri-
tion presents problems. Animal species differ from each other and from
humans in their nutritional requirements, rates of growth, and suscep-
tibility to infections (Chandra 1983). The amounts of protein in a diet, for
example, and the duration of feeding, the age, and the species of animal
studied can all influence immune responses (Jose and Good 1973).

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Infections and Immunity 0

Key Scientific Issues

o Effects of Malnutrition on the Immune System
o Effects of Infection on Nutritional Status
o Role of Diet-Immune System Relationships in Food-Associated Ill-
nesses

Effects of Malnutrition on the Immune System

Role of Generalized Malnutrition

Throughout the world, generalized malnutrition is a common cause of
acquired, correctable immune system dysfunction (Chandra 1983; Suskind
1977; Stinnett 1983). Deficits in both calories and protein tend to be closely
linked during generalized malnutrition, and it has not been possible to
separate their effects on the immune system. Infectious diseases are ex-
tremely prevalent in children with either the marasmus or kwashiorkor
forms of generalized malnutrition (Brown et al. 1981). The impact of mal-
nutrition on infectious illnesses is not clearly evident when the malnutrition
is mild.

Generalized malnutrition increases both the likelihood of contracting an
infectious disease and the severity of infections such as tuberculosis,
whooping cough, herpes, bacterial and viral diarrheas, as well as systemic
parasitic infections. Severe malnutrition suppresses a person's ability to
generate fever, inflammatory responses, or leukocytic reactions (Garre,
Boles, and Yovinov 1987). In persons with severe, prolonged diseases,
generalized malnutrition increases susceptibility to all infections, but espe-
cially those caused by opportunistic organisms that do not usually cause
disease in healthy individuals (Baron 1986).

Malnutrition's effects on infection may be synergistic, antagonistic, or
show no apparent interaction. In synergistic interactions, infections are
made worse by malnutrition, whereas antagonistic interactions occur when
an infection is milder than would be expected in a malnourished host.
Although most bacterial infections become more severe with malnutrition,
nutrient deficiencies have attenuated some viral infections (Scrimshaw,
Taylor, and Gordon 1968). The generalized weakening of host defensive
mechanisms, including those of the immune system, can explain syn-
ergistic interactions. Antagonism occurs because host cells and invading

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O Nutrition and Health

micro-organisms compete for available nutrients and because host-immune
reactions that normally produce disease symptoms are suppressed. Vi-
ruses, for example, must use metabolic processes of the host cell to
multiply, and nutritionally deprived cells may not contain the nutrients
needed for viral proliferation (Beisel 1982b). Parasites such as malaria may
also be less able to multiply when the patient is malnourished (Murray and
Murray 1977; Solomons and Keusch 1981). Tuberculosis may be acutely
exacerbated by feeding starving people; the body's inflammatory reaction
to the tuberculous bacillus, which was suppressed by starvation, may
flourish after feeding and cause symptoms, particularly if the patient has
not received antituberculosis drugs (Murray and Murray 1977).

Malnutrition due to starvation produces different effects on metabolism
and body composition than those due to illness or injury, and this difference
profoundly affects susceptibility to infection (Beisel 1987). During uncom-
plicated starvation, extensive metabolic changes serve to conserve body
protein stores. Metabolic rate is reduced, nitrogen is conserved, and the
use of body fat as a source of energy is increased. Because protein is saved,
immune system competence and resistance to infection persist until starva-
tion is greatly advanced (Kemdt et al. 1982).

In contrast, the extreme body wasting (cachexia) caused by acute illness or
injury is associated with rapid protein breakdown and a concomitant
weakening of resistance mechanisms. Metabolic rate and loss of body
nitrogen increase, and large quantities of gluconeogenic amino acids are
metabolized to produce glucose; branched chain amino acids are oxidized
in muscle cells to produce energy; and the metabolic destruction of tryp-
tophan and phenylalanine is accelerated (Beisel 1985). Such diversions of
free amino acids reduce their availability for the synthesis of new proteins.
The adequacy of immune functions and other host defense mechanisms
ultimately depends on the ability of body cells to synthesize a variety of
new proteins. But protein synthesis is impaired when the supply of free
amino acids is inadequate or when an imbalance exists among the essential
free amino acids. Thus, when overwhelming disease or trauma causes
severe generalized malnutrition, the resulting deficits of body protein and
free amino acids can be linked directly to a depression in host resistance
(Beisel 1985). In short, the metabolic consequences of fever and loss of
appetite lead to poor nutritional status, deficits in immune system compe-
tence, and an increased susceptibility to infectious disease within a rela-
tively short time period (Beisel 1984).

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Infections and Immunity 0

Severe malnutrition due to any cause will impair cell-mediated immunity
and may affect immunity mediated by antibodies circulating in the blood
and secreted by mucosal surfaces (Suskind 1977; Chandra 1983; Stinnett
1983; Gershwin, Beach, and Hurley 1985; Watson 1984). Patients with
severe generalized malnutrition consistently exhibit atrophy and other
defects of the lymphoid tissues of the immune system. The total number of
lymphocytes is reduced, with the greatest losses occurring among T lym-
phocytes (Suskind 1977). These abnormalities lead to poor T cell function,
diminished ability to reject grafted tissue, and a reduction in secretion of
lymphokines and other anti-infective substances.

Even with severe malnutrition, however, total antibody production remains
normal and may even be accelerated if infection is present (Chandra 1983).
The capacity to produce or to secrete the immunoglobulin IgA into the
fluids that cover mucosal surfaces of the body is diminished, however, and
specific antibody responses to new vaccines or other new antigens are
clearly depressed despite maintenance of nonspecific blood immu-
noglobulin levels.

When infections occur in malnourished patients, concentrations of individ-
ual components of the complement system tend to decline rather than to
show a typical infection-induced increase (Suskind 1977; Keusch and
Farthing 1986). Complement system deficiencies depress immune system
function (Watson 1984) and increase the risk of bacterial infections
(Chandra 1983).

With severe generalized malnutrition, the production and mobilization of
phagocytes (the cells of the immune system responsible for ingesting
microbes or other cells and foreign materials) are often reduced in number.
Phagocytic cell function is also impaired, including their responses to
stimuli, their participation in inflammatory processes, and their ability to
ingest and kill invading micro-organisms (Beisell984; Keusch 1984; Garre,
Boles, and Yovinov 1987).

Severe generalized malnutrition impairs tissue integrity and causes damage
to epithelial surfaces, loss of respiratory tract cilia, and reduction of
mucosal secretions. The bacteria in the intestine may be altered, and the
normally sterile upper small bowel may become colonized. The stomach's
secretion of hydrochloric acid is reduced (Kemdt et al. 1982). All of these
defects in the nonspecific defense mechanisms can increase the risk for
infection by pathogenic micro-organisms. Dietary replenishment to cor-
rect the identified deficiencies can resolve these problems.

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O Nutrition and Health

Role of Specific Dietary Factors in Immunity
Certain nutrients described in the following sections are particularly impbr-
tant to immune system function.

Protein. Proteins in food provide the body with essential and nonessential
amino acids as well as contribute 4 kcal/g to the body's overall energy
needs. An adequate intake of animal protein, or certain mixtures of vegeta-
ble proteins in the diet, will yield the balance of free amino acids necessary
to allow for an optimal synthesis of new body proteins, including those that
maintain immune functions. If dietary protein intake is excessive, the
unneeded amino acids are broken down (deaminated), and their carbon
skeletons are either diverted into energy generation or stored as fat. On the
other hand, a prolonged deficit in protein intake will contribute to gener-
alized undernutrition.

There is a normal continuous turnover of proteins in the body, with both the
catabolism and anabolism of individual body proteins taking place concur-
rently. Anabolic protein synthesis predominates during periods of active
body growth and during convalescence from illness if protein intake is
adequate. Both the anabolic and catabolic processes are accelerated during
acute infectious illnesses, but catabolic activity predominates. The role of
protein and amino acid metabolism in body defensive reactions will be
described in subsequent portions of this chapter.

Carbohydrate. Dietary carbohydrate serves chiefly as a source of meta-
bolic energy for the body. Like excessive dietary protein, excessive carbo-
hydrate in the diet will be diverted into fatty acid molecules and deposited
in body fat depots. During infection, most of the extra energy needed to
produce hypermetabolism and fever comes from the oxidation of glucose.
Various hormonal and metabolic stimuli accelerate the manufacture of new
glucose (chiefly within the liver) during infection. If the body is unable to
sustain the gluconeogenic process, severe hypoglycemia may occur as a
terminal complication of infection. This problem is most likely to develop
during neonatal sepsis, gram-negative septicemia, or severe hepatitis.

Fats. Dietary fats contribute about 9 kcal/g to body energy needs as their
principal metabolic function. In addition, a small quantity of essential
unsaturated fatty acids in the diet is required for maintaining the integrity of
the exterior surface membrane of body cells and for mounting primary and
secondary antibody responses (Chandra 1981). However, a dietary excess
of polyunsaturated fatty acids, such as linoleic acid, can suppress cell-
mediated immune functions in mice (Mertin and Hunt 1967). The greatest

438


Infections and Immunity 0

immune suppression in experimental animals seems to occur when the
excess polyunsaturated fatty acids have the highest numbers of unsaturated
carbon:carbon bonds per molecule (Beisel 1982a).

Fatty acid-derived mediators of inflammation are important in allergic and
other inflammatory diseases. For example, asthma patients were put on
diets enriched with high- and low-dose eicosapentaenoic acid (EPA) for 8
weeks (Payan et al. 1986). When leukocytes from study patients were
examined, it was found that those taken from patients on the high-dose
regimen had inhibition both of white cell migration to sites of inflammation
(chemotaxis) and the generation by white cells of potent chemical me-
diators (Ieukotrienes) of the inflammatory component of chronic asthma
when compared with those on the low-dose regimen. However, the clinical
role of EPA is still open to question because EPA at either dose did not
affect the clinical course of asthma.

There is little doubt that excess quantities of host lipids, occasioned by
high-fat, high-energy diets or by lipid infusions, can initiate changes in
immune function. However, solid evidence directly linking obesity, high-fat
diets. and hyperlipidemia with the outcome of human infection is meager
(Edelman 1981). The incidence of only one category of infections,
postoperative wound infections, is clearly increased in obese patients, and
the mechanisms of this effect may be other than nutritional. Moreover,
there are no convincing data in humans on the interaction of obesity, body
lipids, and autoimmune diseases (Edelman 1981).

Vitamins and Minerals. As discussed throughout this report, deficiency
diseases such as scurvy (from vitamin C deficiency), pellagra (niacin defi-
ciency), beriberi (thiamin deficiency), and anemia (iron deficiency) are
often associated with decreased resistance to infection. Of special recent
interest, for example, are the findings that adequate vitamin A protects
against complications of measles (Anonymous 1987) and is associated with
overall improvements in mortality rates (Sommer et al. 1986). Subclinical
deficiencies of vitamins and minerals may also affect host defense mecha-
nisms (Beisel et al. 1981; Beisel1982a; Good, Hanson, and Edelman 1982).
The lack of information about threshold values at which a nutritional deficit
might impair the immune system, however, makes research in this area
difl?cult .

Deficiencies of zinc, pyridoxine, iron, folate, vitamin B,,. choline. or
methionine have been associated with reduced function of T cells (Good
Hanson, and Edelman 1982; Chandra 1985). Zinc is required for adequate

439


0 Nutrition and Health

function of T lymphocytes and cell-mediated immunity in several animal
species (Fraker, Caruso, and Kierszenbaum 1982; Beisel 1982a). In hu-
mans, persons with acrodermatitis enteropathica, an inherited inability to
absorb zinc, have severe immune system failure, widespread infections of
skin and mucosa, and early death. When instituted early enough, correc-
tion of body zinc deficits in these patients has been followed by functional
recovery of the immune system, elimination of infections, and a return to
good health (AUen, Kay, and McClain 1981; Castillo-Duran et al. 1987).
When volunteers ingested excessive zinc, however, the phagocytic func-
tions of neutrophils and the response of lymphocytes to mitogens were
impaired (Chandra 1984).

Deficiencies of ascorbic acid, iron, vitamin B,*, folate, and zinc all impair
neutrophil function, although in different ways (Good, Hanson, and
Edelman 1982). Although deficiency of vitamin C blocks the mobility of
neutrophils, clinical trials have failed thus far to demonstrate that massive
daily doses of vitamin C either prevent or cure the common cold or that it
improves immune system functions beyond normal (Beisel 1982a; Gersh-
win, Beach, and Hurley 1985).

As discussed in the chapter on anemia, iron deficiency has been associated
with increased incidence of certain infections (Chandra 1981), perhaps
because it impairs the function of peroxidase enzymes and leads to deficits
in the production of free oxygen radicals and hydrogen peroxide that can
kill ingested bacteria (Beisel 1982a; Stinnett 1983).

Age-Related Issues

Infants. As discussed in the chapter on maternal and child nutrition,
prematurity and low birth weight increase the risk for infectious disease,
other complications, and consequent mortality. The fetus receives immu-
noglobulins from the mother by selective transfer across the placenta, but
infants born to undernourished mothers typically have abnormally low
antibody concentrations in plasma once autonomous antibody production
begins. In developing countries where standards of sanitation are poor and
children are exposed to multiple infections, children may in fact demon-
strate a precocious rise in antibody concentrations compared with adult
values (Chandra 1983). Nevertheless, the infant's immune system can be
easily overwhelmed by gastrointestinal infections. Such infections prevent
intake, absorption, and utilization of food energy and nutrients and initiate
the debilitating cycle of infection, diarrhea1 disease, malnutrition, and,
often, death.

440


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Breastfeeding provides an infant both with nutrients and some degree of
immunity against infections (Chandra 1979; Welsh and May 1979). Even
under conditions of poor sanitation and poverty, breastfeeding protects an
infant and fosters normal growth (Mata 1975). Once an infection is estab-
lished, breastfeeding provides additional protection against its severity
(see, for example, Victora et al. 1987). Such protection has been observed
in studies in the United States (Duffy et al. 1986) although its overall
clinical significance in industrialized societies is uncertain (Leventhal et al.
1986; Bauchner, Leventhal, and Shapiro 1986). In bottle-fed infants, un-
sanitary conditions, use of contaminated water in preparing bottles, and the
lack of maternal antibodies all contribute to infections, especially diarrhea1
illnesses (see chapter on maternal and child nutrition).

Older Persons. The extensive anatomical and physiologic changes that
characterize aging are reviewed in the chapter on aging. One change is a
gradual senescence of some-although not all-components of the immune
system. Studies in experimental animals and in humans reveal a gradual
atrophy of the thymus gland along with decreases in the numbers of T
lymphocyte helper/inducer cells and in cell-mediated immune functions
(Katz 1982). Such changes are similar to those observed in malnutrition. As
discussed in the chapter on aging, distinguishing such age-related phys-
iologk changes from those due to malnutrition in older persons has not yet
heen possible. Progressive impairment of cellular immunity with age might
cause the older population to have more infections than younger people of
equivalent nutritional and health status, and if malnutrition is responsible
for depressed immune functions, improved diet should restore such func-
tions and improve disease resistance. Research has not yet resolved these
issues, and the relationships among malnutrition, infections, and changes
in immune system functions in elderly persons have yet to be clarified
(Thompson, Robbins, and Cooper 1987).

Effects of Infection on Nutritional Status

As noted earlier, severe infections can compromise nutritional status
through a variety of mechanisms: hypermetabolism, appetite depression
and reduced food intake, decreased intestinal absorption of nutrients,
altered nutrient metabolism, increased nutrient excretion, and internal
diversion of nutrients (Beisell984). Additional nutritional losses occur with
vomiting, diarrhea, sweating in fever, or loss of sputum in pneumonias.
Liver damage caused by hepatitis can disrupt nutrient metabolism. Anti-
microbial drugs may affect nutrient digestion and absorption or aher intes-
tinal flora (Braude 1985). Many of these losses can be overcome by im-
Proved feeding methods (Siegel 1987).

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0 Nutrition and Health

Hypenetabolism

Acute-Phase Responses. Acute-phase responses during acute infectious
illnesses are of major nutritional importance because they involve many
body functions and because they speed up the consumption of nutrients in
the body and deplete nutritional stores (Beisel 1985). They result in general
symptoms and signs of illness, including fever, loss of appetite, increase in
numbers of white blood cells, heightened body metabolism, muscle pains
and breakdown of skeletal muscle protein, use of some free amino acids
from this breakdown for generating energy rather than for synthesizing new
protein, altered metabolism of sugars and fats, redistribution of trace
minerals, and stimulation of the immune system. The nutrient costs of
these acute-phase responses depend on the severity and duration of the
infectious process, the prior nutritional status of the patient, and the
effectiveness of therapeutic interventions (NRC 1976; Beisel et al. 1977).

Acute-phase responses to infection are initiated by a common mecha-
nism-the release of IL-l and other hormone-like mediators from cells.
The nutritional consequences of this release are similar regardless of the
infecting organism. These include an increase in secretion of insulin and
glucagon from pancreatic islets and alterations in the metabolism of carbo-
hydrate, fat, and protein (Kluger, Oppenheim, and Powanda 1985; Din-
arello 1985; Movat et al. 1987) that increase use and loss of body nutrients
(Keusch 1984).

In some infections, especially those caused by gram-negative bacteria,
body macrophages are stimulated by lipopolysaccharide toxins to release
another hormone-like mediator. This mediator was initially termed cachec-
tin, although it has proved to be tumor necrosis factor (TNF). Because TNF
inhibits the membrane-bound enzyme lipoprotein lipase, it contributes to
the accumulation of triglycerides in the plasma during gram-negative sepsis
as well as to other alterations in body lipid metabolism. TNF also plays a
role in the development of hypotensive shock during sepsis. Experimental
evidence shows that TNF and IL-I act synergistically, thereby amplifying
the loss of body nutrients that lead to cachexia (Tracey `et al. 1988).

Fever. Fever causes metabolic rates to increase about 7 percent for each
increase of 1" F. This hypermetabolism affects all cells of the body. In
addition, phagocytic cells increase their rate of oxygen consumption when-
ever they take up bacteria or other particles. Because this extra energy
comes largely from amino acid metabolism (Siegel 1987; Bell et al. 1983),
the body stores of muscle protein amino acids and nitrogen are rapidly
depleted (Beisel 1985). Loss of nutrients may also occur through sweating

442


Infections and Immunity 0

associated with fever. Controlling the infection minimizes fever and re-
duces losses of body nutrients.

Loss of Appetite. Severe loss of appetite is a common symptom during
most infectious diseases and often leads to an almost total cessation in food
consumption. Based on studies in laboratory animals, the effects of IL-l
and other monokines on the appetite centers in the brain may cause this
anorexia (Kluger, Oppenheim, and Powanda 1985; Dinarello 1988).

Reduced Absorption. Vomiting, diarrhea, altered bowel motility, and infec-
tion-induced decreases in synthesis of intestinal enzymes further reduce
the absorption of nutrients from the intestinal tract. Antibiotics and other
medications also modify intestinal absorption and motility, as discussed in
the chapter on drug-nutrient interactions.

Altered Metabolism

Protein. Some proteins break down (catabolize) and others are formed
during acute-phase reactions, but the catabolic aspects predominate and
lead to clinically evident losses of muscle mass and body nitrogen (Rennie
and Harrison 1984). IL-l induces the release of amino acids from con-
tractile proteins (Kluger, Oppenheim, and Powanda 1985) and the preferen-
tial oxidation of branched-chain amino acids (leucine, isoleucine, valine) to
provide metabolic energy in muscle. Alanine, synthesized in muscle from
glucose and components of the branched-chain amino acids, is then taken
up by the liver and used to manufacture glucose.

Despite the accelerated input into plasma of free amino acids from muscle,
concentrations of most free amino acids are lowered because of increased
use of body cells and reduced dietary intake due to loss of appetite. These
free plasma amino acids are used to manufacture the new body cells and
proteins needed for defense against infection. As described previously, the
liver takes up large amounts of free plasma amino acids during infection
and uses them to synthesize glucose and to make compounds that contrib-
ute to nonspecific host defenses (Powanda and Canonico 1981).

Excess nitrogen derived from these processes is metabolized to urea and
excreted in urine, thereby accounting for most of the nitrogen lost during
infection. Infection-induced nitrogen losses can be quite extensive. For
example, malaria, which was once used as a form of therapy for neu-
rosyphilis (Howard, Bigham, and Mason 1946), has caused extensive losses
of body nitrogen and advanced cachexia in as little as 30 days. Even brief,
self-limited viral infections and brief fevers induced by bacterial infections

443


0 Nutrition and Health

can cause sizable losses of nitrogen (Beisel et al. 1977); although protein-
nitrogen losses of mild or promptly treated infections do not lead to
cachexia, they suggest that large losses of body protein can occur in even a
week-long infection accompanied by fever. The magnitude of body protein
catabolized can be quantitated roughly by the excesses of total nitrogen in
the urine. The breakdown of contractile protein in skeletal muscle can be
estimated by the amount of 3-methyl-histidine excreted in urine (Beisel
1985).

Although the catabolism of body proteins is a predominant feature of the
acute-phase response, the anabolism of certain proteins is also stimulated.
Proteins needed for the reproduction of white blood cells and immu-
noglobulins account for some of this anabolic activity. The liver is stimu-
lated to synthesize a large number of proteins for intracellular use (e.g.,
enzymes and metallothionines) as well as a variety of proteins that enter the
plasma. These include components of the complement system, the kinin
system, and the coagulation system. Also synthesized within the liver are a
group of plasma glycoproteins termed acute-phase reactants. In humans,
these include haptoglobin, C-reactive protein, ceruloplasmin, alpha-anti-
trypsin, and orosomucoid, all of which appear to play some protective role
during infection (Beisel 1985).

Lipids. During infections, hormonal influences on the liver lead to the
synthesis of excessive amounts of free fatty acids (Powanda and Canonico
1981) and a reduction in the conversion of free fatty acids to ketones, a
process that normally occurs during periods of reduced food intake. These
phenomena lead to increased production of triglycerides, the accumulation
of fat droplets within liver cells, and an increase in triglyceride concentra-
tions in blood. These changes are especially pronounced in infections
caused by endotoxin-containing bacteria, apparently because of the release
of the monokine TNF, which inhibits lipoprotein lipases on cell walls
(Beisel 1985). In addition, IL-l is thought to activate phospholipase en-
zymes in cell walls that stimulate the production of arachidonic acid,
which, in turn, is converted into prostagiandins or leukotrienes within
body cells (Kluger, Oppenheim, and Powanda 1985).

Vitamins. Tissue and plasma concentrations of most vitamins have been
reported to decline during infections, perhaps because of increased metab-
olism or excretion. The concentration of vitamin C, for example, declines
in neutrophils and in the adrenal cortex during active steroid production,
which may occur during the stress of illness. The accelerated metabolism
or loss of vitamins during infections may precipitate recognizable deficien-
cy states (Scrimshaw et al. 1968; Beisel 1985).


Infections and Immunity 0

Minerals. During infection, all of the principal intracellular elements are
lost from the body, roughly in proportion to the losses of nitrogen (Beisel
1985). Blood mineral concentrations decline slightly and may be severely
reduced under certain circumstances. Calcium (in conjunction with cal-
modulin) is intimately involved in many altered molecular responses of
body cells during febrile infections, but calcium is not generally lost from
the body unless an infection causes muscle paralysis or requires prolonged
bed rest. These mineral losses are readily replaced by supplying adequate
intake during convalescence (Beisel 1985).

Responses induced by IL-1 also cause the redistribution of iron, zinc, and
copper within the body. Both iron and zinc leave the plasma and are held in
a storage form for as long as the infection persists. Zinc is held in hepatic
cells by newly produced binding proteins (metallothionines), and iron is
stored as ferritin or hemosiderin. In contrast, copper leaves the liver and
accumulates in blood as a component of ceruloplasmin. This redistribution
appears useful for host defenses against infection, although specific func-
tions have not been established (Beisel 1982a).

Electrolyte metabolism is altered in most systemic infections by the renal
retention of sodium and chloride and, therefore, of extracellular water. In
some infections, especially those that localize in the brain, an inappropriate
secretion of antidiuretic hormone causes more intense retention of body
water and dilution of the electrolytes in body fluids (Beisel 1985). Con-
versely, significant quantities of sodium, chloride, and other nutrients may
be lost through the sweating associated with fever and infection, and any
infection that causes diarrhea will induce fecal losses of sodium, chloride,
potassium, and bicarbonate, as well as water. Cholera, for example, in-
duces extensive water and electrolyte losses from the gastrointestinal tract,
and cholera deaths are from dehydration rather than from the infection
itself. Such losses are especially dangerous in already malnourished infants
and children (Beisel 1985).

AIDS: A New Example of Complex Infection-Nutrition-Immunity
Interactions

AIDS (acquired immunodeficiency syndrome), caused by the human im-
munodeficiency virus (HIV), is a disease with multiple pathologies, most of
which are the consequence of a profound immunodeficiency. The CD4-
bearing T lymphocytes appear to be the primary population of target cells
that are lost in HIV-infected patients. This loss includes the majority of
helper T cells that help killer T cells and B cells function properly. There-
fore, killer cell function is reduced, which leads to a loss of recognition and

445


0 Nutrition and Health

elimination of body cells infected with other micro-organisms. Reduced B
cell function disables the body's ability to make new antibodies for the
neutralization or elimination of micro-organisms located in extracellular
body fluids. In addition, there is a profound loss of the lymphokine me-
diators normally produced by helper T cells. This loss reduces the activa-
tion of macrophages and the maturation and effectiveness of natural killer
cells that help combat infections and cancer (Weissman 1988).

Weight loss and deteriorating nutritional status are critical features of the
AIDS disease process (Anonymous 1985; Kotler, Wang, and Pierson 1985).
Anorexia, nausea and vomiting, fever, and diarrhea are common features of
advanced AIDS, as are malabsorption of fats, carbohydrates, and protein
and some intestinal injury and dysfunction (Garcia, Collins, and Manse11
1987; Kotler 1987). The underlying causes of these gastrointestinal symp-
toms include infections by viral, parasitic, or bacterial pathogens as well as
disseminated Kaposi's sarcoma. Even before recognition of AIDS, several
research groups reported unique and multiple enteric pathogens in homo-
sexual men (Quinn et al. 1983; Baker and Peppercorn 1982). These infec-
tions are strongly associated with depressed appetite, decreased food
intake, and severe wasting typical of illness-induced malnourished states
(Kotler, Wang, and Pierson 1985; O'Sullivan, Linke, and Dalton 1985).

As noted earlier, such severe malnutrition is associated with impaired
function of specific components of the immune system and a generalized
reduction in the energy resources needed to support cell growth and
proliferation. The similarity of immune abnormalities resulting from mal-
nutrition and those seen in AIDS has led to suggestions that malnutrition
might predispose to AIDS or that nutritional therapy might improve im-
mune status and prevent AIDS (Jain and Chandra 1984) or improve its
prognosis (Kotler 1987). Little evidence, however, supports either of these
suggestions. Although the most severely malnourished AIDS patients are
at highest risk, severe malnutrition is more likely to be a result of AIDS-
related intestinal injury than a cause of this condition. As in other condi-
tions, correction of malnutrition would be expected to improve response to
therapy and to decrease susceptibility to opportunistic infections, but
complications of intravenous nutritional support-electrolyte imbalances,
excessive concentrations of blood sugar and fat, and infections of the
intravenous access routes-have made it difficult to test these hypotheses
in AIDS patients (Kotler 1987). Although some preliminary studies have
observed improved weight maintenance in AIDS patients receiving nutri-
tional support (Domaldo and Natividad 1986), others indicate that weight
gain is due to water retention rather than to repletion of body cell mass

446


Infections and Immunity 0

(Kotler, Wang, and Pierson 1985; Kotler 1987). To date, suggestions that
AIDS-specific immune dysfunctions can be either arrested or reversed by
nutritional therapy are not supported by clinical or biochemical evidence
(Kotler 1987).

Nutritional Rehabilitation

The early convalescent period following a serious infection is an important
time to restore normal metabolic processes and replenish energy reserves.
Frequently, this period is accompanied by a marked hunger. An appropri-
ate refeeding program can replace nutrient losses rapidly and stimulate the
recovery of normal host defensive and immunologic functions. However,
nutritional support for severely wasted patients with infections is often
difficult (Siegel 1987; Bell et al. 1983) because of nutrient imbalances and
other complications (Baron 1986) and because of insufficient knowledge of
the actions, or side effects, of nutrients administered parenterally (Siegel
1987). Other problems are caused by severe weaknesses of the respiratory
musculature in wasted patients (Bell et al. 1983), who may be unable to get
rid of the large quantities of carbon dioxide produced when extra energy
sources are provided to the body. Further research is needed to develop
more effective methods to overcome malnutrition induced by severe infec-
tious diseases.

Role of Diet-Immune System Relationships in
Food-Associated Illnesses

Adverse reactions to food involve both immunologic and nonimmunologic
mechanisms. Immunologic reactions are known commonly as food al-
lergies. Nonimmunologic intolerances include those that are biochemical
(food toxicities, poisonings, and digestive disorders) or psychologic.
Foods may also transmit micro-organisms that cause infectious illnesses.
The numerous causes of food-associated illness are listed in Table 11-l.

immunologic Mechanisms (Allergies)

Although the immune system usually protects the body against foreign
substances, antigen-specific immune responses can sometimes produce
adverse, even fatal, effects. Food is the largest antigenic challenge con-
fronting the human immune system (Sampson, Buckley, and Metcalfe
1987). Food allergies are examples of the negative consequences of im-
mune function on the gastrointestinal tract, skin, lungs, and other organ
systems. Symptoms can include acute abdominal pain, swelling, nausea.
vomiting, rashes, vascular collapse, chronic itching, headache, tension,
and fatigue. Eczema, asthma, and rhinitis are more common in children
than in adults (Metcalfe 1985).

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       Table 11-l
Causes of Food-Associated Illness

Food-borne infections    Food Origin Toxemias
    Due to:              Due to:

Food Allergies
  Due to:

    Nonallergic Food Intolerances
Due to Natural Products:    Due to Chemicals:

Bacteria
Salmonella

ii    Shigella
    Campylobacter
     Escherichiu coli
    Vihrio paruhrma1~vticw.s
    Listericr monocyt0gene.s
     Yersinia

Parasites
Trichinella
Toxoplasma
Amoeba
Giardia

Botulinum toxins
Staphylococcal
Enterotoxins
Escherichia coli
Enterotoxins
Verocytotoxins
Clostridial
Perfringen toxins
Difftcile toxins
Bacillus cerws
Enterotoxins

Mushroom toxins

Milk

Eggs

Wheat

Peanuts

Soybean
products

Nuts

Fish

Lactose
Sucrose
Galactose
Gluten
Borad beans
(favism)
Laythyrus peas
(laythyrism)
Caffeine
Theobromine
Histamine
Tyramine
Tryptamine
Serotonin

Sulfites
Nitrites
Nitrates
Monosodium
glutamate
Tartrazine dyes
Benzoic acid
Organophosphates
Oxalates
Heavy metals
Mercury
Lead
Arsenic
Copper


Isosporia (Coccidia)
Cryptosporidia

    Viruses
    Hepatitis A virus
    Norwalk agent
     Other Norwalk-like
      viruses
     Rotaviruses
     Adenovirusesa
     Astrovirusesa
$     Echoviruses
    Snow Mountain agent
    Cockle agent
     Coxsackie B viruses
     Calicivirusese

Fungal toxins
Ergot, mycotoxins
Trichothecenes
Atlatoxins

Shellfish

Other foods

Phenylethylamine
Solamine

Puffer fish
Tetrodotoxin
Ciguatoxins
Scrombroid fish toxin
Shellfish saxitoxin

Aspartame
Butylated-
hydroxytoluene
hydroxyanisole

*Viruses that cause gastroenteritis and may be food borne.


0 Nutrition and Health

To distinguish a true allergic reaction from an intolerance due to a bio-
chemical or psychologic disturbance, the specific food causing the reaction
must be clearly identified, a proper diagnostic procedure followed, and the
cessation of symptoms documented when the offensive food is eliminated.
A scientifically rigorous diagnosis requires additional diagnostic tools such
as the Radioallerogosorbant Test (RAST), the Enzyme Linked Immu-
nosorbant Assay (ELISA), and skin testing (although all of these are of
limited value), elimination diets, and double-blind food challenges
(Sampson, Buckley, and Metcalfe 1987). The efficacy of cytotoxic testing,
provocative subcutaneous testing, and provocative sublingual tests of food
extracts to diagnose food hypersensitivity are unproved, and use should be
limited to well-constructed diagnostic trials. At present, no single diag-
nostic test appears to be definitive in the diagnosis of food allergy (AAAI
1984).

Allergic reactions are caused by an adverse interaction between a protein
antigen and an IgE immunoglobulin antibody. The IgE antibody first binds
to the surface of a mast cell, a cell that is capable of releasing histamines
and other factors. This binding prepares the mast cell for subsequent
binding of a food antigen, which, in turn, triggers the cell to release
histamine and other vasoactive mediators that produce the signs and
symptoms of food allergies (AAAI 1984). This type of allergic hypersen-
sitivity occurs within minutes to hours and, in rare instances, can be life
threatening. The molecules of several antigens in foods capable of trigger-
ing mast cell reactions have been isolated and their structures identified
(Moroz and Yang 1980; Metcalfe 1985).

The most common foods to which people are allergic are egg, milk, wheat,
peanut, soybean, chicken, fish, shellfish, and nuts (Atkins 1983). Re-
sponses to such foods are not always consistent, however, because they
depend on the amount and form of the food consumed and the presence of
other foods in the diet or of medications. Thus, foods that have not caused
reactions in the past may induce allergic responses when other mitigating
factors are present (Atkins 1983).

Estimates of the incidence of food allergies in infants range from 0.3
percent to 20 percent. Because allergies tend to be outgrown, the incidence
decreases to less than 3 percent in adults (Butkus and Mahan 1986; Bock
and Martin 1983). Because only about one-fourth of histories of adverse
food reactions can be confirmed by diagnostic tests (May 1980; AAAI
1984), these estimates may be too high (IFT 1986).

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Infections and Immunity 0

Enteric pathogens are thought to alter the permeability of the intestinal
mucosa, permitting entry of normally excluded, immunogenic mac-
romolecules, although conclusive evidence is lacking. Uptake of intact egg
protein (ovalbumin) in humans and animals with gastroenteritis has been
demonstrated (Keljo et al. 1987; Walker 1981; Gruskay and Cooke 1955). If
operative, the effect of such uptake may result in induction of allergy,
autoimmunity (particularly immune complex-mediated disease), and other
disorders (Walker 1981).

Nonimmunologic Mechanisms

The causes of nonimmunologic adverse reactions to foods include food
toxicities, food poisonings, and pharmacologic or metabolic reactions.
Such intolerances occur more frequently than true food allergies and are
related to dose as well as to the concurrent presence of medications, other
diseases, or genetic errors of metabolism.

One example is sulfite-induced asthmas. Sulfur dioxide and sulfiting agents
are widely used to retard deterioration of perishable produce, to condition
dough, to prevent microbial growth, and to provide antioxidant action. The
average intakes of sulfite and sulfite derivatives are estimated to be 6 mg
per capita per day but are higher for wine and beer drinkers and for
individuals consuming larger amounts of sulfite-treated foods. These
amounts may exceed current estimates of safe levels of intake (IFT 1986).
Approximately 1 to 8 percent of people with asthma are sensitive to
ingestion of sulfite, and those using steroid control agents are affected
more frequently. Adverse reactions vary with the individual's sensitivity
threshold, the type of sulfiting agent, and the type of food in which it is
consumed (Bush, Taylor, and Busse 1986). The FDA has proposed that
sulfite be declared on labels when levels exceed 10 ppm as total sulfite
dioxide and that its "Generally Recognized As Safe" (GRAS) status be
rescinded, but no final rules have been issued.

Other examples include asthma induced by tartrazine, a yellow dye used to
color medicines, soft drinks, and foods; a syndrome caused by mono-
sodium glutamate (see chapter on neurologic disorders); and symptoms
caused by preservatives such as benzoic acid and sulfiting agents (Butkus
and Mahan 1986). Nonimmunologic reactions also include lactose intol-
erance (an intestinal deficiency of the digestive enzyme lactase) and celiac
sprue, the inability to metabolize gluten (see chapter on gastrointestinal
diseases). In addition, toxic contaminants such as bacteria, insect parts,

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O Nutrition and Health

and molds; vasoactive amines (e.g., histamine) found in tomatoes, avo-
cados, cheeses, pineapples, and wines; and caffeine may cause symptoms
in sensitive individuals. Other gastrointestinal diseases, such as reflux
peptic esophagitis, peptic ulcers, gallbladder disease, and mesenteric vas-
cular insufftciency are associated with acute symptoms after eating. Per-
sons suffering adverse reactions may mistakenly attribute the cause to a
food allergy rather than to their underlying illness (AAAI 1984). Finally,
psychologic mechanisms can provoke physical and mental symptoms of
food sensitivity that do not appear to be mediated by the immune system.
In individuals with psychologically induced allergic symptoms, no phys-
iologic or biochemical nonimmunologic mechanisms can be identified
(May 1984) and true immunologic mechanisms are rarely found (Johansson
1984).

Prevention and Treatment

Individuals with food intolerances should exclude the offending foods from
their diet either completely or partially. Those with potentially life-threat-
ening sensitivities should carry an epinephrine-containing syringe (Atkins
1983) and wear a bracelet identifying the problem. Desensitization shots,
oral desensitization, and use of bee pollen are not effective treatments for
food allergies (Butkus and Mahan 1986).

The likelihood of an infant developing an IgE-mediated reaction is esti-
mated at 58 percent when both parents are affected, 38 percent when one
parent is affected, and 12.5 percent when neither parent is affected (Butkus
and Mahan 1986). Special precautions should be taken in feeding infants at
high risk, especially during the first year (GIaser 1966). Some research
suggests that the incidence of food allergies is decreased if breastfeeding is
continued for 3 to 6 months (Hamburger et al. 1983; Saarinen and Kajosaari
1980; Chandra 1979). Other research, however, disputes this suggestion
(Kovar et al. 1984). Because some food antigens are transferred through the
breast milk to the infant, mothers should avoid foods to which the infant is
sensitive. Likewise, formula-fed infants sensitive to cow milk or to soy-
bean-based formulas should be given formulas prepared from casein hy-
drolysate (Butkus and Mahan 1986). Delaying the introduction of solid
foods, especially those most likely to induce allergies, may prevent or
minimize the development of food allergies (Chandra 1979; Hamburger et
al. 1983). As a general rule, new foods should be introduced into the infant
diet one at a time to permit observations of allergic reactions (see chapter
on maternal and child nutrition).

452


Infections and Immunity 0   .-

Food-borne Microbial Diseases

Ingestion of water or foods that are contaminated with chemicals, patho-
genic micro-organisms, or the toxins they elaborate can lead to illness.
Food-borne pathogens commonly cause diarrhea, vomiting, abdominal
cramps, or other gastrointestinal symptoms. Less commonly, they affect
the liver or nervous system. Symptoms range from minor discomfort to
severe disease and even death. Their causes are listed in Table 1 I-1, In
1982, the factors most common to food-borne disease outbreaks. in order
of frequency, were (1) improper food handling, (2) food from an unsafe
source, (3) inadequate cooking, (4) poor personal hygiene. and (5) contami-
nated equipment (CDC 1985). Appropriate public health procedures relat-
ed to food handling and storage can usually prevent these problems.

The preferred treatment for most forms of food-borne illnesses is fluid and
electrolyte replacement for dehydration caused by diarrhea (Rohde et al.
1983). Antimicrobial drugs may be useful in some instances: in rare cases,
such as botulism poisoning, an antitoxin should be administered. How-
ever, because most food-borne illnesses are self-limiting and antibiotics
may disturb normal bacierial flora and prolong the illness, antibiotic thera-
py is not routinely used (Altman 1985). Food-borne infections that trigger
an acute-phase response will be accompanied by nutritional losses com-
parable to those seen in other infections.

The major microbial causes of food-borne illness are bacteria, viruses, and
parasites. Chemical contamination of foods occasionally causes illness.
Bacterial food poisoning, the most common type, is caused by ingestion of
water or food that contains living organisms or toxins they produce or
enterotoxins produced in the intestine after their ingestion. These diseases
are most common in the developing world where the water supply is
inadequately treated and food easily becomes contaminated.

As mentioned earlier, food-borne illnesses affect large numbers of people
in the United States. For example, more than 40,000 cases of salmonellosis
(excluding typhoid fever) were reported to CDC in 1982 (CDC 19831,
although only about 2,000 of them were confirmed. Among these cases,
eight deaths were reported (CDC 1985). More than 18,000 cases of
shigellosis were reported in the United States in 1982; although the true
incidence is thought to be considerably higher (CDC 1983), only 116 of the
reported cases were confirmed (CDC 1985). At least one outbreak of
gastrointestinal disease has been traced to Campylobacter fetus contami-

453


0 Nutrition and Health

nation of raw milk (Klein et al. 1986), but some investigators believe that
the incidence of campylobacter-induced illness is greater than the total
combined cases of salmonellosis and shigellosis (Blaser 1983; Skirrow
1977; Archer and Kvenberg 1985). Clostridium perfiingens was confirmed
as the etiologic agent in nearly 2,000 cases of food-borne illness in 1982
(CDC 1985). Clostridium botulinurn causes an average of 15 outbreaks of
food-borne botulism annually in the United States, with 21 outbreaks
involving 30 people and 8 deaths reported for 1982 (CDC 1985). An esti-
mated 20,000 cases of Yersiniu infection occur annually in the United
States, causing acute abdominal symptoms (Kvenberg and Archer 1987).
Although more than 23,000 cases of hepatitis A were reported to the CDC
in 1982 (CDC 1983), only 325 cases were confirmed (CDC 1985). Hepatitis
A is transmitted almost exclusively by the fecal-oral route through food
and water contaminated by food handlers. In 1982, approximately 5,008
cases of food-borne Norwalk gastroenteritis were reported to the CDC
(CDC 1985). These derived from two large outbreaks, one related to eating
bakery items with contaminated icing and the other associated with eating
contaminated coleslaw. Other outbreaks have involved shellfish and drink-
ing water.

Implications for Public Health Policy

Dietary Guidance

General Public

Adequate nutrient and energy intake is critical to the maintenance of
optimal immune function. However, evidence related to the role of specific
dietary factors such as fatty acids, vitamin C, or zinc is insufficient to
recommend changes in dietary guidance policy for the general public.
Evidence related to the role of microbial and chemical contamination of
food and water in human health suggests that the general public should
receive information on appropriate food handling and storage methods to
prevent outbreaks of food-borne disease.

Although the overall public health significance of breastfeeding in the
United States is uncertain, studies in developing countries have shown the
importance of breastfeeding in preventing diarrhea1 diseases and in reduc-
ing their severity. The immune protection conferred by breastfeeding also
helps reduce the severity of certain infectious diseases among infants.
Breastfeeding should continue to be recommended to pregnant women and
to new mothers as the optimal method of infant feeding.

454


Infections and Immunity O

Although the relationship between malnutrition and changes in immune
function observed with aging is not well understood, it is clear that ade-
quate intake of nutrients is basic to the adequate immune protection in
older Americans.

Special Populations

Infections produce well-documented adverse effects on nutritional status,
and nutritional rehabilitation restores immune function and reduces the
severity of infectious disease complications. Thus, the nutritional status of
persons with infectious illnesses should be assessed regularly, and appro-
priate nutritional support measures should be instituted whenever neces-
sary. Qualified health professionals should advise persons with food al-
lergies and intolerances on the diagnosis of these conditions and on diets
that exclude foods and food substances that induce symptoms.

Nutrition Programs and Services

Food Labels

Evidence related to diet-immune function interactions reinforces the need
for food manufacturers to include explicit and complete ingredient state-
ments to protect individuals who may have severe adverse reactions to
foods.

Food Services

Current evidence about the role of dietary factors in the maintenance of
optimal immune function has no special implications for change in policy
related to food service programs. Evidence related to the spread of infec-
tions suggests that food service personnel should receive adequate training
in sanitary food handling and storage procedures.

Food Products

Evidence related to diet-immune function interactions suggests that food
product manufacturers should take special precautions to use good man-
ufacturing practices to avoid contamination with ingredients that may
produce severe reactions and to reduce microbial and chemical contatnina-
tion during production and storage. Manufacturers should continue to
develop new products that are free of substances likely to induce allergic
symptoms in susceptible individuals.

455


-

u Nutrition and Health

Special Populations

Patients with infectious diseases should be treated as rapidly and effective-
ly as possible to minimize the depletion of body nutrients. Convalescing
patients should be counseled and assisted in the development of diets that
provide adequate intake of nutrients to regain an appropriate nutritional
status. Patients with food intolerances should be counseled and assisted in
the development of diets that omit foods and food factors that induce
symptoms.

Research and Surveillance

Research and surveillance issues of special priority related to interactions
between diet, infection, and immunity should include investigations into:

o The mechanisms by which generalized malnutrition depresses the
function of specific components of the immune system.
0 The effects of deficient or excess intake of single nutrients such as
vitamin A, zinc, iron, or dietary fat on specific elements of the immune
system and on immune function.
0 The mechanisms by which deficient or excess intake of single nutrients
might depress or improve immune system function.
o The factors in breast milk that protect infants from infectious disease.
o The role of breast milk in transmitting allergens, infectious agents, or
toxicants such as drugs.

o The role of nutrition in maintaining adequate immune function in older
persons.

o The mechanisms by which infectious diseases alter nutrient metabo-
lism and impair nutritional status.
o The most effective means of restoring nutritional status to mal-
nourished individuals recovering from infectious illnesses.
o The identification of natural food products and chemical additives that
induce adverse physiologic responses and the mechanisms by which
they do so.

o The basic biochemistry of food antigens and biologically active com-
ponents.

o The effects of processing and digestion of food substances with conver-
sion to or inactivation of allergenic fractions.
o The value of therapeutic procedures designed to induce tolerance to
food antigens.

456


Infections and Immunity 0

o The prevalence of food-borne infections and intolerances and immuno-
logic reactions to food in the population.
o The identification of behavioral determinants of unsanitary food han-
dling and storage procedures and the development of effective educa-
tional methods to prevent transmission of food-borne illnesses.
o The effect of nutritional status on susceptibility to infectious diseases,
including HIV infection, and on the complications of AIDS.

457


O Nutrition and Health

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463


Chapter 12

Anemia

She was very anaemic. Her thin lips were
pale, and her skin was delicate, of a faint
green colour, without a touch of red even in
         the cheeks.
    W. Somerset Maugham
   OfHuman Bondage, 1915

Introduction

Anemia occurs when the concentration of the pigment hemoglobin in red
blood cells falls below normal. Hemoglobin is essential for delivering
oxygen from the lungs to the body's tissues, and anemia impairs the
capacity of the blood to supply the tissues with oxygen for the production
of cellular energy in the form of adenosine triphosphate. Severe deficits in
the delivery and use of oxygen increase fatigability, decrease work capaci-
ty, impair brain function, and lessen ability to maintain body temperature
(Bothwell et al. 1979; Dallman, Siimes, and Stekel 1980; Finch 1982;
Dallman 1986).

Historical Perspective

Chlorosis, the green sickness or "virgin's disease," was a condition associ-
ated with anemia that afflicted young women in Europe and North America
from about 1500 to 1900 (see quotation). Chlorotic women appeared pale
and suffered weakness, lassitude, breathlessness, and menstrual disor-
ders. This condition was attributed to lovesickness, ovarian insufficiency,
or the pressure from a tight corset on the spleen. Treatment consisted of
bloodletting and the administration of iron tonics and pills, especially in the
19th century after it was established that the disease involved iron deficien-
cy (Loudon 1980). Today, with improved nutrition and better health care,
chlorosis is no longer observed. However, iron deficiency is still prevalent
(Crosby 1987).

The credit for introducing iron into therapeutic use is usually given to the
18th~century English physician Sydenham, who observed improvements

465


O Nutrition and Health

in his anemic patients when he prescribed a "steel tonic" prepared by
steeping iron filings in Rhine wine (McCollum 1957).

Iron was one of the first substances identified as essential in the human
diet. The physiologic function of iron in hemoglobin and its role in anemia
was determined over a 200-year period, from the 1680's, when Boyle first
analyzed the chemical composition of blood, to the 1860's, when iron was
first recognized as an essential nutrient for animals.

Although chlorosis disappeared during the first part of the 20th century, a
relatively rare but more deadly nutritional anemia continued to puzzle
clinicians and scientists until the 1920's. In 1849, Addison first described
pernicious anemia, so called because no cure could be discovered. Not
until 1926 was it learned that extracts of liver-now known to contain
vitamin B,,-could cure the disease (Herbert 1984). A few years later, Wills
discovered that an impure extract of liver could reverse a macrocytic
anemia found in Hindu women in Bombay, particularly in those who were
pregnant. Scientists now know that this extract contained folic acid and that
requirements for this vitamin increase during pregnancy.

The first public health efforts in the United States to prevent iron deficien-
cy occurred during World War II when the Food and Drug Administration
developed regulations for the fortification of cereal and grain products,
including flour (Food and Nutrition Board 1974; Yetley and Glinsmann
1983). Infant cereals were first fortified with iron after about 1950, and
infant formulas began to be fortified with iron in the late 1950's (Marsh,
Long, and Stierwolt 1959). As a result of this and other public health
measures reviewed in this chapter, rates of iron deficiency have declined
rapidly.

Significance for Public Health

Anemia has genetic, environmental, and nutritional causes. For example,
the most frequent causes of anemia among older persons are infection and
chronic disease. Iron deficiency, however, is the most common cause of
anemia among young women and children and is the major focus of this
discussion. When used precisely, the terms anemia, iron deficiency, and
iron deficiency anemia all have distinct meanings. Anemia signifies a blood
hemoglobin concentration that is two standard deviations below the mean
for normal individuals of the same age and sex. Although iron deficiency is
generally the most common cause of anemia, there are many other nutri-
tional, genetic, and environmental causes as well. In this chapter, iron
deficiency refers to a lack of iron that not only results in loss of iron stores,

466


Anemia 0

but that also would be expected to impair iron-dependent physiologic
functions. The term "impaired iron status" has a similar connotation
(LSRO 1984b) and is applied to individuals in whom two or more laboratory
tests of iron metabolism are abnormal. Iron deficiency anemia refers to
anemia that results from iron deficiency or impaired iron status. Iron-
dependent physiologic functions can become impaired before anemia de-
velops. These issues are discussed in greater detail below.

Iron deficiency has received much attention over the years in the United
States, although its overall prevalence is low. The best recent estimates of
impaired iron status are derived from the second National Health and
Nutrition Examination Survey (NHANES II), conducted by the National
Center for Health Statistics between 1976 and 1980 (LSRO 1984b;
Dallman, Yip, and Johnson 1984).

Iron-dependent physiologic functions can be impaired before anemia be-
comes apparent (see below). To estimate the prevalence of impaired iron
status, with or without concurrent anemia, survey results were analyzed
by averaging the results of three methods that detect iron deficiency at
varying stages of development of anemia. The prevalence of impaired iron
status revealed by these methods is given by age and gender in Table 12-1.
These methods found the highest prevalences of iron deficiency among
children ages 1 to 2 (9.3 percent), women ages 15 to 19 (7.2 percent), and
women ages 20 to 44 (6.3 percent). The lowest prevalence, less than 1
percent, was in men between the ages of 15 and 64.

Because iron deficiency anemia represents a late stage of impaired iron
status, rates of clinical anemia would be expected to be even lower than
these figures. Both anemia and iron deficiency were less common in
NHANES II than was anticipated from the limited data of earlier surveys
(Dallman, Yip, and Johnson 1984). Furthermore, the anemia surveillance
data collected primarily on low-income children by the Centers for Disease
Control show a gradual decline in overall prevalence of anemia (as as-
sessed by stringent laboratory criteria), from 7.8 percent in 1975 to 2.9
percent in 1985 (Anonymous 1986; Stockman 1987; Yip, Binkin, et al.
1987). Prevalences among middle-income children were even lower (Yip,
Walsh, et al. 1987). The paucity of moderate or severe anemia in recent
analyses may indicate that iron deficiency is becoming less common in the
United States.

Among infants and younger children in the United States, increased breast-
feeding, greater use of iron-fortified infant formula and cereals, and de-
creased consumption of cow milk during infancy have also improved iron

467


u Nutrition and Health

               Table 12-l
Estimates for Percent Prevalence of Impaired Iron Status:
Average of Estimates Using Three Methodsa: NHANES II, 1976-90

As-
(years)

Males and
Females          Males           Females
     Average percent prevalence (range)

l-2        9.3 (9.2-9.4)
3-t        4.3 (3.6-5.5)
S-10       3.9 (3.2-4.5)
11-14                    4.1 (3.5-12.1)      2.8 (2.7-6.1)
15-19                  0.6 (0.1-0.9)      7.2 (2.5-14.2)
2OA4                   0.7 (0.648)      6.3 (4.0-9.6)
45-64                    2.0 (1.9-2.0)       4.4 (3.8-4.8)
65-74                  2.8 (1.8-3.6)      3.2 (2.7-3.7)
*Three methods:
1. Prevalence of two or three abnormal laboratory values using serum ferritin, transferrin
  saturation, and erythrocyte protoporphyrin.

2. Prevalence of two or three abnormal laboratory values using mean red cell volume,
transfenin saturation, and erythrocyte protoporphyrin.
3. Relative prevalence of anemia derived from the rise in median hemoglobin after
exclusion of persons with abnormal laboratory values.

Source: Life Sciences Research office. 1984. Assessment of the iron nutdtional status of
   the U.S. population based on the data collected in the second National Health
   and Nutrition Examination Survey, 1976-1980, ed. S.M. Pilch and F.R. Senti,
   p. 65, Bethesda, MD: Federation of American Societies for Experimental Biology.

status. Some of these changes may have resulted from public health
programs aimed at prevention of iron deficiency.

Although iron deficiency anemia can occur in all socioeconomic groups, it
has historically been most common among the poor (LSRO 1984b; DHHSI
USDA 1986) and is still the case today (Yip, Binkin, et al. 1987; Yip, Walsh,
et al. 1987). This observation provides a basis for the particular attention to
iron nutrition in Federal programs such as the School Lunch Program and
the Special Supplemental Food Program for Women, Infants, and Children
(WIG). The WIC program provides iron-fortified formulas and cereals and
periodic health screenings and has been associated with improved iron
status in its participants independent of socioeconomic status (Yip, Binkin,
et al. 1987).

Studies in Sweden have shown a decline in anemia rates among women,
from 30 percent in 1%5 to 7 percent only 10 years later (Hallberg et al.
1979). This declim! was attributed to a relatively high level of fortification


Anemia 0

offood with iron, and the increased use of iron tablets, increased consump-
tion of ascorbic acid, and the effects of oral contraceptive use. Extrapola-
tion of these results to women in the United States, however, must be made
with caution because both the severity of anemia and levels of fortification
differ in the two countries.

Variations in diagnostic criteria according to age and sex present an addi-
tional difficulty in interpreting data on prevalence rates of anemia. Screen-
ing programs often use hemoglobin status as an initial criterion for diag-
nosis. Hemoglobin levels, however, differ with age and gender and must be
compared with appropriate standards. They may also differ with race. Data
from NHANES indicate that hemoglobin levels are somewhat lower
among black than among white Americans (LSRO 1984b). and some stud-
ies have suggested that such differences remain even after diet, gender, and
socioeconomic factors are taken into account. However. other studies
found that the small differences of mean hemoglobin values between
blacks and whites may be attributable to a subset of blacks who have mild
hereditary anemia such as thalassemia traits (Yip. Schwartz, and Deinard
1984; Castro et al. 1985). Whether these observations mean that the hemo-
globin levels of blacks and whites should be compared with different
standards is as yet uncertain.

Scientiic Background

Causes of Anemia

There are three main causes of anemia: (1) reduced production of red blood
cells and hemoglobin; (2) hemolysis, or increased destruction of red blood
cells; and (3) loss of blood from the circulation, as in internal or external
bleeding. Because the synthesis of blood cells requires many cellular and
metabolic steps, a deficiency of any nutrient essential to hemoglobin
production produces adverse effects on these processes. Good nutrition is
fundamental to adequate red cell production. Nutritional anemia may be
due to a dietary deficiency of iron, folate, vitamin B,*, protein, vitamin E,
vitamin A, vitamin B,, riboflavin, vitamin C, zinc, or copper. Because the
most common nutritional cause of anemia in the United States and in other
developed countries is iron deficiency (LSRO 1984b; Dallman, Yip, and
Johnson 1984), it is the principal focus of this discussion. Deficiencies of
folate (LSRO 1984a), vitamin Blz, and other nutrients are far less signifi-
cant causes. Other causes of anemia include the inherited or acquired
inability to use nutrients required for hemoglobin production, chronic
inflammatory or infectious diseases, and lead poisoning. Normal levels of
hemoglobin also vary according to genetic factors such as race. Thus,


O Nutrition and Health

diagnosis of anemia must distinguish nutritional from other potential
causes and must relate hemoglobin levels to appropriate standards.

Nutritional anemia should be distinguished from deficiencies per se of iron,
folate, or vitamin B,,, because an individual may have manifest any one of
these deficiencies without being anemic. Iron deficiency, for example, in
its early stages is typically present without anemia. The term "iron defi-
ciency anemia" signifies that the iron deficiency has become severe enough
to depress the hemoglobin concentration below the normal range. Al-
though this chapter focuses on nutritional anemia, there are many addition-
al health consequences of nutritional deficiencies that occur concomitantly
with anemia but are not caused by the anemia itself. For example, iron is
not only required for hemoglobin biosynthesis but is also an essential
component of many enzymes required for the production of energy in cells
throughout the body. In iron deficiency, the impairment of these and other
iron-dependent processes may account for disorders in immune function
and behavior that are not directly attributable to the anemia. Similarly, the
impaired nerve function of vitamin B,, deficiency occurs independently of
anemia. Thus, anemia is just one possible consequence of these nutritional
deficiencies.

Role of iron in the Body

The total amount of iron in the body is slightly less than the weight of a 5-
cent coin, about 4 g for adult males (Bothwell et al. 1979). Most of this iron
is used to transport and use oxygen in the production of cellular energy.
The distribution of iron in the bodies of men, women, and infants is given in
Table 12-2. An average of about 58 percent of the body's iron for men and
73 percent for women is contained in hemoglobin, and 11 percent for men
and 14 percent for women is present in myoglobin (which stores oxygen
and makes it available to the muscle when it is needed during contraction).
A smaller but critically important amount of iron, about 3 percent, is
present in iron-containing enzymes such as the cytochromes, which are
required for the production of cell energy.

In addition to these essential iron compounds that fulfill physiologic func-
tions, two proteins, ferritin and hemosiderin, serve as a storage reserve.
These storage compounds account for an average of 25 percent of body
iron in men and 10 percent in women and are located primarily in the liver,
spleen, and bone marrow. There, they serve as alternate sources of iron to
produce essential compounds when dietary supplies are insufflcient. The
vulnerability of an individual to iron deficiency depends on the abundance
of these iron reserves. In some individuals, however, these reserves can
accumulate to toxic levels, most often as a result of a genetically deter-

470


Anemia O

Table 12-2

Total Body Iron and Storage Iron

             Men


Total iron, g        4.0
Hemoglobin iron, %  58
Myoglobin iron, %   11
Enzyme iron, %     3
Storage iron, %     25

Source: Bothwell et al. 1979.

Women


2.7
73
14
3
10

Infants
(age 1 year)

  0.45
78
  6
  5
  11

mined failure to reduce iron absorption when stores are adequate. This and
other causes of iron overload suggest a need for prevention of excessive
iron intake in certain individuals.

Almost all compounds containing iron in the body are continuously broken
down and resynthesized (Bothwell et al. 1979). The iron released by the
degradation of hemoglobin and other iron-containing proteins is efficiently
conserved and reused to replace these compounds. An important conse-
quence of this metabolism is that very little iron is lost from the body on a
daily basis, except when bleeding occurs. In adult men, normal iron losses
in the feces, sweat, and sloughed cells amount to about 0.9 mg/day,
equivalent to less than one-tenth of 1 percent of iron stores. This amount is
readily absorbed from the diet. Women in their childbearing years require
an average of 1.3 mg/day to make up for the additional iron that is lost in
menstrual blood (Bothwell et al. 1979). In children, a proportionately more
generous amount of iron is required for growth (Dallman, Siimes, and
Stekell980). Consequently, premenopausal women and children are more
likely to develop iron deficiency than are men.

Iron Absorption

The bioavailability of iron-that is, the amount absorbed from food-is
determined both by the nature of the diet and by regulatory mechanisms in
the intestinal mucosa that reflect the body's physiologic need for iron. Two
types of iron are present in food: heme iron, which is found principally in
animal products, and nonheme iron, found mainly in plant products.

Nonheme Iron. Most of the iron in the diet, usually more than 80 percent, is
present as nonheme iron and consists primarily of iron salts. The composi-
tion of a meal determines nonheme iron solubility in the upper part of the
small intestine, which, in turn, determines the absorItion of the iron

471


0 Nutrition and Health

(Hallberg 1981; Charlton and Bothwell 1983). Consequently, the amount of
iron finally absorbed is influenced by other constituents of the diet that
either enhance absorption by increasing iron solubility or inhibit absorp-
tion by decreasing solubility in the intestine. For example, nonheme iron
absorption from a representative meal containing enhancers such as meat,
fish, or chicken is about four times greater than when foods containing
inhibitors (e.g., milk, cheese, or eggs) are substituted (Cook and Monsen
1976).

Iron absorption tends to be poor from meals in which whole grain cereals
and legumes predominate, but the addition of even relatively small amounts
of meat or foods containing vitamin C (ascorbic acid) substantially in-
creases the absorption of iron from the entire meal. Compared with water,
orange juice or foods containing vitamin C increase absorption of nonheme
iron from a meal. Tea and coffee, on the other hand, decrease absorption of
nonheme iron when compared with water (Hallberg 1981; Rossander,
Hallberg, and Bjom-Rasmussen 1979).

Breast milk is relatively low in iron, but its iron is relatively well absorbed
(Saarinen, Siimes, and Dallman l'977) in comparison with iron in cow milk
or unfortified cow milk formula. This increased iron absorption may ex-
plain why breastfed infants are less vulnerable to iron deficiency than
infants fed unfortified cow milk formula.

The absorption of iron from infant foods varies with the form of iron, its
concentration, the total iron content and composition of the meal, and,
presumably, the iron status of the child. For example, one study found that
only about 4 percent of the iron was absorbed from a cow milk formula that
was fortified with about 12 mg of iron per liter in the form of ferrous sulfate
and with ascorbic acid (Rios et al. 1975; Saarinen and Siimes 1977). Even at
this low percentage of absorption, the amount of iron in fortified formula
meets the Recommended Dietary Allowances for this age group. Other
investigators have reported higher rates of absorption, especially from
formulas supplemented with both iron and ascorbic acid (Stekel et al.
1986).

Heme Iron. Heme iron comes from the hemoglobin and myoglobin in meat,
poultry, and fish. Although heme iron accounts for a smaller proportion of
iron in the diet than nonheme iron, its role is important; the body absorbs a
much greater percentage of heme iron, and its absorption is less affected by
other dietary constituents than absorption of nonheme iron (Hallberg
1981).

472


Anemia 0

When both forms of iron in the diet are considered, men absorb an average
of about 6 percent of total dietary iron and women absorb 13 percent in their
childbearing years (Charlton and Bothwell 1983). The higher absorption in
women is related to their lower iron stores and helps to compensate for iron
losses of menstruation.

Intestinal Regulation. The regulation of iron entry into the body takes place
in the mucosal cell of the small intestine (Charlton and Bothwell 1983), and
transferrin may act as an iron carrier (Huebers and Finch 1987). If iron
stores are low, as is true for most women and children, transfertin in the
intestinal mucosa readily takes up iron and increases the proportion ab-
sorbed from the diet. The saturation of transferrin is decreased in iron
deficiency. Conversely, the high iron stores typical of men and older
women reduce the percentage of iron absorbed, thereby offering some
protection against iron overload (which is discussed later in this chapter).

Key Scientific Issues

o Role of Iron in Anemia
o Role of Folate and Vitamin B,, in Anemia

Role of Iron in Anemia

Because iron is one of the earth's most abundant elements, it may seem
surprising that iron deficiency should ever become a nutritional problem.
One explanation is that the most common forms of iron in food are rela-
tively insoluble and cannot be absorbed from the intestine. Other factors
predisposing to iron deficiency are related to evolving changes in the diet,
not only during past millennia, but also within the last century (Eaton and
Konner 1985). As noted above, iron is best absorbed from diets that are rich
in meat, poultry, fish, and ascorbic acid and is poorly absorbed from diets
consisting primarily of whole grain cereals and legumes (Hallberg 1981;
Charlton and Bothwell 1983). Even though whole grain foods contain
substantial amounts of iron, the form of iron cannot be as readily dissolved
and absorbed. Thus, in some cases, the iron content of whole grain cereals
and legumes may not wholly compensate for their decreased absorption.
This problem may be one reason that iron deficiency anemia remains much
more common in developing countries than in the United States where
cereal grain products are commonly fortified with iron (Florentino and
Guirriec 1984.

473


0 Nutrition and Health

Stages of Iron Depletion

Iron depletion occurs in three stages (Cook and Finch 1979). The first
involves a decrease in iron stores (as measured by a decrease in serum
ferritin) without loss of essential function. This stage is not associated with
adverse physiologic consequences, but it does represent a condition of
vulnerability. In the United States, women of childbearing age, for exam-
ple, may characteristically have very low iron stores, but in only a very
small number is there a progression to anemia (LSRO 1984b). The risk of
developing anemia is minimized by the body's ability to increase iron
absorption as iron stores diminish.

The second stage is characterized by biochemical changes that reflect the
lack of sufficient iron for normal production of hemoglobin and other
essential iron compounds, as indicated by a fall in transferrin saturation
levels and an increase in erythrocyte protoporphyrin. Because the hemo-
globin concentration has not yet fallen below levels considered anemic, this
stage is regarded as iron deficiency without anemia.

The third stage is frank iron deficiency anemia, which occurs when hemo-
globin production has been sufficiently depressed to result in a hemoglobin
concentration (and mean corpuscular volume) below the normal reference
range for individuals of the same age and sex. In this chapter, the term iron
deficiency refers to the second and third stages.

Causes of Iron Deficiency

The major causes of iron deficiency are insufficient assimilation of iron
from the diet, dilution of body iron by rapid growth, and blood loss
(Bothwell et al. 1979; Dallman, Siimes, and Stekel 1980). Because the
manifestations of iron deficiency are rarely obvious, most cases are de-
tected by laboratory tests done at a routine examination. The groups at
highest risk for iron deficiency are infants, children, adolescents, and
women, especially pregnant women, between the ages of menarche and
menopause (LSRO 1984b).

Age-Related Factors in Susceptibility

Infants. The prevalence of iron deficiency among infants is highest between
about 4 months, when neonatal iron stores accumulated during fetal life are
first likely to become depleted, and 3 years of age (Dallman, Siimes, and
Stekel 1980). During this period, total iron in the body should more than
double to accommodate a rapid rate of growth and an increase in red cell
mass. Excessive consumption of cow milk, which is a poor source of iron
and commonly associated with occult intestinal blood loss in early infancy,

474


Anemia O

is a frequent cause of iron deficiency in young infants (Fomon et al. 198 1).
In premature infants and in twins, iron deficiency anemia may develop as
early as 3 months after birth because their neonatal iron stores are smaller
and weight gain is proportionately greater than in full-term or single infants.
In older children, iron deficiency results from inadequate dietary intake
and is associated with poverty (DHHSIUSDA 1986).

Adolescents. Iron deficiency is common during adolescence (LSRO 1984b;
Dallman, Yip, and Johnson 1984). Boys gain an average of 10 kg, or 22 lb,
during the peak year of their growth spurt, usually between 12 and 15 years
of age. At about the same age as the growth spurt. and in relation to sexual
maturation, the concentration of hemoglobin increases between 0.5 and 1 .O
g/dl/year towards values that are characteristic of adult men. The double
burden of increased red cell mass and increased hemoglobin concentration
requires an increase of about 25 percent in total body iron during the year of
peak growth. Adolescent girls also need more iron. Their average weight
gain during the peak years of the growth spurt-9 kg, or 20 lb, usually
between 10 and 12 years of age-is almost as great as in boys. Although the
concentration of hemoglobin changes very little during this period, the
onset of menstruation imposes additional iron needs.

Women of Childbearing Ages. The major factors that predispose to iron
deficiency anemia in this group are menorrhagia (excessive loss of blood
during menstruation) and pregnancy (Bothwell et al. 1979). Heavy blood
loss occurs in about 20 percent of women (Hallberg et al. 1966). The use of
intrauterine devices increases the prevalence of menorrhagia to about 30 to
50 percent of women, depending on the type used (Israel, Shaw, and Martin
1974). Oral contraceptives, on the other hand, decrease menstrual blood
loss by about half and are rarely associated with menorrhagia (Hefnawi,
Askalani, and Zaki 1974).

Many women with menorrhagia are usually unaware that they have greater-
than-normal menstrual blood loss (Hallberg et al. 1966). For this reason,
blood tests at routine health examinations can sometimes detect anemia in
women, even when the history of menstrual blood loss is unimpressive.

Iron deficiency anemia may develop during pregnancy (Svanberg et al.
1975) because of the increased requirements for iron to supply the expand-
ing blood volume of the mother as well as the rapidly growing fetus and
placenta. True anemia, however, must be distinguished from low hemo-
globin values that normally occur as a result of blood volume expansion and
must be diagnosed with the use of appropriate standards. Healthy women
who are not pregnant have about 2.6 g of total body iron, but only about 0.3

475


0 Nutrition and Health

g of this amount is storage iron. The total iron requirement during the entire
course of pregnancy averages 1 g and, therefore, exceeds the amount of
storage iron in most women. However, an increase in efftciency of dietary
iron absorption compensates in part for the limited iron stores. Most of the
additional iron is needed for growth of the fetus and placenta during the last
half of pregnancy (Bothwell et al. 1979).

Even with the normal adaptive increase in iron absorption that takes place
during pregnancy, iron stores may become depleted. For this reason,
clinicians commonly recommend an iron supplement that provides the
equivalent of about 30 mg of elemental iron or more per day during the last
half of pregnancy. After delivery, the iron requirement of the mother is
temporarily reduced below normal as the expanded mass of red cells
decreases to baseline levels.

Mild iron deficiency in the pregnant woman generally has no detectable
effect on hemoglobin concentration in the newborn. However, the severe
iron deficiency anemia seen in pregnant women in some developing coun-
tries can cause decreased placental weight and birth weight as well as
anemia in the newborn (Singla et al. 1978).

Men and Postmenopausal Women. Normally, iron stores increase through-
out adult life in men and after menopause in women (Cook, Finch, and
Smith 1976), so overt nutritional iron deficiency rarely develops in these
groups. Among older persons, anemia is more commonly associated with
chronic diseases, inflammation, and infections than with iron deficiency.
However, factors that can predispose these groups to iron deficiency ane-
mia include frequent blood donations (three or more times a year) and
blood losses due to chronic aspirin ingestion, bleeding ulcers, and colorec-
tal cancers.

Frequent aspirin consumption impairs blood coagulation and leads to
blood loss from the intestine, usually in minute- amounts that can be
detected only by sensitive tests. For example, one study found that 300 mg
of aspirin taken three times a day for a week increased intestinal blood loss
to 5 ml/day (which averages several times normal menstrual losses) from a
normal average of 0.5 ml/day (Pierson et al. 1961).

When there is no known basis for iron deficiency anemia, lesions such as a
peptic ulcer or carcinoma may cause chronic and inapparent blood loss
from the intestine. Parasitic infestation, particularly with hookwormcom-
monly causes inapparent intestinal blood loss in some developing coun-
tries, but is relatively rare in the United States.

476


Anemia 0

Consequences of Iron Deficiency

The manifestations of iron deficiency can be subtle and depend on the
relative severity of functional impairment caused by reduced levels of the
"essential" iron compounds (Dallman 1982). These manifestations are
related to the effects of iron deficiency on other tissues, to the resultant
anemia, or to a combination of the two (Dallman 1986). One difficulty in
interpreting studies in this area is that the effects of impaired iron status
may differ among iron-deficient individuals who are-or are not-anemic.

Work Performance. Studies in humans as well as in rats show that iron
deficiency causes a substantial reduction in work capacity, particularly
when the concentration of hemoglobin falls below 10 g/dl, which is 2 to 4 g/
dl below the lower limit of normal for adults. Some studies in humans
indicate that even mild anemia can decrease performance in brief, hard
exercise (Viteri and Torun 1974). To determine the practical significance of
these findings for productivity, manual laborers in developing countries
who were suffering from iron deficiency anemia were studied. For exam-
ple, among men on a rubber plantation in Indonesia (Basta et al. 1979) and
women on a tea plantation in Sri Lanka (Edgerton et al. 1979), the produc-
tivity of iron-deficient individuals was significantly less than that of work-
ers with a normal hemoglobin concentration. After iron supplementation,
the performance of the iron-deficient subjects improved, with the greatest
improvement occurring in those who had the lowest initial hemoglobin
concentrations.

In these studies, it has not been possible to distinguish the extent to which
this impaired work performance is due to anemia per se or to the tissue
abnormalities accompanying iron deficiency. Experiments with rats have
shown that dietary iron deficiency also results in a marked impairment in
the oxidative production of cellular energy in skeletal muscle (Finch et al.
1976; McLane et al. 1981; Davies et al. 1984). The major consequence of
this muscle impairment is a lessened capacity for prolonged exercise or
physical endurance, whereas anemia primarily restricts the performance of
brief, strenuous exercise (McLane et al. 1981; Davies et al. 1984).

Body Temperature Regulation. An impaired capacity to maintain body
temperature in a cold environment is another characteristic of iron defi-
ciency anemia. This abnormality is related to decreased secretion of thy-
roid-stimulating hormone and thyroid hormone (Beard et al. 1984) and to
the anemia itself; studies of the iron-deficient rat show that a transfusion of
red blood cells corrects the abnormality. Furthermore, normally fed rats

477


u Nutrition and Health

develop impaired heat production when they are made anemic by an
exchange transfusion that replaces red blood cells with plasma that lacks
hemoglobin.

Behavior and Intellectual Performance. Increasing evidence suggests that
changes in behavior and impaired development and intellectual perfor-
mance may result from iron deficiency (Lozoff and Brittenham 1986; Pollitt
1985). Most studies have evaluated infants between 6 months and 2 years of
age using the Bayley Scale of Infant Development, a test to evaluate
sensory development, fine and gross motor skills, and language develop-
ment in this group. By this standard, infants who are even mildly iron
deficient have a statistically significant decrease in responsiveness, activi-
ty, and attentiveness and have increased body tension, fearfulness, and
tendency to fatigue (Lozoff et al. 1982b). The long-term significance of
these observations has not been determined. Of particular interest is the
observation that these deficits are most profound in the oldest infants (19 to
24 months), in whom iron deficiency may have been present for the longest
period (Lozoff et al. 1982a). Another important finding is that even infants
with very mild iron deficiency anemia, or simply with early evidence of
impaired hemoglobin production, do not score as well as infants with no
laboratory evidence of iron deficiency or evidence merely of depleted iron
stores (Lozoff et al. 1982b; Oski et al. 1983; Walter, Kovalskys, and Stekel
1983). Although the results of these studies are not as conclusive, the
behavioral abnormalities are significant because the brain's rapid rate of
growth and differentiation during infancy might make it particularly vulner-
able to nutrient deficiencies. Because the same adverse environmental
factors that lead to iron deficiency could also be responsible for behavioral
deficits, these studies are difficult to interpret. This complexity may help to
explain why some children display a rapid improvement in the Bayley score
after iron treatment (Oski et al. 1983), whereas others do not (Lozoff et al.
1982a, 1982b).

Resistance fo Infections. Decreased resistance to infection is characteristic
of iron deficiency in both humans and experimental animals (Beisel 1982;
Vyas and Chandra 1984; Dallman 1986). Iron-deficient children have abnor-
malities in lymphocytes and neutrophils, two types of white blood cells that
help defend against infections (see chapter on infections and immunity).
Although infections are associated with decreases in measures of iron
status, these decreases may not be related to deficient iron intake.

Despite numerous studies that show an impaired resistance to infection
under laboratory conditions, no conclusive evidence demonstrates that
iron deficiency itself causes an increased rate of infections in free-living

478


Anemia O

individuals. Iron deficiency anemia and infections are both common among
poor populations, but a cause-and-effect relationship, although plausible,
has not been established (Strauss 1978). These issues are discussed further
in the chapter on infections and immunity.

Lead Poisoning. Iron deficiency substantially increases the risk of lead
poisoning, particularly in young children. Iron-deficient individuals absorb
increased amounts of lead (Watson et al. 1986). and elevated blood lead
concentrations have been observed among some children with laboratory
evidence of iron deficiency (Yip and Dallman 1984).

Prevention of Iron Deficiency

Iron deficiency can be prevented by increasing dietary iron intake, improv-
ing the bioavailability of iron in the diet, or decreasing body losses of iron.
Dietary iron intakes can be improved by increasing the consumption of
iron-rich foods, administering iron supplements to specific target popula-
tions, and fortifying certain food products with iron. Parental awareness of
appropriate diet is especially important for infants, whose diet is relatively
simple. Typically, an infant's diet is discussed during routine health mainte-
nance visits.

Fortification of cereal and grain products is a relatively inexpensive and
effective means of increasing iron intake (International Nutritional Anemia
Consultative Group 1982; Clydesdale and Wiemer 1985). These foods
usually reach the population as a whole in adequate amounts to make a
difference without the need for individual counseling. Nevertheless, sev-
eral aspects of fortification are controversial. Because some iron com-
pounds are poorly absorbed (Cook and Reusser 1983; Yetley and Glins-
mann 1983; Hurrell 1984), it is difficult to document that eating fortified
foods helps prevent iron deficiency, especially because baseline data are
unavailable. Readily absorbed forms of iron react with foods and some-
times decrease shelf life. One compound that may strike a reasonable
compromise between shelf life and bioavailability is finely powdered metal-
ic iron, although some studies find that this form, too, is poorly absorbed
(Elwood et al. 1968; Hallberg, Brune, and Rossander 1986).

Continuation of breastfeeding for 6 months or more confers substantial
protection against development of iron deficiency in full-term infants (AAP
Committee on Nutrition 1985). Iron-fortified infant formula, which was
introduced about two decades ago in the United States, has gradually
supplanted most unfortified formulas and fresh cow milk as infant food
during the first year of life (Martinez and Nalezienski 1979). In a large

479


O Nutrition and Health

survey conducted in 1984, 77 percent of 5- to 6-month-old infants in the
United States who were receiving cow milk formula were consuming the
iron-fortified form (Martinez 1985). Today, iron deficiency in otherwise
healthy infants is almost entirely restricted to those on a diet of fresh cow
milk (Sadowitz and Oski 1983) or unfortified cow milk formula (Saarinen
1978).

Vitamin C (Ascorbic Acid) Fortification. The absorption of iron from
fortified cereals can be increased twofold to threefold if the cereals are also
fortified with about 5 mg of vitamin C per mg of iron (International Nutri-
tional Anemia Consultative Group 1982; Cook and Bothwell 1984). Some of
the effectiveness of iron-fortified infant formulas in preventing iron defi-
ciency has been attributed to their fortification with this vitamin (Stekel
1984).

Iron Supplements. Supplementation has the disadvantage of requiring
extra effort and expense compared with fortified foods. People do not
always remember to take medications consistently and regularly. Supple-
ments are less available to the poor and other groups most likely to be iron
deficient. Supplementation is, however, a reasonable approach to preven-
tion of iron deficiency in breastfed premature infants, in pregnant women,
and in targeted high-risk -population groups. In these situations, a large
amount of dietary iron is provided over a short period of time. Its useful-
ness for a given individual requires evaluation by a qualified health profes-
sional. Iron supplement use and recommendations to increase dietary iron
intake are usually not necessary for the general population. Among Ameri-
cans as a whole, poor iron status is relatively rare (LSRO 1984b) and iron
supplements are not associated with improved iron status (Looker et al.
1987). An additional concern is that increased iron intake can harm individ-
uals who are susceptible to iron overload (LSRO 1984b).

Federal Food Progrums. Because iron deficiency is more common among
the poor than among persons above the poverty line (DHHS/USDA 1986),
iron status should improve as a result of Federal food programs that serve
socioeconomically disadvantaged groups. In one study, infants and chil-
dren who had not received aid from the WIG program in 1973-74.were far
more frequently anemic than a similar population in 1977 who were en-
rolled in the WIG program since birth (Miller, Swaney, and Deinard 1985).
.Although differences unrelated to iron intake probably-existed between the
two groups, which might account for differences in iron status, the foods
provided by the WIG program included several sources of iron or enhan-


Anemia O

cers of iron absorption: formula fortified with 12 mg of iron per liter for
infants up to 12 months of age, and iron-fortified infant cereal and ascorbic
acid-fortified fruit juice for infants between 6 and 12 months of age.

Potentially Adverse Consequences. Under ordinary circumstances, a mod-
est excess of dietary iron (over requirements) does not have adverse
consequences. On the other hand, increased iron intake might be harmful
for some individuals. A much discussed example is the hereditary condi-
tion hemochromatosis, in which abnormal amounts of tissue iron accumu-
late over the years as a result of a genetic defect in absorption, eventually
damaging the liver, heart, pancreas, and adrenal glands (Bothwell et al.
1979). A subset of homozygous individuals with hemochromatosis usually
develops symptoms by middle age. Heterozygous carriers of the hemo-
chromatosis gene may be at slightly increased risk for iron overload (Brown
1981), but the clinical significance of this risk is uncertain. Although there is
no direct evidence that current levels of iron fortification are harmful,
concerns have been raised that any increased level of iron in the food
supply may harm individuals susceptible to iron overload. Individuals who
require repeated blood transfusions for relatively rare conditions, such as
thalassemia, may also accumulate excess iron, which is then deposited in
soft tissues. Fortification iron adds an undesirable, but relatively small,
load compared with that administered by transfusion.

Excessive iron intake may affect the absorption of other trace elements.
Although a high dose of iron medication impairs the absorption of zinc or
copper administered at the same time (Solomons and Jacobs 1981), this
interaction probably does not occur at the much smaller fortification levels.
Of greater concern is the possibility of compromised zinc or copper absorp-
tion in groups who take larger amounts of iron as supplements, such as
infants and pregnant women (Breskin et al. 1983; Hambidge et al. 1987).

Excessive iron administration may increase the risk of infection (Pearson
and Robinson 1976; Beisel 1982). The basis for this concern is that a high
degree of unsaturation in the iron-binding protein transfertin suppresses
the growth of many bacteria. Conditions of iron overload are associated
with very low levels of unsaturation. Although this issue may be important
in clinically diagnosed iron overload, recent U.S. survey data have found a
low prevalence of abnormally high transferrin saturation values in the
general population (LSRO 1984b).

481


O Nutrition and Health

Role of Folate and Viimin B,, in Anemia

Although deficiencies of folate or vitamin B,* are relatively rare among the
general U.S. population, certain groups are particularly at risk for develop-
ing these nutrient deficiencies. Folate deficiency is of special concern. Its
extent in the general population is virtually unknown. Low socioeconomic
groups at vulnerable stages of the life cycle are at greatest risk-pregnant
women (especially adolescents), infants (especially those who are small or
premature), young children, and older persons (Shojania 1984). Surveys of
the folate status of these groups have been too limited in sample size and
methodology to permit adequate evaluation (LSRO 1986).

Folate requirements for pregnant women are greatest in the last trimester
of pregnancy; however, most women's diets meet these requirements.
Oral folate supplementation during this period is often recommended for
high-risk groups. Premature infants, particularly those of very low birth
weight, may need more folate to support their growth than is provided by
infant formula or breast milk. Under a physician's guidance, this folate can
be supplied as an oral supplement. Infants fed primarily unfortified goat
milk are also at risk for folate deficiency because of the unusually low folate
content of this food.

Other risk factors for folate deficiency include chronic disease and use of
alcohol and drugs. Chronic and severe diarrhea, as in tropical sprue or
celiac disease, for example, can cause folate deficiency. Folate deficiency
also occurs among alcoholics (see chapter on alcohol). As discussed in the
chapter on drug-nutrient interactions, individuals who use oral contracep-
tives and other medications may be at increased risk for folate deficiency,
but the extent and public health significance of these interactions is uncer-
tain (LSRO 1984a).

A dietary vitamin B ,Z deficiency can occur in strict vegetarians who avoid
all foods derived from animals, including eggs and dairy products. Nursing
infants of women consuming such diets or of women who are vitamin B,,-
deficient are also at risk because the vitamin B ,* content of the breast milk
decreases as the mother's vitamin B,, stores decline (Shojania 1984). Any
strict vegetarian who becomes pregnant should be advised to supplement
her diet with vitamin B,,.

482


Anemia O

Implications for Public Health Policy

Dietary Guidance

General Public

Prevention of nutrition-related anemia depends on adequate dietary intake
of iron, vitamin B,,, and folate as well as the full complement of other
essential nutrients. Except for younger children and women of reproduc-
tive age, who are at greater risk for iron deficiency, it appears that current
iron consumption levels are sufficient for most of the population.

Special Populations

Routine health care for infants and pregnant women, the groups at highest
risk for anemia, should include laboratory evaluation for anemia and
nutritional advice on methods to ensure adequate iron intake. Nonpreg-
nant women in their childbearing years and adolescents are also at greater
risk for iron deficiency anemia; these individuals should be monitored and
should receive special counsel on preventing iron deficiency. Frequent
blood donors, another high-risk group, should be advised by blood bank
personnel about dietary methods to enhance iron intake and absorption.
Groups who may need iron supplements, such as premature infants, preg-
nant women, women with excessive menstrual bleeding, frequent blood
donors, strict vegetarians, and regular aspirin users, should also receive
advice from health professionals on enhancing iron bioavailability from the
diet. Specific education efforts directed toward these special groups, even
though difficult, are needed.

Folate deficiency anemia usually occurs among women late in the course of
pregnancy, among small and premature infants, and among alcoholics.
These groups, especially from low-income families, should receive advice
about dietary and supplemental sources of this vitamin.

Strict vegetarians who consume no foods of animal origin, especially
women who are pregnant or nursing, should be advised to consume supple-
mental sources of vitamin B,,.

Nutrition Programs and Sewices

Food Programs
Because groups that benefit from food programs are those at highest risk
for anemia, such programs should continue to be made available to high-

483


0 Nutrition and Health

risk groups and should encourage consumption of foods rich in iron and
folate. Evidence suggests that current levels of iron fortification are safe
and adequate, and no changes should be recommended at this time.

Food Labels

Evidence related to the role of iron and folate in anemia suggests that food
labels should indicate the content of these nutrients.

Special Populations

Patients with anemia should receive counseling and assistance to develop
diets that have adequate amounts of bioavailable iron, folate, or vitamin B ,*
from dietary or supplemental sources.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in anemia should include investigations into:
o Screening for earlier stages of iron deficiency using tests that identify
iron depletion (e.g., erythrocyte protoporphyrin).
o Elucidation of the health consequences of conditions of iron depletion
prior to development of anemia.
o Validation of methodologies for identification of the extent of deficien-
cies of iron, folate, and vitamin B,, in the general population and in
high-risk groups.

o Interactions between iron, folate, vitamin B,,, and other nutrients
consumed in the diet.

o Improved methods for analysis of the folate content-of food.
                           . .
o Determination of iron requirements at various stages of the life cycle
and under various physiologic conditions.
o Identification of appropriate levels and types of iron in the food supply
for individuals with hereditary conditions of excess iron absorption.
o Identification of the level of iron intake that confers maximum protec-
tion against major infections.

o betermination of trends in iron fortification in the U.S. food supply.
o Development of effective methods to educate the general public and
high-risk groups about consuming-diets adequate in iron and folate.

484


Anemia cl

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489


Chapter 13

Neurologic Disorders

The man is, above all else, the mind of the
man, and not only the mind as an organ of
conscious thought but the mind as an organ
    of bodily nutrition. . . .
        James J. Putnam
Boston Medical and Surgical Joumul ( 18991

Introduction

Historical Perspective

Since biblical times, brain function and certain nutritional factors have
been thought to be related, but knowledge of the interaction between
nutrition and neurology is still sparse. Scientific interest in the link between
nutrition and brain function began in the early 19th century when Magendie
proposed that the central nervous system controlled appetite (Anand 1961;
Widdowson 1982). Due to the predominance of theories that hunger was
purely a peripheral sensation (Cannon and Washburn 1912). it was not until
the 1930's that control of feeding began to be attributed to specific regions
of the brain.

Classically, nutritional deficiencies have also been related to brain func-
tion. Starvation was shown to produce a variety of overt behavioral
changes as well as mental deterioration (Blanton 1919), and severe mal-
nutrition in animals is now associated with impaired brain development and
learning (Winick 1976). The absence of specific vitamins or minerals from
the diet has been known for many years to produce behavioral or neu-
rologic symptoms in animals (Funk 1911). In the early 20th century, disor-
ders of the human nervous system were observed as consequences of
deficiencies of certain vitamins, copper, and magnesium in the diet (Wid-
dowson 1972). In most industrialized societies, however, only a few nutri-
tional deficiency diseases, such as those associated with alcoholism (see
chapter on alcohol), occur with sufficient frequency to be of substantial
concern to policymakers and the public.

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cl Nutrition and Health

Because the brain appears to be protected by the blood-brain barrier from
fluctuations in plasma nutrient levels caused by eating, it has been difficult
to demonstrate effects of specific foods or dietary components on brain
function. Furthermore, the nutrient transport and cellular uptake mecha-
nisms as well as the factors affecting the nutrient content of the brain are
not fully understood (Pardridge 1986). In laboratory animals, brain levels of
certain essential constituents have been reported to vary markedly as a
function of the nature and timing of food consumption (Pardridge 1977;
Wurtman, Hefti, and Melamed 1981; Blusztajn and Wurtman 1983), but
whether human neurotransmitter systems are affected by the intake of
dietary precursors (Wurtman, Wurtman, and Growdon 1981b; Blusztajn
and Wurtman 1983) is as yet uncertain.

This chapter reviews these and other nutritional aspects of neurologic
phenomena, and because cerebrovascular diseases account for such a large
proportion of neurologic cases and hospital admissions, it also reviews the
relationship between diet and stroke.

Significance for Public Health

Stroke is the most common life-threatening neurologic disease in the
United States: It ranks third after heart disease and cancer as a cause of
death and is also a major cause of long-term disability (NCHS 1986).
Although stroke mortality rates have declined dramatically in recent years
(see chapter on high blood pressure), in part as a result of improved high
blood pressure management, about 500,000 new cases still occur annually.
About 2 million Americans are estimated to suffer from stroke-related
disabilities at an annual cost of more than $1 I billion (NINCDS 1986). The
mortality rate among black Americans is almost twice that of whites.
Because a significant portion of the important risk factors for stroke are
under behavioral control, efforts to reduce these risks seem to be especial-
ly worthwhile.

Other neurologic conditions are also prevalent in the U.S. population.
Approximately 2 million Americans suffer from epilepsy, at an estimated
health care cost of $3 billion. Chronic headaches afflict 40 million people in
the United States and are responsible for 8 million annual visits to a
physician and 64 million days of work lost due to pain. Alzheimer's disease
affects 2 to 3 million Americans, at an estimated annual health care cost of
up to $50 billion (NINCDS 1986). Whether any appreciable fraction of these
conditions can be prevented or ameliorated by dietary means is unknown
but seems unlikely given current evidence.

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Scientific Background

Nutritional Needs of the Nervous System
The brain and nervous system probably require the full complement of
essential nutrients and energy to develop and to maintain their neurons and
supporting cells. Although it seems reasonable to expect that a deficiency
of any one of the essential nutrients or of energy would impair the develop-
ment and subsequent maintenance of these structurally and functionally
complex tissues, evidence to support this hypothesis has been difficult to
obtain (Shoemaker and Bloom 1977; Nowak and Munro 1977).

The human brain normally metabolizes 100 to 150 g of glucose per day as
fuel, but the mature nervous system is relatively insensitive to restrictions
of energy and protein. During starvation, it adapts and uses ketones,
derived from breakdown of body fat stores, for energy-and thus spares
blood glucose and conserves body protein. The documented behavioral
changes that occur in starving individuals-depression, apathy, irritability,
and loss of libiddo not necessarily reflect damage to the nervous system
(Kemdt et al. 1982).

Most direct research on the neurologic effects of nutritional deprivation has
been performed on experimental animals. In part because of species vari-
ability in the time course of neurologic development, the results of this
research may not be applicable to humans.

Additional information on the effects of dietary deficiencies on human
brain development and nervous system function derives from "natural
experiments" of human starvation or inadequate dietary intake. With a few
notable exceptions, it has been difficult to separate the effects of nutritional
deficits in these situations from those of other environmental, social, and
medical problems that often accompany poor nutritional status (Pollitt and
Thomson 1977).

Nonetheless, severe deficiencies of vitamins, especially the B-complex
group, impair nervous system function (Dreyfus 1988; Lipton, Mailman,
and Nemeroff 1979). Thiamin deficiency causes beriberi neuropathy as well
as a peripheral neuropathy and polyneuritis that leads to Wemicke-Kor-
sakofYs syndrome (paralysis of the eye muscles, loss of muscular coordina-
tion, and memory loss) in long-term alcoholics (Dreyfus 1988; see chapter
on alcohol). Inadequate niacin intake causes pellagra, with symptoms that
include intellectual impairment and dementia, in individuals of all ages.
Deficiency caused by vitamin B,, malabsorption in untreated pernicious

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anemia or as a result of a long-term vitamin B ,2 deficient vegetarian diet can
result in subacute degeneration of the spinal cord, optic nerves, cerebral
white matter, and peripheral nerves (Dreyfus 1988). Severely deficient
intakes of other vitamins of the B-complex group also affect neurologic
function. In the early stages, these symptoms are readily overcome by
increased dietary intake of the appropriate vitamin, but nerve damage in
later stages appears to be irreversible (Lipton, Mailman, and Nemeroff
1979). Whether subclinical deficiencies of these vitamins affect nervous
system function is as yet uncertain (Goodwin, Goodwin, and Gary 1983).

Deficiencies of other nutrients may relate to defects in nervous system
function. For example, iodine deficiency during brain development causes
mental retardation and neuromotor abnormalities. Chronic iron deficiency
is associated with deficits in cognitive abilities (Lozoff et al. 1987). A few
cases of vitamin E deficiency-induced spinal cord, cerebellar, and periph-
eral nerve degeneration with muscle wasting have been reported among
patients with severe cholestatic liver disease or malabsorption syndromes
(Muller, Lloyd, and Wolff 1983; Laplante et al. 1984; Weder et al. 1984).
Levels of vitamin E are greatly reduced in the peripheral nerves of such
patients (Traber et al. 1987). In most cases, neurologic damage resolves
with administration of vitamin E (Sokol et al. 1985), suggesting that vitamin
E deficiency may be responsible.

The effects of nutritional deficiencies on the developing nervous system are
difficult to interpret. Studies in rats have almost always restricted total
dietary intake rather than that of specific nutrients. These studies have
indicated that nutritional deprivation at various stages of fetal and postnatal
development produces its own constellation of defects. Early maternal
malnutrition reduces fetal brain weight and brain protein and DNA con-
tent. Postnatal malnutrition also induces deficits in brain weight and, in
addition, reduces myelination and dendrite formation and retards develop-
ment of mature enzyme patterns (Shoemaker and Bloom 1977). These
changes persist even after adequate nutrition is restored (Nowak and
Munro 1977; Winick 1976). In experimental studies of pregnant animals,
diets deficient in zinc and folate result in high rates of malformations such
as neural tube defects and spina bitida in the offspring (Hurley and Shrader
1972; see chapter on maternal and child nutrition). Supplementation of
these animals resulted in a significant reduction in the incidence of these
congenital nervous system defects.

Studies in animals have shown that the neuropathology resulting from
intrauterine starvation or postnatal malnutrition does not produce recog-
nizable focal lesions but instead produces diffuse anatomical effects that

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Neurologic Disorders O

appear to be spread throughout the brain. Different effects occur in differ-
ent brain regions depending on the rate of cell division within each region.
Because changes of this type provide little information about functional
connections, the significance of these changes for cognitive and behavioral
function is uncertain (Nowak and Munro 1977).

The relevance of animal studies for human brain development and cog-
nitive functioning is also uncertain. Reduced cellularity and myelination
have been shown to occur in the brains of severely nutritionally deprived
human infants. Malnutrition during and after pregnancy produces human
infants with lower birth weights, smaller stature, and, therefore, smaller
head circumferences and lower brain weights. None of these changes,
however, has been demonstrated to affect higher mental processes (Dob-
bing 1984).

Dietary Precursors of Brain Neurotransmitters

Nervous system function is mediated through the work of various neu-
rotransmitters such as serotonin, the catecholamines (dopamine and nor-
epinephrine), and acetylcholine. These neurotransmitters are manufac-
tured by the action of enzymes in the brain on the precursor amino acids
tryptophan, tyrosine, and choline, respectively. Because the brain cannot
make adequate quantities of the various precursors, it must rely on uptake
from the bloodstream. Studies in animals have suggested that meal com-
position can affect plasma levels of the precursors and, therefore, synthesis
of these neurotransmitters (Wurtman, Hefti, and Melamed 198 1; Pardridge
1977).

Whether the various high dose dietary contributions to precursors of brain
neurotransmitters affect neurologic function in animals other than the rat is
uncertain (Trulson 1985). The effects of dietary precursors of neu-
rotransmitters on animal function and behavior are also uncertain (see
chapter on behavior). Also unknown is whether dietary precursors of
neurotransmitters can alter normal human behavior (Spring 1986; Young
1986) or correct abnormal behavior (Growdon 1979a; Van Praag and Lemus
1986).

Clinical investigators have tested the utility of neurotransmitter precursors
as treatments for diseases associated with neurotransmitter deficiencies
such as Alzheimer's and Parkinson's diseases, depression, and sleep disor-
ders (Growdon 1981; Growdon and Wurtman 1982; Growdon and Gibson
1982; Young 1986; Van Praag and Lemus 1986). There is no evidence that
such conditions result from nutritional deficiencies. Thus, tryptophan,
tyrosine, and choline (as such or as phosphatidylcholine) were given in

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these studies in purified form independent of other food constituents. In the
case of choline, doses were greater than would ordinarily be consumed in
the normal diet.

Pharmacologic amounts of L-tryptophan, for example, have been adminis-
tered to human subjects to induce sleep (Hartmann 1982), treat insomnia in
older persons (Jenicke 1985), relieve anxiety and suppress food consump-
tion in obese persons (Wurtman, Hefti, and Melamed 1981), suppress
posthypoxic myoclonus (Growdon 1979b), and treat certain pain syn-
dromes (Hosobuchi, Lamb, and Bascom 1980; Lieberman et al. 1982; King
1980). However, the effectiveness of tryptophan for these purposes has not
been established, and its use remains controversial (DeFeudis 1987). Simi-
larly, tyrosine, the dietary precursor of the neurotransmitters dopamine
and norephinephrine, has been used to accelerate dopamine turnover in
patients with Parkinson's disease (Growdon and Melamed 1982) and to
treat patients with mild Parkinson's disease (Growdon 1981) or endogenous
depression (Van Praag and Lemus 1986); however, these applications are
also preliminary and require further confirmation.

Large doses of choline and purified phosphatidylcholine, precursors for
the neurotransmitter acetylcholine, have been reported to improve the
symptoms of patients with tardive dyskinesia (Growdon and Wurtman
1982) and mania (Cohen et al. 1980). These observations remain to be
confirmed. Similar treatment of patients with Huntington's disease, Gilles
de la Tourette's syndrome, familial ataxias, and epilepsy has produced
negative or inconclusive results (Wood and Allison 1982).

Despite a single report that suggests that the administration of phos-
phatidylcholine for at least 6 months might retard the progression of
Alzheimer's disease in a subset of older patients with this disorder (Little et
al. 1985), more than a dozen additional studies have found choline to be
ineffective in the treatment of this condition (Bartus et al. 1982). Evidence
is also lacking for the hypothesis that Alzheimer's disease is a consequence
of the breakdown of phosphatidylcholine in neuronal membranes to pro-
duce choline for acetylcholine biosynthesis (Blusztajn and Wurtman 1983).

Key Scientific Issues

o Role of Diet in Cerebrovascular Disease (Stroke)
o Role of Diet in Other Neurologic Disorders
0 Role of Noncaloric Dietary Components in Neurologic Disorders

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Role of Diet in Cerebrovas&tar Disease (Stroke)

Stroke is the sudden loss of brain function caused by one of four vascular
events: thrombosis, or blood clot, in a cerebral artery; embolism, or
blockage, of a cerebral artery by a circulating clot; stenosis, or narrowing,
of a cerebral artery by atherosclerosis; or hemorrhage from rupture of a
cerebral artery. These events deprive the brain of blood and oxygen and
-cause tissue death and irreversible damage to nervous tissue. The effects of
the damage depend on the location and size of the tissue loss. Symptoms
range from those too trivial for the victim to notice to major sensory
deficits, blindness, paralysis, speech loss, coma, and death. Although
some return of function is possible in tissues damaged but not destroyed,
losses persisting beyond weeks are likely to be permanent.

Persons at greatest risk for stroke are those with hypertension-and diabetes
and those who smoke cigarettes and display impaired cardiac function due
to coronary heart disease, congestive heart failure, or-hypertensive heart
disease. These major risk factors for stroke are in part related to nutri-
tional, dietary, and lifestyle factors. Current evidence suggests that certain
dietary substances that promote. high blood pressure or diabetes may
increase the likelihood of stroke. Thus, excessive dietary consumption of.
calories (ifit results in obesity), sodium, and alcohol may increase the risk
for stroke. The evidence that links dietary factors to high blood pressure
and diabetes is reviewed in detail in the chapters devoted to those topics.
Although there is a wealth of evidence supporting the relationship between
diet, blood cholesterol levels, and atherosclerotic coronary disease (see
chapter on coronary heart disease), the link to cerebrovascular disease is
less clear.

Persons with hypertension are at greatly increased risk for stroke. This risk
increases with elevations in blood pressure regardless of age and sex; it
decreases when blood pressure is reduced. How hypertension predisposes
to stroke is not fully understood, but it appears to injure cerebral artery
walls. Diabetes and high blood cholesterol may also act, alone or in
concert, to injure the inner wall of a cerebral artery. Through consequent
platelet interaction, the injury becomes the site of plaque formation and
subsequent atherosclerosis. Thus, hypertension seems to be the precursor
of the hemorrhagic, the stenotic, and the embolic types of stroke.

Moderate sodium restriction (Koolen and Van Brummelen 1984; Kawasaki
et al. 1978), high potassium intake (Treasure and Ploth 1983; Langford 1983;
Kaplan et al. 1985), vegetarian diets (Ophir et al. 1983), calcium (Blaustein

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u Nutrition and Health

and Hamlyn 1983; McCarron et al. 1984), weight reduction, and alcohol
restriction all have been suggested as factors associated with blood pres-
sure lowering. Gfthese, weight reduction and restriction of sodium have the
most evidence to substantiate this association, but excessive consumption
of alcohol is associated with increased rates of hypertension (Klatsky et al.
1977; MacMahon and Norton 1986; Potter and Beevers 1984). Epi-
demiologic evidence associates excessive drinking with increased frequen-
cy of subarachnoid hemorrhage and cerebral infarction (Hillbom and Kaste
1978,1982), and heavy alcohol intake has been identified as an independent
risk factor for stroke in humans (Gill et al. 1986).

The effect of dietary potassium on stroke has also been investigated re-
cently. In a prospective study, individuals consuming somewhat higher
levels of potassium from food sources had a reduced risk for stroke-
associated mortality (Khaw and Barrett-Connor 1987). The effects of spe-
cific dietary factors on causation of stroke warrant further investigation.

Role of Diet in Other Neurologic Disorders

Headache

Headache, one of the most common complaints evaluated by neurologists,
is estimated to affect 40 million Americans. Clinical investigations of the
role of foods in precipitating vascular or migraine headaches remain con-
troversial (Dreyfus 1988). The foods most frequently implicated often
contain tyramines (e.g., cheese, red wines) or more rarely phenylethyl-
amine (e.g., chocolates) (Dreyfus 1988; Egger et al. 1983). The "Chinese
Restaurant Syndrome" is associated with numbness around the mouth,
tingling, flushing of the face, dizziness, and headache (Kenny 1980). Use of
the artificial sweetener aspartame has been found not to be associated with
increased susceptibility to headache (Schiffman et al. 1987).

Current evidence suggests that dietary factors are unlikely to be responsi-
ble for most cases of headache, although toxicity of vitamin A, caused by
excess intake of supplements, has been reported to cause headaches. Until
conclusive evidence has established the link between certain foods and the
occurrence of headaches, especially migraine, it may be prudent for such
individuals to abstain whenever possible from those foods thought to
provoke an attack (Dreyfus 1988).

Epilepsy

Low levels of magnesium can cause seizures, and the magnesium-deficient
rat is used as a model of experimental epilepsy (Buck, Mahoney, and

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Hendricks 1978). Magnesium deficiency in humans most often results from
kidney disease and is not a significant cause of epilepsy in people. A wide
variety of neurobehavloral symptoms common in the general population,
including epilepsy, have been reported to occur in people consuming the
artificial sweetener aspartame (Wurtman 1985). No well-controlled clinical
studies have indicated that a causal relationship exists. Ketogenic diets
(low in carbohydrate) have been used for decades to treat certain forms of
intractable epilepsy. The mechanism of action of this diet is not understood
(Withrow 1980), and it is tolerated poorly by some patients (Trauner 1985).
Furthermore, it is nutritionally inadequate, unpalatable, and inappropriate
for use in young children. Other specific nutrients such as vitamin D, have
been suggested to have beneficial effects on seizure thresholds in rats
(Siegel et al. 1984), but more information is needed before conclusions can
be drawn about the role of diet in epilepsy.

Role of Noncaloric Dietary Components in Neurologic Disorders

Excessive Vitamin Intake

Vitamin A intoxication can result from the chronic use of relatively low
levels (14,000 IU/day in infants and 25,000 to 50,000 IU/day in adults) of the
vitamin (Farris and Erdman 1982), and toxic symptoms may appear sud-
denly with the onset of liver dysfunction due to other causes (Hatoff et al.
1982). Excessive intake of vitamin A causes reversible intracranial hyper-
tension, which when not so identified has led to needless surgery; it can
also occasionally result in headache, blurred vision, seizures, and encepha-
lopathy. High doses of pyridoxine (vitamin B6) have been used to treat
conditions such as carpal tunnel syndrome; however, excessive pyridoxine
in gram quantities has recently been associated with peripheral nerve
deterioration, and more recent studies indicate that lesser amounts may
produce toxic symptoms (Ditmars and Houin 1986; Dreyfus 1988; Schaum-
berg et al. 1983).

Endogenous and Exogenous Toxins

Naturally occurring food-borne toxins either consumed in the diet or
produced by the body as a result of rare metabolic diseases also affect the
mature nervous system; brain damage resulting from lung, liver, or kidney
failure is a common example. Moreover, rare metabolic diseases or inborn
errors of metabolism can cause naturally occurring food constituents to
become toxic (e.g., copper in Wilson's disease, phenylalanine in phen-
ylketonuria) (Dreyfus 1988). The seeds of certain cycad plants contain
neurotoxic substances that, when ingested by experimental animals, cause
symptoms similar to those of amyotrophic lateral sclerosis (ALS), parkin-


O Nutrition and Health

sonism, or Alzheimer's disease (Spencer et al. 1987). However, in man, the
role of cycad plants and other dietary factors in ALS is still controversial
(Garruto and Yase 1986). Other neurotoxins have caused acute poisonings
on those rare occasions when they have contaminated foods in large
quantities. These include ingestion of lead-contaminated paint, soil, or
food and water (Mahtiey 1981); industrial contamination of shellfish with
methyl mercury; and paralytic poisons produced by certain shellfish (Hat-
ten et al. 1983).

Specific dietary constituents, such as heavy and trace metals, may have
especially adverse effects on the nervous systems of older adults. For
example, increased amounts of aluminum and calcium have been reported
in brains of patients with Alzheimer's disease, and concentrations are
especially high in the damaged neurons of the cortex (Linton et al. 1987),
particularly in association with the senile plaques and tangles. Whether
aluminum causes the cellular damage or accumulates simply because the
cells are dying has not been established (see chapter on aging).

Food Additives

Numerous compounds added to foods can affect the nervous system.
Some investigators have reported that very high levels of the dipeptide
sweetener aspartame raise brain levels of tyrosine in rats and, as a conse-
quence, impair synthesis of catecholamine neurotransmitters (Yokogoshi
et al. 1984; Pardridge 1977), but others have not been able to identify such
effects (Potts, Bless, and Nutting 1980; Torii et al. 1986). The rat, unlike
humans, rapidly converts phenylalanine (a component of aspartame) to
tyrosine. Until aspartame has been tested in well-controlled human clinical
studies, its effects on the nervous system remain speculative.

Drug-Nutrient Interactions

Some of the drugs used to treat neurologic diseases can lead to vitamin
deficiencies by changing the metabolism of the vitamins, causing a second-
ary impairment of brain function (see chapter on drug-nutrient interac-
tions). Dilantin, used to treat epilepsy, can increase folate requirements and
cause vitamin K deficiency in the infants of mothers treated with this drug.
In addition to the hypertensive medication effects on mineral metabolism
described in the chapter on drug-nutrient interactions, hydralazine is a
vitamin B, antagonist that can cause peripheral neuropathy. Tranquilizers
such as chlorpromazine and other phenothiazines may cause hyperphagia
and weight gain. Monoamine oxidase inhibitors can cause acute hyperten-
sive crises, including excruciating headaches or fatal intracranial hemor-


Neurologic Disorders 0

rhages, when taken with foods or beverages high in tyramine. Long-term
intake of Sinemet, used to treat parkinsonism, may cause niacin deficiency
(Bender, Earl, and Lees 1979).

Caffeine is a pharmacologically active agent found in foods and drugs
(Snyder et al. 1981) that can enter the brain because of its lipid solubility.
Animal studies have suggested that foods can impair the efficacy of drugs
by blocking their uptake into the brain. For example, a high-protein meal
may diminish the efficacy of L-dopa (used to treat parkinsonism) or of
Aldomet (used for high blood pressure) because these drugs are trans-
ported into the brain by the same carrier molecules that transport certain
amino acids. The significance of these suggestions for either animal (Peter
and Harper 1985) or human drug metabolism is uncertain at this time.

Implications for Public Health Policy

Dietary Guidance

General Public                               :       .-
Nutrients of concern in stroke are those associated with its major diet-
related risk factors-hypertension, diabetes, and obesity. Evidence sug-
gests that diets low in sodium and alcohol, as well as caloric intake and
physical activity to achieve and maintain desirable body weight, should be
recommended as public health measures to prevent stroke and its related
conditions. Excessive drinking has been associated with stroke; hence,
this practice should be avoided. Although some evidence links very large
exposures of major dietary components (e.g., amino acids, choline) to
nervous system disorders other than stroke, this evidence is, for the most
part, preliminary and remains to be confirmed by additional clinical evi-
dence before implications can be drawn.

Over- or underconsumption of certain vitamins and minerals can damage
the nervous system as in the occurrence in alcoholics of thiamin deficiency-
related Wemicke-Korsakoff s syndrome.

Special Populations

Studies in patients with major diet-related risk factors for stroke indicate
that similar dietary changes can reduce the level of the risk factor and help
prevent cardiovascular disease (see chapters on high blood pressure, di-
abetes, and obesity). Qualified health professionals should provide patients
with information on the means to achieve these changes. In addition to a

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focus on weight reduction and sodium restriction, this information should
emphasize the importance of alcohol restriction in patients with high blood
pressure and/or high glucose levels.

Suggestions that certain foods or food components might influence head-
ache or epilepsy have yielded conflicting research results and are too
preliminary to draw conclusions.

Nutrition Programs and Services

Food Labels

Evidence related to the role of dietary factors in stroke and other neu-
rologic diseases supports the need for sodium labeling of packaged food
products.

Food Services

Food service programs should emphasize diets low in sodium and calories
to maintain ideal body weight and to control obesity and diabetes.

Special Populations

Patients at high risk for stroke and other neurologic conditions should be
provided with counseling and assistance in the development of diets appro-
priate to their conditions.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in neurologic disease should include investigations into:
o The role of specific dietary factors in the etiology and prevention of
  stroke.

o The relationship, if any, between specific dietary factors and specific
brain functions such as memory, alertness, and response time.
o The mechanisms by which food components, such as dietary precur-
sors of neurotransmitters and certain additives and toxins, might affect
nervous system function.

o The role, if any, of specific dietary factors in the etiology and preven-
tion of Alzheimer's disease.

o The nutritional needs of the brain and nervous system in health and
throughout life.

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Neurologic Disorders Ll

o The effects of excessive intake of nutrients and supplements (vitamins
A, B,, etc.) on nervous system function.
o The mechanism or mechanisms by which excessive alcohol intake
increases the risk for stroke.

o The ability of diets low in calories, sodium, alcohol. and, perhaps,
other dietary factors to prevent stroke.
o The most effective methods to educate the public about diet-related
risk factors for stroke, and to assist the public in making recommended
dietary changes.

o The comparative effects of dietary insufficiency on cognitive function
and neurologic disease.

o The understanding of the blood-brain barrier nutrient transport proc-
esses and the mechanisms by which diet may influence brain function
and health.

o The role of preexisting nutritional disease and nutritional status on the
impact of neurotoxins.

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Growdon, J.H., and Wurtman. R.J. 1982. Lecithin treatment of neuroleptic-induced tardive
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Hartmann, E. 1982. Effects of L-tryptophan on sleepiness and on sleep. In Research strat-
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Hosobuchi, Y.; Lamb, S.; and Bascom, D. 1980. Tryptophan loading may reverse tolerance to
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Chapter 14

Behavior

Thus it may appear, that there ought to be a
great reciprocal influence between the mind
     and alimentary duct.
      David Hartley
     Observations on Man,
Vol. I, Chapter II, Section 2 (1749)

Introduction

The disciplines of nutrition and behavior are not usually considered to be
closely related, but there are in fact several key areas of overlap between
these fields. Behavioral factors determine the choice of foods in the diet,
and any attempt to change dietary patterns must necessarily involve
changes in behavior. Because eating itself is a behavior controlled by the
brain, all disorders of eating inherently involve the central nervous system
and may be associated with mood changes. Although considerable public
attention has focused on suggestions that ingestion of certain foods or
nutrients might influence behavior, it has been difficult to confirm such
effects. Similarly, suggestions that some nutrients can modify specific
aspects of brain function and behavior also require further confirmation.
This chapter reviews relationships between nutrition and behavior. For
more detailed discussion of these issues, the reader is referred to recent
volumes on this topic (Miller 1981; Olson 1986; Wurtman and Wurtman
1977-86) and to the chapter on neurologic disorders in this Report.

Historical Perspective

That diet influences behavior is an ancient human belief. Primitive people
attributed friendly and unfriendly feelings to plants and animals and ex-
pected these feelings to be transferred to anyone who ate such foods.
Eating the heart of an aggressive animal, for example, was thought to
confer strength and courage, whereas consumption of timid or weak crea-
tures would undermine desirable attributes (Farb and Armelagos 1980).

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In religious teachings, the behavior of mankind was said to change instantly
when Eve ate the apple. Solomon, suffering the pangs of love, was com-
forted with apples (Cussler and deGive 1952). The ancient Greeks pro-
posed that the human body is composed of four "humors"--hot, cold, wet,
and dry-that control health, feelings, and behavior, and extended these
categories to foods and other factors in the environment. Imbalances in
these humors were thought to cause disease; physical and mental health
could be restored by consuming foods in the opposite, complementary
categories. Anger, for example, was considered hot and dry, and melan-
choly was cold and dry. These ill humors could be corrected by consuming
foods that were cold and wet, or hot and wet, respectively (Barb and
Armelagos 1980). Such ideas have carried forward to the present day, when
many cultural groups believe in hot/cold or yin/yang approaches to food
and health (Ludman and Newman 1984).

Systematic study of cultural influences on food intake began early in this
century as anthropologists examined the use of food in isolated cultures
and ethnic groups. These studies recognized the importance of societal
influences on food selection and use, and they indicated that food intake is
not an isolated, individual response to the sensory properties of food but
instead depends greatly on the symbolic meanings of food in each culture
(Goode, Curtis, and Theophano 1981). Even in contemporary times, foods
are endowed with magical powers (Kimmens 1975) and are believed to
symbolize feelings such as those of satisfaction and security (Bruch 1973).

Significance for Public Health

The reduction of behavioral risk factors for chronic disease and the devel-
opment of effective means to do so are major public health goals, and
improvement of the food choices and dietary practices of individuals and
populations is the key to control of the conditions reviewed in this Report.
Obesity, for example, is a common nutritional problem in the United States
today, affecting about 34 million adults. Dietary fat and cholesterol in-
crease the risk for a number of chronic diseases, including the Nation's
leading killer, cardiovascular disease. These conditions are discussed in the
respective chapters.

Other eating-related problems such as anorexia nervosa (self-starvation) or
bulimia (binge/purge syndrome) are relatively uncommon. Anorexia ner-
vosa occurs most often in females from the upper and middle social classes
and usually begins between the ages of 13 and 20. Even among persons at
highest risk, the prevalence is less than 1 percent. In the general popula-
tion, approximately 1 in 250 suffer from anorexia nervosa in any given year

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(APA 1987). Furthermore, despite ageneral impression to the contrary, the
incidence of anorexia nervosa does not appear to be rising significantly
(Williams and King 1987). Because of difficulties in its diagnosis, estimates
of the incidence of bulimia vary from 2 to 19 percent among college women,
thegroup at highest risk (Lustic 1985; Zuckerman et al. 1986), and are about
5 percent for men (Halmi, Flak, and Schwartz 1981). A recent survey of
university students, however, identified only 1.3 percent of the female and
0.1 percent of the male respondents as meeting standard diagnostic criteria
for this condition (Schotte and Stunkard 1987).

Pica (consumption of nonfood substances) is another eating disorder of
concern. Because definitions of pica vary and individuals who practice pica
are reluctant to admit it, it has been difftcult to establish the prevalence of
this condition. Thus, estimates of the proportion of individuals in selected
groups of children, pregnant women, or other adults who practice pica have
varied from 0 to 66 percent (Danford 1982), and no conclusions can as yet
be drawn about its prevalence in the general population.

Other behavioral disorders commonly associated with food choices in-
clude childhood hyperactivity, antisocial behavior, and hypoglycemia.
Neither the prevalence nor the nature of these conditions is reliably estab-
lished.

Scientific Background: Methodological Issues

Although many research reports have concluded that food and nutrients
influence behavior, most of these accounts do not meet criteria for con-
trolled scientific research. Environmental, cultural, socioeconomic, and
psychologic factors can induce symptoms such as anxiety, depression,
fatigue, insomnia, or irritability, and it is difficult to demonstrate that such
symptoms are caused by dietary factors unless research studies are de-
signed to rule out other potential causes (Kanarek and Orthen-Gambill
1986).

Understanding of nutrition and behavior is also limited by unresolved
questions about the applicability of much animal research to humans and
by inadequacies in present knowledge of the effects of nutrients on brain
function. Imprecise and inappropriate definitions and methods of measur-
ing normal behavior also limit understanding. Such difftculties explain why
research studies produce results that are often inconsistent and cause
public and professional controversy.

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O Nutrition and Health

Various authorities have emphasized the importance of methodologically
rigorous research in this field and have urged investigators to design studies
that include appropriate standards of measurement, adequate sample sizes,
controls for confounding variables, elimination of sources of investigator
and subject bias, appropriate statistical treatments, and caution in the
interpretation of results (Sprague 1981; Anderson and Hrboticky 1986).
These issues are especially important in establishing cause or effect as well
as in establishing policies for regulation or labeling (Sobotka 1986).

Key Scientific Issues

o Behavioral Determinants of Eating Habits
o Behavioral Aspects of Eating Disorders
o Effects of Foods and Nutrients on Behavior

Behavioral Determinants of Eating Habits

Behavioral Issues in Food Selection

Although infants do not begin life with a choice of food, some of the most
obvious reflexes at birth are those associated with eating. Infants learn to
associate eating with security and relief from anxiety, tension, and distress.
Later, children eat in conformance to cultural and familial standards.
Throughout life, food symbolizes and mediates social relationships and is
strongly linked to deep feelings of acceptance and comfort or deprivation
(Bruch 1973). These ingrained meanings attached to the roles of food in
society suggest reasons that food habits often can be changed only with
difficulty.

Although the choice of certain foods as opposed to others may greatly
affect nutritional status, surprisingly little is known about the factors that
determine food selection beyond the fact that they include multiple en-
vironmental, cultural, genetic, social, and sensory variables that interact in
complex ways (Rozin 1984). People must choose foods from those that are
available, but the foods selected to be grown and sold vary greatly among
different cultures. Within a given culture, individual food choices depend
greatly on sociocultural systems that govern food production, distribution,
and consumption (Goode, Curtis, and Theophano 1981; Harris 1985).

Individual preferences are the chief factors in food choices, but the ele-
ments that determine food preferences are poorly understood. Preferences
for flavor and taste are learned, culturally determined, and dependent on

512


Behavior 0

the degree of exposure (Story and Brown 1987). The one exception appears
to be an innate preference for foods that are sweet. This preference is
observed in early childhood and continues throughout life (Desor, Mallor,
and Greene 1977). Aversions to foods are also learned and seem to occur
most often when associated with gastrointestinal distress or the introduc-
tion of novel foods (Rozin 1984).

Selection of foods for nutritional or health reasons is also a learned behav-
ior. Contrary to a commonly held opinion, infants have not been shown to
have an inborn ability to select a balanced, nutritious diet (Story and Brown
1987). Recent studies indicate that the variety of foods available has an
important effect on food consumption; the more the available foods are
varied, the more of them people will eat (Rolls 1985).

Behavioral Aspects of Dietary Change

Behavior change-especially in dietary practices-is a key element in
reducing the risk for chronic disease. Individual and public health efforts to
induce beneficial changes in dietary habits are based on the assumption
that people who understand the risks associated with their present prac-
tices will alter them to prevent illness. Although this assumption appears
self-evident, education may not have as great an impact on food behavior as
might be expected unless it can overcome counteracting barriers, includ-
ing, perhaps, a general belief that some dietary practices are worth the risk
(Syme 1986).

Extensive societal and behavioral forces inhibit dietary change. Eating
behaviors are acquired over a lifetime; to change them requires alterations
in habits that must be continued permanently-long beyond any short-term
period of intervention. Dietary advice is often restrictive and viewed as
depriving or unpleasant. It may also be incompatible with cultural or
familial standards of appropriate food intake. Dietary changes may require
increased cost, skill, time, or effort needed for food preparation (Glanz
1986).

Furthermore, environmental factors such as peer pressure, advertising of
high-calorie foods and alcoholic beverages, or other cultural determinants
may strongly counteract recommended changes (Syme 1986). Social and
political values and economic considerations may also be obstacles (Som-
ers and Weistield 1986). Together, these barriers suggest that dietary advice
(like much other advice) is far easier to give than to accept.

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O Nutrition and Health

Despite these difficulties, considerable evidence supports the effective-
ness of nutrition education in changing dietary intake to reduce risk factors
for or symptoms of conditions such as coronary heart disease, diabetes,
hypertension, and renal disease. For reasons that are poorly understood,
public health efforts to reduce the incidence of obesity have been consider-
ably less effective (Glanz 1986) and are discussed below.

Although no single method of counseling for dietary change is universally
effective, the key elements of the more successful strategies have been
identified repeatedly. These are (Zifferblatt and Wilbur 1977; Glanz 1986):
o To set realistic, achievable, and measurable goals.
o To tailor recommendations to individual lifestyle and dietary prefer-
   ences.

o To use whatever social support systems are available to provide train-
ing in skills as well as to provide information.
o To establish good communication between educator and clients.
o To provide systematic followup, reinforcement, and monitoring.

Behavioral Aspects of Eating Disorders

Obesity

Obesity is the excessive accumulation of fat in the body. As discussed in
the obesity chapter, approximately one-fourth of Americans are classified
as overweight (Abraham et al. 1983). The definition, prevalence, cause,
and treatment of obesity are discussed in that chapter.

At one level of understanding, the cause of obesity is quite simple: fat
accumulates when more calories are consumed than are expended. It is
difficult to demonstrate a positive correlation between total food consump-
tion and the extent of obesity in specific individuals, although such rela-
tionships can be observed in population studies (Rolland-Cachera and
Bellisle 1986). Human obesity is often a familial disorder; obese parents
tend to produce obese offspring. While this observation does not dis-
tinguish the influences of heredity and environment, studies of twins
suggest that there is a substantial genetic component to human obesity
(Stunkard et al. 1986). It is also possible that some people become obese
and sustain their obesity because mechanisms that normally regulate food
intake are impaired (Wurtman et al. 1981; Rosenthal, Sack, James, et al.
1984). Obesity is more common among women than among men at all ages,
and its prevalence increases with age but decreases among irdividuals of
higher socioeconomic status and greater levels of physical activity.

514


Behavior O

Behavioral Determinants. Behavioral and psychiatric contributions to
obesity-those factors that affect eating behavior-have been the focus of
extensive investigation, based largely on the assumption that overeating is
the primary cause of obesity. The evidence for this assumption is, at best,
only partially correct (see chapter on obesity). Once obesity is established,
food choices and caloric intake are no longer "normal," and personality
differences between obese and normal-weight individuals may be due more
to the results of physiologic changes, social discrimination, or dieting than
to behavioral factors.

Because of these complexities, which impede scientific understanding at
basic levels, numerous behavioral hypotheses have been proposed to
account for the differences in weight between obese and normal-weight
individuals. These hypotheses have been reviewed recently (Striegel-
Moore and Rodin 1986) and are summarized in Table 14-I.

Considerable research supports many of these theories, but none has yet
been demonstrated to account consistently for group differences between
obese and normal-weight individuals. For most variables measured, no
group differences have been found. Instead, the many tests of these hy-
potheses suggest that variation between individuals is greater than that
between the groups; that behavioral correlates might be the result of
obesity rather than its cause; and that even when a behavioral effect is
identified, its relation to the etiology of obesity is uncertain (Striegel-
Moore and Rodin 1986). The precise causal role of behavioral factors in
obesity is still to be determined.

              Table 14-1
Behavioral and Psychologic Hypotheses to Explain Obesity

Unconscious personality conflicts
Response to anxiety or depression
Neurotic personality traits
External locus of control
Preference of immediate gratification
Abnormal eating styles
Excessive food intake
External eating cues
Response to food palatability
Taste perception
Response to food variety
Restrained eating (response to dieting)
Arousal misperception

Source: Striegal-Moore and Rodin 1986.

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Behavioral Associufions. Of the various emotional disturbances to which
obese persons are subject, three are specifically related to their obesity:
disparagement of body image, psychologic complications of dieting, and
binge eating (Wadden and Stunkard 1985). A fourth complication-fear of
obesity-has also been reported. Binge overeating occurs in only a small
percentage of obese persons and is discussed below with regard to bulimia.

Disparagement of body image affects a larger percentage of obese persons
than nonobese persons who characteristically dislike their own bodies.
Such feelings are closely associated with self-consciousness and impaired
social functioning, and these feelings are not unexpected in view of the
pervasive social biases and discrimination against the obese in this society
(Brownell 1984). They are usually observed in persons who have been
obese since childhood. Even among this group, however, fewer than half
suffer from impaired body image.

Psychologic complications of dieting include anxiety, depression, irritabil-
ity, and preoccupation with food. These disturbances may arise from the
same mechanisms that occur in normal-weight persons who restrict their
food intake (Stunkard and Rush 1974) and are discussed further in the
chapter on obesity. Fear of obesity has been reported as a cause of self-
induced dieting and subsequent weight loss, growth retardation, and de-
layed puberty in a small group of boys and girls ages 9 to 17 (Pugliese et al.
1983).

Behavioral Treatment. Although weight reduction ought to confer great
benefits upon obese persons and be simple to accomplish, clinical experi-
ence has shown obesity to be remarkably resistant to treatment. The basis
of weight reduction is deceptively simple: Establish an energy deficit by
consuming fewer calories than are expended or by expending more calories
than are consumed. As discussed in the obesity chapter, the most effective
treatment methods involve combinations of diet, exercise, and behavior
modification. Most such treatment in the United States is carried out under
the direction of nonmedical groups and counselors in programs that pose
minimal hazard, although they are of uncertain long-term effectiveness.

The role of behavioral strategies to enhance the effectiveness of weight loss
programs has been the subject of active investigation. These strategies
derive from the key assumptions and characteristics of behavior therapy:
Behavior is acquired; treatment measures should be specified and out-
comes evaluated; treatment should be individualized; and treatment effec-
tiveness should be assessed (Wilson and O'Leary 1980). Behavioral weight
control programs usually include group participation at weekly meetings

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for periods of 2 months or longer and involve techniques of stimulus
control (e.g., shop from a list, do not save leftovers), eating behavior (do
nothing else while eating, chew thoroughly), reward, self-monitoring, nu-
trition education, physical activity, and cognitive restructuring in which
patients are encouraged, for example, to set reasonable weight goals and to
think about progress rather than failure (Stunkard and Berthold 1985).

Evaluations of the effectiveness of such programs have indicated that
when spouses of obese patients were included during treatment, followup
weight loss is greater (Brownell et al. 1978). Obese patients who partici-
pated in regular peer group meetings following the completion of formal
treatment have been observed to maintain their weight loss better than
those who do not participate in such meetings (Pert-i et al. 1984). Other
behavioral studies have described factors associated with prevention of
relapse following weight loss programs, such as strategies to cope with the
presence of favorite foods (Marlatt and Gordon 1985).

Effects of Mood Disorders. It has been known for many years that distur-
bances of appetite and weight regulation are important symptoms of cer-
tain mood disorders. In pioneering work on manic-depressive disorders,
for example, body weight was observed to fall early in a depressed phase,
while a rise in body weight was often one of the earliest signs of recovery
(Kraepelin 1921). Other patients, however, gained weight during pro-
tracted depression. In later large-scale studies of depression, eating and
weight disturbances were found in 70 percent of depressed subjects
(Leckman et al. 1984) and weight gain was observed in 70 percent of 263
depressed subjects during their recovery from depression (Kraines 19.57).
Depression can be accompanied by either gain or loss of weight, and in
general, disturbances in appetite and weight regulation are accepted as
central features of mood disorders (Herzog and Copeland 1985; Rosenthal,
Sack, James, et al. 1984b; Slochower 1983), although it is important to
distinguish such effects from those of antidepressant medications. Never-
theless, because disturbances in eating behavior may be characteristic of
specific subcategories of depression, the study of eating behavior may
provide an excellent source of objective information regarding the phys-
iologic mechanisms that underlie particular psychiatric disorders.

Different patterns of appetite, eating behavior, and weight gain may reflect
fundamental differences in brain biochemistry. Although there is consider-
able information on central neurotransmitters that may be involved in the
regulation of appetite, much less is known about the neurophysiology of
human mood states. Certain hypothalamic nuclei implicated in the control
of feeding appear to be associated with reward or pleasure centers in the

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brain (Morley and Levine 1983). and abnormal neurotransmission in these
areas might produce concurrent disorders of eating habits and mood.
Disturbed hypothalamic function has for some time been postulated as a
fundamental defect in depression (Sachar 1976). Unfortunately, interpreta-
tion of data concerning such centers is complicated by the fact that the
destructive lesions used to study them also damage other areas of the brain.

Several types of neurotransmitters are thought to play a role in appetite
regulation, including the monoamines, opioid peptides, other neuropep-
tides, and gamma-aminobutyric acid. Disturbed regulation of these neu-
rotransmitters has been postulated to be associated with depression, be-
cause abnormalities of both serotonin and norepinephrine metabolism, for
example, seem to be present in depression (Murphy, Campbell, and Costa
1978; Jimerson 1984). Serotonin may also play a role in regulating carbohy-
drate intake, because ingestion of carbohydrate foods increases brain
serotonin synthesis and release (Femstrom and Wurtman 1972). Its ago-
nist, fenfluramine, has been reported to decrease the proportion of dietary
carbohydrates chosen by a group of so-called "carbohydrate cravers"
(Wurtman and Wurtman 1983).

While decreased appetite and weight loss have long been recognized as
prominent symptoms in endogenous depression (also known as endo-
genomorphic depression or melancholia), this weight loss is not usually
observed in patients with nonendogenous, or neurotic, depression
(Hopkinson 1981), whose symptoms instead are overeating, weight gain,
and oversleeping (Davidson et al. 1982). In one study, patients observed to
have an increased appetite during depression were predominantly female,
neurotically rather than endogenously depressed, less severely depressed,
and possibly more obese prior to the onset of depression (Paykel 1977).
Although it might be beneficial for clinical and research purposes to cate-
gorize depressed patients into those who do and those who do not have
increased appetite and weight gain, few investigators have evaluated these
matters in depressed populations. In one attempt, decreased appetite was
the symptom with the greatest value for discriminating between endoge-
nous and nonendogenous types of depression (Feinberg and Carroll 1982),
but in another, it was the severity of depression that determined whether
weight was gained or lost (Weissenburger et al. 1986).

In a study of seasonal depression (with episodes during the winter but not
in spring or summer), 71 percent of 125 patients experienced an appetite
increase during their depressions, 17 percent a decrease, 9 percent a mixed
reaction, and only 2 percent reported no appetite change (Rosenthal, Sack,
Gillin, et al. 1984; Rosenthal, Sack, James, et al. 1984). Changes in weight,

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as expected, paralleled appetite changes, with 72 percent reporting in-
creased weight, 13 percent decreased weight, 3 percent a mixed picture,
and 12 percent no change. These patients were predominantly women with
a less severe, nonendogenous type of depression (Paykel 1977).

An association between weight change and sleeping patterns in depression
has been noted (Crisp and Stonehill 1973). Depressives who lost weight
differed from those who gained. The sleep duration for those losing weight
was shorter, they awakened earlier, and their sleep was more disrupted. In
a recent study, sleep-disrupted depression was associated with increased
appetite and weight gain (Garvey, Mungas, and Tollefson 1984). In similar
studies, overeating and weight gain were also associated with sleep disor-
ders in patients with seasonal mood problems (Rosenthal, Sack, Gillin, et
al. 1984).

Such patients also appear to crave carbohydrates (Rosenthal, Sack, James,
et al. 1984), a symptom that has been associated with premenstrual tension,
depression, and fluid retention in a survey of 300 nurses (Smith and Sauder
1969) and that has also been reported as a side effect of treatment with the
antidepressant drug amitriptyline (Paykel, Mueller, and de la Vergne
1973). Studies of these and other relationships between mood and weight
require further explanation and confirmation before their significance for
obesity can be determined.

Anorexia Nervosa

Anorexia nervosa is a condition characterized by extreme weight loss,
amenorrhea, and a constellation of psychologic problems that have been
described as "the relentless pursuit of thinness" (Bruch 1979; Garfinkel and
Garner 1982). The term anorexia is technically incorrect because there is
no loss of appetite in this condition until advanced stages of cachexia have
been reached. The American Psychiatric Association's diagnostic criteria
for anorexia nervosa are listed in Table 14-2.

The most common course of the disease is a single episode with full
recovery, but anorexia nervosa can also be episodic or unremitting until it
causes death by starvation (APA 1987). Thus, it may become necessary to
hospitalize anorectics to prevent death. Followup studies indicate that
rates of overall mortality are between 15 and 21 percent, among the highest
levels recorded for psychiatric disorders (Herzog and Copeland 1985).

Etiology. Most teenage girls who develop anorexia nervosa are described
as having been model children (Bruch 1973). Unlike many other psychi-
atric disorders. anorexia nervosa tends to occur in intact families and is

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            Table 14-2
Diagnostic Criteria for Anorexia Newosa and Bulimia

Anorexia Newosa

A. Refusal to maintain body weight over a minimal normal weight for age and
height, e.g., weight loss leading to maintenance of body weight 15 percent
below that expected; or failure to make expected weight gain during period
of growth, leading to body weight 15 percent below that expected.
B. Intense fear of gaining weight or becoming fat, even though underweight.
C. Disturbance in the way in which one's hody weight, size, or shape is experi-
enced, e.g., the person claims to "feel fat" even when emaciated, believes
that one area of the body is "too fat" even when obviously underweight.
D. In females, absence of at least three consecutive menstrual cycles when
otherwise expected to occur (primary or secondary amenorrhea). (A woman
is considered to have amenorrhea if her periods occur only following hor-
mone, e.g., estrogen, administration.)
Bulimia

A. Recurrent episodes of binge eating (rapid consumption of a large amount of
food in a discrete period of time).
B. A feeling of lack of control over eating behavior during the eating binges.
C. The person regularly engages in either self-induced vomiting, use of laxatives
or diuretics, strict dieting or fasting, or vigorous exercise to prevent weight
gain.

D. A minimum average of two binge eating episodes a week for at least 3
  months.

E. Persistent overconcern with body shape and weight.
Source: American Psychiatric Association. 1967. Diagnostic and statistical manual of
   mental disorders, third edition, wised, pp. 67-69. Washington, DC: American
   Psychiatric Association. Copyright 1987. reprinted with permission.

often precipitated by seemingly minor events during adolescence. Various
psychologic and physiologic hypotheses have been advanced to explain
anorexia nervosa, but none is generally accepted. Most theories fall into
one of four categories: (1) organic, (2) psychodynamic, (3) familial, and (4)
sociocultural (Johnson, Thompson, and Schwartz 1984). The organic theo-
ries of anorexia nervosa are predominantly genetic and endocrinologic and
have focused on the hypothalamic-pituitary axis (Gold et al. 1986). Support
for a genetic basis of the disease is weak, but the disorder does occur with
greater frequency among sisters, with a high incidence of various psycho-
pathologies seen in relatives of such patients. Most theories of anorexia
nervosa focus on psychologic trauma or unempathetic and overly domi-
neering mothering as possible underlying causes of the disease (Johnson,
Thompson, and Schwartz 1984), but these too are unproved. Sociocultural

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theories suggest that the disease represents an exaggeration of the current
inordinate weight consciousness of adolescent girls at a time when high-
calorie foods are readily available and fewer calories are expended through
exercise (Strober 1986).

Clinical Features. Typical symptoms of the disease include depression and
obsessive-compulsive behaviors, although it is not clear whether these
psychiatric problems precede weight loss or occur as a later result of
semistarvation. Depression is often the fust visible sign of anorexia ner-
vosa, but sometimes it develops only after recovery. Abnormal hormonal
patterns characteristic of starvation also occur (Mitchell 1986).

The clinical features of anorexia nervosa are personality characteristics
such as rigidity or perfectionism, fear of obesity preceding the onset of the
disorder, and the symptoms of starvation accompanying it. Serious body
image disturbance is common, manifested by a lack of recognition of the
severe emaciation and a belief that one is too fat. Individuals are usually
preoccupied with food, thinking about it much of the time, preparing meals
for others, and often engaging in bizarre eating rituals. Many anorectics
engage in very extensive physical exercise. The disorder is also associated
with a pervasive sense of personal ineffectiveness.

Anorectics have been divided into two general types, each comprising
about half of the afflicted population. "Restricters," who confine their
eating disorder to restriction of food intake, ditfer in a number of psycho-
logic dimensions from "bulimics," who engage in eating binges and subse-
quent vomiting and purging (see below). Bulimic anorectics tend to be
older, manifest other impulsive behaviors such as kleptomania, alcohol
and drug abuse, and sexual promiscuity, and have a poorer prognosis
(Garfiiel and Kaplan 1986).

Anorectics typically deny their weight-losing behaviors and the existence
of any illness and avoid treatment even when they have become severely
emaciated. Family members often must insist upon medical treatment.
Some anorectic persons effectively hide their weight-losing behaviors even
after they are forced to seek medical assistance, which makes establish-
ment of an accurate diagnosis diicult.

Treatment. Most persons with anorexia nervosa are resistant to entering
treatment because of their fear of weight gain and so are usually brought by
their families under protest. No treatment method has proved unusually
effective. Because starvation plays such an important role in the clinical
picture of anorexia nervosa, some clinicians begin treatment with a period

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in the hospital designed to restore body weight. In patients 35 to 40 percent
below normal weight, the provision of enteral nutritional support may be
necessary (Winston 1987). Such treatment, which removes the patient
from the environment supporting the illness, may permit the use of behav-
ioral rewards for weight gain and provides the opportunity to work on
issues of control. Some medications have proved helpful in the treatment
of anorexia nervosa. These include cyproheptadine (an appetite stim-
ulant), antidepressant medication, and chlorpromazine. Family therapy is
increasingly used in treatment, a course that seems reasonable in view of
the disordered functioning of many of these families. In addition, cog-
nitive-behavioral therapy is useful for inpatient and outpatient therapy
(Garner 1986).

Bulimia

Bulimia is a disorder characterized by recurrent episodes of binge eating in
which large amounts of food are consumed over a short period of time
(Hawkins, Fremouw, and Clement 1984). These episodes are usually ter-
minated by abdominal pain, self-induced vomiting, sleep, or the appear-
ance of another person on the scene. Standard diagnostic criteria for this
condition are given in Table 14-2.

As noted above, bulimia is present in half the patients with anorexia
nervosa but in a much smaller percentage of obese patients. Recent interest
in bulimia has focused on the disorder as it occurs among persons of normal
weight. The severity of binge eating ranges from occasional episodes of
morbid overeating at a party to the severe form of the disorder, bulimia
nervosa, in which vomiting or purging follows frequent episodes of binge
eating.

There are many similarities between patients with anorexia nervosa and
those with bulimia. Both occur primarily in young women, although the
onset of bulimia occurs in slightly older individuals; both may relate to the
current preoccupation with thinness and dieting; and both usually begin
with a period of dieting (Boskind-White 1986.)

First-degree relatives of bulimic patients have an increased prevalence of
affective disorders, and probably of obesity as well. Thus, the symptoms of
depression in the majority of bulimic patients and the presence of biologic
markers of depression suggest that bulimia may represent a variant of a
mood disorder (Agras and Kirkley 1986). Treatment for bulimia, still in the
early stages of development, is cognitive-behavioral and pharmacologic.
Behavioral treatments include modification of the behavioral program
designed for obese patients and a combination of cognitive-behavioral and

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insight-oriented approaches. Controlled clinical trials of these methods
have produced encouraging results, although the size and number of stud-
ies are too small to permit firm conclusions about efficacy. The results of
studies using antidepressant medications have similar difficulties, and
conclusions are also uncertain (Wilson 1986).

Pica

Pica is the intentional and compulsive consumption of substances not
commonly regarded as food. It occurs worldwide and is common among
people of either sex and of all ages and races. Because pica is often
associated with nutritional deficiencies or toxicities, it is of special concern
among young children and pregnant women (Danford 1982).

Pica is usually classified into four categories distinguished by the substance
consumed. Geophagia is the consumption of earth and clay; amylophagia is
the consumption of starch and paste; and pagophagia is the eating of ice.
The fourth (miscellaneous) category includes consumption of ash, chalk,
antacids, paint chips, plaster, wax, and other substances (Crosby 1976).

The origin of this practice is poorly understood. One common hypothesis is
that people are driven to consume these substances by nutritional deficien-
cies, but pica is not necessarily correlated with poor nutritional status
(Grivetti 1978). Theories that it represents a method for reducing stress,
preventing nausea during pregnancy, or obtaining calcium, iron, or other
nutrients are equally unproven. Despite recent reports of similarities be-
tween clay and standard antidiarrheal medications (Vermeer and Ferrell
1985), geophagia has not been shown to prevent diarrhea1 diseases.

The nutritional hazards most frequently associated with pica are lead
poisoning and iron deficiency anemia, but whether pica is a cause of these
problems, their result, or both is as yet uncertain (Danford 1982).

Effects of Foods and Nutrients on Behavior

Normal Behavior

At least three types of food constituents have been evaluated in controlled
studies for their possible behavioral effects on healthy people: amino acid
precursors of brain neurotransmitters, other protein and carbohydrate
foods, and caffeine.

Amino Acid Neurotransmitter Precursors. Certain large neutral amino
acids found in substantial amounts in protein-containing foods are the

523


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precursors of important brain neurotransmitters. These amino acids are
transported across the blood-brain barrier into the brain where they could
affect behavior. One of these is tryptophan, the precursor of the neu-
rotransmitter serotonin. When pure tryptophan is administered to experi-
mental animals, it increases brain tryptophan and serotonin levels. Tryp-
tophan supplements have been reported to affect normal human mood,
sleep, and pain sensitivity, functions believed to be regulated in part by
serotonin neurons (Hartmann, Spinweber, and Ware 1976; Hartmann 1983;
Lieberman et al. 1983; Seltzer et al. 1982; Young, 1986). They have also
been reported to modify the appetites of certain patients (Wurtman, Hefti,
and Melamed 1981). Qrosine, the precursor of the neurotransmitters
dopamine and norepinephrine, has also been reported to affect the neu-
rotransmitter biosynthesis.

There is some evidence that certain doses of tryptophan are sedative and/or
hypnotic. Investigators have demonstrated the effects of gram quantities of
tryptophan on human alertness, as measured by self-report mood ques-
tionnaires, and on the period of time needed to fall asleep (Hartmann 1983).
These effects are consistent with reports implicating brain serotonin-neu-
rons in the regulation of sleep. Although tryptophan does not appear to be
as potent as prescription hypnotic drugs, it may have some clinical utility as
a treatment for mild insomnia.

Profein and Curbohydrure Foods. In experimental animals, high-protein
and high-carbohydrate meals have opposite effects on brain levels of tryp-
tophan and its neurotransmitter product, serotonin. Meals of relatively
high carbohydrate proportions tend to increase brain levels of tryptophan
and serotonin, even though protein contains tryptophan but carbohydrate
does not (Wurtman, Hefti, and Melamed 1981). Because serotonin-respon-
sive neurons participate in the onset and maintenance of sleep, meals with a
high ratio of carbohydrate to protein would be expected to increase sleep-
iness. The results of the few behavioral tests of this hypothesis have not
been definitive (Lieberman, Spring, and Garfield 1986).

Caffeine. About three-fourths of the caffeine consumed in the United
States is in coffee. Of the types of coffee regularly consumed in the United
States, drip-method coffee usually contains the highest amounts of caf-
feine, about 112 mg per cup, and instant coffee the least, about 60 mg per
cup. A cup of tea made with a tea bag contains about 42 mg of caffeine, and a
typical serving (12 oz) of a cola beverage contains about 38 mg of caffeine
(Roberts and Barone 1983).

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Caffeine classically has been considered to have stimulant-like effects on
behavior, and it has clear behavioral and pharmacologic effects at high
doses. However, considerable controversy exists concerning its effects at
the lower doses present in ordinary food and drink. The scientific literature
on the behavioral effects of caffeine is quite extensive and quite contradic-
tory. Many studies have failed to detect any effects on mood, such as
increased alertness and improvements in vigilance, with even high doses of
caffeine, while others have shown rather large effects as measured by tests
ofperformance (Curatelo and Robertson 1983; Raebel and Black 1984). The
most likely effects of moderate doses of caffeine are an improvement in
aspects of performance (such as vigilance) and an increase in feelings of
alertness, but these effects almost certainly depend on the individual's
usual level of caffeine intake and inherent sensitivity to this substance.

Childhood Hyperactive Behavior

Numerous unconfirmed reports have found effects of various food and
food constituents on children. Some of the more common ones are dis-
cussed below. Behavioral responses to food allergies are reviewed in the
chapter on infections and immunity.

Food Colors. The childhood behavior problem most commonly discussed
in relation to nutrition is termed Attention Deficit Hyperactivity Disorder,
or, more popularly, hyperactivity. This condition is characterized by prob-
lems of inattention, excessive motion, impulsivity, learning disabilities,
and related problems of conduct.

The contention that food additives, especially artificial dyes and colors, are
causes of childhood hyperactivity (Feingold 1975) has stimulated many
studies of the behavioral toxicity of food additives in children, notwith-
standing the implausibility that such a wide variety of chemical structures
would lead to a common result. A statistical analysis of the results of 23 of
these studies concluded that artificial colors have, at most, a negligible
effect on the behavior of children (Kavale and Fomess 1983). This conclu-
sion is consistent with that of other reviewers (Mattes 1983; Rumsey and
Rapoport 1983; NIH 1982; Lipton and Golden 1984). At most, a few
predisposed preschool and school-aged children may be adversely affected
by artificial colors (Connors 1984b; Rimland 1983; Weiss et al. 1980).
Because it remains possible that a few children may respond to diets that
eliminate food colors, and such diets are not harmful, there is no reason to
advise against therapeutic trials of food additive avoidance in individual
cases.


0 Nutrition and Health

Sugar. Sugar, by elevating brain levels of serotonin, would be expected to
have a calming effect on behavior (Glinsmann, Irausquin, and Park 1986).
Nevertheless, the suggestion that sugar consumption induces hyperactive
behavior is an old one (Seham and Seham 1929; Randolph 1947; Rinkel,
Randolph, and Zeller 1951), and many parents have been reported to
believe that sugar is a cause of uncontrolled behavior in their children
(Crook 1975). Data to support this idea are limited. One retrospective
review of glucose tolerance curves of hyperactive children found that 75
percent of 261 hyperkinetic children had abnormal glucose tolerance
curves following a j-hour glucose tolerance test (Langseth and Dowd 1978).
Other studies have not found abnormal glucose tolerance curves. An
association was suggested between destructive agressive behavior and
sugar intake in hyperkinetic children, but not in other normal 4-to 17-year-
old children, based on 7-day food diaries kept by the mothers and video-
taped observations of behavior by trained observers blinded to the protocol
(Prinz, Roberts, and Hantman 1980). Another study noted an inverse
relationship between sugar consumption by children and standardized
measures of intelligence and school achievement (Lester, Thatcher, and
Monroe-Lord 1982). None of these studies has shown a cause-and-effect
relationship between sugar and behavior.

One way to study cause and effect, in contrast to correlation and associa-
tion, is with a double-blind challenge study in which subjects are exposed
to a test substance or to a placebo and the results compared. To date,
however, only short-term challenges have been carried out; their results
show little effect. For a group of 21 boys whose families responded to an
advertisement seeking children with adverse behavioral reactions to di-
etary sugar loads, the ingestion of sugar produced a slight but significant
decrease in gross motor activity (as would be expected on neurochemical
grounds), and no differences were found in attentional measures (Behar et
al. 1984). One hyperkinetic j-year-old male and his mother both became
frustrated, hyperactive, and difticult to control after a double-blind chal-
lenge with sugar in lemonade. However, not 1 of 50 other hyperkinetic
children tested in the same way responded to a sugar challenge (Gross
1984).

The effects of acute challenges of sucrose in comparison to the artificial
sweetener aspartame in grade school children were compared using 37
behavioral (playroom observation and examiner ratings) and cognitive
(learning and memory tasks) measures (Wolraich et al. 1985). No differ-
ences in any measure of performance were found. No systematic change in
activity was observed in eight school-aged children exposed to three differ-

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ent doses of sucrose or to an aspartame placebo, and no clear effect was
found on the Continuous Performance Task (Ferguson 1984).

To date, the only double-blind challenge that has reported an increase in
activity after consumption of sugar was a pilot study of 13 psychiatrically ill
children given regular orange juice orjuice with sugar added in the form of
sucrose or fructose (Connors and Blouin 1983). A subsequent study of 37
children who were psychiatric inpatients appears to suggest that during
classroom observation less motor activity is seen with the sucrose and
fructose challenges compared with aspartame (Connors 1984a). Overall,
acute challenges with dietary sugar have failed to show that sugar causes
hyperactivity, inattention, or impulsiveness (Rapoport 1986; Ferguson,
Stoddard, and Simeon 1986).

Co&&e. Caffeine has been a concern of consumer groups because of
possible deleterious effects upon children's behavior (Rumsey and
Rapoport 1983). In a series of studies of the effects of caffeine in normal
grade school children, habitual dietary caffeine intake was found to be a
significant predictor of behavior (Elkins et al. 1981; Rapoport, Elkins, et al.
1981; Rapoport, Jensvold, et al. 1981; Rapoport 1983; Rapoport et al.
1984). Children who habitually consumed greater amounts of caffeine
became more anxious and difficult to arouse when they were deprived of
caffeine. When children were challenged with caffeine, the habitually high
consumers felt little effect, but children who normally consumed little
caffeine experienced adverse effects. Because no caffeine was consumed
for 2 weeks preceding the challenge in this study, these effects are not likely
to be due to caffeine tolerance, but instead suggest a possible physiologic
basis for caffeine effects in children.

Considerable research has been conducted on the possible therapeutic
effects of caffeine on behavior in children. In an uncontrolled cross-over
trial with hyperactive children that compared the effects of caffeine, meth-
ylphenidate, and no treatment, caffeine significantly improved behavior
(Schnackenberg 1973). In one study, caffeine has also been reported to
improve the reaction times of hyperactive children (Reichard and Elder
1977), but not in more carefully controlled studies (Huestis, Arnold, and
Smeltzer 1975; Garfinkel, Webster, and Sloman 1975; Firestone et al. 1978;
Connors 1979). Comparisons of caffeine with stimulants such as
amphetamine or methylphenidate have consistently found the prescription
agents to be superior (Garfinkel, Webster, and Sloman 1975; Gross 1975;
Huestis, Arnold, and Smeltzer 1975; Arnold et al. 1978; Firestone et al.
1978). Thus, a therapeutic role for caffeine in hyperactivity is uncertain.

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Hypoglycemia

Hypoglycemia (low blood sugar) can occur either after a fast (fasting
hypoglycemia) or several hours after the consumption of a meal (reactive
hypoglycemia). Many individuals believe they suffer from reactive hypo-
glycemia because they experience symptoms of weakness, confusion, and
irritability after eating sugars or other carbohydrate foods. However, it has
not been possible to document an association between these symptoms and
low blood sugar or insulin levels, and most authorities believe that symp-
toms are due to causes unrelated to blood sugar levels (Green 1981). Some
authors believe a high percentage of patients referred with symptoms of
hypoglycemia have emotional disorders rather than actual hypoglycemia
(Johnson et al. 1980; Ford, Bray, and Swerdloff 1976).

True reactive hypoglycemia is diagnosed by an oral glucose tolerance test
in which the administration of a large dose of glucose is followed by a
collection of blood samples at hourly intervals for the next 5 hours. These
tests are often unreliable (Lev-Ran and Anderson 1981; Charles et al. 1981).
The generally accepted dividing line between normal and abnormal blood
sugar of 50 mg/dl in whole blood may be too high, because lower levels have
been observed in many individuals who experience no hypoglycemic
symptoms (Hofeldt, Adler, and Herman 1975; Cahill and Soeldner 1974).
Only when symptoms of hypoglycemia such as sweating, tremor, anxiety,
and irritability occur at the same time as the documented low blood sugar
level can a valid diagnosis of reactive hypoglycemia be made. Such a
diagnosis may indicate the early presence of a disease such as diabetes.

Antisocial Behavior

Before the 1970's. interest in a possible relationship between diet and
criminal behavior was generally limited to food faddists, but more recently,
scientists have given serious attention to this matter (Hippchen 1978, 1981;
Reed 1977; Rimland 1981; Rimland and Larson 1981; Schauss 1980;
Schoenthaler 1983b). Advocates of a link between diet and criminality do
not agree on a single mechanism by which diet might influence criminal
behavior. Among the suggested explanations are reactive hypoglycemia,
food allergies, and other undocumented adverse reactions to food, to
vitamin and mineral deficiencies, and to toxicities (Feingold 1979; Green
1976; Hippchen 1978, 1981; Rimland 1981; Rimland and Larson 1981;
Schauss 1980; Schmidt, Brajkovich, and Asch 1981; Schoenthaler 1983a,
1983b). Experts in criminology and psychiatry have reviewed these claims
and have strongly concluded that no evidence for such a connection exists.
The studies that purport to show such a link are seriously flawed, lack

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appropriate controls, and are subject to bias (Gray and Gray 1983; Gray
1986; Pease and Love 1986).

Implications for Public Health Policy

Dietary Guidance

General Public

Behavioral factors clearly influence food selection, dietary change, and
chronic disease risk, but research in this area is still too preliminary to draw
more than a few implications for the general public; exceptions generally
apply to specific chronic disease conditions. Similarly, beyond the dietary
guidance implications presented in the chapter on obesity, current evi-
dence is insufficient to recommend specific dietary changes to prevent or
treat the eating disorders-anorexia nervosa, bulimia, and pica. Sugar,
certain food additives, and caffeine have been suggested as predisposing
dietary factors to the development of behavioral disorders in children and
adults, but evidence is weak and contradictory, and there is no reason to
expect that a reduced intake of these substances would affect the incidence
or severity of behavioral disorders. In addition, current evidence does not
support any implications at present about the effects of amino acid precur-
sors of neurotransmitters on behavior.

Special Populations

Studies in patients with eating disorders and other chronic disease condi-
tions (reviewed in other chapters of this report) emphasize the importance
of modification of diet-related behavior in these conditions. Such patients
should receive advice from qualified health professionals on the application
of dietary principles appropriate for their conditions. Although evidence
linking dietary caffeine, refined sugars, and food additives to behavioral
disorders is uncertain, their elimination from the diet will not impair
nutritional status and can be recommended to patients on an individual trial
basis.

Nutrition Programs and Sewices

Food Labels

Evidence related to the role of dietary factors in behavioral disorders holds
no special implications for food labeling policies.

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Food Services

Evidence related to the role of dietary factors in behavioral disorders
currently holds no special implications for change in policies related to
food programs beyond those suggested by the Dietary Guidelines for
Americans.

Food Products

Evidence related to the role of dietary factors in behavioral disorders holds
no special implications for change in policies related to food products at
this time.

Special Populations

Patients with eating disorders should be provided with ready access to
counseling and assistance in the development of diets that provide safe and
adequate levels of energy and nutrients.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
behavior in the prevention of diet-related chronic disease and to the role of
diet in behavioral disorders should include investigations into:
o Behavioral factors that influence food selection patterns and dietary
change.

o The most effective behavioral methods to encourage appropriate di-
etary changes.

o Behavioral factors that increase the risk for diet-related chronic dis-

ease.

o Behavioral factors that increase the risk for obesity, anorexia nervosa,
bulimia, and pica.

o The prevalence of these eating disorders among different groups.
o Behavioral techniques effective in treatment of these disorders.
o Effects of foods and nutrients on etiology and treatment of behavioral
disorders.

0 Behavioral interventions that increase the long-term effectiveness of
health promotion and chronic disease treatment programs.

530


Behavior 0

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538


Chapter 15

Maternal and Child Nutrition

Further it must be known that the children
must be fed only milk and pap until they
have grown the front teeth. Then one can
give them somewhat stronger food-bread
softened with milk or in a meat or pea broth.
    Bartholomaus Metlinger
      Kinderbuch (1473)

Introduction

The health and productivity of our society have roots in the quality of the
reproductive experience and the subsequent nurturing strategies of parents
and childhood caretakers. Much can be done to enhance the well-being of
mothers and infants, and adequate nutrition during pregnancy and lactation
is an important component of this process. Societies throughout history
have recognized the unique needs of pregnant and lactating women and
have made special provisions for their health care and nutritional needs.

This chapter reviews key issues related to the nutrition of pregnant women
and lactating mothers and their infants, children, and adolescents and to
the improvement of their health and survival. It also discusses aspects of
chronic disease prevention that especially concern these younger age
groups.

Historical Perspective

Although the unique health status of pregnant women has long been recog-
nized, dietary recommendations for this group have reflected incomplete
knowledge about human reproduction and growth and nutrition. Likewise,
while a healthy, vigorous infant has always been the desired outcome of
pregnancy, only recently has nutrition been recognized as influencing that
outcome.

Infants were weighed at birth during Talmudic times, but it was not until the
17th century that the French obstetrician Mauriceau recognized the health

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0 Nutrition and Health

significance of adequate birth weight (IOM 1985). Mauriceau's ideas did not
gain currency, perhaps because his estimate of 15 lb as a normal birth
weight was obviously incorrect. It was not until the 19th century that birth
weights, on the basis of their variability, were used as indicators of nutri-
tional status and physical growth (IOM 1985).

Beliefs about the effects that various foods might have on the mother or
child influenced dietary recommendations for pregnant women in the 19th
century. For example, to prevent a child from having an unpleasant disposi-
tion, pregnant women were cautioned against eating salty, acidic, or sour
foods. Obstetrical problems also influenced dietary recommendations.
During the time of the Industrial Revolution, rickets commonly impaired
normal pelvic bone formation. As a result, women who had had rickets in
childhood faced major risks in childbirth, and both maternal and infant
mortality were high. To combat this problem, Prochownick, a German
physician, prescribed a fluid-restricted, low-carbohydrate, high-protein
diet for the last few weeks of pregnancy. Because the infants of women who
followed this diet were smaller and more easily delivered, it became a
standard recommendation for women throughout pregnancy, one that per-
sisted even when rickets, the original reason for it, was no longer a problem
(Worthington-Roberts, Venneersch, and Williams 1985).

In the early 20th century, scientists began to study the relationship of low
birth weight (LBW) to shortened gestation and to infant mortality. After
World War I, attempts to relate food shortages to reduced birth weights
were inconclusive. In 1930, the Finnish pediatrician Yllpo suggested that
infants were at high risk below a birth weight of 2,500 g (about 5.5 lb). The
World Health Organization subsequently adopted this standard, despite
recognition that birth weight below this level is not synonymous with
prematurity (IOM 1985).

Although research on diet and pregnancy did not begin until the 1930's,
obstetric practitioners voiced strong opinions about what pregnant women
should-and should not-eat. Obstetrical authorities commonly warned
the pregnant woman against accepting either advice to ". . . eat largely
because she is eating for two" or to ". . . eat sparingly because if she does
not her baby will be too large" (Danforth 1933), holding the view that the
weight of the unborn child could not be influenced by diet except within
very narrow limits. At the same time, pediatricians argued that the mother's
health and nutritional status did indeed influence the size of the newborn
child. Studies conducted by the Research Laboratory of the Children's
Fund of Michigan demonstrated that the mother's nutritional state before
and at the time of conception and the adequacy of her diet during pregnancy

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Maternal and Child Nutrition 0

influence the well-being of the infant. There was an upswing of research in
maternal nutrition in the 1940's, influenced by the impact of wartime food
shortages on maternal health (Egan 1987). Some of the famine studies
during World War II showed a marked fetal impact from extreme food
deprivations of the mother, but correlational studies were inconsistent in
relating nutritional intake to birth outcomes (IOM 1985). There was suffr-
cient interest and concern in the United States about the relationship of
maternal nutrition to problems of prematurity, congenital malformations,
and infant mortality to stimulate the National Academy of Sciences to
appoint a Committee on Maternal Nutrition and Child Feeding in 1946. Its
charge was to "implement improved health of the nation through better
coordination of scientific advances in the field of obstetrics and pediatrics."
The Committee's 1950 report, Maternal Nutrition as It Relates to Child
Health-An Interpretive Review, served as the chief reference for maternal
and child health nutrition programs for many years (Egan 1987).

Uncertainties about the role of nutrition in the management of pregnancy
led to discussion between the service community and the research commu-
nity in 1966 that resulted in formation of a Committee on Maternal Nutri-
tion of the National Academy of Sciences. In 1970, the Committee issued a
hallmark research report, Maternal Nutrition and the Course of Pregnan-
cy, stimulating the following:

0 Significant changes in clinical practices related to the routine restric-
tion of weight gain and sodium intake during pregnancy.
0 Reaffirmation of the priority needs of pregnant women and infants in
supplemental food programs.

o Development, adoption, and dissemination of policy statements and
guidelines related to nutrition and maternal health by professional
organizations.

o Increased emphasis on training of nutrition personnel as well as on
education in nutrition for physicians.
o Increased funds for research on maternal and perinatal nutrition, and
renewed interest of the National Institutes of Health in this area (Egan
1987).

Maternal and infant nutrition was a focus of the White House Conference
on Food, Nutrition, and Health in 1969, and its Conference Panel on
Pregnant and Nursing Women and Young Infants identified adequate diet
as one factor "known to be necessary for favorable outcomes of pregnan-
cy" (White House Conference 1969). The panel recognized the increased
and special needs of pregnant and nursing women and infants and con-

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0 Nutrition and Health

eluded that optimal nutrition for women throughout life is the best way to
promote infant health. In 1970, the White House Conference on Children
called for expansion and improvement of existing food programs as well as
promotion of nutrition education in the schools. In 1971, the White House
Conference on Youth demanded Federal food assistance for all young
Americans in need, and a National Nutrition Education Conference later
that year also focused attention on the nutritional needs of adolescents
(Egan 1972).

Federal Maternal and Child Nutrition Programs

Despite scientific uncertainties about the relation among nutrition and
human reproduction, growth, and development, Federal programs have
addressed the nutritional needs of mothers and children since early in this
century (Egan 1977). The Children's Bureau issued dietary advice to par-
ents and teachers and conducted nutritional surveys of low-income chil-
dren (Egan 1977). School feeding programs began in the early 1900's when
free, compulsory, and universal education was instituted. These programs
were also supported by philanthropic organizations, local school districts,
and private donors. Several States authorized schools to serve meals at
cost, and a few States even served meals at reduced or no cost to needy
children (CBO 1980). Increasing Federal involvement in these programs
resulted from the burden on local and State entities during the 1930's. An
amendment to the Agricultural Act of 1933 established a fund to purchase
surplus agricultural commodities for donation to needy families and to
child nutrition programs, including school lunch programs. The Social
Security Act of 1935 authorized grants to the States for health services for
mothers and children and established the basis for a national program of
nutrition services (including assessment, counseling, referral, and fol-
lowup) for this population (Select Panel 1981).

When the supplies of surplus commodities declined during World War II,
Federal involvement in child feeding programs shifted to general income
assistance. To avoid the uncertainties of congressional appropriation of
cash subsidies, the National School Lunch Act, authorizing permanent
grants-in-aid to States, was enacted in 1946. To receive cash and commodi-
ty assistance, the States had to operate school lunch programs on a non-
profit basis, provide free or reduced-price lunches for needy children, and
serve lunches that would meet specified Federal standards (CBO 1980).

The Child Nutrition Act of 1966 enlarged the scope of Federal efforts by
establishing numerous programs to expand food assistance year round to
children of all ages and to provide assistance to pregnant women and

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Maternal and Child Nutrition 0

infants. For the first time, high-risk families enrolled in comprehensive
maternity and infant health projects and children and youth projects re-
ceived direct nutrition services as an integral part of their health care (Egan
1977). These programs and policies led to authorization of the Special
Supplemental Food Program for Women, Infants, and Children (WIC) by
Congress in 1972. Modified versions of many of the Federal food assistance
programs that developed during the 1960's and 1970's remain in place today.

U.S. Department of Agriculture Programs. Current food assistance pro-
grams of the U.S. Department of Agriculture (USDA) include:
0 School Breakfast and Lunch Programs: help schools to serve nourish-
ing, low-cost meals to children and to provide free or reduced-price
  meals to children from low-income families.

0 Summer Food Service Program: helps communities serve meals to
needy children when school is not in session. Operates in areas where
the concentration of low-income families is high.
0 Child Care Food Program: subsidizes meals and snacks for children up
to age 18 in nonresidential child care programs.
0 Special Supplemental Food Program for Women, Infants, and Chil-
dren: provides selected foods rich in specific nutrients, nutrition edu-
cation, and health care referrals to pregnant, lactating, and postpartum
women and children up to age 5. Participants must be certified as
nutritionally at risk and of low income.
o Commodity Supplemental Food Program: distributes certain agricul-
tural commodities at no cost to supplement the diets of low-income
infants, children under 6 years, and pregnant and postpartum women
who are vulnerable to malnutrition.

o Special Milk Program: makes it possible for school children to pur-
chase milk at reduced price or receive it free; subsidizes milk served to
children in schools, day care institutions, and summer camps.
0 Food Stamps: provide eligible individuals and households with cou-
pons free of charge that can be exchanged for food at authorized food
stores. The redemption value of the food stamps depends on the
household's size and financial circumstances. Food stamps are meant
to supplement what a family spends on food.

Although there are intrinsic limitations in methods, evaluations of the
school feeding and WIC programs have generally shown that they improve
the health and nutritional status of the target populations (see Systems
Development Corporation 1983; Rush 1985).

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O Nutrition and Health

Nutrition Programs of the U.S. Department of Health and Human Ser-
vices (DHHS). Nutrition services are an important component of many of
the health and social service programs administered by DHHS. These
programs include:

o Title V Maternal and Child Health Program: provides for nutrition
assessment, dietary counseling, nutrition education, and referral to
food assistance programs to women of childbearing age, infants, pre-
school and school-aged children, adolescents, and children with spe-
cial health care needs served through a wide range of health care
programs. In addition, it supports training in nutrition for nutrition
personnel and other health professionals who lead the development of
nutrition services. It supports nutrition projects of regional and nation-
al significance to advance and improve nutrition services for mothers
and children.

o Medicaid-Early Periodic Screening, Diagnosis, and Treatment: re-
quires assessment of the nutritional status of eligible children and
provision of appropriate referral and treatment services.
o Head Start: provides preschool children from low-income families
with nutritious meals and snacks; provides nutrition education for the
children and their families; and provides training and technical assis-
tance in nutrition for Head Start staff.

o Primary Care-Community Health Centers, Migrant Health Programs:
provide nutrition services as an integral component of these compre-
hensive health care programs.

Nutrition Education Programs. Both USDA and DHHS sponsor nutrition
education programs targeted to parents and children. Major programs are
the USDA Extension Service's Expanded Food and Nutrition Education
Program and Food and Nutrition Program, the Nutrition Education and
Training Program of the Food and Nutrition Service, and the educational
component of the WIC program. DHHS funds maternal and child nutrition
education programs through the programs administered by its various
agencies: the health care programs of the Health Resources and Services
Administration and the Indian Health Service of the Public Health Service,
and the Head Start Program of the Administration on Children, Youth, and
Families of the Office of Human Development Services (Select Panel
1981).

National Goals and Recommendations

Within the past decade, Federal reports and conferences have established
goals and produced recommendations designed to improve the nutrition
and health of mothers and children. Some of these goals and reports are
listed below.

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Maternal and Child Nutrition 0    -

Healthy People: The Surgeon General's Report on Health Promotion and
Disease Prevention. This report defines broad goals for the improvement
of health and reduction of mdrtality rates among infants, children, and
adolescents. Nutrition is included as a key health promotion strategy to
achieve these goals (DHEW 1979).

1990 National Health Objectives. At least 35 of the 226 specific objectives
to achieve the goals defined by Healthy People are related to nutrition and
the health of pregnant women, infants, children, or adolescents (DHHS
1980). Table 15-l presents a selection of these objectives.

Table 15-l

Seiected National Objectivea to be Achiked by the Year 1990
     Mated to Maternal and Child NutritioW

Pregnancy and Infant Health

o Reduce the national infant mortality rate (deaths for all babies up to 1 year of
age) to no more than 9 deaths per 1,000 live births
0 Ensure that no county nor racial or ethnic group of the population has an in-
fant mortality rate in excess of 12 deaths per 1 ,ooO live births
o Reduce the maternal mortality rate to no more than 5 per 100,000 live births
for any county or for any ethnic group
0 Reduce to no more than 5 percent of all live births the percentage of low birth
weight babies (2,500 g and under)

o Ensure that 85 percent of women of childbearing age can state the special nu-
tritional needs of pregnancy and can understand the hazards of alcohol use
during pregnancy and lactation

o Ensure that virtually all infants receive adequate primary health care, includ-
ing nutrition services, when needed
Fluoridation and Dental Heakhb

0 Eliminate cariogenic foods from school vending machines and school breakfast
or lunch programs

0 Ensure that at least 95 percent of school children and their parents are able to
identify the principal risk factors related to dental diseases and be aware of the
importance of fluoridation in controlling these diseases
Misuse of Alcoholb
0 Reduce the proportion of adolescents 12 to 17 years old who report acute
drinking-related problems during the past year to below 17 percent
o Increase the proportion of women of childbearing age who are aware of the
risks associated with drinking during pregnancy to greater than 90 percent
o Increase the proportion of high school seniors who recognize the risk of alto-
ho1 intoxication to 80 percent or more

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O Nutrition and Health

Table 15-l (continued)

Nutrition

0 Increase the proportion of women who breastfeed their babies to 75 percent at
hospital discharge and to 35 percent at 6 months of age
o Increase the proportion of school cafeteria managers who are actively promot-
ing the USDA/DHHS Dietary Guidelines to more than 50 percent
0 Ensure that all States include nutrition education as part of required school
health education at elementary and secondary levels
Physical Fitness and Exerciseb

o Increase the proportion of children and adolescents ages 10 to 17 participating
regularly in appropriate physical activities to more than 90 percent
~someobjectivesappiytomcwethanonecategory.
bThegeissuesaredisarssedfwtherinthecheptersondentaldiseases,alcohol,and
obesity*respectively.

Source: U.S. Department of Health and Human Services 1980.

Better Health for Our Children: A National Strategy. A chapter of the
report of the Select Panel for the Promotion of Child Health emphasizes the
importance of nutrition in maternal and child health and gives specific
recommendations for improved information and education, health care
services, and research in nutrition for this population (Select Panel 1981).

Surgeon General's Workshop on Maternal and Infant Heafth. This report
recommends that nutrition services become integrated into all maternal
and child health programs, that maternal and child health professionals
receive improved training in nutrition, and that further research be con-
ducted on infant feeding patterns, the development of dietary patterns and
tastes, and the role of social and cultural factors in human nutrition (DHHS
1981).

Surgeon General's Workshop on Breastfeeding and Human Lactation.
This report recommends specific strategies to promote breastfeeding
through improved public and professional education, health care systems
and support services, and research (DHHS 1984).

Significance for Public Health

Although the precise contribution of nutrition to maternal and infant health
cannot yet be distinguished from genetic, environmental, or behavioral
factors that affect risk, an inadequate diet during pregnancy increases the
probability of a LBW infant, who, in turn, has an increased risk of mor-

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Maternal and Child Nutrition O

bidity and mortality. Well-nourished mothers who gain appropriate
amounts of weight during pregnancy generally give birth to heavier, healthi-
er babies. Poorly nourished mothers who eat well and gain adequate weight
during pregnancy can greatly improve their chances of giving birth to
healthy infants. Diet is also critical in the control of diabetes, hypertension,
and gastrointestinal disorders when such conditions are present during
pregnancy.

Infant Mortality

In the United States, the infant mortality rate (the number of deaths of
infants under 1 year of age per 1,000 live births) has declined rather steadily
throughout this century, largely due to improvements in control of iafec-
tious diseases, health care, and nutrition. In 1900, the rate was about 100
deaths per 1,000 births; by 1978 it had declined to 13.8 and by 1985 to 10.6
(NCHS 1987~). Recent information suggests that the rate of decrease is
slower than it has been in the past, as indicated by a provisional rate of 10.4
for 1986 (Kleinman 1987). Infant mortality rates in several industrialized
countries are considerably lower-for example, 6.5 and 6.6, respectively,
for Finland and Japan in 1983 (NCHS 1986). However, rates among coun-
tries are not strictly comparable due to differences in definitions.

Although marked improvements in infant survival have occurred among all
racial and ethnic groups, the infant mortality rate among black Americans
remains nearly twice as high as that among white Americans. From 1978 to
1985, the infant mortality rate among whites fell from 12.0 to 9.3 per 1,000,
and that among Native Americans fell from 13.7 to 9.1 per 1,000. The rate
among black Americans, however, was 23.1 in 1978; it declined, but in 1985
it was still l&2-nearly twice the rate of whites (NCHS 1987b).

Low Birth Weight

In the United States, the most important factor contributing to the infant
mortality rate is a low birth weight-less than 2,500 g, or 5.5 lb. Low birth
weight occurs as a result of birth prior to 37 weeks' gestation, intrauterine
growth retardation, or both. Infant deaths and illnesses increase sharply as
birth weight declines within the normal weight range and even more sharply
below 2,500 g. They are highest among infants of very low birth weight
(VLBW), below 1,500 g. LBW infants are at increased risk for developmen-
tal handicaps, birth defects, respiratory and other infectious diseases,
behavior problems, and complications of medical interventions. These
conditions greatly increase the emotional and financial burden to the
infant's family and to the Nation (IOM 1985).

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Ll Nutrition and Health

Although overall rates of infant mortality have decreased greatly, the
prevalence of LBW has declined more slowly. In 1971, babies with weights
below 2,500 g accounted for 7.6 percent of all live births; in 1985, they
accounted for 6.8 percent. Infants of moderately low birth weight (1,500 to
2,500 g) accounted for over 5.5 percent of all live births in 1985 and those of
VLBW for over 1.2 percent. Together, the 6.8 percent of infants. born at
weights less than 2,500 g are responsible for 67 percent of all infant deaths
during the first month of life and approximately 60 percent of all infant
deaths (NCHS 1987a).

Much of the higher infant mortality among black Americans is explained by
the high proportion of LBW infants born to this group. LBW infants
comprised 12.4 percent of all black births in 1985. For Americans of Puerto
Rican descent, the percentage of LBW infants was 9.1. It ranged from 6.2
to 6.9 percent for Americans of Japanese, Filipino, other Asian and Pacific
Island, and American Indian ancestry, and from 5.6 to 5.8 percent for
Mexican, Cuban, and other white Americans. The lowest percentage of
LBW (5.3 percent) occurred among Chinese Americans (Secretary's Task
Force 1985). Of special concern in these figures is the continuing racial
disparity in birth weight. Between 1973 and 1983, rates of moderately low
birth weight decreased more among whites than among blacks. Overall
rates of VLBW decreased, but they actually increased among blacks
(Kleinman and Kessel 1987).

Risk Factors for Low Birth Weight

Medical, social, behavioral, and dietary factors before and during pregnan-
cy contribute to the risk for LBW. Medical risk factors include a previous
reproductive history that includes many pregnancies, anemia, hyperten-
sive disorders of pregnancy, inadequate weight gain, or delivery of a LBW
infant; low prepregnancy weight; chronic illnesses such as diabetes or
hypertension; and poor weight gain during pregnancy. Social, demograph-
ic, and behavioral risk factors have been identified as low socioeconomic
status, low educational level, minority race, single marital status, adoles-
cence, inadequate prenatal care, and use of drugs, alcohol, or cigarettes.

Dietary risk factors include an inadequate intake of calories or essential
nutrients such as protein, vitamins, and minerals. Evidence indicates that
the more of these risk factors present, the greater the risk to mother and
child (IOM 1985). Because these risk factors interact and affect one an-
other, it is difficult to determine the role of nutrition separate from these
other risk factors.

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Maternal and Child Nutrition 0

Estimates of Cost

The personal cost of the death or severe illness of a LBW infant is incalcula-
ble. Quantitative estimates of the economic costs of care of LBW infants
have been published. In 1987, the average hospital cost was estimated at
$12,000 to $39,000. Costs increase, however, as birth weight falls; the
average cost for a VLBW surviving infant is $3 1,000 to $7 1,000. For infants
born at under 750 g, the average hospital stay was 98 days, and the costs
ranged as high as $150#30 (OTA 1987). In 1984, the rehospitalization rate
during the first year of life was 38.3 percent for VLBW infants and 19
percent for moderately LBW infants. Such infants remained rehospitalized
an average of 16.2 and 12.5 days, respectively. In addition. nearly 20
percent of LBW infants who survive will have long-term morbidity during
the first year that requires medical care (IOM 1985). Even taking into
consideration the increased costs of providing adequate prenatal care. the
savings to the Nation from prevention of even a small proportion of LBW
infants would be considerable.

Scientific Background

Pregnancy and Lactation

Normal pregnancy is accompanied by anatomical and physiologic changes
that are necessary to promote fetal growth and development and prepare
the mother for labor, birth, and lactation. Many of these changes are
apparent in the early weeks of pregnancy.

Physiologic. During both pregnancy and lactation, hormonal changes af-
fect retention, utilization, and excretion of nutrients (Hytten and Leitch
1971). These changes lead to physiologic adjustments that result in expan-
sion of blood volume and accumulation of fluid. They include an increase in
cardiac output, heart rate, and basal metabolic rate. Preparation of the
mammary glands for lactation begins during pregnancy, when the duct
system enlarges and the alveolar cells proliferate. Lactation is initiated and
maintained by hormonal changes that occur in response to the infant's
sucking stimulus. Milk proteins, lipids, and lactose are synthesized by the
alveolar cells. Stored fats are secreted into the milk, as are a variety of
nutrients and other compounds. Although recent evidence suggests that
lactation is associated with physiologic changes that conserve energy and
reduce the need for increased energy intake (Butte, Garza, Stuff, et al.
1984). additional studies are needed to evaluate this matter (Lawrence
1985).

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0 Nutrition and Health

Biochemical. During pregnancy, decreases in plasma concentrations of
albumin, most minerals, and most water-soluble vitamins occur as a result
of the dilution effect of the expanded plasma volume. Because expansion in
red cell mass is not as great as the expansion in plasma volume, the
hematocrit, which is the percentage of red blood cells in a sample of
centrifuged blood, typically drops during pregnancy. Other nutrients, how-
ever, increase in plasma concentration, perhaps as a result of improved
intestinal absorption.

Physical. During pregnancy, body weight, lean body tissue, and fat in-
crease. Increases in tissue fluid levels are most significant in the third
trimester, but women vary substantially in the timing and degree of fluid
accumulation. After childbirth, blood volume and extracellular fluids re-
turn to prepregnant levels. The uterus also returns to normal size, but
breast size remains enlarged throughout lactation. Loss of the body fat
stores accumulated during pregnancy occurs gradually and is usually com-
plete by the time the nursing infant is about 6 months old (Lawrence 1985).

Normal Growth and Development

In humans, intrauterine growth and development require about 40 weeks of
gestation. From the third month until term, fetal weight increases nearly
500-fold, from about 6 g (0.2 oz) to 3,000 to 3,500 g (6.5 to 7.6 lb) at birth.

Znfants. Immediately after birth, weight is lost, but birth weight is usually
regained by the 10th day. After this time, weight increases at a rapid but
decelerating rate. Most infants double their birth weight by the age of 4
months and triple it within 1 year. Length increases by 50 percent during
the first year. These changes are accompanied by changes in body com-
position. Fat accumulates rapidly; by 6 months, it makes up about 25
percent of the total body weight. During the second 6 months, the relative
increase in lean body mass is much greater than the increase in fat (Fomon
et al. 1982).

Children and Adolescents. The very rapid rate of growth in infancy is
followed by slower growth during the preschool and early school-age
years. Weight gain approximates 2.5 kg/year until 9 to 10 years of age.
Length increases by an average of 11 to 12 cm in the second year, about 7
cm during each of the next three. Children become leaner between 6
months and 6 years, after which a gradual increase in fat thickness occurs
in both males and females until puberty; females have a relatively greater
body fat content than males at all stages of development (Fomon et al.

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Maternal and Child Nutrition 0

1982). The brain reaches 50 percent of its adult size by age 2,75 percent by
age 4, and 100 percent by age 6 to 10. Body growth is measured by increases
in length and weight; skin-fold measurements may be used to evaluate
body fat. The heights and weights for representative samples of boys and
girls have been used to establish growth reference curves, developed by
the National Center for Health Statistics (NCHS) (Hamill and Moore 1976;
Hamill et al. 1977; Hamill et al. 1979). As a genera1 rule, growth patterns
follow percentile lines on these growth charts.

When growth performance for a given child is measured at regular intervals
and plotted on such charts, unusual changes in weight and height percentile
can identify children who are at nutritional risk from either under- or
overnutrition. Growth patterns are highly individual, however, and aver-
age growth rates do not always apply to individual children. This observa-
tion is especially applicable in adolescence.

The velocity of physical growth in adolescence is second only to infancy.
The most rapid period of growth in adolescence is known as the growth
spurt. It precedes menarche in females and spermatogenesis in males. The
age at which peak growth occurs is later and the growth spurt more intense
in males than in females. There are also differences in its timing and length.
The growth spurt usually begins between ages 8 to 12 in females and ages 10
to 14 in males; peak growth velocity occurs at ages 10 to 14 in females and
12 to 16 in males (Lucas, Rees, and Mahan 1985). Linear growth stops
toward the end of adolescence, usually between the ages of 14 to 16 in
females and 16 to 18 in males (Tanner 1962). The magnitude and duration of
growth vary widely among adolescents, making chronologic age an un-
satisfactory index of nutritional needs. Instead, individual body size, stage
of sexual maturation, and current rate of growth must be considered.

Key Scientific Issues

o Role of Dietary Factors in Maternal Health
0 Role of Dietary Factors in Fetal Health
0 Role of Dietary Factors in Infant Health
o Role of Dietary Factors in the Health of Children
o Role of Dietary Factors in the Health of Adolescents
o Role of Dietary Factors in Chronic Disease in Childhood

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O Nutrition and Health

Role of Dietary Factors in Maternal Health

Nutritional Needs of Pregnant and Lactating Women
Extra energy and nutrients are needed to support the growth of maternal
tissues, such as the uterus and breast, and the increased metabolic de-
mands of pregnancy as well as the growth of the fetus and placenta. During
lactation, the energy and nutrients provided in the milk, and those required
for its production, must be replaced.

Weight Gain. Research has demonstrated that both maternal prepregnancy
weight and weight gained during pregnancy are important determinants of
infant birth weight. Inadequate weight gain during pregnancy and low
prepregnancy weight combined with low weight gain are associated with
lower-than-average infant birth weights and greater risks for fetal or neo-
natal death and neonatal disease; these problems decline as weight gain
increases.

Such associations do not necessarily prove causality, however; healthy
infants of average birth weight have been born to women whose weight
change during pregnancy ranged from loss to high gain. For this reason,
and because genetic and behavioral factors other than weight gain also
influence infant birth weight, it has been difficult to define the optimal
weight gain during pregnancy for women of varying prepregnancy weights.
Most studies that have correlated average weight gain with birth outcome
in normal weight adult women with normal pregnancies have found the
optimal weight gain to fall within the range of 22 to 27 lb (Naeye 1979;
Rosso 1985), yet one-fifth of white ,adult women and one-fourth of black
adult women did not gain this much weight during normal pregnancies of 40
or more weeks' duration in 1980 (Taffel 1986). When all pregnancies in this
study, regardless of length of gestation, were considered, one-third of
black mothers gained no more than 20 lb, and black mothers were nearly
twice as likely as white mothers to gain less than I6 lb (20 percent as
compared with 1 I percent). Nevertheless, inost of these women gave birth
to healthy babies.

The influence of prepregnancy weight on birth outcome also makes it
difficult to define an optimal weight gain; a low weight gain by women with
a low prepregnancy weight is associated with the highest incidence of
LBW, but higher weight gains during pregnancy reduce the risk (Taffel
1986). This relationship may not hold for adolescents, however. Although
the mean weight gain of adolescent women during normal pregnancy has
been shown in several studies to average about 35 lb, their risk of having a

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Maternal and Child Nutrition 0

LBW infant was still higher than that for adult women (Meserole et al.
1984; Frisancho, Matos, and Flegel 1983; Garn et al. 1984; Loris, Dewey,
and Poirier-Brode 1985).

The effect on infant birth weight of differing levels of weight gain by obese
women during pregnancy is also uncertain. Obesity during pregnancy is
linked to an increased risk of maternal complications such as hypertensive
disorders, gestational diabetes, infections, and surgical deliveries (Abrams
and Laros 1986; Kliegman and Gross 1985; King 1986; Garbaciak et al.
1985). Obesity is also associated with higher rates of infant mortality
(Naeye 1979). These risks are reduced when obese women do not gain
more than 24 lb during pregnancy (Naeye 1979; Kliegman et al. 1984;
Abrams and Laros 1986; Garbaciak et al. 1985), but the lower limit of
weight gain that can produce optimal birth outcome has not been defined.
This issue is important because caloric restriction and diet-induced weight
loss in pregnant obese women has been associated with reduced infant
birth weight (Naeye 1981; Campbell and MacGillivray 1975; Grieve,
Campbell-Brown, and Johnstone 1979), suggesting that obese women
should gain at least some weight during pregnancy (Campbell 1983).

Energy. The recommended intake of energy during pregnancy includes an
increment of 300 kcal/day over the energy allowances for nonpregnant
women (NRC 1980). This amount was obtained by calculating the total
energy cost of synthesizing maternal and fetal tissues and dividing this
figure by the number of days of pregnancy (Hytten and Leitch 1971).
Although the 300 kcaYday increment has been widely accepted, actual
measurements of the energy balances of pregnant women in several inter-
national populations have demonstrated that they may consume as few as
SO kcal/day over prepregnancy energy intake levels yet gain weight nor-
mally and produce infants of normal birth weight (Durnin 1987). Although
the reason for this discrepancy is not yet known, preliminary observations
suggest that the metabolic needs of pregnant women do not increase
significantly (Durnin et al. 1985; McNeil and Payne 1985; Saha 1986).
Nevertheless, caloric supplementation of pregnant women in a poor com-
munity where the average caloric intake was 1,500 kcaYday increased the
average birth weight and reduced the incidence of LBW infants (Lechtig et
al. 1975).

Recent investigations show that lactating women also require fewer calo-
ries than the 500 kcal/day calculated as needed above prepregnant energy
levels (Butte, Garza, Stuff, et al. 1984). Present knowledge thus does not
permit the precise definition of caloric requirements during pregnancy and
lactation (Worthington-Roberts, Vermeersch, and Williams 1985).


13 Nutrition and Health

Protein. The RDA for protein during pregnancy includes an additional 30 g/
day beyond the 44 g/day recommended for nonpregnant women (NRC
1980). Protein is abundant in the American diet, and inadequate intake
during pregnancy is reported infrequently. Studies that have associated
diets containing 20 percent of total calories from protein (as compared with
the 12 to 14 percent usually recommended) with a higher risk of premature
deliveries and neonatal mortality suggest that protein intakes significantly
higher than those recommended may be harmful (Rush, Stein, and Susser
1980a, 1980b).

Vihmins and Minerals. The RDA for vitamins and minerals for pregnant or
lactating women include increased levels above those for nonpregnant
women (NRC 1980). In healthy women with normal pregnancies, vitamin
and mineral needs can usually be met by consuming an adequate diet. With
the possible exceptions discussed below, supplements, although usually
recommended, have not been associated with measurable health improve-
ments in this population (Hemmiki and Star-field 1978).

American women may have a low intake of dietary folate. Some European
studies have suggested an association of folate deficiency (along with
deficiencies of other vitamins) with the development of neural tube defects.
These observations stimulated clinical trials in which folate and multi-
vitamin supplements appeared to reduce the risk of neural tube defects in
subsequent children born to women who had previously given birth to
infants with these defects (Smithells et al. 1981; Smithells et al. 1983:
Laurence et al. 198 I). These studies, however, were poorly controlled and
flawed methodologically (Dobbing 1983). A recent report has found no
difference in folate or vitamin B,, concentrations in blood samples from
early pregnancy taken from mothers of infants with or without neural tube
defects (Molloy et al. 1985).

The need for iron is increased during pregnancy, with about 500 mg needed
to increase the number of maternal red blood cells, about 600 mg needed for
the fetus and placenta, about 200 mg needed to replace normal maternal
losses, and another 200 mg needed to replace the red blood cells lost during
delivery. Because menstruation ceases for 9 months, about 300 mg of iron
are saved, and the total additional iron needed for a pregnancy with a
normal delivery is about 1,200 mg (King 1986), or about 4 mg/day. As
discussed in the anemia chapter, iron deficiency occurs infrequently in the
general population. Nevertheless, the National Research Council recom-
mends an iron supplement of 30 to 60 mg/day to prevent depletion of iron
stores during pregnancy and lactation (NRC 1980). Even when women are
not anemic, they may complete pregnancy with low iron reserves (Taylor et

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Maternal and Child Nutrition O

al. 1982). Clinical studies indicate that iron absorption increases progres-
sively throughout pregnancy (Lind 1982). Although as much as 90 percent
may be absorbed under these defined experimental conditions. the true
efficiency of dietary iron absorption under normal situations of food intake
is unknown (King 1986). For these reasons, pregnant women should be
evaluated periodically to determine their level of iron stores and should
receive supplements when stores are low (Romslo et al. 1983).

The RDA for zinc includes a 5 mg/day increment during pregnancy over the
15 mg/day recommended for nonpregnant women (NRC 1980). Zinc defi-
ciency is teratogenic in rats (Hurley 1980, 1981). and abnormal brain
development and behavior have been described in the offspring of zinc-
deficient monkeys (Sandstead et al. 1977, Sandstead et al. 1978). Evidence
from human populations suggests that the rate of fetal malformations and
other poor outcomes of pregnancy may be higher in populations where zinc
deficiency has been recognized (Sever and Emanuel 1973; Cavdar et al.
1980; Bergmann, Makosch, and Tews 1980; Jameson 1976; Soltan and
Jenkins 1982; McMichael et al. 1982; Kiilholma et al. 1984; Buamah,
Russell, and Bates 1984). However, conflicting reports have also been
published (Mukherjee et al. 1984; Hunt et al. 1984; Ghosh et al. 1985), and
questions remain about satisfactory measures of zinc status. The role of
zinc deficiency in the adverse outcome of human pregnancy remains
uncertain at present (Swanson and King 1987) and supplements are not
recommended.

Adolescent Pregnancy

Maternal age influences fetal and infant mortality rates and birth weight.
Mothers 15 years of age or younger (approximately 60,000 per year) have
increased rates of pregnancy-induced hypertension and premature deliv-
ery, are more likely to deliver infants of LBW, and have higher rates of fetal
loss and infant mortality (AAP Committee on Nutrition 1985b). In 1985,
among live-born infants in the United States with birth weights under 2,500
g, 0.5 percent were born to mothers under 15 years of age and 6.7 percent to
those 15 to 17 years of age (NCHS 1987~). A high proportion of adolescent
mothers are nonwhite and of low socioeconomic status (IOM 1985). While
nutrition is by no means the only issue in caring for the pregnant adoles-
cent, it is a controllable risk factor that can be reduced by programs that
provide support, prenatal care, and extra food (Heald and Jacobson 1980).

Disorders During Pregnancy
Pica. Pica, a persistent compulsion to eat unsuitable substances of little or
no nutritional value, is a recognized complication of pregnancy. Although

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u Nutrition and Health

the pica of pregnancy most often involves consumption of dirt or clay
(geophagia) or of starch (amylophagia), compulsive ingestion of many other
nonfood substances has been noted. Examples include ice, burnt matches,
hair, stone or gravel, charcoal, soot, cigarette ashes, mothballs, antacid
tablets, milk of magnesia, baking soda, coffee grounds, and the inner tubes
of tires. The practice of pica is not new, nor is it limited to any geographical
area, race, or culture. The medical implications of pica are not well under-
stood. Inadequate absorption of iron is the hazard most commonly at-
tributed to pica. Other less commonly reported complications include
congenital lead poisoning resulting from the consumption of wall plaster
(Pearl and Boxt 1980) and small bowel obstruction from the ingestion of
laundry starch (Worthington-Roberts, Vermeersch, and Williams 1985).
These issues are discussed in more detail in the chapter on behavior.

Hypertension. Preeclampsia and eclampsia are hypertensive conditions
induced by pregnancy. Preeclampsia is characterized by a rise in blood
pressure, generalized'edema that may cause sudden, large weight gain from
retained water, and loss of protein in the urine. Eclampsia is the most severe
form of the disorder, characterized by convulsions that may lead to coma.
Both present serious health risks to mother and fetus (Lindheimer and Katz
1985). Pregnancy-induced hypertension occurs among young women (es-
pecially those under 15 years), primiparas, especially older primiparas, and
those who are underweight or of low socioeconomic status (Pritchard and
MacDonald 1980). The cause of these conditions is uncertain. Whether
dietary variables may be part of the cause cannot be determined from
available data. Hypertension existing before pregnancy may also adversely
affect pregnancy.

Diabetes. Infants born to women with diabetes are at greatly increased risk
for prematurity, congenital defects, excessively high birth weight, respira-
tory distress syndrome, and other conditions that increase overall mor-
tality, especially when the mother's blood glucose levels remain high during
pregnancy (see chapter on diabetes). Risks of maternal complications are
also increased by established diabetes. These problems are reduced by
maintaining strict control of blood glucose levels before and throughout
pregnancy (Freinkel, Metzger, and Potter 1983); dietary counseling is
important in helping patients to achieve such control (Fuhrmann et al.
1983).

In some women who are not otherwise diagnosed as diabetic, pregnancy is
associated with significant alterations in carbohydrate metabolism such
that overnight fasting leads to lower-than-normal blood sugar and insulin
levels and carbohydrate consumption leads to higher-than-normal levels

556


Maternal and Child Nutrition O

(Kalhan and Hertz 1985). These changes, which are most marked near the
end of pregnancy, are referred to as gestational diabetes (Second lnterna-
tional Workshop 1985). Because current diagnostic methods cannot easily
distinguish between established and gestational diabetes, it is uncertain
whether gestational diabetes itself-in the absence of preexisting undiag-
nosed diabetes-increases risks to mothers and infants (Scherger and
Hudson 1985.)

Ail authorities agree that diabetes screening is indicated for pregnant
women with risk factors for overt diabetes: a previous history of gestational
diabetes, a large-for-gestational-age infant, excess amniotic fluid during
pregnancy, excretion of sugar in urine, increased thirst or urination, or
recurrent vaginal or urinary tract infections. Because diabetes screening
can identify diabetes in mothers who may not have been diagnosed pre-
viously and who might benefit from preventive services, various au-
thorities recommend screening for all pregnant women (Second lnterna-
tional Workshop 1985; CDC 1986), including administration of an oral
glucose tolerance test between the 24th and 28th weeks of pregnancy, or
earlier for women with risk factors. Others, however, believe that current
understanding of gestational diabetes is insufficient to justify universal
screening at this time (Scherger and Hudson 1985). Dietary components of
prenatal care of women found to have diabetes or gestational diabetes are
discussed in the chapter on diabetes.

Role of Dietary Factors in Fetal Health

Nutritional Needs of the Fetus

Because no one animal model is appropriate for all studies of the human
fetus, and because direct investigation of the fetus is limited by ethical and
technological considerations, knowledge of the nutrient needs of the
human fetus is fragmentary. This section reviews information about fetal
and placental nutrient requirements and their response to maternal nutri-
tion.

Energy. Current evidence indicates that glucose and amino acids, rather
than fatty acids, are the primary metabolic fuels for the fetus. Fetal energy
requirements increase during pregnancy to a maximum estimated from
110 kcal/day (Widdowson 1981) to 150 kcaYday (Ross0 1983) near term.
These are modest values when compared with the mother's estimated
energy requirement of 2,000 to 2,800 kcal/day (Widdowson 1981).

The glucose concentration in the maternal circulation is always higher than
that in the umbilical vein, and maternal glucose levels greatly influence the

557


O Nutrition and Health

rate of glucose transfer across the placenta. For example, in a woman with
diabetes and chronic hyperglycemia, larger amounts of glucose than nor-
mal are transported to the fetus. Conversely, during maternal caloric
restriction, the rate of transfer may be markedly reduced. The placenta
uses about half of the oxygen and glucose that are removed from maternal
circulation (Nichols and Nichols 1983), and there is some evidence that the
glucose needs of the placenta are met preferentially to those of the fetus
(Jones and Rolph 1985).

Protein. A fetus near term requires about 6 g (Widdowson 1981) to 8 g
(Ross0 1983) of protein per day. Most of this comes as small amounts of
essential and nonessential amino acids received continuously from the
placental circulation. The free amino acid concentrations in the umbilical
artery and vein are higher than those in the mother's blood, indicating that
amino acid transport across the placenta is an active metabolic process.
Presumably, active transport of amino acids protects the fetus against
inadequate maternal protein intake. Another source of protein occurs in
amniotic fluid the fetus swallows. This could amount to as much as 750 mg/
day. Animal studies indicate that glucose and amino acids can be taken up
from amniotic fluid more rapidly than can be accounted for by swallowing
alone (Charlton 1984). Administration of nutrients directly into the fetal
stomach can normalize the birth weight and length of fetuses born to
nutritionally deprived dams (Charlton and Johenger 1985).

Vitamins. Vitamin requirements of the human fetus have not been estab-
lished. Fat-soluble vitamins cross the placenta by simple diffusion, so that
maternal dietary intake would be expected to influence fetal levels. Most
water-soluble vitamins are transported from the placenta to fetus by active
uptake processes, so that fetal blood vitamin concentrations are higher
than those in maternal blood. Although specific vitamin deficiencies have
been shown to induce reproductive loss and developmental defects in
experimental animals, similar data for human fetuses are not available.

Fetal Risk From Vitamin A. Isotretinoin is a vitamin A acid that is known to
cause birth defects or developmental disability in 25 percent of children
exposed to it in the first trimester of pregnancy. There are case reports of
birth defects associated with large doses of vitamin A. Moreover, vitamin A
is well known to cause birth defects in laboratory animals. It has been
suggested that women who are pregnant or likely to become pregnant
should avoid taking supplements containing more than the RDA level (see
introduction and background chapter) for pregnant women (CDC 1987).

558


Maternal and Child Nutrition 0

Minerals. Mineral requirements of the fetus, estimated from studies on
fetal body composition, seem to be higher during the last few weeks of
pregnancy than at any other time during prenatal or postnatal development
(Widdowson 1981). Little is known, however, about the specific needs for
individual minerals. In experimental animals, prenatal calcium deficiency
causes rickets in the infant. In animals and humans, iron is stored in fetal
red blood cells, and term infants are born with ample reserves. Because
premature infants have a smaller red cell mass, they are at increased risk for
iron deficiency after birth.

Effects of Other Dietary Factors

Alcohol. During the past 15 years, health researchers have become aware
that excessive alcohol consumption adversely affects fetal development.
Fetal alcohol syndrome (FAS) was first described among infants born to
women who were chronic alcoholics (Jones 1973). These infants exhibited
specific abnormalities ofthe eyes, nose, heart, and central nervous system;
irritability and hyperactivity after birth as a result of alcohol withdrawal;
and impaired physical and mental development despite nutritional rehabili-
tation. The minimum level of alcohol consumed during pregnancy that
causes FAS has not been established. Some studies show that even one or
two alcoholic drinks per day are associated with higher rates of spon-
taneous abortion, premature detachment of the placenta, and LBW infants
(Council on Scientific Affairs 1983). Other studies, however, find that this
level of alcohol intake during pregnancy does not increase congenital
malformations (Mills and Graubard 1987). Because it is difficult to obtain
accurate information about alcohol intake (see chapter on alcohol), this
issue is not easy to resolve. Thus, as a prudent measure, the Surgeon
General has suggested that women avoid alcohol use during pregnancy
(FDA 1981).

The mechanism by which alcohol injures the fetus has not yet been defined.
Alcohol can cross the placenta and produce direct toxic effects. Another
possible mechanism may be the induction of nutrient deficiencies similar to
those that have been shown to produce fetal abnormalities in experimental
animals (Hurley 1980).

Although the adverse effects of maternal alcohol consumption on fetal
development have been known for more than a decade, a significant
number of women still consume alcohol while they are pregnant. For
example, one study of women delivering in a large urban hospital reported
that 82 percent consumed alcohol during pregnancy (Lillien, Huber, and

559


O Nutrition and Health

Rajala 1982). Because pregnancy course and outcome can be significantly
improved if problem drinkers change their habits after conception (Rosett
1983; Rosett, Weiner, and Edelin 1983), routine health and prenatal care
should include counseling about the hazards of alcohol use.

Caffeine. Caffeine, which is contained in many widely consumed bev-
erages, does cross the placenta and reach the fetus. Caffeine is an animal
teratogen, but there is no clear epidemiologic evidence of a similar effect in
humans. Exposure of the pregnant rat to bolus doses of caffeine by intuba-
tion, approximately 80 mgikg or above, results in signs of maternal toxicity,
increased resorptions, decreased fetal weight and size, teratogenic effects
involving limbs, and skeletal ossification deficiencies (Collins et al. 1981).
At doses as low as 6 mg/kg, there is little evidence of maternal or fetal
toxicity, although the offspring do display delayed skeletal ossification, a
condition that has been shown to be reversible (Collins et al. 1987). The
importance of the dosing method in producing teratogenic and other effects
is reflected in that caffeine given to pregnant rats at doses of 204 mg/kg in
the drinking water results in no teratogenic effects, although signs of
maternal and fetal toxicity occur at doses of 87 mg/kg/day, and delayed
skeletal ossification occurs at doses as low as 27 mg/kg/day (Collins et al.
1983).

Other studies in rodents have also been conducted to determine the effects
of perinatal exposure to caffeine on the neurobehavioral development of
offspring. Evidence indicates that gestational exposure of rodents to caf-
feine either in drinking water or by intubation may affect neurofunctional
development at doses of approximately 25 mg/kg/day or greater (Glavin and
Krueger 1985; Butcher, Vorhees, and Wootten 1984; Holloway and Thor
1982; West et al. 1986; Peruzzi et al. 1983).

Human studies have also produced inconsistent results. A study of 5,200
maternity cases in Germany reported lower birth weights in women with
"high" coffee consumption, regardless of cigarette smoking, socioeconom-
ic class, age, or number of children (May and Netter 1974). A survey of 800
Mormon households found that women who drank coffee had a higher rate
of spontaneous abortions, but this effect was not related to dose (Weath-
ersbee, Olsen, and Lodge 1977). Japanese researchers studied the effects of
caffeine ingestion in a sample of 9,921 healthy women pregnant for 6
months or longer and reported that women who drank more than five cups
of coffee per day had a higher incidence of premature labor, fetuses small
for gestational age, and infants with birth defects, but this study did not
control for socioeconomic variables (Furuhashi 1985). Other recent reports
have found caffeine intake to be associated with increased risk of late first

560


Maternal and Child Nutrition O

and second trimester spontaneous abortion (Srisuphan and Bracken 1986)
and reduced infant birth weight (Martin and Bracken 1987).

Other studies, however, have suggested that coffee drinking has little or no
effect on fetal health. A study of over 20,000 pregnancies absolved coffee
drinking from contributing to fetal defects or other untoward outcomes of
pregnancy (Van den Berg 1977). An analysis of interview and medical
record data for over 12,000 pregnant women evaluated the relation between
coffee consumption and adverse outcomes of pregnancy, controlled for
smoking and other relevant variables, and found no effect on birth weight,
gestation period, or birth defects (Linn et al. 1982). Similarly, a case-
control study of over 200 infants with selected birth defects found that the
caffeine consumption patterns of their mothers did not differ significantly
from those of control mothers (Rosenberg et al. 1982). Finally, an examina-
tion of almost 500 cases of birth defects recorded in Finland showed no
difference in coffee consumption between the mothers of these infants and
control mothers (Kurppa et al. 1982). Although data from human popula-
tions do not provide significant evidence that caffeine affects pregnancy
outcome, the Food and Drug Administration advises pregnant women to
eliminate or limit consumption of caffeine-containing products as a precau-
tionary measure (FDA 1980).

Role of Dietary Factors in Infant Health

Nutritional Needs of Normal Infants

The nutritional requirements of normal infants have been investigated to
the extent possible with this population, and RDA's have been established
(NRC 1980). These recommendations are largely based on analyses of
human milk and on the nutrient content of foods that healthy, thriving
infants consumed. A number of studies have measured nutrient needs
directly. The best measure of the adequacy of an infant's diet is the growth
rate in length and weight. This is usually evaluated by plotting the data from
repeated measurements over time on standard NCHS charts (Roche and
Hines 1980; Baumgartner, Roche, and Hines 1986).

Energy. Infants require three to four times greater amounts of energy per
kilogram of body weight (90 to 120 kcaYkg/day) than do adults to support
their relatively high metabolic rate and needs for growth (Heird and Cooper
1988). Energy requirements of individual infants are determined by body
size and composition, rates of physical growth, and activity patterns. The
RDA of 115 kcaYkg/day in the first 6 months and 105 kcaYkg/day for the
second 6 months meets the needs of most normal, well-nourished infants.
but infants' needs vary considerably, and the energy intake of any one

561


O Nutrition and Health

infant may vary from day to day. Normal infants appear to adjust intake to
needs, provided the mother is sensitive to cues of satiation: loss of interest
in food, releasing the nipple from the mouth, or turning the head from the
nipple or pushing the bottle or cup away. Many infants who are growing
normally consume less energy than RDA levels. One study, for example,
found the average intakes of breastfed infants to decline from 110 kcaYkg/
day at 1 month to 71 kcal/kg/day at 4 months (Butte, Garza, Smith, et al.
1984).

Water. The evaporative, fecal, and urinary water losses determine water
requirements for infants. Evaporative losses in healthy, full-term normal
infants range from 30 to 70 ml/kg/day. Fecal losses average 1 to 4 ml/kg/day
(up to 10 ml/kg/day in breastfed infants) but can increase suddenly and vary
greatly in infants with diarrhea. Because of their large surface area relative
to mass, infants lose proportionately more water by skin evaporation than
do adults. Infants also have less renal concentrating capacity than adults.
Thus, infants are vulnerable to water imbalance. Nevertheless, breast milk
and infant formulas provide adequate water, and healthy infants rarely
require supplemental water except in very hot weather (AAP Committee on
Nutrition 1985b). Instead, dehydration problems are most likely to occur
during episodes of vomiting, diarrhea, or fever, when dehydration can
occur so suddenly as to constitute a medical emergency (Fomon 1974).

Protein. Protein requirements are also proportionately greater in infants
than in adults. Dietary protein must be sufficient to support increases in
body protein that range on average from 3.7 g/day for the first month in
males and 3.3 g/day for the first month in females down to 1.8 and 1.7 g/day,
respectively, for months 9 to 12. These needs generally can be met by
protein intakes of about 1.8 g/100 kcal for infants during the first month of
life, decreasing to 1.2 g/100 kcal for infants 4 to 6 months of age (Fomon et
al. 1986). The Infant Formula Act of 1980 established a minimum standard
for the protein content of infant formulas, 1.8 g/100 kcal, which is based on
a protein equivalent in nutritive quality to casein (AAP Committee on
Nutrition 1976). The RDA of 2.2 g/kg for the first 6 months and 2.0 g/kg for
months 7 to 12 also considers protein quality (NRC 1980).

Fut und Curbohydrate. Because dietary fat is a concentrated source of the
calories needed to meet infants' high energy needs, infants should consume
3.8 to 6.0 g of fat per 100 kcal, or 34 to 54 percent of total calories (Fomon
1974). Dietary fat is required for normal brain development. Three percent
of total calories should be provided by linoleic acid. an essential fatty acid
(AAP Committee on Nutrition 1976). Carbohydrate should supply 30 to 60
percent of the total daily energy intake in infancy.

562


Maternal and Child Nutrition O

Vitamins and Minerals. Although infant requirements for micronutrients
are not as well defined as those for energy and protein (Heird and Cooper
1988), RDA's have been established for many vitamins and minerals (NRC
1980). Full-term infants who obtain breast milk from a well-nourished
mother will receive most necessary vitamins (AAP Committee on Nutri-
tion 1985b), although, under some circumstances, vitamins D and K are
exceptions. If breastfed infants have limited exposure to sunlight, vitamin
D supplementation may be required to prevent rickets (Reeves, Chesney,
and DeLuca 1982). Human milk is low in vitamin K, and this vitamin
should be routinely administered parenterally to all infants at birth to
prevent bleeding disorders (AAP Committee on Nutrition 1985b). Infants
fed a commercially available formula that is properly prepared should
receive an adequate intake of vitamins (AAP Committee on Nutrition
1976).

The bioavailability of minerals generally is greater from human milk than it
is from formulas. The RDA for calcium is designed to meet the need of
formula-fed infants, who retain 25 to 30 percent of the calcium in cow milk-
based formula. Breastfed infants retain about 65 percent of the calcium
consumed. Studies suggest that the bioavailability of zinc from human milk
is 41 percent, compared with 28 percent from cow milk, 31 percent from
cow milk formulas, and 14 percent from soy formula (Sandstrom, Ceder-
bald, and Lonnerdal 1983).

Iron deficiency is the most common nutrient deficiency in infancy (see
chapter on anemia). Rapidly growing infants absorb 49 percent of the iron
in human milk, 10 percent of the iron in cow milk, and 3 percent of the iron
in iron-fortified formulas (Saarinen, Siimes, and Dallman 1977). For this
reason, some authorities believe that breastfed infants do not need addi-
tional iron until the age of about 6 months (Saarinen 1978). Current recom-
mendations are that infants begin consuming iron-fortified cereals at 4 to 6
months of age to prevent anemia (Garry et al. 1981; AAP Committee on
Nutrition 1985b). Because human milk is low in fluoride and because
enamel development in permanent teeth is significant during the first year
of life, a fluoride supplement may be desirable for children who do not have
access to adequately fluoridated drinking water (see chapter on dental
diseases). Requirements for other minerals have been reviewed (AAP
Committee on Nutrition 1985b).

Infant Feeding

The available information on infant feeding has been reviewed extensively
and was the subject of a 1984 report commissioned by the Assistant
Secretary for Health (Task Force 1984).

563


O Nutrition and Health

Human Milk. Human milk is the food of choice for infants. It provides
appropriate amounts of energy and nutrients, it contains factors that pro-
vide protection against infections, and it rarely causes allergic responses.

Breastfeeding of the newborn in the hospital increased from 24.7 percent in
1971 to 62.5 percent in 1984, but only 27.5 percent of infants are still
breastfed by 6 months of age (Martinez and Kreiger 1985). Rates of
breastfeeding are highest among mothers who live in the western part of the
United States, have had at least some college education, are from upper
income families, and are white. Numerous investigations and reports have
discussed the unique values of human milk, trends in rates of breastfeeding
in the United States, and methods for promoting breastfeeding (DHHS
1984).

Table 15-2 compares the average content of selected nutrients in human
milk, infant formulas, and other kinds of milk used to feed full-term infants
(AAP Committee on Nutrition 1985b). The nutrient content of human milk
reflects the maternal diet, the time of day the milk is expressed, and the
length of time the mother has been breastfeeding. Protein concentrations,
for example, decrease from the first week through the sixth to ninth month
(Anderson, Atkinson, and Bryan 1981), and the concentrations of iron,
copper, and zinc also decrease during that period (Vuori and Kuitunen
1978; Siimes, Vuori, and Kuitunen 1979).

Fat provides about 50 percent of the calories in human milk, most in the
form of triglyceride, with the fatty acid pattern reflecting the maternal diet.
Linoleic acid provides an average of 4 percent of the calories in human
milk. The cholesterol content averages 20 mg/lOO ml but varies consider-
ably, and values up to 47 mg/lOO ml have been reported (Jensen, Hagerty,
and McMahon 1978). Lactose is the major carbohydrate. Human milk has a
lower content of the amino acids tyrosine and phenylalanine and a higher
content of taurine and cystine than cow milk.

The concentrations of water-soluble vitamins in human milk generally
reflect the maternal dietary intake and nutritional status. Providing folate
supplementation to a woman deficient in this vitamin increases milk folate
levels (Cooperman et al. 1982). Vitamin B,, deficiency has been reported in
breastfed infants whose mothers are strict vegetarians (Johnson and Roloff
1982). As noted above, breastfed infants require supplemental vitamin K at
birth and may require vitamin D supplementation if exposure to the sun is
inadequate.

564


                 Table 15-2
Content of Selected Nutrients in Human Milk, Commercial Formulas,
  and Other Milks Used for Feeding Normal Full-Term Infants

                        Mature
                    Human Milka   Milk-based    Soy Protein-    Whole Cow   Skimmed     Goat
               Per     (21.6 2 1.5    Formulasb    based Formulas     Milk       Milk       Milk
   Nutrient        Liter     kcalloz)    (20 kcal/oz)    (20 kcal/oz)    (20 kcal/oz)   (I 1 kcal/oz)   (2 I kcal/oz)

   Protein          g       10.5 * 0.2       15         18-21         34        35         37
   Fat            is      39.0 + 0.4      36-38        36-39         37          2         43
   Carbohydrate      g      72.0 iz 0.25      6s72.3       66-69         48         50        46
E   Calcium         m8      280 + 26      400-510      630-700      1,219      1,270      1,380
   Phosphorus       mg      140 * 22      300-390       420-500        959      1,050      1,140
   Sodium       mEq      7.8 2 1.7       7-10        9-15         22         23         23
   Potassium      mEq     13.4 k 0.9      14-21        19-24         38         44         54
   Chloride       mEq      11.8 ? 1.7       11-14        1 l-15          27         31         44    s
                                                                           B
   Iron           w      0.3 k 0.1      1.1-1.5        12-12.7         0.4        0.4        0.5
                            (12-12.7)c                   i
   Estimated      mOsm       73        92-105       122-138        226        240        269     is
    renal solute
    load                       i
  a Average values with standard deviations for comparison.                                             z
  b Values listed are subject to change. Refer to product label or packaging for current information. Milk-based formulas contain lactose, and soy
   protein-based formulas do not.                            2
   c Iron content of iron-fortified formulas.                                                                      3.
                                                                           c.

Source: Adapted from the American Academy of Pediatrics Committee on Nutrition 1985b.


O Nutrition and Health

In addition to nutrients, human milk contains antibodies and other anti-
infective factors that are thought to protect infants against gastrointestinal
infections. For example, lactoferrin may slow bacterial growth by depriv-
ing infective organisms of necessary iron. Lysozymes may destroy bac-
terial cell membranes after they have been inactivated by peroxidases and
ascorbic acid present in human milk. Secretory immunoglobulins in milk
protect against organisms that infect the gastrointestinal tract (Welsh and
May 1979). Perhaps most important, breast milk fosters colonization of the
infant digestive tract with protective Lactobacilli. In addition, a number of
other cellular and soluble factors may provide specific and nonspecific
defenses against infectious agents (Ogra and Greene 1982).

Infant Formulas. The Food and Drug Administration specifies the nutrient
composition of commercial infant formulas (CFR, Title 21, Section
107.100-Nutrient Specifications). As suggested by Table 15-2, infant
formulas are designed to simulate human milk. Manufacturers modify cow
milk by replacing its fat with vegetable oils that are well absorbed, diluting
it to a more appropriate concentration of minerals and other solutes,
heating it to improve protein digestibility, and adding vitamins and miner-
als. Soy-based substitutes are available for infants who develop allergic or
other sensitivities to substances in cow milk-based formulas. Soy formulas
contain isolated soy protein, methionine, corn syrup or sucrose, vegetable
oils, vitamins, minerals, camitine, taurine, and stabilizers. Other products
are available for infants who cannot tolerate either soy or cow milk. When
properly prepared, commercial formulas support normal growth and de-
velopment. Errors in preparation, however, have resulted in medical prob-
lems. Inadequately diluted formula increases the concentrations of calo-
ries, protein, and solutes circulated to the kidney for excretion and can
increase levels of sodium and other substances in blood, resulting in
disturbances of acid-base balance and toxic symptoms (Chambers and
Steel 197.5). Overdiluting the formula reduces the level of sodium and other
salts in the blood, thereby causing adverse reactions (Partridge et al. 1981)
and it does not provide adequate energy and nutrients for growth.

Imitation Milks. Substitute or imitation milks inadequate in calories and
nutrients are not suitable for feeding to infants (AAP Committee on Nutri-
tion 1984). Malnutrition has been observed in infants fed a formula made of
barley water, corn syrup, and whole milk (Fabius et al. 1981) and in those
fed nondairy creamer (Sinatra and Merritt 1981).

Cow Milk. Unmodified whole cow milk is inappropriate to feed to young
infants because it causes occult bleeding from the gastrointestinal tract in
some infants, leading to anemia and, occasionally, to allergies (see chapter

566


Maternal and Child Nutrition O

on infections and immunity). Its lipids are less digestible than the lipids of
human milk or most vegetable oils, and its concentrations of minerals and
other solutes nearly exceed the excretory capacity of the immature kidney
(AAP Committee on Nutrition 1983b). Intestinal blood loss has been noted
in younger infants and those who have consumed large volumes of milk.
although this usually presents no problem after the age of 6 months or so
(Fomon et al. 1981). As indicated in Table 15-2, cow milk has a higher renal
solute load than either human milk or infant formulas. By 6 months of age.
the kidneys of most normal infants have matured and can excrete excess
solutes sufliciently. If infants receive at least one-third of their calories
from foods and consume no more than 1 liter of milk per day, there is little
disadvantage to the use of whole cow milk after 6 months of age (AAP
Committee on Nutrition 1983b). Sometimes, however, infants consuming
whole cow milk may not receive adequate dietary iron to meet their
nutritional requirements (Tunnessen and Oski 1987).

For infants, 2-percent and nonfat milks are deficient in energy, essential
fatty acids, and certain vitamins, and they contain excessive protein and
minerals per calorie provided. They are not recommended during the first
year of life (AAP Committee on Nutrition 1985b; Fomon et al. 1977). When
supplemented with vitamin C and iron, evaporated milk formula (3 oz of
evaporated milk, 4.5 oz of water, 2 tsp of corn syrup) is an acceptable, low-
cost substitute for infants less than 6 months of age (Fomon et al. 1979).

Gout Milk. Goat milk should be used carefully during infancy because it is
low in iron, folate, and vitamins B, C, and D (AAP Committee on Nutrition
1985b). It requires supplementation with these nutrients. As shown in
Table 15-2, solute concentration is even higher than in cow milk (Harrison
et al. 1979).

Solid Foods. By the age of 4 to 6 months, infants have usually matured
enough to sit and to control movements of the head, tongue, lips, and jaw.
They can indicate when they do and do not want to eat. At this point,
feeding pureed solid foods becomes appropriate. The recommended rou-
tine is to introduce single-ingredient foods to the diet, one at a time, at
weekly intervals (AAP Committee on Nutrition 1980a, 1985b). Iron-sup-
plemented cereals are usually the first foods added. If properly prepared
and stored, pureed foods made at home are nutritionally equivalent to
those prepared commercially. By the age of 1 year, foods should provide
more than 50 percent of the energy intake of infants (Montalto, Benson,
and Martinez 1985). Salt need not be added to foods prepared for normal
infants, and sugar should be added sparingly, or not at all. Infants should
not be fed hot dogs, nuts, grapes, popcorn, uncooked carrots, round

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O Nutrition and Health

candies, and similar food items that can cause choking (AAP Committee on
Nutrition 1985b).

Low Birth Weight Infants

Infants born prematurely or after intrauterine growth retardation are at
high risk for malnutrition and may require special feedings. Before 26
weeks of gestation, the fetus's gastrointestinal system is too immature to
digest proteins, fats, or lactose. Fully competent digestive processes do
not develop until about 32 to 36 weeks of gestation. Infants born prior to 32
to 34 weeks of gestation may not be able to suck effectively. LBW infants
may have medical problems such as necrotizing enterocolitis (a potentially
lethal bacterial infection of the intestine), fluid and electrolyte imbalances,
and respiratory distress syndrome (difficulty exchanging oxygen and car-
bon dioxide due to immature lungs) that increase needs for energy and
nutrients (AAP Committee on Nutrition 1977). Whether the goal of nutri-
tional support for such infants should be to maintain normal (AAP Commit-
tee on Nutrition 1985a) or slower-than-normal weight gain (Keen and
Pearse 1985; Steen 1985) is as yet undecided. The challenge is to provide
adequate calories and nutrients in a form that the immature digestive and
excretory systems can handle and that does not cause complications.

Providing 95 to 160 kcal and about 3 g of protein per kg per day (maintained
at about 10 percent of calories ingested as the infant grows), 2 to 4 percent
of calories as linoleic acid. 40 to 50 percent of calories as carbohydrate, and
sufficient water to compensate for the unusually high losses from skin
helps achieve adequate nutrition for LBW infants (Heird and Cooper
1988). Mineral and electrolyte intake may also need to be adjusted to
compensate for these infants' unusual requirements (AAP Committee on
Nutrition 1985a). Human milk and formulas designed for full-term infants
contain insufficient calcium and phosphorus to meet the needs of LBW
infants and must be supplemented to permit adequate bone growth and
mineralization (Greer, Steichen, and Tsang 1982). Because iron supple-
ments increase susceptibility to vitamin E deficiency, recommendations
for iron supplementation in the LBW infant are cautious, advising 1 mg of
iron per 100 kcal (Heird and Cooper 1988). Recommendations for vitamins
are generally the same as those for full-term infants, although fat-soluble
vitamins may pose special problems due to poor fat absorption. Preventing
bone disease in LBW infants depends not only on adequate calcium and
phosphorus, but also on an intake of at least 500 IU of vitamin D per day
(AAP Committee on Nutrition 1985a). Vitamin E requirements may be
higher for LBW infants than for term infants. Although 15 to 30 IU of
supplementary vitamin E per day has been suggested for LBW infants


Maternal and Child Nutrition O

(AAP Committee on Nutrition 1985a), the data are not sufficient to support
firm recommendations (CDC 1984). The recommendation for folate in
LBW infants is 50 pg/lOO kcal (Heird and Cooper 1988). This vitamin must
be added separately to liquid multivitamin preparations because of its
instability (AAP Committee on Nutrition 1985a).

Methods for meeting nutritional goals for LBW infants usually include a
combination of human milk (from the mother or pooled from other
sources); other special supplements, formulas, or products fed by mouth or
tube (enteral nutrition); or intravenous feeding (parenteral nutrition). Milk
from mothers of LBW infants contains more energy; has higher average
concentrations of protein, fat, and sodium; has lower concentrations of
lactose and phosphorus; and contributes to a more rapid growth rate than
does milk produced by term mothers (Anderson, Atkinson, and Bryan
1981; Atkinson et al. 1980; Atkinson, Bryan, and Anderson 1981; Chessex
et al. 1983; Gross et al. 1981; Schanler and Oh 1980). Human milk also has
the advantage of passive transfer of antibodies. Some LBW infants can be
nourished adequately on their mother's milk, whereas others thrive better
when provided with additional supplements. One such supplemental prod-
uct, a human milk fortifier that contains protein, carbohydrate, calcium,
phosphorus, trace minerals, and vitamins, has been associated with im-
proved growth and prevention of bone demineralization in LBW infants
(Ronnholm, Spila, and Siimes 1982).

Special formulas for LBW infants contain more protein, calcium, and
phosphorus than formulas for term infants (Atkinson 1983). Although the
composition of these formulas varies, all can support growth (AAP Com-
mittee on Nutrition 1977; Gross 1983). The composition of several formulas
for premature infants are provided in a publication of the American Acade-
my of Pediatrics Committee on Nutrition (AAP Committee on Nutrition
1985a).

Parentera nutrition is often used in the first few days or weeks of life to
support anabolism in LBW infants who cannot tolerate full enteral nutri-
tion. Amino acids are usually used as the nitrogen source, and concentra-
tions administered are limited to those that do not produce elevated plasma
levels or the accumulation of ammonia in the blood (Heird and Cooper
1988). Glucose concentration must be adjusted to prevent hyperglycemia
and local irritation of peripheral veins. Excessive lipids must be avoided to
mitigate hyperlipidemia. Vitamins, minerals, and electrolytes must be
added to meet individual requirements (AAP Committee on Nutrition
1983a, 1985b).

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O Nutrition and Health

Cholestasis, or a suppression of the flow of bile, is a common complication
of prolonged parenteral nutrition in LBW infants. While the etiology of this
condition is unknown, the degree of prematurity and length of time on
parenteral nutrition are important correlates (Gibbs 1980). Lack of oral
feedings may also play a role. Although this complication is often reversible
when parenteral administration is discontinued, it may progress to hepatic
toxicity, cirrhosis, and liver failure (Reynolds 1985).

Role of Dietary Factors in Child Health

Energy

The energy requirements of children are determined by their individual
basal metabolic rates, rates of growth, and activity patterns. Therefore,
appropriate intakes for children of the same age, sex, and size vary. The
RDA's recommend a range of energy allowances that average 105 kcal/kg/
day for children 1 year of age to 80 kcal/kg/day for children 2 to 10 years of
age (NRC 1980). Higher levels of energy intake are required to compensate
for inadequate body weight due to low birth weight, growth retardation, or
other factors (Ashworth and Millward 1986).

Nutrients

Children need protein for the maintenance of body tissues, changes in body
composition, and synthesis of new muscles. During growth, the protein
content of the body increases from about 15 percent at 1 year to 18 to 19
percent by 4 years, which is also the value for adults (Fomon et al. 1982).
Estimates of protein needs for growth range from 1 to 4 g/kg/day (Ashworth
and Millward 1986). The RDA decreases from 1.8 g/kg/day at 1 year to 0.8 g/
kg/day at 18 years (NRC 1980).

Inadequate intakes of vitamins and minerals will be reflected in slow
growth rates, inadequate mineralization of bones, and very low body
reserves of the micronutrients. Clinical signs of vitamin deficiency in
children are reported infrequently. The most common mineral deficiency,
iron, appears to be declining, although children from low-income families
are at greater risk (see anemia chapter). With the relatively low prevalence
of clinical signs of vitamin and mineral deficiency in the general population
of children, there is no evidence that supplementation is necessary for this
group (AAP Committee on Nutrition 1980b). Although vitamin and mineral
supplements increase the quantity of these nutrients in the diet (Cook and
Payne 1979), they have not been shown to improve biochemical indices of
nutrient status in children who are already well nourished (Breskin et al.
1985). For this reason, recommendations on vitamin and mineral supple-

570


Maternal and Child Nutrition O

mentation for children target those at high risk, those from socioeconom-
ically deprived families, and those who have poor appetites or eating habits
(AAP Committee on Nutrition 1980b).

Eating Patterns

Preschool children are a nutritionally vulnerable group. Their growth rate is
slower than it was in infancy and their nutritional needs in relation to body
size proportionately reduced. Thus, they often want and eat relatively little
food. Food intake can be reduced even further by the increasing indepen-
dence (expressed as refusals to eat) and immature feeding skills that are
characteristic of very young children. Despite these problems, surveys
have indicated that, with the exception of a small subgroup, American
preschool children are in relatively good nutritional health. Children of
lower socioeconomic status are at higher risk of inadequate nutrient intakes
(especially iron deficiency) and poorer growth. Although parents have the
main responsibility for providing adequate and appropriate food for pre-
school children, day care providers supply an increasing proportion of the
food that children consume.

Parents continue to be the main influence on the food intake of school-aged
children, although an increasing proportion of the diet is consumed in
schools, day care centers, and fast food restaurants (Select Panel 1981).
Between the ages of 4 and 6, children increase the varieties of foods they are
willing to eat (see behavior chapter). Snacks become an important source of
calories and nutrients (Crawford, Hankin, and Huenemann 1978) and may
contribute as much as one-third of calories and fat, one-fifth of the protein,
and nearly one-half of the carbohydrate lo-year-old children consume
(Farris et al. 1986). These patterns emphasize the need for parents and
schools to provide appropriate meals and snacks and guidance in food
choices. Of special concern is the need to encourage appropriate levels of
daily physical activity (Select Panel 1981) and choice of nutritious snacks
that do not promote tooth decay.

Role of Dietary Factors in Adolescent Health

Energy and Nutrient Requirements

Energy and nutrient requirements are directly related to the stage and rate
of growth, and demands are greatest during the peak velocity of growth.
Because individuals enter adolescence at different ages and have different
rates of growth for different time periods, it is difficult to establish specific
nutrient requirements for individuals. Few studies have been conducted on
the nutritional needs of adolescents, and the RDA's are established mainly

571


0 Nutrition and Health

by extrapolation from adult age groups (NRC 1980). For most nutrients,
RDA's are similar to those for adults. The RDA's provide a wide range of
energy intakes for two age groups, 11 to 14 years of age and 15 to 18 years of
age (NRC 1980). However, many girls experience their peak growth ve-
locity before the age of 11.

The RDA for calcium, 1,200 mglday, is higher for adolescents than for
adults and is designed to meet the needs of the adolescent who is growing at
the fastest rate. Achieving maximum bone mass during the teens and
twenties can reduce the risk of developing osteoporosis later in life (Lucas,
Rees, and Mahan 1985; see chapter on skeletal diseases). The higher RDA
for iron for adolescent males is also related to rapid growth, which is
accompanied by increases in blood volume, muscle mass, and iron-con-
taining enzymes. Although there are few data on the zinc requirements of
adolescents, this population may be at risk for marginal intakes (Mahan and
Rosebrough 1984). Vitamin requirements are correlated with growth de-
mands rather than age. For example, males have higher needs for folate
than females, and the values for both sexes increase with physical maturity
(Daniel, Gaines, and Bennett 1975).

Eating Patterns

The growth spurt of adolescence demands significant increases in calories
and nutrient intake to support the rapid growth rate and increased body
size. In early adolescence, children still depend on their parents for food,
but by the end of adolescence they are largely independent (Select Panel
1981). Irregular eating patterns are common in adolescence, reflecting this
growing independence from the family and the teenager's increasingly busy
social life and athletic, academic, and vocational activities. Breakfast and
lunch are often skipped or eaten on the run. Snacking is characteristic of
this age group and contributes significantly to nutrient intake; these snack
foods are often higher in calories, fat, and sugar-and lower in vitamins,
minerals, and fiber-than foods consumed at family meals (Hampton et al.
1967; Pao 1980). Because lifetime dietary patterns are established during
these years, adolescents should be encouraged to choose nutritious foods,
to develop good eating habits, and to maintain appropriate levels of phys-
ical activity (Select Panel 1981).

Role of Dietary Factors in Chronic Disease in Childhood

Several chronic diseases have special implications in the nutrition of
infants, children, and adolescents. Some of these are discussed elsewhere
in this Report. Childhood hyperactivity (or attention deficit disorders) and
eating disorders such as anorexia nervosa and bulimia, for example, are

572


Maternal and Child Nutrition O

reviewed in the chapter on behavior, and juvenile diabetes is reviewed in
the diabetes chapter. Children with chronic disease and other handicap-
ping conditions frequently require therapeutic diets accompanied by inten-
sive nutrition counseling and support (see, for example, Baer 1982). Dis-
cussion of issues related to most of these conditions is beyond the scope of
this Report, but a few examples follow.

Coronary Heart Disease

The relationship between diet in infancy, childhood, and adolescence and
the development of adult atherosclerosis and coronary heart disease (see
chapter on coronary heart disease) is of great current interest. Within the
past 5 years, cholesterol-lowering diets for children with elevated blood
cholesterol levels (Consensus Development Panel 1985). as well as for
those with normal levels (Weidman et al. 1983), have been recommended
to prevent onset of the adult disease. These recommendations are that all
children older than 2 years adopt a diet that reduces dietary fat intake to 30
percent or less of calories, saturated fat to less than 10 percent of calories,
and daily cholesterol intake to 250 to 300 mg or less. However, other
groups have advised against specific recommendations because they find
insufficient evidence for the safety and efficacy of such diets in children
(AAP Committee on Nutrition 1983c, 1986).

Increasing evidence suggests that atherosclerosis begins in childhood.
Cholesterol concentrations, which are lower in cord blood than in maternal
blood, rise after infants begin to be fed. Infants fed human milk or cow milk
have higher blood cholesterol levels at age 6 months than do those fed
formulas containing vegetable oils, but these differences are reduced once
cholesterol-containing foods are added to the diet (Farris et al. 1982). By
the age of 1 year, blood cholesterol levels correlate with dietary intake of
saturated fat and cholesterol; they rise rapidly during the first 2 years of life
(Berenson et al. 1979). Blood cholesterol levels at age 6 months are
correlated with levels at age 7 years (Freedman et al. 1987). Childhood
blood cholesterol levels have a strong genetic component, and children
whose parents have high levels are two to three times more likely to be in
the 95th percentile for blood cholesterol than children of parents with low
to normal levels (Berenson et al. 1979).

Atherosclerotic plaques have been identified in the coronary arteries of
young soldiers killed in the Korean and Vietnam wars (Strong 1986) and in
adolescents and even younger children who suffered accidental death
(Velican and Velican 1980). Children in the United States exhibit higher
blood cholesterol levels and have a higher dietary intake of fat and choles-
terol than children in populations with lower heart disease rates (Weidman

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et al. 1983). Measurements of other heart disease risk factors such as high
blood pressure (Burke et al. 1987) or obesity (Harsha et al. 1987) made in
early childhood are highly correlated with those made in the same children
at age 7. Thus, pediatricians have been urged to identify and to treat
children with elevated blood cholesterol levels (Wynder et al. 1983; Con-
sensus Development Panel 1985).

On the other hand, no data are available from prospective studies to
demonstrate that feeding cholesterol-lowering diets to children can either
support normal growth and development or reduce later heart disease
rates. Thus, the American Academy of Pediatrics (AAP) recommends that
children's diets follow current dietary trends with moderation, including
decreased consumption of saturated fats, cholesterol, and salt and an
increased intake of polyunsaturated fats (AAP Committee on Nutrition
1986). It also stresses that current data indicate that no changes in the
current diet for infants and children under the age of 2 are necessary.
Whether a diet consisting of 30 percent of calories from fat should be
advised for the general population of children over age 2 remains contro-
versial, but a fat intake over 40 percent of calories is excessive (La Rosa
and Finberg 1988). Until better data are available, the AAP recommends
screening high-risk children for early detection and treatment for heart
disease risk factors such as high blood cholesterol, high blood pressure,.
and obesity (AAP Committee on Nutrition 1986).

Obesity

The increased rate of pediatric obesity in the United States is an important
public health issue (Gortmaker et al. 1987). Childhood obesity can lead to
adult obesity and all its complications; currently, insufficient information is
available about the causes and prevention of early onset of obesity (see
chapter on obesity).

The cause of obesity in infants is poorly understood. Speculations that
formula feeding and early introduction of solid foods might be responsible
are not supported. by research studies (Ferris et al. 1980; Dubois et al.
1979), and no differences in subsequent fatness have been observed among
children who were breast or bottle fed (Fomon etal. 1984). Both genetic and
environmental factors are involved (see obesity chapter). A recent study of
adopted children, for example, found a strong correlation of body weights
to the weight of the biologic rather than the adoptive parents (Stunkard et
al. 1986). Lower-than-normal activity levels are also related to childhood
obesity (Berkowitz et al. 1985). One study observed a direct relationship
between body weight and number of hours spent watching television (Die&
and Gortmaker 1985).

574


Maternal and Child Nutrition 0

Studies examining the role of early infant obesity as a risk factor for later
obesity are also inconsistent. Some studies found that most obese infants
become thinner as they grow older and concluded that early weight gain
does not predict later obesity (Shapiro et al. 1984). Others have found that
body weights at the age of 1 year strongly predict body weights at age 7
(Harsha et al. 1987). Nearly all studies agree, however, that the correlation
between childhood obesity and later obesity increases as children grow
older (AAP Committee on Nutrition 1981). These and other issues related
to obesity are reviewed in the chapter devoted to that topic.

Cognitive Performance

LBW infants are at greater risk for developmental disorders than are
normal-weight infants (Parkinson, Wallis, and Harvey 1981). Infants with
early intrauterine growth retardation (prior to 26 weeks' gestation) are at
greater risk than infants whose growth retardation begins after 26 weeks'
gestation (Fancourt et al. 1976). Early intrauterine growth retardation is
associated with less successful school performance, lower intelligence, and
more behavioral and other handicaps (Harvey et al. 1982).

The role of maternal and early infant malnutrition, as distinguished from
other causes of fetal and infant growth retardation, is uncertain. Animal and
human studies have shown that severe malnutrition during fetal growth and
early infancy retards brain cell division and alters nerve myelination, but
cognitive and behavioral effects of less severe nutritional deprivation can-
not easily be distinguished from other environmental effects.

Data from populations in which malnutrition is endemic indicate a relation-
ship between growth retardation of infants and young children and low
performance in mental development tests (Lasky et al. 1981). Children with
protein-energy malnutrition in infancy who were tested at ages 5 to 11 years
had poorer academic performance than children who were well nourished
in infancy, which is reflected in classroom behavior problems such as lack
of attention, poor memory, poor motivation, and easy distractibility (Gal-
ler, Ramsey, and Solimano 1984). However, socioeconomic disadvantages
as well as poor nutritional status could cause these problems. Children
subjected to prenatal malnutrition because of war-induced famine or to
acute periods of malnutrition during infancy can overcome nutritionally
induced growth deficits and can exhibit cognitive function levels that
correlate most strongly with the parents' educational status (Stein et al.
1972; Beardslee et al. 1982). Malnourished children adopted by socioeco-
nomically advantaged families have been able to catch up in mental devel-
opment (Graham and Adrianzen 1972).

575


O Nutrition and Health

Studies of the relationship between maternal nutritional supplementation
and the behavioral development of offspring have produced inconsistent
results. In some studies, no differences in cognitive function occurred
among offspring of women who did or did not receive nutritional supple-
ments (Rush, Stein, and Susser 1980a, 198Ob; Higgins 1976), but others
have reported significant benefits of improving prenatal nutritional status
(Villar et al. 1984).

As discussed in the anemia chapter, lower mental and behavioral test scores
improved relative to controls among iron-treated iron-deficient infants only
when the amount of iron administered corrected both the anemia and
biochemical indices of iron deficiency (Lozoff et al. 1987). Short-term
studies on the effects of omitting breakfast on cognitive performance have
reported that adequate nutrition benefits learning (Pollitt, Leibel, and
Greenfield 1981, 1983; Conners and Blouin 1982/83). Well-nourished chil-
dren ages 9 to 11 who skipped breakfast displayed higher rates of inaccurate
responses to problem solving.

Inborn Errors of Metabolism

Early identification and nutrition intervention can help prevent subsequent
mental retardation in infants born with many kinds of metabolic disorders.
All States have screening programs to detect newborns with inborn meta-
bolic disorders (Infant Metabolic Diagnostic Laboratory 1987). Such chil-
dren require long-term dietary management. One example of such a disor-
der is phenylketonuria (PKW) (AAP Committee on Genetics 1982).

PKU results in excessive and potentially toxic blood levels of the amino
acid phenylalanine. The goals of therapy are to provide adequate intakes of
energy and nutrients but only enough phenylalanine to maintain normal
growth and development. Meeting these goals requires special formulas
and food products with reduced phenylalanine content, as well as consider-
able support from health professionals (Trahms 1984). Current recommen-
dations are to continue the phenylalanine-restricted diet throughout the
reproductive years, because experience with its discontinuation at ages
ranging from 4 to 10 years indicates progressively decreasing cognitive
functioning, learning difficulties, poor attention span, and behavioral dfi-
culties (Smith et al. 1978; Koch et al. 1982; Holtzman et al. 1986). Evidence
suggests also that phenylalanine restriction during pregnancy improves the
outcome for women with PKU and their infants (Mabry, Denniston, and
Coldwell 1966; MacCready and Levy 1972; AAP Committee on Genetics
1985; Drogari et al. 1987).

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Maternal and Child Nutrition O

Implications for Public Health Policy

Dietary Guidance

General Public (Including Children and Pregnant Women)
Assessment of nutritional status is an integral part of maternity care at the
beginning of pregnancy and periodically throughout pregnancy and lacta-
tion to provide continuing monitoring and recommend appropriate inter-
vention.

Evidence related to the role of diet in maternal and child health indicates
that well-nourished mothers produce healthier children. Intake of sufftcient
energy and nutrients to attain optimal nutritional status, including appro-
priate weight before pregnancy and adequate weight gain during pregnan-
cy, improves infant birth weight and reduces infant mortality and mor-
bidity. Avoiding potentially toxic substances such as alcohol or drugs
during pregnancy seems to improve infant birth weight and health, but the
evidence regarding low exposures to these agents is not conclusive. Infor-
mation on appropriate dietary intake, with consideration of ethnic and
cultural food habits, should be provided as early as possible to pregnant
women and to women expecting to become pregnant.

Evidence related to the role of diet in infancy indicates that breast milk is
the optimal food for infants. Whenever possible and as early as possible,
health professionals should provide guidance and support to pregnant
women and new mothers on the importance of breastfeeding and on meth-
ods for its initiation and maintenance. Mothers who cannot or choose not to
breastfeed should receive information about appropriate formulas.

Consuming the appropriate amount and form of energy and nutrients for
developmental age is important for good health, as is early education about
lifelong dietary patterns that help prevent disease. Parents should guide
their children in developing positive eating behaviors and on age-appropri-
ate food patterns that meet nutritional requirements but avoid excessive
intake of fat, sodium, and sugar. Parents should also help adolescents
develop healthy eating habits and should emphasize the importance of
including sufftcient quantities of low-fat, nutritious foods in meals and
snacks.

Special Populations

Some factors present at the onset of pregnancy place women at increased
nutritional risk. These include: adolescence, short interconceptional peri-

577


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od, poor reproductive performance, economic deprivation, food faddism,
substance use, chronic systemic disease, and inadequate or excessive
prepregnant weight (below 85 percent or above 120 percent of standard
weight for height). Other nutritional risk factors such as anemia and inade-
quate or excessive weight gain may develop during pregnancy.

Attaining appropriate prepregnancy body weight and nutritional status,
gaining adequate body weight, and avoiding alcohol during pregnancy are
important for all women. Qualified health professionals should provide
close nutritional monitoring and individualized counseling to women ap-
propriate to their educational level and cultural food habits before and
throughout pregnancy.

Specialized professional counseling on feeding should be provided to par-
ents of LBW infants, other infants at high risk, and infants who require
special formulas. Parents of children who are at high risk because of
developmental disorders, inborn errors of metabolism, physical dis-
abilities, or chronic disease should also receive ongoing professional ad-
vice on appropriate diets and feeding methods. Because children from
families with a history of diet-related chronic disease have a high risk for
such conditions, they should be evaluated for these conditions. Children of
families whose blood cholesterol, blood sugar, or blood pressure exceed
appropriate levels should be advised on dietary and other means to reduce
these risk factors.

Physicians, nurses, and other health professionals caring for children and
women of childbearing age should receive education and training in nutri-
tion assessment, nutrition intervention for prevention of disease, and pro-
motion of maternal and child health.

Nutrition Programs and Services

Nutrition Services

Evidence related to the role of nutrition in maternal, infant, and child health
suggests that all health care programs for these groups should provide
nutrition services, especially to those people at special health or economic
risk. Such services include nutrition assessment, dietary counseling, nutri-
tion education, and referral.

Food Products
Evidence related to the role of dietary factors in maternal and child health
suggests that food manufacturers should develop nutritious, low-fat, low-

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Maternal and Child Nutrition O

salt, low-sugar snack food products for children and adolescents. Quality
and safety of infant formulas and other infant foods require continued
monitoring to prevent untoward health consequences.

Special Populations

pregnant women, infants, and children with diet-related disease conditions
and physical disabilities that impair food intake should receive counseling
and assistance in dietary management. Low-income families should have
access to an adequate diet. Those with poor education, limited understand-
ing of English, and different cultural patterns require nutrition education
approaches appropriate to their needs.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in maternal, infant, and child health should include investigations into:
o The amounts of energy and essential nutrients pregnant women must
consume to achieve optimal birth outcome and promote long-term
  maternal health.

0 The optimal weight gain during pregnancy.
0 The diet during pregnancy that best prevents complications of chronic
disease conditions in the mother.
0 The effects of potentially toxic dietary factors such as alcohol on fetal
health.

0 The optimal feeding methods and diet for improving growth and devel-
opment of LBW infants.

o The diet in childhood that will best prevent later development of
chronic disease conditions.

0 The influence of nutritional status on teratogenic outcomes, particu-
larly neural tube defects.

o Nutritional care for optimal development of infants and children with
special health care needs due to chronic illness or developmental
disorders.

o Effective educational methods to teach parents how to develop good
dietary practices for themselves and their children.
0 Effective educational methods for teaching good nutritional practices
to children and adolescents.

579


O Nutrition and Health

0 Effective strategies to integrate nutrition screening, education, and
intervention services into health care programs.
o The impact of social changes on nutritional status, including those
related to meal sources and eating patterns.

580


Maternal and Child Nutrition O

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Chapter 16

Aging

If thou well observe

The rule of not'too much, by temperance taught
In what thou eat and drink, seeking from thence
Due nourishment, not gluttonous delight,
  Till many years over thy head return:
So may thou live, till like ripe Fruit thou drop
  Into thy Mother's lap, or be with ease
Gathered, not harshly plucked, for death mature.
          John Milton
    Paradise Lost, Book XI (1667)

Introduction

Life expectancy at birth is now 75 years, compared with about 47 years at
the beginning of this century (NCHS 1988). The average age and the
proportion of the older population are also increasing. Individuals over age
65 now comprise 12 percent of the population, compared with 4 percent in
1900. This percentage is expected to rise to 21 percent by the year 2030.
People who survive to old age are living longer. For example, persons
reaching age 65 in 1984 had an average life expectancy of an additional 17
years (19 years for women and 14.5 years for men), and life expectancy at
age 65 has increased 2.5 years just since 1960 (NCHS 1986). This increased
life expectancy for older Americans is resulting in an even more rapid
growth in the populations over age 75 and over age 85.

The lack of a satisfactory definition of old is a problem. What is old? Who is
old? When does one become old? Clearly, physiologic age is not the same
as chronologic age. On the other hand, numerous attempts to find a simple
and accurate indicator of physiologic age have not yet yielded a satisfactory
instrument. This discussion employs simple chronologic cutoffs, recogniz-
ing, however, that there is tremendous heterogeneity within the popula-
tions over 65, over 75, and over 85. The general term older will refer to
Americans over age 65.

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Historical Perspestive

Nutritional issues are prominent in the history of gerontology, and dietary
advice for the aged can be traced back as far as recorded history. The field
of nutrition and aging can be divided into studies in humans on dietary
adequacy, requirements, guidelines, etc. and studies in animal models
aimed at retarding the aging rate via diet. This chapter discusses the human
studies but does not examine in detail the large amount of literature on
animals.

Certain theories about the basic causes of aging are related directly to
nutrition. One theory proposed at the beginning of this century, for exam-
ple, was that the gradual accumulation of toxins secreted by intestinal
bacteria caused aging and that eating certain types of yogurt could prevent
this accumulation (Mechnikova 1921). Aldous Huxley satirized this theory
in his novel After Many a Summer Dies the Swan, in which a character eats
raw carp in an attempt to populate his intestines with the "good" micro-
organisms of this long-lived fish. More recent theories attribute aging to the
gradual oxidation of membrane lipids throughout life and promote con-
sumption of compounds with antioxidant properties (Harman 1982). Di-
etary caloric restriction without malnutrition in rodents and other diverse
animals substantially prolongs lifespan and retards most aspects of biologic
aging (Masoro 1985; Weindruch and Walford 1988). Dietary restriction is
effective in rodents when started in early life or mid-adulthood. This result
has been reproduced many times since it was first described in the 1930's
(McCay, Crowell, and Maynard 1935), but underlying mechanisms remain
vague. Dietary restriction is attracting broad attention because it provides
the best model now available to study the biology of decelerated aging.
How calorie-restricted regimens affect aging in primates is not well known.

Older persons are susceptible to` extravagant claims for the effects of
nutritional manipulations and supplements. Nutritional science provides
an important service by evaluating these claims and limiting the damage
resulting from such quackery (see chapter on dietary fads and frauds).

In the past two decades, the scientific community has increased attention
on the nutritional status of older people. Although specific nutritional
problems have been documented among older Americans, the relationship
of diet to morbidity and mortality in this age group is not always clear. What
is clear is that prevention of many of the health problems of old age must
necessarily begin much earlier in life.

5%


This chapter reviews age-related physiologic, psychologic, and socioeco-
nomic changes that can influence nutritional status of older Americans;
discusses issues related to the nutritional requirements of older persons;
and describes the effects of nutritional deficiencies on the health of the
older population.

Significance for Public Health

Although not inevitable, health and mobility often change and decline with
advancing age. The increasing life expectancy at age 65 observed through-
out this century suggests that diet, exercise, and other personal and socio-
economic factors can help prolong good health for most people (Rowe and
Kahn 1987). Nevertheless, the chances are great that an individual in the
eighth or ninth decade of life will be limited in activity and require health
and social services. Many older Americans suffer from arthritis, heart
disease, hypertension, hearing loss, diabetes, obesity, gastrointestinal
conditions, liver disease, and cancer and other chronic diseases. More than
60 percent of people over age 65 have high blood pressure and approximate-
ly 30 percent have heart disease. Heart disease, cancer, and stroke account
for over three-quarters of the deaths among older persons and 50 percent of
all days of bed confinement (U.S. Senate 1987/88; NCHS 1986).

Such chronic conditions as well as dementia prevent functional indepen-
dence and increase the need for dietary and other long-term care services.
In 1985, for example, more than 5 million persons over age 65 needed
special care to remain independent, and this figure is expected to exceed 7
million by the year 2000. Nearly 3 million older Americans residing outside
institutions have been estimated to require assistance with basic activities
related to food consumption such as shopping, meal preparation, or eating
(Posner and Krachenfels 1987). One survey has estimated that three-
fourths of all patients receiving home health care require therapeutic diets
and could benefit from the services of trained nutrition professionals
(Gaffney and Singer 385).

The total costs of health care for older persons are not known precisely. In
1986, health expenditures made up 29 percent of the nearly $270 billion paid
by the Government for programs and services for the older population, but
older Americans still disbursed an estimated average of 15 percent of their
personal income for health care (U.S. Senate 1987/88).

One difficulty in determining the effect of nutrition on the health of older
Americans is that there are no recent national food consumption and

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O Nutrition and Health

nutritional status data on this group, and hence no data on national trends.
Currently available national data come from the Nationwide Food Con-
sumption Survey (NFCS) conducted in 1977-78 and the National Health
and Nutrition Examination Surveys (NHANES I and II) conducted from
1971-74 and 1976-80 (see chapter on dietary patterns and practices). Some
of this information will be discussed below in the section on energy and
nutrient status of the older population. New national data on food con-
sumption and/or nutritional status of older individuals will be provided by
the U.S. Department of Agriculture's (USDA's) 1988 NFCS and DHHS's
NHANES III, which began data collection in 1988. In addition, plans are
being developed to conduct a special survey of food consumption of older
persons as part of USDA's Continuing Survey of Food Intakes by Individu-
als.

Policy Background

Nutrition Services and Programs

Until the early 1970's, nutrition services for the older population, with the
exception of food stamps, were based almost exclusively in hospitals and
long-term care facilities and included routine dietary screening, nutritional
status assessment, dietary counseling, oral or intravenous nutritional sup-
port, and food service. These services continue to be provided. Because
they are not usually reimbursable under current cost-containment guide-
lines, they are especially vulnerable to fiscal constraints (Posner and
Krachenfels 1987).

In 1973, in response to the growing population of older Americans, to rising
health care costs, and to greater interest in preventive health care, the
Nutrition Program for the Elderly was established under the Administra-
tion on Aging to expand food and nutrition services from the hospital to
include communities and homes. Current Federal programs support the
functional independence of older individuals in ambulatory care centers,
adult day care centers, hospices, and home settings. These food and
nutrition activities include the USDA's Food Stamp Program, which serves
more than 2 million older Americans, and two programs administered by
the Nutrition Program for Older Americans-Congregate Meals, which
also serves about 2 million individuals, and Home-Delivered Meals, which
serves 0.5 million, Despite limitations in size and scope, these programs
have been demonstrated to improve the dietary intake and nutritional
status of participants (Czajka-Narins et al. 1987).

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Surgeon General's Workshop on Health Promotion and Aging
The 1988 Surgeon General's Workshop on Health Promotion and Aging
addressed nutrition and aging issues (DHHS 1988). The workshop report
regarding nutrition and aging was based on the premise that "good nutri-
tional status is essential for a high quality of life and food contributes to the
quality of life through psychological, social, as well as physical mecha-
nisms." This premise is based on the assumptions that older people vary
greatly in their social, economic, and lifestyle situations, functional capaci-
ty, and physical conditions; that nutrition policy should be crafted from a
multidisciplinary framework; that a critical shortage of knowledgeable
personnel in the areas of nutrition education, research, and service now
exists; and that because the research base for nutrition of older Americans
is evolving, specific recommendations must be periodically reviewed and
updated.

The workshop report identified priorities related to (1) sound public educa-
tion tailored to the special concerns of old age, such as multiple drug
regimens, appropriate energy intakes, and the effects of existing chronic
diseases on nutritional status; (2) professional education on geriatric con-
cerns integrated into the core curriculum, inservice training, and continu-
ing education of dietitians and other health care professionals; (3) counsel-
ing provided by credentialed nutrition professionals in institutional or
community-based programs providing health services to older adults; and
(4) appropriate financing for nutrition services delivered to older people as
part of routine and long-term care.

Key Scientific Issues

0 Effects of Aging on Nutritional Status
o Evaluation of the Nutritional Status of the Older Population
0 Effects of Nutritional Deficiencies on the Older Population

Effects of Aging on Nutritional Status

Aging is accompanied by a variety of physiologic, psychologic, economic,
and social changes that may compromise nutritional status. All of these
changes do not necessarily occur in all individuals, however, and many
older people remain in excellent health until very old age. Older persons
have a high prevalence of chronic disease, use medications heavily, and are
relatively sedentary. Many of the seemingly inevitable consequences of
aging may actually be caused by these other factors (Letsov and Price

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0 Nutrition and Health

1987). The role of exercise in the health of older tiersons has been reviewed
recently (Smith, Smith, and Gilligan 1988).

Physiologic Changes

Many physiologic functions, including the senses of smell and possibly
taste, decrease with age (Schiffman, Mors, and Erickson 1976; Kamath
1982; Smith, Smith, and Gilligan 1988; Chauhan et al. 1987). These changes
may result in decreased appetite as well as impaired utilization of nutrients
and limitations of function.

Dental problems, common in old age, decrease the ability to chew certain
foods (Albanese 1978). Physical disabilities such as diminution of vision
may make eating less pleasant (Roe 1985). Although the decreases in basal
metabolic rate and physical activity noted with increasing age in some
studies reduce nutrient needs, older people may still consume insufficient
calories and essential nutrients (McGandy et al. 1966; McGandy 1986).
Decreased physical activity also may predispose individuals to the devel-
opment of osteoporosis (see chapter on skeletal diseases).

Changes such as osteoarthritis, which affects 16 million people in this
country, can affect mobility and decrease an older person's ability to
purchase and prepare food (Garetz 1976). Another possible hindrance to
adequate nutrition in the aged is malabsorption, which can be caused by a
decrease or absence of gastric acid secretion and by interactions with
medications commonly prescribed for older persons (Butler and Lewis
1977; Russell 1986; Roe 1985; Hathcock 1987). Whether these changes
contribute to nutrient deficiencies in older people has not been established,
nor is it known whether such changes are related more to the use of
medications, to poor health, or to sedentary lifestyle than to age itself
(Letsov and Price 1987). Recent studies, for example, have demonstrated
that exercise prevents or delays the onset of musculoskeletal disabilities in
older adults (Lane et al. 1987).

Psychologic Changes

The most common psychologic factor affecting nutrition is depression
(Garetz 1976). Of all psychiatric diagnoses, depression is most strongly
correlated with increased morbidity and mortality, regardless of the age of
the subjects (Widgor and Morris 1977; Nielsen, Homma, and Bjorn-
Henriksen 1977), and is most often related to chronic disease and to
poverty, which are common among older persons. At least 30 percent of
noninstitutionalized men and women over the age of 65 live alone
(Todhunter 1976; AARP 1985). Neither institutionalization nor solitary

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living necessarily induces depression, but such life changes may be associ-
ated with poor self-esteem, which, in turn, can lead to significant changes
in eating patterns (Letsov and Price 1987). Depression is one psychiatric
disorder that can be treated successfully, but recent advances in therapy
are not disseminated to health professionals widely or rapidly enough to
make maximum impact (NIA 1987).

Economic and Social Changes

Older Americans as a group have a lower economic status than other adults
in the United States (U.S. Census Bureau 1977; U.S. Senate 1987/88).
Although the percentage of older individuals living below the poverty level
(12.4 percent in 1984) has decreased substantially over the past two dec-
ades and is now less than the percentage of those under 65 living in poverty
(14.7 percent in 1984), poverty continues to be too high. The decline in
income most often results from retirement from the workforce, the effects
of inflation on fixed incomes, death of a wage-earning spouse, or failing
health (U.S. Senate 1987/88). Income and health status have been found to
be important determinants of life satisfaction in the older population (Chat-
field 1977). Low income is also a major risk factor for inadequate nutrition
in older individuals (DHEW 1974; Guthrie, Black, and Madden 1972).

Most older people do not live in institutions, but older Americans as a
group are more likely to be institutionalized temporarily or permanently
(Kane 1984). Although institutional food is likely to meet minimal stan-
dards for nutrient content, factors such as a lack of choice or limited day-to-
day variety may increase the risk of inadequate consumption. Many resi-
dents of nursing homes consume a therapeutic diet (NCHS 1981) that may
further discourage adequate intake. An important issue for demented
institutionalized individuals is that they may not consume the food, not that
the menu is inadequate (Sandman et al 1987).

Evaluation of the Nutritional Status of the Older Population

Methodological Issues
Assessing the nutritional status of the older population-and other popula-
tions-requires clinical studies to evaluate physical signs of nutritional
health or disease, dietary studies to evaluate nutrient intakes with accepted
standards, and laboratory investigations to provide data about quantities of
particular nutrients in the body or to evaluate certain biochemical functions
that are dependent on an adequate supply of a particular nutrient. Because
use of a single measure is rarely sufficient to establish the level of malnutri-
tion in a population, nutritional assessment is best accomplished using a

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combination of these methods. The greater the number of measurements
yielding values below standard, the more likely a population is to suffer
from poor nutritional status.

Nutritional status evaluation of older people is complicated, and a number
of methodological caveats should be kept in mind when evaluating the
results. Clinical and dietary standards for younger adults may not be
appropriate for older persons, yet few data are available on nutritional
requirements or recommended intakes of older adults. The Recommended
Dietary Allowances (RDA's), for example, were deveioped largely from
research on the nutrient needs of young healthy people. The present
standards for adults over age 50 are, for the most part, identical to those for
people ages 23 to 50 (NRC 1980). Because these standards fail to consider
the great heterogeneity of adults whose ages may differ by as much as 50
years (Schneider et al. 1986) and because they were often not developed
from actual measurements on older populations, their appropriateness for
older Americans is not known (Suter and Russell 1987).

Collection of dietary data in older individuals based on recording or recall-
ing food eaten over a specified period of time is complicated by an In-
creased prevalence of dementia and forgetfulness in older persons, which
may result in underreported nutrient intakes (Beaton 1985; Hunt et al.
1983). It has also been difficult to separate behavioral changes in dietary
intakes from the effects of aging processes on dietary and nutritional status.
For example, 70 percent of a sample of older subjects indicated some
change in food habits in recent years for health reasons, changes in living
status, beliefs, or finances (Todhunter 1976). The Ten State Nutrition
Survey found that two-thirds of the older population had changed their
diets in the 4 years before the study (DHEW 1972). Male participants in the
Baltimore Longitudinal Study of Aging reduced their cholesterol intake
significantly during the period 1961-75 (Elahi et al. 1983). Whether advice
from health professionals is responsible for such changes has not been
established. However, these changes need to be considered when making
inferences about the effects of aging processes on nutrition in older persons
taken only from surveys conducted at a single point in time.

Similar issues apply to use of laboratory tests, body measurements, and
body weights to assess the older population's nutritional status. Evaluation
of height and weight measurements to define obesity, for example, is
complicated by the loss of stature that accompanies aging (Bowman and
Rosenberg 1982). Measurements of actual heights, weights, and body
skinfolds in older populations have led to the development of standards
substantially different from those for younger adults (Frisancho 1984).

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Health status also affects such measurements; nutritional measures of
older homebound individuals differ significantly from those of younger and
less restricted groups (Sherman et al. 1983).

It is also difficult to make generalizations about clinical signs of undemutri-
tion in older persons. For example, changes in subcutaneous tissue and
skin that occur normally with age may mask clinical signs of vitamin
deficiency (McClean, Dodds, et al. 1976). However, NHANES did not find
high percentages of older people with biochemical indications of nutrient
deficiencies.

Perhaps the most serious problem in nutritional status assessment of older
people is the lack of correlation between dietary intake data and clinical and
laboratory assessment methods. For example, over the past 20 years,
several comprehensive nutritional surveys that included persons over age
60 have been performed in this country (DHEW 1972, 1974; Agricultural
Research Service 1972; USDA 1980; DHHS 1983). All of these studies have
identified a substantial proportion of older men and women who fell below
the RDA for calories-as well as for protein, vitamins, calcium, and iron
(Bidlack, Kirsch, and Meskin 1986; Young and Rivlin 1982). However,
estimates of obesity from anthropometric (body) measurements generally
show an increase in percent of body fat for both sexes as age increases
(Schlenker et al. 1973). NHANES I (DHEW 1974) and the Ten State
Nutrition Survey (DHEW 1972) found obesity to be a substantial problem
in the aged, especially in women. The findings of diminished calorie intake
and increased obesity are difficult to reconcile. The contradiction may
result from differences in criteria for evaluating the adequacy of dietary
versus biochemical data (DHHS/USDA 1986), the diversity of the study
populations, diminished physical activity among many older persons, or as
yet unknown metabolic factors. However, it is well established that body
composition changes in older people: the extremities lose fat that is re-
distributed to the trunk, and lean body mass is lost. Thus, the term obesity
in older populations may need redefinition.

Energy and Nutrient Status of the Older Population
Bearing in mind the methodological considerations discussed above, this
section highlights results from clinical, laboratory, anthropometric, and
dietary assessments of energy and nutrient status of the older population.

Energy. The national dietary and food consumption surveys conducted
during the 1970's reported lower energy intakes among older persons than
among younger adults (DHEW 1979a; DHHS 1983; USDA 1984), a finding

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that has been supported by smaller studies. A study of male executives in
the Baltimore Longitudinal Study of Aging, for example, found a steady
decline in average energy expenditure from 2,700 k&/day at age 30 to 2,100
kcaYday at 80 years of age. The decline in energy expenditure was at-
tributed to reduced physical activity (400 kcal) and to a 200 kcal decline in
basal energy metabolism as a result of a reduction in lean body mass with
age (McGandy et al. 1966). Aging was also inversely associated with energy
intake among 180 male participants (35 to 74 years old) in the same study of
aging (Elahi et al. 1983). A 4-year longitudinal study of free-living healthy
older men and women whose average age was 7 1 showed a decline in energy
intake of 162 and 152 kcal, respectively, to an average energy intake of 2,118
kcal/day for men and 1,545 kcal/day for women (Garry, Goodwin, and Hunt
1985). These levels of energy intake were determined from 3-day diet
records and were substantially higher than those recorded for older sub-
jects between 65 and 74 years of age in NHANES I and II and in the 1977-78
NFCS (DHEW 1979a; DHHS 1983; USDA 1984).

NHANES I reported lower caloric intake among older black Americans
than among white Americans (DHEW 1979a), as did the 1977-78 NFCS for
older black versus white men (USDA 1984). NHANES II did not present
data by race within age, sex, and income groups because the number of
black persons within those groups was too small to provide reliable esti-
mates (DHHS 1983). However, NHANES II indicates that the percentages
of overweight women are greater than men, although both sexes increase in
weight until late mid-life when rates plateau and then decline into old age.
Black women become overweight earlier in life than whites, but weight
patterns of black males are similar to their white counterparts. of the ap-
proximately 3,500 older persons examined in the NHANES I sample,
which is representative of the U.S. civilian, noninstitutionalized popula-
tion between 65 and 74 years of age, the mean energy intakes for the white
and black males were 1,828 and 1,571 kcal/day, respectively; for white and
black older females, the mean energy intakes were 1,3 19 and 1,186 kcal/day
(NCHS 1977). These energy intakes represented 77 percent of the RDA's
for white females and 69 percent for black females. The percents of the
RDA standard were 75 and 64 for white and black males, respectively. Even
when a conservative estimate of the 67 percent of the RDA standard is
used, about 50 percent of the individuals 65 years and older met this level of
intake. These levels were related to income: energy intake for those with
income below the poverty level was less than the population mean regard-
less of sex and race. These surveys were conducted on healthy free-living
individuals; most surveys of institutionalized older individuals have re-
ported even less energy intake than that of individuals living at home
(Stiedemann, Jansen, and Harrill 1978; Hart-ill and Cervone 1977; Jordan
1976).

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Although it is difficult to interpret dietary intake studies of older Americans
because of methodological problems, existing studies almost always reveal
decreases in energy intake with age that may also be influenced by income,
race, food preference, and drug use. A low-calorie diet may not impair
health as long as the nutrient density of the diet is high and can provide
adequate amounts of essential nutrients. However, this issue has not been
examined in great detail because nutrient requirements in old age remain
largely unkown.

Consequently, the increasing level of obesity among older persons, as
indicated by higher weight-for-height with age (Frisancho 1984), requires
explanation. Whether the inconsistency between reported low energy in-
take and increasing body weight is due to measurement errors, inappropri-
ate standards, loss of height with age (Bowman and Rosenberg 1982), or
lack of physical activity has not been established.

Prorein. A 30-day continuous metabolic balance study of seven men and
eight women over 70 years of age who consumed RDA levels of protein and
energy found that about half were unable to maintain nitrogen balance on
this level of protein (0.8 g of protein/kg/day). The results suggested that
higher intakes were required (Gersovitz et al. 1982) to meet protein require-
ments. Other studies that examined protein requirements of older persons
have also concluded that protein requirements may be higher (Munro 1983)
even though mean protein intake usually exceeds the RDA (Brown et al.
1977; Jordan 1976; McClean, Weston, et al. 1976; Grotkowski and Sims
1978; Garry, Goodwin, Hunt, Hooper, et al. 1982; McGandy et al. 1986).
Other studies reported lower protein intakes: at least 24 percent of the
women in nursing homes and 29 percent in private homes consumed less
than the RDA for protein (Jansen and Harrill 1977; Justice, Howe, and
Clark 1974), and in another study, 12 percent of the men and 40 percent of
the women living at home failed to meet this criterion (Jordan 1976).
Because the RDA for protein includes a substantial safety margin and
because clinical measurements have rarely found signs of protein deficien-
CY among healthy older persons, it is not possible to conclude from these
data that persons with intake below the RDA are protein deficient or that
they would benefit from additional protein intake.

Calcium. Older people, especially Caucasian women, lose bone mineral
and have a higher incidence of fractures than younger persons (Seeman and
Riggs 1981). The mechanism behind the age-related loss of bone calcium is
discussed in the chapter on skeletal diseases. Metabolic and absorptive
factors as well as low intake may contribute to chronic negative calcium
balance (Heaney, Reeker, and Saville 1978; Horsman et al. 1980; Spencer,


O Nutrition and Health

Kramer, and Osis 1982). Reduced efficiency of intestinal calcium absorp-
tion (Avioli, McDonald, and Lee 1965; Gallagher et al. 1979; Alevizaki,
Ikkos, and Singuelakis 1973; BulIamore et al. 1970; Ireland and Fordtram
1973) may be due to inadequate dietary intake (Heaney, Reeker, and Saville
1977; Vinther-Paulsen 1981; Garry, Goodwin, Hunt, Hooper, et al. 1982;
Omdahl et al. 1982; Koplan et al. 1986), age-related changes in gastric
acidity, and/or interactions of intestinal constituents such as fiber, bacteria,
and other nutrients. Perhaps in some individuals a negative effect on
calcium nutriture may be caused by age-related changes in hormonal
control (parathyroid hormone, calcitonin, prolactin, steroids, growth hor-
mones), aberrations in vitamin D metabolism, and imbalances of protein,
phosphorus, alcohol, and electrolytes with calcium (Riggs and Melton
1986).

The RDA for calcium of 800 mg/day (NRC 1980) may not be sufficient to
maintain calcium balance in populations consuming Western-type diets
(Heaney, Reeker, and Saville 1978; Matkovik et al. 1979; Reeker and
Saville 1977; Reeker and Heaney 1985; Consensus Development Panel
1984).

NHANES and NFCS reported mean intakes of about 700 to 720 mg for
older men and 540 to 590 mg for older women (DHEW 1979a; DHHS 1983;
USDA 1984). Other surveys have also reported that dietary calcium intake
by older people is often marginal. For example, 43 percent of women in
nursing homes failed to get two-thirds of their calcium requirement
(Stiedemann, Jansen, and Harrill978; Brown et al. 1977). Women living at
home consumed even less calcium than those in nursing homes (Brown et
al. 1977). One study reported that women, on the average, consumed only
two-thirds of the RDA for calcium (Grotkowski and Sims 1978). Whereas
some studies have reported similarly low calcium intakes among men (660
mg/day) (Brown et al. 1977; McClean, Weston, et al. 1976), others have
found that intakes among older males equaled or exceeded the RDA of 800
mg/day (Stiedemann, Jansen, and Harrill 1978; Grotkowski and Sims
1978). Older people may have reduced calcium intake because they avoid
dairy products containing lactose, to which they are intolerant (Goodwin,
Hunt, et al. 1985; Heaney et al. 1982).

Iron. As with people of all ages, the frequency with which anemia occurs in
the older population and determination of its etiology depend on the
criteria used for diagnosis (see chapter on anemia). Few data on the iron
status of older persons in the United States are available, and most studies
report conclusions based on hemoglobin and hematocrit values with, at
most, only one other index of iron nutrition (Lynch et al. 1982). One


national study-NHANES 1 (DHEW 1979b) and three regional studies
(O'Neal et al. 1976; Fisher, Hendricks, and Mahoney 1979; Htoo, Kofkoff,
and Freedman 1979), for example, found that more than 10 percent of older
white men were anemic (when a hemoglobin level less than 14 g/d1 was
considered diagnostic). When a hemoglobin level less than 12 g/d1 was used
to identify anemia in women, these same studies found older white women
to have a lower prevalence of anemia than men. These studies included
older men who were not screened for diseases that can greatly reduce red
blood cell production, such as chronic infections, renal disease, and neo-
plasms that result in chronic blood loss. Such data may indicate that the
standard for low hemoglobin levels for men are too high. although age-
related lower testosterone levels may reduce hematopoiesis and might also
account for this difference (Lipschitz, Mitchell, and Thompson 1981).

Another study examined biochemical measures of iron status in healthy
older persons and concluded that anemia or impaired iron status was no
more prevalent in this population than in younger healthy adults when
identical criteria were used to assess iron nutritional status (Garry, Good-
win, and Hunt 1983). A later longitudinal study revealed significant vari-
ability in the population mean values for all biochemical measures of iron
nutriture except plasma iron; however, none of the changes suggested an
increased risk of anemia. Comparison of older subjects who took iron
supplements with those who did not showed no clinically significant differ-
ences in the biochemical measures of iron status (Garry, Goodwin, and
Hunt 1985).

Because iron stores or reserves, as determined by plasma ferritin measure-
ments, increase with age, studies that examine only dietary intake of iron in
older people need to be interpreted cautiously (Casale et al. 1981). Low
dietary iron intake at one point in time does not necessarily increase the
risk for anemia because iron may still be available from body stores and
because absorption increases when intake and stores are low. In addition,
the type of iron and other components of a meal such as ascorbate also
influence the amount absorbed (see anemia chapter).

Some clinicians believe that an increased incidence of anemia in some
older people, compared with younger groups, is a direct and common
physiologic response to aging (Lipschitz, Mitchell, and Thompson 1981).
Evidence that bone marrow erythroid precursors are reduced in some
anemic older individuals supports this theory; whether this reduced blood-
forming capacity is due to aging per se or to some age-associated phenome-
non such as chronic disease or use of medications is not certain (Lipschitz
et al. 1984). Studies of very old healthy individuals find little evidence of


O Nutrition and Health

anemia and, therefore, support the contention that this condition is rare in
healthy older people (Zauber and Zauber 1987).

Data from NHANES II are illustrative here. The mean iron intakes for men
ages 65 to 74 years were 14.1 mg (about 1.4 times the RDA) and the
prevalence of impaired iron status correspondingly low. The values for
women of the same age were 10.2 mg, or about equal to the RDA for women
age 55 and over, with a corresponding low prevalence of impaired iron
status (DHHS 1983; LSRO 1984).

B Vitamins. Vitamin deficiency may be a result of decreased dietary intake,
absorption defects, decreased hepatic avidity for folate in Laennec's cir-
rhosis, decreased storage and conversion to active metabolic forms, or
excessive utilization, destruction, or excretion (Cherrick et al. 1965).

No comprehensive study of all the vitamins and their related enzyme
systems has been conducted, perhaps because laboratory facilities and
analytical technology are not sufficient to do all the necessary biochemical
evaluations (Brin and Bauemfeind 1978). Most studies have examined the
status of one or two vitamins. For example, a Boston study of older
subjects reported that 37 percent had inadequate blood levels of riboflavin
and 21 percent had low thiamin levels (Davidson et al. 1962). Biochemical
pyridoxine deficiency in older individuals has also been noted in enzyme
functional tests (Hoom, Filkweert, and Westerink 1975). A number of
studies have indicated a great risk for vitamin deficiencies in older persons
on the basis of low dietary intakes, but such deficiencies are not always
confirmed by biochemical or clinical results (Garry and Hunt 1986). In
addition, interpretation of biochemical parameters is hampered by lack of
data on normal standards for the older population (Kirsch and Bidlack
1987). For example, a New Mexico study revealed that more than one-
fourth of the older population consumed less than 75 percent of the RDA's
for folate and vitamins B, and B,, from diet alone (Garry, Goodwin, Hunt,
Hooper, et al. 1982). However, biochemical studies failed to confirm that
these individuals were at risk for developing clinical symptoms associated
with low intakes of these vitamins (Garry, Goodwin, and Hunt 1984).
Intake of vitamin supplements may explain part of this apparent discrep-
ancy, although analysis showed little statistical difference in mean dietary
intake for those individuals taking a specific supplement compared with
those who did not take the supplement (Garry, Goodwin, Hunt, Hooper, et
al. 1982).

Vitamin C. Studies have shown that the total body pool of ascorbic acid
reaches a maximum of approximately 20 mg/kg and that this level can be

608


achieved at a steady state plasma concentration of 1.0 mg/dl (Kallner,
Hartman, and Hornig 1979). Women require an intake of 75 mg/day and
men require an intake of 150 mg/day to achieve this ascorbic acid level in
plasma (Garry, Goodwin, Hunt, and Gilbert 1982). This finding was sup-
ported by a clinical trial that showed that a daily intake of 60 mg was
insufficient to maintain this plasma concentration (VanderJagt, Garry, and
Bhagavan 1987). The clinical significance of maintaining maxima1 plasma
ascorbic acid levels, however, has not been determined.

Some studies have reported low vitamin C intake and blood levels in both
institutionalized and free-living older persons (Leevy et al. 1965; Davidson
et al. 1962). Other studies reported intakes significantly greater than RDA
levels and very few individuals with clinical symptoms of hypovitaminosis
C (Garry, Goodwin, Hunt, and Gilbert 1982; Garry, Goodwin, Hunt,
Hooper, et al. 1982). For instance, one study found that less than 2 percent
of 270 free-living and healthy older persons over 60 years of age were at risk
for developing clinical symptoms of hypovitaminosis C, as measured by
plasma vitamin C concentrations below 0.2 mg/dl (Garry. Goodwin, Hunt,
and Gilbert 1982). The mean steady state plasma vitamin C level for
persons not taking supplemental vitamin C was 1.02 mg/dl-a level re-
po;ted to be sufficient t2 maintain a maximal body pool. Additional supple-
mental intake had little effect in raising plasma levels. Mean intakes of
vitamin C from the diet in that population were 137 mg/day and 142 mg/day
for women and men, respectively-approximately 2.4 times the RDA
(Carry, Goodwin, Hunt, Hooper, et al. 1982). In addition, over half were
taking supplemental vitamin C-mean levels of approximately 600 mg/day.

Vitrttnin A. Vitamin A deficiency does not seem to be a particular problem
in older persons. Although NHANES I and NHANES II reported that
about half the study population over age 65 had vitamin A intakes at or less
than two-thirds of the RDA, only 0.3 percent of the NHANES I older
Population had low vitamin A blood levels (Bowman and Rosenberg 19%
l)HHS 1983). Serum vitamin A was not available for adults from NHANES
ll (LSRO 1985). Whether vitamin A supplement use can account for the
klhrved discrepancy is unknown, but similar data suggest that older
individuals can maintain normal vitamin blood levels even with reportedly
h dietary intakes (Yearick, Wang, and Pisias 1980; Garry et al. 1987).

"i~~~t~litl 1). Previous studies have revealed a generally lowered vitamin D
"iitu\ in older people, chronically ill individuals (Petersen, Hall, and
Hrk\ 1981: Weisman et al. 198l), and those living in institutions (W&man
et ;tI. 1% I: Corless et al 1979. Vir and Love 1978) with little or no exposure
(" `l'nli&t (Lund and sore&en 1979; Baker, Peacock, and Nordin 1980;

609


0 Nutrition and Health

Lawson et al. 1979). Because the vitamin D endocrine system is the major
regulator of intestinal calcium absorption (Christakos and Norman 1978) a
reduced vitamin D status might promote a negative calcium balance in
older people (see chapter on skeletal diseases).

Two recent studies in the United States have found dietary intake of
vitamin D to be approximately 50 percent of the RDA for older subjects
(Garry, Goodwin, Hunt, Hooper, et al. 1982; Lee, Lawler, and Johnson
1981), and inadequate intake (especially of vitamin D-supplemented dairy
products) was well correlated with low blood levels of 25-hydroxyvitamin
D (Omdahl et al. 1982). However, ultraviolet light induced endogenous
production of vitamin D is the main external factor in maintaining adequate
vitamin D status. Because sunlight exposure activates vitamin D precur-
sors in skin, it has been recommended that older people obtain at least
minimal sunlight exposure (IO to 15 minutes) two or three times a week
(Holick 1986). Increased sun exposure may help compensate for aging
skin's decreased capacity to produce these precursors (MacLaughlin and
Holick 1985; Holick 1986). Supplements may be necessary to compensate
for inadequate sunlight exposure due to seasonal variation in northern
latitudes (Bouillon et al. 1987). Moderation in sun exposure should be
recommended because overexposure to the sun is a strong risk factor for
skin cancer.

Vitamin E. There is no evidence that older individuals are deficient either
in dietary intake or tissue levels of vitamin E (Kelleher and Losowsky
1978; Vatassery, Johnson, and Krezowski 1983; Garry and Hunt 1986),
despite statements that megadose vitamin E supplements retard the aging
process and prevent atherosclerosis and cancer (Bieri, Corash, and Hub-
bard 1983). Therapeutic doses of vitamin E have prolonged survival of red
blood cells in some inherited hemolytic anemias (Corash, Spielburg, and
Bartsocas 1980), but its use to treat or prevent other conditions has not
been established (Bieri, Corash, and Hubbard 1983).

Nutritional Supplements. It has been estimated that 37 percent of Ameri-
can adults consume a daily multivitamin preparation, fueling a more than
$2 billion per year industry (the Gallup Organization 1982; Herbert 1980;
Koplan et al. 1986). NHANES II indicated that the persons most likely to
take supplemental nutrients are less likely to need them, and those most in
need of them are least likely to take them (Koplan et al. 1986). In older
persons, vitamin use has increased dramatically in the past decade (Garry,
Goodwin, Hunt, Hooper, et al. 1982; Scheider and Nordlund 1983).
Whether such supplements improve the health of these people cannot be
determined from existing data (Mann et al. 1987), but it is clear that

610


excessive supplementation may be harmful. High doses of the fat-soluble
vitamins A and D are toxic.

Drug-Nutrient Interactions

Although older Americans constitute about 12 percent of the U.S. popula-
tion, they use about 25 percent of all prescription drugs (Lecos 1984/85).
This is not surprising because many chronic diseases associated with aging
are managed with prescription drugs. Over half of the older people take at
least one medication daily and many take six or more a day for multiple
diseases (Lecos 1984185). Cardiovascular drugs (e.g., diuretics) are most
widely used by the aging population, followed by drugs to treat arthritis,
neurologic disorders, and respiratory and gastrointestinal conditions.
Many unwanted drug-nutrient interactions in older persons have been
documented (see chapter on drug-nutrient interactions). The drug-nutrient
interactions outlined in another chapter of this Report apply to the older
person. However, this population requires special consideration because
aging per se changes the absorption, disposition, and elimination of drugs.
The older person with multiple diseases is at risk for additional drug-
nutrient interactions linked to separate drug therapies for primary and
secondary health problems. Even over-the-counter antacids, laxatives,
analgesics, and vitamin and mineral supplements may result in unwanted
drug-nutrient side effects in the older person (Roe 1985).

Effects of Nutritional Deficiencies on the Older Population

Morbidity and Mortality

Severe malnutrition-protein, calorie, vitamin, or mineral-is associated
with increased morbidity and mortality, and the relationship of malnutri-
tion to morbidity and mortality in older persons is of current interest. While
less severe forms of malnutrition may be detrimental to health, the evi-
dence has been more difficult to establish. Among severely ill or injured
hospital patients of any age, protein-energy malnutrition greatly increases
the risk for postoperative complications and overall morbidity and mor-
tality (Mullen et al. 1979; Kaminski, Fitzgerald, and Murphy 1977). This
association between nutritional status and survival does not prove a causal
relationship because poor nutritional status may be the result of the illness
or injury and not its cause. It is also difficult to demonstrate that moderate
nutrient deficiencies increase morbidity and mortality.

Several investigators have tried to correlate blood levels of vitamin C, for
example, with morbidity and mortality in an aging population. Among
patients admitted to an acute care geriatric unit, those with low ascorbate

611


cl Nutrition and Health

levels had a significantly higher mortality, but vitamin C supplements did
not improve survival in these patients (Wilson et al. 1972, 1973). One
prospective study reported dietary intake of vitamin C to be a significant
predictor of mortality in an aging population (Hodkinson and Exton-Smith
1976), although it was not possible to separate cause from effect in this
instance. Some older subjects with low vitamin C levels in blood exhibit
clinical signs of scurvy (Andrews and Brook 1966), but some do not
(McClean, Dodds, et al. 1976). Signs of scurvy may be slow to resolve with
supplementation in older subjects (Andrews, Letcher, and Brook 1969).
The clinical significance of this observation has not been established.

Immune Status

Considerable evidence documents an age-related decline in immune com-
petence, characterized by losses in T-lymphocyte and other functions.
Certain of these changes resemble those induced by malnutrition
(Thompson, Robbins, and Cooper 1987), but whether malnutrition is a
significant cause of depressed immune function in large numbers of older
individuals is uncertain. The large number of rodent studies that describe
well-nourished old animals regularly displaying weak immune responses
argues against the hypothesis that immunosenescence is due to malnutri-
tion (Shock et al. 1984).

As described in the chapter on infections and immunity, protein-energy
malnutrition in individuals of any age alters the proportion of T cell types,
depresses T cell function, impairs delayed hypersensitivity reactions, and
impairs thymic factor activity. Such changes are strongly associated with
increased susceptibility to infectious diseases (Mullen et al. 1979; Falchuk
et al. 1977). Impairment of delayed hypersensitivity and thymic factor
activity have also been documented for deficiencies of single nutrients
(Beisel 1982). Severe malnutrition is clearly related to impaired immune
function in some older people, and improved dietary intake can at least
partially correct these impairments. Current evidence is insufficient, how-
ever, to decide which, if any, age-related losses in T cell function are caused
by nutritional deficiencies or some other physiologic or environmental
factor (Thompson, Robbins, and Cooper 1987). The possible role of zinc
deficiency in loss of immune function in older people has received consid-
erable attention (Sandstead et al. 1982; Gershwin, Beach, and Hurley
1983).

If nutritional deficiencies are related to impaired immune function in older
people, correcting the deficiencies should improve this function. Among
hospitalized patients, intensive nutritional support does increase immu-

612


nocompetence (Law, Dudrick, and Abdou 1973). Among older people,
dietary supplements have been associated with improved antibody re-
sponses to viral vaccines (Chandra and Pm-i 1985) and several studies have
reported improved immune function as a result of zinc supplementation
(Duchateau et al. 1981; Thompson, Robbins, and Cooper 1987); others
have not (Brader et al. 1988). Whether these effects represent correction of
nutrient deficiencies or are secondary to some nonspecific effect of supple-
mentation is uncertain (Goodwin and Garry 1983).

Nemous System and Cognitive Function

Whether mental functions necessarily decline with age is questionable, and
whether dietary factors can influence mental status in older persons is also
uncertain. Results of psychometric testing in older people vary depending
on the group studied. Although large population studies have reported
gradual decreases in many mental functions with age (Nandy and Sherwin
1977), healthy, active older subjects do not display significant decrements
(Botwinick 1977). This discrepancy suggests that the reported decrements
in mental function are not inevitable age-associated events; rather, such
changes are secondary to the various diseases and physical conditions that
frequently accompany aging (Palmore 1974).

Alzheimer's Disease

Alzheimer's disease affects between 2 and 3 million Americans. The preva-
lence of this disease increases with age; while only 5 to 8 percent of people
age 65 and over are affected, 35 percent of those over age 85 are affected.
The cost of institutional care alone for Alzheimer's disease patients is
estimated to exceed $38 billion per year in direct costs and up to $80 billion
per year if indirect costs are considered (Huang, Cartwright, and Hu 1988).

The causes of Alzheimer's disease have not been established, but potential
risk factors include age, family history of Alzheimer's disease, and head
injuries. Further studies are needed to determine the validity and reliability
of these risk factors. Whether nutritional factors can alter the risk for this
condition is not known. High concentrations of aluminum have been found
in the neurofibrillary-containing neurons of deceased patients, suggesting a
relationship between aluminum and Alzheimer's disease. Such foci are not
observed in the brains of people who die from other causes (Per1 and Brody
1980). Despite these observations, there is no evidence that renal dialysis or
use of aluminum antacids, antiperspirants, or cookware increases the risk
for Alzheimer's disease (Katzman 1986), and the significance of the in-
creased brain aluminum concentrations is unknown. The roles of certain

613


u Nutrition anct Health

dietary antioxidants and toxic amino acids (Spencer et al. 1987) are under
study.

Because Alzheimer's disease is a neurodegenerative syndrome involving
cell loss and dysfunction, and because there is evidence that nutrient
variables can affect brain metabolism, it might be speculated that neurotox-
ins acquired through the food chain may be involved in brain cell death.
Therefore, researchers and clinicians should consider nutritional factors in
the etiology of Alzheimer's disease.

Implications for Public Health Policy

Dietary Guidance

General Public

Aging is accompanied by a variety of physiologic, psychologic, economic,
and social changes that may compromise nutritional status. However, ways
in which the aging process affects energy balance, specific nutrient require-
ments, and nutrient status remain to be fully elucidated. Older adults may
not necessarily have the same nutritional requirements as younger adults,
yet current estimates of the nutrient requirements of older persons are
based almost entirely on values extrapolated from data from studies of
younger adults. The ways in which nutritional status might influence
changes in tissue and organ function change with age and may influence the
relationships between dietary components and the occurrence of chronic
diseases of old age. Until more appropriate age-specific RDA's are estab-
lished, the current RDA's should continue to be used as standards for
nutrient intake of healthy older persons.

Until more is known, older Americans should consume sufficient nutrients
and energy and maintain levels of physical activity that maintain desirable
body weight and may prevent or delay the onset of chronic disease.
Because it is often difficult to maintain adequate nutrient intake on low-
calorie diets, older people should be advised to maintain at least moderate
levels of physical activity so as to increase caloric needs. Recommenda-
tions to the general population about calcium intake (see chapter on skel-
etal diseases) are true for older Americans. Because many of the chronic
diseases common to older persons may originate earlier in life (see chapter
on maternal and child nutrition), dietary guidance to prevent them should
be provided throughout life (as discussed in other chapters).

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Health promotion messages from the public and private sectors should
utilize advanced communication techniques, recognizing different life-
styles, decrements in vision and hearing, different cultural experiences,
and different learning styles that may be common to older people. Federal
and State agencies should provide information about successful public-
private sector models for nutrition, health promotion, and education for
older adults-for example, Healthy Older People, Age Well, and OASIS
(Older Adult Service Information System).

Special Populations

Sedentary older individuals should be counseled on appropriate methods
to increase caloric expenditure. Older persons who do not (or cannot)
consume adequate levels of nutrients from food sources and those with
dietary, biochemical, or clinical evidence of inadequate intake should
receive advice on the proper type and dosage of nutrient supplements.
Such supplements may be appropriate for some older persons, but self-
prescribed supplementation, especially in large doses, may be harmful and
should be discouraged. Older people who suffer from diet-related chronic
diseases should receive dietary counseling from credentialed health profes-
sionals, and those who take medications should be given professional
advice on diets that minimize food-drug interactions.

Nutrition Programs and Services

Food Labels

Evidence related to the role of diet in the aged currently holds no special
implications for change in policy related to food labeling, although the size
of the type on the label is a factor for most older consumers. Information
provided on food labels should be scientifically sound, understandable,
and nonmisleading.

Food Services

Food services, especially those receiving Government funds, should be
required to pay special attention to meeting the caloric and nutrient needs
of older clients. Nutritional assessment and guidance should be done at
hospital admission or enrollment in or discharge from institutional or
community-based services for older adults (e.g., acute and long-term care
inpatient services, hospital-based outpatient services, alcohol and drug
treatment programs, community health services, and home-delivered
meals programs).

61.5


O Nutrition and Health

Food Products

Evidence suggests that older people would benefit from food products that
provide a high proportion of available nutrients to calories, that have taste
appeal, and that are easy to prepare.

Special Populations

Older people who are homebound, who live in isolation, or who suffer from
chronic disease have special needs for nutrition services that are tailored to
their particular conditions. Considerable evidence supports the nutritional
and health benefits of dietary, economic, and social support programs for
the older population.

Research and Surveillance

Research on nutrition and aging currently focuses on two general areas-
the nutritional requirements and status of aging people and the influence of
diet on aging processes and related pathologies. Psychosocial interactions
with nutrition cut across both areas,

Research and surveillance issues of special priority related to the role of
nutrition in the aged should include investigations into:
o The nutrient and energy requirements of older adults, currently ex-
trapolated from younger age groups.
0 The effects of dietary restriction and overconsumption -on longevity
and age-related pathology. -
o The interactions among nutritional status, lifestyle and behavior, and
  the environment in older Americans.

0 The effects of nutrition on age-related impairment of the cardiovascu-
lar, gastrointestinal/oral, immune, musculoskelctal, and nervous sys-
tem functions and on prevention and treatment of disorders of those
systems.

o The effects of marginal nutrient and energy deficiencies on the mental
and physical health of older persons.
o Interactions among nutrients and between nutrients and drugs in older
adults.

0 Development of data bases for use by pharmacists and dietitians in
counseling older persons on drug-nutrient interactions.
0 Age-specific methods and standards to assess the nutritional status
and body composition of older adults.

.616


o The educational methods and program strategies that best promote
adequate food consumption by older persons.
o Improved methods to monitor the nutritional status of older popula-
tions and individuals, including institutionalized older adults, over
time.

o The educational and public health strategies that can be used to elimi-
nate nutrition-related health fraud directed toward older citizens.

617


O Nutrition and Health

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O'Neal, R.M.; Abrahams, O.G.; Kohrs, M.B.; and Eklund, D.L. 1976. The incidence of
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Chapter 17

Alcohol

Inflaming wine, pernicious to mankind,
    unnerves the limbs,
   and dulls the noble mind.
         Homer
  The Iliad, VI 261 (850 B.C.)

Introduction

Alcohol (ethanol) is of importance to nutrition because it provides energy
and because its ingestion can affect the requirements for and the intake,
digestion, absorption, transport, storage, metabolism, and excretion of
many other nutrients. Few generalizations can be made regarding the
effects of alcohol on nutritional status because these depend on complex
interactions between the type, quantity, and duration of alcohol consumed
and the overall nutrient intake from the diet. These interactions are highly
dependent upon behavioral and socioeconomic factors and predisposing
genetic factors. Chronically excessive alcohol use is often associated with
symptoms, signs, and biochemical evidence of nutritional deficiencies, but
these are largely the secondary effects of reduced consumption of other
kinds of food and drink. The effect of moderate or occasional drinking is
less well documented.

Historical Perspective

Fermented beverages have been consumed in most societies since antiq-
uity, in part because fermentation provided one of the earliest methods of
food preservation (Ghalioungui 1979). In some societies, indigenous foods
that contained alcohol as a result of fermentation may have offered protec-
tion against the development of deficiencies of vitamins, amino acids, and
other essential nutrients (Steinkraus 1979; Darby 1979).

Socioeconomic factors have always affected the pattern of alcohol abuse
and its complications in different societies. In ancient Greece, for example,

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wine drinking was confined largely to the upper classes, and beer drinking
to the lower classes. In industrialized England of the 18th century, gin was
the drink of the poor, while port was drunk by the affluent, whose episodes
of gout were attributed to the contamination of port with lead.

Distilled spirits, in contrast to fermented foods and beverages, provide
concentrated sources of alcohol and calories largely without other nu-
trients. Although the process of distillation was known at least as early as
the fourth century B.C. (Ghalioungui 1979), the consumption of distilled
spirits tended for centuries to be limited to the more affluent who also had
access to varied diets. In Western Europe, distilled alcoholic beverages
were not widely available to the poor until the Industrial Revolution. In
England, government policies that liberalized controls on production and
distribution of alcoholic beverages led to the widespread "gin epidemic,"
and further legislation was then required to prohibit sales and prevent
adverse consequences (Roe 1979).

Out of this history grew a series of health and social reform movements,
including the prohibitionist movement in the United States. In their efforts
to change society's behavior, most health reform advocates focused on the
extreme consequences of alcohol abuse, using selected medical and scien-
tific data to support their arguments (Whorton 1982). This, in turn, led to
distortions in understanding the nutritional consequences of alcohol use.
For example, many studies examined the habits of accessible derelict or
vagrant alcoholics or provided descriptive reports that were easier to
obtain than biologic determinations of specific pathophysiologic mecha-
nisms.

The attitudes toward alcohol of the 19th and early 20th centuries remain
prevalent today, and many people are uncertain and misinformed about
interactions between alcohol and nutrition. Recent efforts from the U.S.
Department of Health and Human Services have focused on providing the
scientific community and the public with current information about this
area. Thus, alcohol consumption has been identified as a dietary practice in
need of change in several Federal publications. Examples include those
listed below.

Healthy People: The Surgeon General's Report on Health Promotion and
Disease Prevention, 1979. This report recommends reducing misuse of
alcohol. It includes information on prevention programs that stress the
importance of educating the public on the effects of alcohol consumption,

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altering the social climate of its acceptability, reducing individual and social
stress factors that might increase consumption, and enforcing existing laws
(DHEW 1979).

Nutrition and Your Health: Dietary Guidelines for Americans (second
edition), 1985. One of the seven recommendations is "If you drink alcohol,
do so in moderation." The discussion of this guideline emphasizes the
caloric contribution of alcohol to the overall diet, especially for individuals
who are overweight, but notes that one to two drinks daily appear to cause
no harm in adults. It warns pregnant women that excessive alcohol con-
sumption may cause birth defects at the same time that it acknowledges that
the "level of consumption at which risks to the unborn occur has not been
established" (USDADHHS 1985).

Promoting HealthlPreventing Disease: Objectives for the Nation, 1980.
These health objectives include specific recommendations for methods to
reduce deaths due to alcohol-related behavior, accidents, and disease by
the year 1990 (DHHS 1980).

Promoting HealthlPreventing Disease: Public Health Service lmplementa-
tion Plans for Obtaining Objectives for the Nation. This report identities
priority objectives for prevention of alcohol misuse and outlines Federal
efforts in education, grant support, technical assistance, economic incen-
tives, and research and surveillance measures aimed at achieving them. It
also assigns to specific agencies the primary responsibility for each of the
implementation steps and provides data on the anticipated date of initiation
of each step (DHHS 1983).

The Sixth Special Report to the U.S. Congress on Alcohol Abuse and
Health from the Secretary of Health and Human Services. This report
provides the most comprehensive statement to date of current knowledge
in the epidemiology of alcohol abuse and alcoholism; the genetics, psycho-
biologic effects, and medical consequences of alcoholism; the effects of
alcohol on pregnancy outcome; the adverse social consequences of alcohol
abuse; trends in treatment, research, and practice; and perspectives on
prevention (DHHS 1987).

The 1990 Health Objectives for the Nation: A Midcourse Review, 1986.
This report provides data on progress toward achieving the 1990 objectives
for prevention of deaths due to alcohol misuse. Although it notes im-
pressive achievements in reducing alcohol-related motor vehicle accident

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fatalities and deaths due to cirrhosis, it stresses the importance of multi-
disciplinary approaches to prevention of the adverse health consequences
of individual behavior associated with alcohol consumption (DHHS 1986).

Significance for Public Health

Although the nutritional elements of the public health impact of alcohol
abuse are still being defined, in and of itself, misuse of alcohol is one of the
most preventable health problems in the United States. As mentioned
above, prevention of the adverse consequences of alcohol misuse is a major
health objective for the year 1990 (DHHS 1986). Excessive alcohol intake is
a prominent contributor to 4 of the 10 leading causes of death in the United
States-cirrhosis of the liver, motor vehicle and other accidents, suicides,
and homicides (NCHS 1986). As discussed in the cancer chapter of this
Report, chronic alcohol abuse also increases the risk for oral, esophageal,
liver, and other types of cancer.

In 1980, it was estimated that nearly 20,000 deaths could be directly
attributed to alcohol use, from alcoholic liver disease, alcoholism, alco-
holic psychosis, alcoholic cardiomyopathy, alcoholic gastritis, alcoholic
polyneuropathy, nondependent use of alcohol, and accidental poisoning by
alcohol. Almost 78,000 fatalities could be indirectly attributed to alcohol
use (Ravenholt 1984). In 1983, about 42 percent of all motor vehicle deaths
were alcohol related. Problems such as homicides and automobile acci-
dents that are indirectly related to alcohol consumption have the highest
rates among young adult males ages 18 to 24. Excessive alcohol intake
during pregnancy is estimated to cause birth defects in 1,400 to 2,000 babies
annually. The costs of the medical and social consequences of excessive
alcohol intake were estimated to be $117 billion in 1983 (DHHS 1987). In
the late 1970's, 19 percent of adolescents reported problems related to
drinking alcohol. Among adults over age 18, approximately 10.6 million are
alcohol dependent and another 7.3 million experience alcohol-related ad-
verse consequences (DHHS 1986).

Recent trends suggest that both the intake of alcohol and its adverse health
consequences are declining in this country. Overall per capita ethanol
consumption increased annually from 1977 to 1980, reached a plateau in
1980 and 1981, and then began an annual decline until 1985, when it was
slightly below the 1977 level (Laforge et al. 1987). Beer consumption in 1985
was 3 percent above the 1977 level; wine consumption per capita increased
over the entire period of 1977 to 1985, and in 1985 it was 31 percent higher
than in 1977. Per capita consumption of spirits, however, declined over this

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Alcohol O

entire period, and in 1985 was 15 percent below the 1977 level (Laforge et
al. 1987). There has also been a slow decline in deaths attributable entirely
to alcohol-related causes since 1980 (Berkelman et al. 1986).

Scientific Background

Quantitative Aspects of Alcohol Consumption Among Individuals
Different units are used to record the quantity of alcohol intake among
individuals. Commonly used units are grams or ounces of pure alcohol.
There are approximately 15 g of alcohol in each of the following standard-
sized drinks: I-% oz of 80 proof liquor, 5 oz of table wine, and 12 oz of beer
(Bennington and Church 1985).

Consumption of Alcoholic Beverages

The proportion of U.S. adults who drink alcoholic beverages depends on
both the region of the country and sociocultural background. Estimates of
the various categories of drinkers in the population are usually based on
survey information, and the estimated quantities consumed are often based
on self-reports. Such surveys indicate that about 33 percent of the general
population say they do not drink alcohol at all; 34 percent are light drinkers,
who say they drink from one to three drinks per week; 24 percent are
moderate drinkers, who report consuming fewer than two drinks a day; and
9 percent are heavy drinkers, who average two drinks a day or more (Moore
and Gerstein 1981). In studies ofthe heaviest drinkers (i.e., alcohol abusers
and alcoholics), the quantity of alcohol consumed is very difficult to
ascertain, and clinical criteria for the diagnosis of alcoholism usually must
depend on factors other than alcohol intake information (Task Force on
Nomenclature and Statistics 1980).

Although this classification into light, moderate, and heavy drinkers seems
reasonable and is used in this chapter, it is arbitrary and not universally
accepted. For example, in the Honolulu Heart Study, consumption of two
to three drinks per day was considered moderate, but, according to the
above classification, it would be considered heavy consumption. The use of
the Michigan Alcoholism Screening Test (a short questionnaire shown to be
efficient in identifying alcoholics) and other alcoholism screening tests
such as the Self-Administered Alcoholism Screening Test (Swenson and
Morse 1975) may prove important in separating alcoholic from non-
alcoholic persons by standard criteria rather than by self-reports.

Surveys also reveal wide regional variations, especially among the percent-
age of individuals who say they abstain completely from alcohol (e.g., 14

633


0 Nutrition and Health

percent in western New York State, 32 percent in San Francisco). The
percentage of heavy drinkers, adults who report drinking two drinks or
more a day, ranges from 9 percent nationwide to 23 percent in Boston and
24 percent in western New York State (Barnes and Russell 1978; Wechsler,
Demone, and Gottleib 1978).

The frequency of alcohol consumption reported by high school students
differs from that reported by adults in national surveys. In a 1985 nation-
wide survey of about 17,000 high school seniors conducted by the National
Institute on Drug Abuse, only 8 percent of seniors said they had never used
alcohol. Nearly 5 percent of seniors drank every day, and 37 percent
reported episodes of heavy drinking (five or more drinks per occasion)
during the previous 2 weeks (DHHS 1987).

Categories of Beverages Consumed and Types of Drinkers

Since 1934. the consumption of alcohol in the United States, based on
statistics from commodity sales, has increased almost continuously, and in
1984 the annual per capita intake in terms of absolute alcohol was 2.65 gal/
person 14 years of age or older (DHHS 1987). As one-third of the U.S. adult
population abstains from alcohol, those who drink consume an average of
1.3 oz of absolute alcohol per day. These distinctions become even more
important when examined more closely: the heaviest drinking 5 percent of
the population accounts for about 50 percent of total alcohol consumption,
and the heaviest drinking 33 percent accounts for over 95 percent of total
alcohol consumption. Given the presumed absence of impact of alcohol on
the nutrition of the one-third of the population who abstain, and negligible
impact on that of the one-third who are light drinkers, the group of primary
interest from this perspective is this latter group.

Over time, consumption of the various types of alcoholic beverages has
changed. Beer is now the most prevalent alcoholic beverage consumed,
accounting for almost 50 percent of the alcohol consumption in the United
States. Distilled spirits account for nearly 39 percent and wine for 12
percent. The wine industry was virtually dismantled as a result of Prohibi-
tion but has recently made significant advances in recapturing part of the
market and appears to be continuing to increase its share of sales. The
types of distilled spirits consumed have also changed with time; in recent
decades, there has been a shift from whiskey to other forms of distilled
spirits, such as gin and vodka.

Alcohol Abuse and Alcoholism
The essential feature of alcohol abuse is a pattern of pathologic moderate to
heavy alcohol use for at least a month that causes impairment in social or

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Alcohol O

occupational functioning. The accepted diagnostic criteria, as defined in
the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) of
the American Psychiatric Association, are useful for such patterns of
chronic, pathologic alcohol consumption (Task Force on Nomenclature
and Statistics 1980). DSM-III criteria describe three main patterns of
alcohol abuse: (1) regular drinking of large amounts, (2) regular heavy
drinking but limited to weekends, and (3) episodic binges of heavy daily
drinking lasting weeks or months, interrupted by long periods of sobriety.
These criteria for the diagnosis of alcoholism also include either a pattern of
pathologic alcohol use or impairment in social or occupational functioning
and either central nervous system tolerance or withdrawal symptoms.

The number of Americans with alcohol problems is estimated to be as high
as 18 million (DHHS 1987). In an outpatient medical setting using the Self-
Administered Alcoholism Screening Test, the prevalence of abstainers was
13 percent and the prevalence of possible or probable alcoholism was 5.4
percent (Hurt, Morse, and Swenson 1980). The prevalence of alcoholism in
general hospitals, estimated by using the Michigan Alcoholism Screening
Test, was 18 percent for men and 5.5 percent for women (Moore 1971). In
emergency room patients, the prevalence of alcoholism may be as high as
30 percent of patients during the evening hours (Rund, Summers, and
Levin 1981). However, precise statistics for the prevalence of alcoholism
are not available now, nor are they likely to become so in the near future,
because alcoholism is diagnosed infrequently, especially in its earlier
stages.

Physiology of Alcohol Use

Absorption. Alcohol is readily absorbed from all levels of the gastroin-
testinal tract, and blood concentrations rise rapidly after ingestion. Overall
absorption of alcohol depends partly on the rate of gastric emptying. Food,
particularly fat, delays gastric emptying and stimulates gastric secretion,
thereby diluting the concentration of alcohol and blunting its rapid absorp-
tion into blood.

Absorption across the gut mucosa appears to occur as a result of passive
diffusion. The rate of absorption varies as a function of the concentration
gradient, the area and permeability of the absorbing surface, and the
volume of regional blood flow (Kalant 1971). During the first 15 minutes
after oral administration, maximum alcohol levels are rapidly found in the
stomach, duodenum, and proximal jejunum; at 90 minutes, peak levels are
found in the mid-jejunum. Alcohol levels in the ileum parallel those in the
blood, suggesting that the ileal concentration results from passage of alco-
hol from the blood back into the lumen rather than from transit along the

635


O Nutrition and Health

small bowel (Halsted, Robles, and Mezey 1973). Infusion of alcohol directly
into the duodenum, the first segment of the small intestine where most
nutrients are absorbed, causes blood levels of alcohol to rise as high as
those following direct intravenous administration, and these levels rise
much more rapidly than those that occur when alcohol is infused into the
stomach.

Distribution. Once absorbed, alcohol diffuses rapidly across capillary and
other cell membranes and is distributed uniformly throughout all extra-
cellular and intracellular body water. At equilibrium, the concentration of
alcohol in all tissues is proportional to the tissue water content, so that
differences in the volume of body water among people can help to explain
why some individuals are apparently more susceptible than others to the
pharmacologic and toxic effects of alcohol. Smaller, lighter people are more
susceptible to the effects of alcohol than larger, heavier people simply
because their fluid volume is less. For a given body weight, the volume of
body water is less in females than in males, and less in older people than in
younger people; therefore, a given dosage of alcohol can be expected to
produce higher blood concentrations in women and older persons and to
affect them more (Vestal et al. 1977).

Metabolism. Alcohol is metabolized by the liver first to acetaldehyde, then
to acetate, and, finally, to carbon dioxide and water. Three separate enzyme
systems can account for the initial oxidation of alcohol to acetaldehyde
(Badawy 1978; Lieber 1984; Pirola 1978). Quantitatively, the most impor-
tant system is that involving alcohol dehydrogenase, an enzyme found in
the cytoplasm of liver cells. The acetaldehyde produced is rapidly oxidized
to acetate by the enzyme acetaldehyde dehydrogenase, resulting in little
accumulation of acetaldehyde in either the liver or blood.

Alcohol and acetaldehyde dehydrogenases exist in several forms, which
oxidize alcohol and acetaldehyde at different rates. These enzyme varia-
tions may account in part for observed differences in rates of alcohol
metabolism among individuals of different genetic backgrounds and may
help explain, for example, why some people of Oriental or American Indian
heritage have lower tolerances for alcohol consumption (DHHS 1985).

A second enzyme system located in the liver, called the microsomal eth-
anol-oxidizing system (MEOS), probably plays a relatively minor role in
alcohol metabolism, at least at low concentrations, but it has significant
activity at higher concentrations of alcohol. This system can be stimulated
by chronic exposure to high levels of alcohol. This is associated with cross
induction of the metabolism of other drugs, such as the anticonvulsants

636


Alcohol 0

hydantoin and phenytoin, the barbiturates, the sedative meprobamate, the
tricyclic antidepressants, the phenothiazine tranquilizers, and oral anti-
coagulants (Pirola 1978). The inducibility of this system results in interac-
tions between alcohol and other drugs that may alter the rate of disappear-
ance of alcohol and other drugs from the body (see chapter on drug-nutrient
interactions) and may activate a variety of hepatotoxic agents and carcino-
gens.

A third enzyme system, the catalase system, appears to be of minor
importance in the metabolism of alcohol and is not stimulated by chronic
consumption of alcohol. Several other minor metabolic pathways, such as
glucuronide and sulfate conjugation and fatty acid esterification, have been
identified, but their importance remains unclear.

Some of the metabolic consequences of alcohol consumption can be ex-
plained by shifts in oxidation-reduction balance that occur as a conse-
quence of ethanol oxidation. Reduced nicotinamide-adenine dinucleotide
(NADH) is produced as a result of the oxidation of ethanol by the alcohol
dehydrogenase enzyme system and by the further oxidation of
acetaldehyde to acetate. An increased supply of NADH relative to NAD
may affect carbohydrate, lipid, and protein metabolism and account for
alterations in the hepatic metabolism of steroids, biogenic amines, some
drugs, and, perhaps, even some toxins. Other deleterious effects of alcohol
ingestion have been attributed to aldehyde or its cytotoxic interactions with
body proteins (Wickramsinghe, Gardner, and Barden 1987).

Excretion. More than 95 percent of the alcohol ingested is oxidized in the
liver to carbon dioxide and water, and the remainder is excreted in the
urine, feces, perspiration, and expired air.

Key Scientific Issuesa

o Effect of Alcohol on Nutritional Status and Energy Balance
0 Role of Alcohol in Diseases of the Liver
0 Role of Alcohol in Diseases of the Nervous System
o Role of Alcohol in Cardiovascular Diseases
o Role of Alcohol in Reproductive Disorders

aThe role of alcohol in cancer, diabetes, and osteoporosis is not covered here but is
reviewed in the chapters devoted to those conditions.

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O Nutrition and Health

Effect of Alcohol on Nutritional Status and Energy Balance

Whether alcohol injures organs directly because of its toxic effects on
tissues or indirectly because of the nutritional deficiencies it causes has
been a subject of debate for decades. In the mid-18th and 19th centuries,
alcohol was considered a toxin and was classified with other poisons, such
as arsenic, mercury, and ergot. The discovery of vitamins in the 20th
century gave momentum to studies of the association between alcohol
consumption and nutritional status, especially between 1920 and 1940.
Similarities between complications of alcoholism such as those affecting
the nervous system and various vitamin deficiency states led to the belief
that most physical manifestations of alcoholism had a nutritional basis.

The malnutrition observed in alcoholics was proposed as the primary
reason for the organ and tissue damage found so frequently in this popula-
tion. Patients with severe alcoholic liver disease and ascites who were
given a diet high in protein and B-complex vitamins had a better prognosis
than those provided with a regular diet, and there was a significant associa-
tion between the occurrence of nutritional deficiency and the occurrence of
alcoholic cirrhosis (Patek and Post 1941). This finding suggested that eating
a diet high in protein and B-complex vitamins would protect an individual
from the effects of alcohol. Because so many nutritional deficiencies were
observed in derelict alcoholics, the assumption naturally was made that
similar but milder nutritional deficiencies were present in all other alco-
holics.

By the early 1960's, however, many of the clinical consequences of alco-
holism were shown to be the direct toxic effects of alcohol itself (Lieber
1966). Most recent evidence points to the toxic effect of alcohol or its
metabolic byproducts as the primary mode of liver injury. In addition,
possible genetic differences in predisposition to the direct toxic effects of
alcohol have been recognized. The effects of alcohol on the nutritional
status of nonalcoholic social drinkers remains to be defined.

Excessive alcohol intake increases the risk for malnutrition through a
variety of pathophysiologic mechanisms, including direct and indirect
alterations in both nutrient intake and requirements, digestion, absorption,
transport, storage, metabolism, and excretion. For any nutrient, alcohol
may affect one or more of these processes. The following sections summa-
rize what is known about the most important interactions between alcohol
and each major nutrient. The reported effects of alcohol vary greatly,
depending on how much and how long it is consumed. In some cases,

638


Alcohol O

marked differences among animal species have led to apparently contradic-
tory and confusing experimental results.

Energy

At the turn of this century, Atwater determined that ethanol provides 7
kcal/g, and ever since then this amount has been used as the basis for
calculating the contribution of alcohol to total energy intake (Passmore
1979). The use of this conversion factor assumes that the energy in alcohol
is fully available to the body. Based on this conversion factor, only 3 to 7
percent of the calories consumed by all Americans over the age of I4 are
derived from alcohol, but if nondrinkers are excluded, alcohol provides
over IO percent of the calories consumed by adult drinkers in the United
States (Williamson et al. 1987).

Many observations suggest that the caloric contribution of alcohol is more
complex than can be explained by the Atwater conversion values, and
therefore, the concept of alcohol and energy balance has recently been
revised. If, for example, alcohol provides an average of 20 percent of the
calories in the diet of the average drinking American adult, then many
alcoholics consuming much larger amounts ought to be obese. Instead,
national data indicate that despite higher energy intakes, drinkers are no
more obese than nondrinkers (Gruchow et al. 1985). Alcoholics tend to lose
weight over time, and abstinence is commonly associated with a gain in
weight (Morgan 1982). In one study, eight malnourished alcoholic patients
lost an average of 9 lb while they were consuming at least 200 g (about 1,400
kcal) of ethanol daily for a minimum of 3 weeks. They then gained an
average of 7 lb after abstaining from alcohol for 2 weeks and eating an
adequate diet (Halsted, Robles, and Mezey 1971). In another study, alcohol
was associated with a substantial reduction in weight among women (Wil-
liamson et al. 1987). The conclusion usually drawn from such studies is that
alcoholics do not consume an adequate diet, which is often true.

Increasing alcohol intake while maintaining an adequate diet, however,
does not necessarily lead to a weight gain. For example, when 56 alcoholic
patients were admitted to a hospital and fed a diet of 2,600 kcal, those who
received an additional 256 g, or 1,800 kcal, of alcohol each day experienced
no greater weight gain than those who received the diet of 2,600 kcal alone
(Mezey and Faillace 1971). Similarly, when alcoholic patients were fed diets
supplemented with 2,000 kcal of alcohol, no consistent change in body
weight occurred, but when the 2,000 extra kcal were provided as chocolate,
there was a consistent weight gain (Pirola and Lieber 1972). This study
showed that substitution of an equal number of kcal of alcohol for carbohy-

639


O Nutrition and Health

drate at a level of 50 percent of total kcal was followed by weight loss, and
the same result was obtained at 25 percent of total kcal (McDonald and
Margen 1976).

The mechanisms accounting for the apparent inefficiency in conversion of
potential energy from alcohol are complex and incompletely understood
(World et al. 1984). Metabolic rate, as measured by oxygen consumption, is
higher in rats fed alcohol than in those fed the same number of calories as
carbohydrate (Pirola and Lieber 1972). Alcohol increases oxygen con-
sumption in normal human subjects and is reported to increase it even more
in alcoholic persons (Lieber 1984).

Several mechanisms have been proposed to explain how the oxidation of
alcohol could result in "inefftcient" energy transfer. The MEOS pathway of
alcohol oxidation requires a reducing equivalent, from nicotine adenine
dinucleotide phosphate (NADPH), and results in the production of heat
rather than high-energy phosphate bonds. Subsequent reduction of NAD to
NADH during the oxidation of acetaldehyde to acetate would result in no
net change in total reducing equivalents. Furthermore, the alteration in the
ratio of NADH to NAD in the cell cytoplasm might temporarily shift
various substrates to the more reduced state and thereby impair the flux of
reducing equivalents into the mitochondria for subsequent oxidative phos-
phorylation. A third mechanism could result from abnormalities in mito-
chondrial membranes, but this would be more likely to occur in alcoholic
individuals and therefore would not explain the acute increase in metabolic
rate following alcohol ingestion in normal drinkers (Lieber 1984).

Recent studies on nonshivering and postprandial thermogenesis (Rothwell
and Stock 1986) may cast some light on another possible mechanism to
explain the observed rise in oxygen consumption following alcohol inges-
tion. Landsberg and Young (1984) have shown that sympathetic nervous
activity plays a central role in the increased heat production following
feeding and the reduced heat production associated with starvation. Alco-
hol ingestion, especially in large amounts, has been associated with in-
creases in catecholamine levels, specifically norepinephrine (Beilin and
Puddey 1984).

The caloric value of alcohol (at least when ingested in large amounts)
cannot be regarded as equivalent to the caloric value of other dietary
sources of energy, as measured by the synthesis of high-energy phosphate
bonds. Loss of weight when alcohol is substituted isocalorically for carbo-
hydrate and the failure to gain weight when an otherwise adequate diet is
supplemented with alcohol have led to the suggestion that alcohol-derived


Alcohol 0

calories should be disregarded completely as an energy source in predict-
ing dietary-induced changes in weight (World et al. 1984). but the factors
may work differently by pattern of alcohol use.

For moderate drinkers, another factor that must be considered is the effect
of alcohol on caloric intake from other foods, especially in individuals who
are chronically dieting. Recently, the concept of the "restrained eater" has
been developed (Herman and Polivy 1980). Briefly stated. the restrained
eater attempts to maintain body weight at a lower-than-set-point level by
chronically undereating. When obligated toeat, or when the self-restraint is
temporarily suspended, rebound overfeeding occurs. This hypothesis is
supported by studies in which volunteers were asked to taste an appealing
food after some of them had been provided a preliminary dose of alcohol.
Among restrained eaters, alcohol increased the amount of food consumed,
but alcohol did not affect the subsequent intake of unrestrained eaters
(Polivy and Herman 1976a, 1976b).

These findings are consistent with the frequent clinical observation that
obese people have greater difficulty dieting and maintaining lower body
weights if they continue to drink alcohol. Whether the signals involved are
psychologic or biologic remains to be determined. Animal studies suggest
that biologic signals may be responsible because similar overeating can be
demonstrated in animals who have been underfed before testing (Herman
and Polivy 1980).

Lipids

Abnormalities in lipid metabolism are common in both alcoholics and mild
to moderate drinkers (Janus and Lewis 1978). Body fat stores usually are
depleted when weight loss results from poor diets. Alcoholics with chronic
pancreatitis and pancreatic insufficiency may not digest fat efficiently
because of a reduced output of pancreatic lipases, the primary enzymes for
digesting lipids. Hepatic insufficiency can also cause fat malabsorption due
to impaired secretion of the bile salts that emulsify fats and make them
more digestible and absorbable. In addition, abnormalities in intestinal
mucosal cells have been found to occur as a direct result of alcohol toxicity
and, more commonly, as an indirect result of malnutrition (Green 1983).

Carbohydrate

Differences among animal species and differences in experimental condi-
tions have led to apparently conflicting results regarding the effects of
alcohol on carbohydrate metabolism (Marks 1978). Two major syndromes
warrant discussion: (1) impaired glucose tolerance and (2) alcohol-induced

641


(3 Nutrition and Health

hypoglycemia. These effects are of special concern in patients with di-
abetes mellitus.

Impaired Glucose Tolerance. Impaired glucose tolerance is most easily
demonstrated if the dosages of alcohol are sufficient to increase sympathet-
ic nervous system activity and, perhaps, to decrease peripheral uptake of
glucose. Doses of alcohol sufficient to produce blood alcohol levels of
approximately 80 mg of alcohol per 100 ml of blood and mild euphoria do
not activate the sympathetic nervous system and do not greatly affect blood
glucose concentrations (Marks 1978). Indeed, some studies have shown an
improvement in glucose tolerance following alcohol ingestion. Mild fasting
hyperglycemia has been observed in more than 20 percent of middle-class
alcoholics at the time of admission for alcoholism treatment (Hurt et al.
1986). It appears that the conditions under which alcohol is consumed, the
associated dietary intake, the level of alcohol consumption, the history of
alcohol consumption, and the presence of organ pathology such as hepatic
insufficiency are responsible for the wide variation in the effects of alcohol
on glucose tolerance.

Hypoglycemia. A rare but often fatal complication of alcohol abuse is
profoundly low blood sugar (Williams 1984). This condition usually occurs
in the context of acute alcohol ingestion after minimal food intake for
several days or more. Victims are found stuporous or deeply comatose,
with blood glucose levels below 20 mg/lOO ml of blood. It has been pro-
posed that alcohol blocks gluconeogenesis by metabolic shifts that result in
reduced conversion of gluconeogenic precursors into glucose and
glycogen. In the absence of glycogen stores, profound hypoglycemia oc-
curs. Alcohol-induced hypoglycemia can be produced experimentally in
normal healthy volunteers by inducing them to fast for 36 to 72 hours before
administering alcohol (Freinkel et al. 1965). Obesity, or pretreatment with
corticosteroids, tends to blunt the hypoglycemic effect of alcohol. In
contrast, malnutrition, adrenocortical insufficiency, thyrotoxicosis, and
consumption of diets high in protein and low in carbohydrate increase
sensitivity to the hypoglycemic effects of alcohol ingestion.

Diabetes Meflirus. The effects of alcohol on the management of diabetes
have been reviewed (McDonald 1980). Of particular importance are altera-
tions in the metabolism of oral hypoglycemic drugs. Sulfonylurea com-
pounds stimulate insulin release from the pancreatic beta cells and, in turn,
inhibit hepatic gluconeogenesis, thus augmenting the hypoglycemic effects
of alcohol. Prolonged alcohol ingestion can stimulate hepatic metabolic
pathways responsible for drug metabolism and thereby shorten the half-life

642


Alcohol 0

of certain drugs (see chapter on drug-nutrient interactions). In such cases,
the effectiveness of these drugs diminishes with prolonged alcohol inges-
tion.

For example, alcohol can impair the action of oral hypoglycemic agents.
Both phenformin-a drug no longer available in the United States, but used
elsewhere-and alcohol inhibit the decarboxylation of pyruvate to acetyl-
CoA and favor the reduction of pyruvate to lactic acid, which would tend to
increase the risk for lactic acidosis. Patients who take chlorpropamide
experience flushing and other symptoms similar to those induced by disul-
firam (Antabuse) when alcohol is consumed. Evidence indicates that there
are genetic predispositions to this drug-alcohol interaction. Finally, alco-
hol-related deteriorations in judgment may be especially serious for per-
sons with insulin-requiring diabetes if inebriation leads to errors in insulin
dosage, administration, and diagnosis. In rare cases, profound hypo-
glycemia with permanent neurologic deficit has occurred.

Protein

Data from animal studies suggest that low-protein diets, sufficient to pro-
duce protein malnutrition, affect the biosynthesis of the alcohol de-
hydrogenase enzyme system and the availability of other cofactors re-
quired for alcohol oxidation (Orten and Sardesai 1971). Furthermore, the
ability of rats, and possibly humans, to oxidize alcohol varies with both the
amount of dietary protein and the types of protein ingested. For example,
egg and milk proteins have been found to be more beneficial in maintaining
normal rates of alcohol oxidation than proteins from cereals or other plant
sources. When measured by indicators such as degree of inebriation and
incidence of death due to alcohol intoxication, however, a mixture of
proteins from vegetable sources has been shown to provide protection
comparable to that from animal protein alone (Lucas, Ridout, and
Lumchick 1%8).

Water-Soluble Vitamins

Thiamin. Poor dietary intake and poor selection of foods, frequently seen
in alcoholics, reduce thiamin intake. Alcohol may interfere with absorption
of thiamin, with its activation to thiamin pyrophosphate, or with the ability
of thiamin pyrophosphate to combine with the enzymes for which it is a
cofactor (Hoyumpa 1983). In addition, hepatic storage of thiamin may be
reduced due to fatty infiltration of the liver, hepatocellular damage, or
cirrhosis. Increased losses of thiamin from the body, as well as increased
requirements due to increased metabolic demands, especially following

643


O Nutrition and Health

refeeding with carbohydrates, have been reported. Wemicke-Korsakoffs
syndrome caused by thiamin deficiency in the alcoholic population is
discussed later in this chapter.

Riboflavin and Niacin. Riboflavin deficiency has been documented in
alcoholics, but the mechanism for this deficiency, other than a presumed
inadequate intake, has yet to be delineated.

In the 1940's, reductions in mortality rates from 90 to 14 percent following
therapy with niacin (nicotinic acid) were reported in a large series of
alcoholic patients who presented with impaired consciousness, delirium, a
particular type of muscular rigidity called cogwheel rigidity, and uncontrol-
lable grasping and sucking reflexes (Jolliffe 1940, 1941). In some patients,
paralysis of the eye muscles and memory defects developed during therapy.
Although these symptoms were attributed to niacin deficiency, deficiencies
of other nutrients, especially thiamin, were probably present as well.

Vitamin B,. Evidence suggests that alcohol inhibits the absorption of
vitamin B, (Baker et al. 1975) and its release from the liver (Sorrel1 et al.
1974). Alcohol also increases the rate of degradation of pyridoxal-5-phos-
phate, one of the active forms of vitamin B,. However, the magnitude of
vitamin B, deficiency, its contribution to morbidity, and the precise mecha-
nisms involved in its effects on alcoholic persons are unknown.

Folate and Vitamin B,,. Folate deficiency is probably the most common
vitamin deficiency observed in alcoholics. Conversely, alcoholism is prob-
ably the most common cause of folate deficiency in the U.S. adult popula-
tion. As with other nutrients, many factors contribute to folate deficiency
in alcoholics, although poor dietary intake is undoubtedly the major cause.
Alcoholics with good diets are less likely to have a folate deficiency than
alcoholics with poor diets. The type of alcoholic beverage typically con-
sumed may be significant because beer contains considerably more folate
than wine or distilled spirits.

Folate malabsorption has been reported to occur among alcoholics, but this
condition may be secondary to the toxic effects of alcohol or to malnutri-
tion, both of which can damage the intestinal mucosa and impair nutrient
absorption. Accordingly, correction of folate deficiency has been followed
by improved absorption both of folate and other vitamins and minerals.

Urinary excretion of folate is increased by alcohol intake. and its tissue
utilization is decreased (Russell et al. 1983). Alcohol may directly inhibit

644


Alcohol 0

enzymes involved in folate metabolism. Several investigators (Sullivan and
Herbert 1964; Lindenbaum 1977) have shown that alcohol antagonizes the
ability of folate to reverse the megaloblastic bone marrow changes seen in
deficiency states, but larger doses of folate can overcome this antagonism.
The suppressive effects of alcohol have been shown to be present whether
folate is given intravenously or orally, suggesting that a metabolic function
subsequent to absorption is involved.

Others have observed that macrocytosis (large red blood cells) occurs
frequently in alcoholics and that this symptom persists despite folate
supplementation unless alcohol intake is curtailed. Because of the high
prevalence of folate deficiency and related anemia in derelict alcoholics,
some investigators have proposed that low concentrations of folate be
added to inexpensive domestic wine and spirits as a way of preventing this
deficiency (Kaunitz and Lindenbaum 1977). However. it should be noted
that even though folate deficiency can cause macrocytosis, the mac-
rocytosis often seen in heavy drinkers is usually not related to folate
deficiency and is not corrected by administration of the vitamin. Instead,
this macrocytosis appears to be due to the direct effect of alcohol on the
architecture of the red cell and is correctable only with abstinence. Be-
cause this kind of macrocytosis is usually unaccompanied by anemia, the
presence of macrocytosis without anemia is a useful clue to alcohol abuse.

Symptoms of vitamin B,2 deficiency are much less common than those of
folate deficiency in alcoholics. Among malnourished alcoholics with liver
disease, the prevalence of vitamin B,, deficiency is similar to that seen
among randomly selected municipal hospital patients. Indeed, in some
studies, the circulating levels of vitamin B,, have been found to be higher in
alcoholics than in normal controls (Bonjour 1980).

The major manifestation of either folate or vitamin B,, deficiency is mac-
rocytic megaloblastic anemia. Macrocytic anemia, without mega-
loblastosis, is also seen in chronic liver disease. Megaloblastic changes in
the intestinal mucosal cells of persons with folate or vitamin B,, deficiency
may further impair nutrient absorption and bioavailability.

Ascorbic Acid (Vitamin C). Serum ascorbic acid levels have been found to
be lower in alcoholics than in nonalcoholics, probably because of inade-
quate diets. However, some data suggest that even when diets are adequate,
increasing levels of alcohol consumption are associated with lower serum
levels of ascorbic acid. Whether ascorbic acid affects alcohol metabolism is
uncertain, as is knowledge of the extent to which this interaction may have
clinical significance (Bonjour 1979).

645


O Nutrition and Health

Fat-Soluble Vitamins

Vitamin A. Vitamin A, as a fat-soluble vitamin, requires for its absorption a
certain level of fat in the diet and adequate quantities of pancreatic lipid-
digesting enzymes (lipases) and bile salts in the small intestine. Some
complications of alcoholism, such as pancreatic insufficiency and biliary
insufftciency, can therefore lead to malabsorption of vitamin A. In addi-
tion, alcoholics with liver disease may have impaired storage or transport
of vitamin A because of an inadequate synthesis of retinol-binding protein,
the protein formed in the liver that transports vitamin A in the blood. Even
moderate alcoholic liver disease is associated with severely decreased
vitamin A concentrations, and these levels are reduced in the liver even
when blood levels of vitamin A, retinol-binding protein, and prealbumin are
normal (Leo and Lieber 1982).

The storage form of vitamin A, retinol, is oxidized to its active form,
retinal, by retinol dehydrogenase, an enzyme similar to alcohol de-
hydrogenase. Impairments in the metabolism of vitamin A have been
reported in alcoholics, and some evidence suggests that retinol and ethanol
compete for the alcohol dehydrogenase enzyme in the liver, testes, and
retina (Shaw and Lieber 1983). Experimental deficiencies of several nu-
trients, including vitamin A, have been shown to enhance carcinogen-
induced tumors in laboratory animals. Whether vitamin A deficiency plays
a role in the reported association between alcohol intake and certain types
of tumors remains to be determined (Committee on Diet, Nutrition, and
Cancer 1982).

Vitamin D. Vitamin D and its metabolites are involved in regulating calcium
and phosphorus metabolism, bone formation and resorption, and various
other physiologic functions, including some aspects of immune function.
Alcoholics have been reported to have low circulating levels of vitamin D,
especially 25hydroxyvitamin D, the metabolite formed in the liver. Not
surprisingly, alcoholic persons with liver disease have lower levels of this
metabolite than persons without liver disease. Higher rates of osteomalacia
and osteoporosis have been reported in alcoholics (see chapter on skeletal
diseases). The specific mechanisms to account for these findings remain
unclear. Certainly, conditions associated with fat malabsorption may lead
to malabsorption of vitamin D. In addition, some evidence suggests that
alcohol induces enzymatic changes in the liver that favor the production of
inactive metabolites of vitamin D. As discussed below in the section on
minerals, the actions of vitamin D are closely linked with the metabolism of
calcium and phosphorus, the levels of which may be altered in response to
heavy alcohol ingestion.


Alcohol 0

Vitamin E. Alcoholic persons may develop severe malabsorption of vi-
tamin E due to pancreatic or biliary insufficiency, but actual reports of
vitamin E deficiency in alcoholics have been uncommon (Losowsky and
Leonard 1967). Available data suggest that vitamin E malabsorption occurs
most commonly in the presence of cirrhosis and steatorrhea, or fat malab-
sorption (Leevy, Tanribilir, and Smith 1971). Whether antioxidants such as
vitamin E protect against alcohol-induced fatty changes in the liver remains
uncertain (French 1971).

Vitamin K. Evidence suggests that at least half of the vitamin K required by
humans is normally synthesized by bacteria in the intestine. In rare cases,
vitamin K deficiency may occur with fat malabsorption, which is common
in alcoholics. In addition, persons with alcoholic liver disease demonstrate
a variety of impairments in the synthesis of vitamin K-dependent and other
blood clotting factors. Bleeding disorders are, therefore, common in alco-
holics. Alcohol also has been shown to affect blood platelets, coagulation
inhibitors, and tibrinolysis (Larkin and Watson-Williams 1984).

Minerals

Iron. Iron deficiency in alcoholics may occur as a result of repeated
gastrointestinal bleeding or clotting disorders. Iron overload, with hemo-
siderosis, may occur because of increased iron intake, either from alcoholic
beverages (especially certain wines) or from iron-containing vitamin-min-
eral supplements that are often taken because of otherwise unexplained
anemia. Iron absorption may be increased due to the increased solubility of
ferric iron in the small intestine caused by stimulation of gastric acid
secretion by alcohol. Increased iron absorption has also been reported in
persons with pancreatic insufficiency, folate deficiency, and cirrhosis. In
addition, disorders in heme synthesis can result in iron deposition in bone
marrow and other organs. Alcoholics may develop sideroblastic anemias,
characterized by the presence of ringed sideroblasts, in which iron is
deposited between the membrane folds of the mitochondria (Eichner and
Hillman 1971). Such anemias may result from vitamin B, deficiency, usu-
ally in association with folate deficiency or other impairments in activity of
enzymes involved in heme synthesis (Larkin and Watson-Williams 1984).
Hepatic hemosiderosis also appears to occur more frequently in alcoholics
and may be exacerbated by coexisting hemolysis, blood transfusion, or the
prolonged administration of therapeutic iron. In most such cases, it is not
possible to separate the causes from the consequences of iron deposition in
the development of hepatic failure (Larkin and Watson-Williams 1984).

647


0 Nutrition anti Health

Magnesium. Low magnesium levels have been demonstrated in the blood,
skeletal muscle, and heart muscle of alcoholics (Wheeler et al. 1977).
Chronic alcohol use can result in both reduced intake and malabsorption of
magnesium. Alcohol ingestion acutely increases the urinary excretion of
magnesium. Because magnesium is necessary for certain thiamin-depen-
dent enzymes, there has been speculation that magnesium plays a role in
the development of some of the neurologic complications of alcohol abuse,
including Wemicke-Korsakoff's syndrome (discussed later in this chapter).
However, the data are inconsistent, and the precise role, if any, of magne-
sium remains to be determined (Thomson 1978). Finally, magnesium insuf-
ficiency can be associated with hypocalcemia, perhaps because hypomag-
nesemia causes resistance to parathyroid hormone and impairment of its
secretion.

Calcium and Phosphorus. Alcohol ingestion increases urinary calcium
excretion, but the mechanisms for this action have yet to be determined.
The possible roles of magnesium, parathyroid hormone, and vitamin D in
this effect are unclear. Chronic alcoholics may have low serum calcium
levels, usually secondary to reduced serum albumin levels from malnutri-
tion, liver disease, or acute pancreatitis. As noted above, vitamin D intake,
absorption, and metabolism may also be impaired in alcoholics, resulting in
abnormalities in phosphorus, calcium, and magnesium metabolism. For
example, low levels of vitamin D impair calcium absorption. Low levels of
dietary calcium result in increased urinary retention of calcium and in-
creased urinary excretion of phosphate. By whatever combination of mech-
anisms, hypophosphatemia occurs in some alcoholics and is easily detect-
able by routine laboratory testing at the time of admission to the hospital,
although its symptoms are similar to those seen in other syndromes associ-
ated with alcohol abuse. In some groups of alcoholics, mild hyper-
phosphatemia has been observed more frequently than hypophosphatemia
(Hurt et al. 1986).

Zinc. Reduced concentrations of zinc have been found in the plasma, red
blood cells, and liver of humans and rats following chronic alcohol inges-
tion. Alcohol appears to increase the urinary excretion of zinc, perhaps
because of increased release of zinc from hepatic stores. Protein catabolism
is also associated with increased urinary zinc losses. The effect of zinc
deficiency on alcohol metabolism has not been established, but prelimi-
nary evidence suggests that zinc-dependent enzymes, such as those in-
volved in vitamin A metabolism, may be inhibited by alcohol (Thomson
1978). Some alcoholic men with night blindness have required both zinc and
vitamin A treatment to correct visual dysfunction (McClain et al. 1979), but

648


Alcohol O

whether the origin of this problem is liver dysfunction or nutrient malab-
sorption is as yet uncertain.

Nutritional Status of Alcoholics

Three types of malnutrition may be observed in alcoholics (Lieber 1983):
(I) primary malnutrition due to a decreased intake of nutrients, (2) second-
ary malnutrition caused by an impairment in the digestion and absorption
of nutrients due to the effects of alcohol, and (3) tertiary malnutrition due to
an alteration in the ability to convert nutrients to their active coenzyme
forms, resulting in nutritional complications that potentiate the direct toxic
effects of alcohol.

The nutritional status of alcoholics remains ill defined because of variations
in the types of studies performed and the groups of alcoholics that have
been studied. The derelict alcoholic has a different baseline nutritional
status than the middle-class alcoholic, and findings derived from studying
one group cannot necessarily be extrapolated to the other.

The preponderance of studies have examined indigent alcoholics who are
readily available and willing to cooperate at least temporarily with re-
searchers. These individuals are probably as different in the type and
amount of alcohol and food consumed as they are in every other aspect of
day-to-day living when compared with nonindigent and middle-class alco-
holics. Although indigent alcoholics make up less than 5 percent of the total
alcoholic population, there is a persistent misconception that this group is
representative of the alcoholic population at large. The almost total exclu-
sion of women in this population is an indication that indigent alcoholics are
not representative of all alcoholics.

Because of the association of alcoholism with serious medical illnesses
such as liver cirrhosis or pancreatic insufficiency, another tendency is to
study the nutritional status of persons with these conditions rather than the
much larger-and healthier-portion of the alcoholic population. A clear
distinction needs to be made between each of these groups. For example,
the dietary intake of a large group of hospitalized alcoholic patients has
been reported to be poor when judged by "traditional standards" (Patek et
al. 1975). The mean daily energy intake in this group was over 3,000 kcal,
but more than 50 percent was derived from alcohol. All of these patients
were hospitalized for the treatment of medical complications ofalcoholism,
and two-thirds had cirrhosis, a much higher prevalence than expected for
the general alcoholic population (Lelbach 1975).

649


O Nutrition and Health

Individuals hospitalized in alcoholism treatment centers may also have
severe alcohol-associated medical problems, but the primary reason for
their hospitalization is alcoholism. Therefore, these patients are probably
more representative of the overall alcoholic population. Despite the high
proportion of caloric intake from alcohol in this group, only a few studies
have reported evidence of malnutrition. Among a small group of male
alcoholics in an inpatient alcoholism treatment program, total caloric in-
take was estimated to be 2,600 to 2,700 kcal, with alcohol providing 22 to 36
percent of calories (Neville et al. 1968). In a similar group of middle-class
alcoholics, the mean intake measured by diet history at admission to an
alcoholism treatment unit was 3,100 kcal, with alcohol accounting for 35
percent of the daily energy intake (Hurt et al. 1981). No severe nutritional
deficiencies were found using anthropometric measurements and blood
studies of protein status in a small group of alcoholic patients hospitalized
in a veterans hospital alcoholism treatment program (Dickson et al. 1983).
Despite adequate protein intake, alcoholic patients, with and without liver
disease, had significantly lower body weights, triceps skin folds, and arm
muscle circumferences than abstainers (Simko, Connell, and Banks 1982),
but no assessment of the socioeconomic status of this group was included.
Thirteen percent of nonindigent alcoholics in another study were mal-
nourished, but because of the method used to analyze the anthropometric
data, the percent was probably higher (Tomaiolo and Kraus 1980). In yet
another study, 13 percent of low-income alcoholics and 10 percent of
middle-income alcoholics were judged to be malnourished, but obesity
occurred in 2 percent and 4 percent, respectively. This latter research
suffered from the vagueness of the nutritional data, which was based on the
overall medical status of the subjects. In a group of 179 middle-class males,
47 of whom were alcoholic inpatients, the consumption of alcohol was
associated with a decrease in energy intake from other sources and a
reduction in the nutrient density of the diet at both moderate and high levels
of alcohol consumption (Hillers and Massey 1985).

A comparison of alcoholics of lower socioeconomic status with those of
higher socioeconomic status showed small but clear differences in the ratio
of height-to-weight, triceps skin fold, mid-arm muscle circumference, and
hematocrit (Goldsmith, Iber, and Miller 1983). Only 8 percent of this
middle-income group were moderately malnourished, compared with 24
percent of the low-income group. In the low-income group, 8 percent were
severely malnourished. Thus, socioeconomic class is an important factor
that often is not taken into full account in nutritional studies of alcoholics.
Furthermore, very few studies have been conducted on middle-income
alcoholics, although these indicate that the nutritional status of this group is

6.50


Alcohol 0

probably adequate for most purposes despite the occasional finding of
selected nutritional deficiencies.

Effect of Alcohol on the Nutritional Status of Nonalcoholics

Few investigations have focused on the effects of alcohol on the nutritional
status of nonalcoholic persons. In three groups of nonalcoholic individuals
who kept a diary of what they ate over a period of 6 to 12 months, 79 percent
reported drinking alcoholic beverages during the study (Bebb et al. 1971).
Half of these reported consuming alcohol on half or more of the days
recorded. For 22 percent of those who drank alcohol, alcohol contributed
approximately 10 percent of average daily total calories; for another 23
percent, it contributed from 5 to 10 percent of daily calories. As the
proportion of calories from alcohol increased, there was little change in
protein intake but a decrease in carbohydrate and fat intake. The overall
quality of the diet could not be related to the proportion of energy derived
from alcohol.

In a recent representative sample of upper-middle-class persons in south-
em California, alcohol did not replace calories derived from other nutrients
(Jones et al. 1982). Using the 24-hour recall method, the authors recorded
that 51 percent of the subjects consumed an average of 30 g or more of
alcohol per day. In a group of "moderate drinking" men, who consumed 25
to 49 g of alcohol per day, there was a significantly lower intake of protein,
carbohydrate, and fat. Despite a higher energy intake, the drinkers were
not more obese than the nondrinkers. Further studies are needed to define
the possible effects of mild to moderate alcohol intake on nutrient intake in
the general population. If these effects are negligible, as indicated by the
two cited studies, public health efforts may be better focused on persons
with alcohol abuse or alcoholism problems.

Role of Alcohol in Diseases of the Liver

Alcohol-related diseases include both the direct toxic effects of alcohol and
the indirect effects caused by the nutritional deficiencies found in alco-
holics. According to the DSM-III criteria, liver diseases that occur in
chronic alcoholics may be found in periodic abusers as well (Task Force on
Nomenclature and Statistics 1980).

Alcoholic Cirrhosis

Research into the etiology of alcoholic cirrhosis has produced many theo-
ries of causation, ranging from a strictly nutritional deficiency to a direct
toxic effect of alcohol. Until about 20 years ago, it was believed that

651


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maintaining normal protein synthesis would allow the liver tissue to return
to normal despite continued alcohol ingestion (Leevy 1967), and protein-
and vitamin-supplemented diets were recommended for prevention of
alcoholic liver disease.

In the mid-1960's, a major change in the theory concerning the cause of
alcoholic cirrhosis occurred (Lieber 1966). At that time, the calorie-for-
calorie substitution of alcohol for carbohydrates in the diets of young
nonalcoholic volunteers was shown to produce fatty liver and ultrastruc-
tural changes in the liver cells, even though the volunteers' blood alcohol
concentration never exceeded 100 mg/lOO ml and the subjects were not
malnourished (Rubin and Lieber 1968). This result was consistent with the
theory that alcohol produces a direct toxic effect on the liver.

The contention that alcohol itself is the primary offender in the develop-
ment of cirrhosis was supported by epidemiologic data. The death rate from
cirrhosis in the United States decreased in proportion to the reduction in
the consumption of alcohol that occurred during Prohibition (Klatskin
1961), and a similar direct relationship between alcohol intake and cirrhosis
was observed in France during World War II when wine was rationed and
the per capita consumption of wine decreased (Pequignot and Cyralnik
1970). Further evidence to support this contention derives from the obser-
vation that countries with the highest per capita alcohol consumption have
the highest rate of mortality from cirrhosis (Sherlock 1981). The death rate
from cirrhosis in the United States has recently declined (Laforge et al.
1987).

The observation that the development of cirrhosis is partly a response to
the long-term consumption of large quantities of alcohol (Lelbach 1975)
does not explain why cirrhosis develops in only 12 to 15 percent of alco-
holics. In addition to the dose of alcohol and duration of consumption,
genetic factors or individual differences among people must be involved.
The best evidence to date of the direct hepatic toxicity of alcohol has been
shown in baboons, where alcoholic liver disease-including fatty liver and
cirrhosisdan be produced in about one-third of the experimental animals
even though they are consuming a nutritionally adequate diet (Lieber and
DeCarli 1974). Despite these studies, the issue of malnutrition in the
genesis of alcoholic cirrhosis continues to be raised, especially in the
context of the hepatic pathology similar to alcoholic liver disease that
occurs in patients who have undergone jejunoileal bypass surgery for
obesity (Patek 1979).

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Alcohol O

Alcoholic Hepatitis

A relationship between nutritional status and alcoholic hepatitis (alcohol-
induced liver inflammation) derives from the Veterans Administration co-
operative study that found features of marasmus or kwashiorkor. the clas-
sic starvation diseases, among alcoholic men (Mendenhall et al. 1984). The
extent of marasmus and kwashiorkor correlated closely with the severity of
the liver disease.

Interest in the nutritional therapy of alcoholic hepatitis was elicited by the
report that parenteral infusions of amino acids reduced the mortality of
persons with severe alcoholic hepatitis (Nasrallah and Galambos 1980).
Among a group of patients with biopsy-proven alcoholic hepatitis, im-
provement (as measured by clinical and biochemical markers) was more
rapid in those receiving the amino acid infusion, although no apparent
difference in liver pathology remained in the two groups at the end of 1
month of treatment (Diehl et al. 1985). The researchers concluded that the
outcome of alcoholic hepatitis is strongly influenced by the metabolic
consequences of alcohol consumption and that it is the resolution of these
consequences that is most influenced by parenteral amino acid supplemen-
tation. The nutritional status of persons with alcoholic hepatitis needs to be
recognized and addressed, but unfortunately at present, its role in the
etiology and treatment of this condition remains uncertain.

Fatty Liver

Several mechanisms have been proposed to explain the fatty changes in the
liver that occur as a result of alcohol consumption. Oxidation of alcohol
results in the production of reducing equivalents, and the acetate from
alcohol can be metabolized to acetyl-CoA. This combination results not
only in reduced hepatic oxidation of fatty acids but also in increased
production of alpha-glycerophosphate, which in turn favors conversion of
fatty acids into long-chain fatty acids and triglycerides that can be depos-
ited in the liver as fat. In addition, catecholamine release, in response to
either intoxicating dosages of alcohol or alcohol withdrawal, can increase
the mobilization of fatty acids from muscle and adipose tissue and, there-
fore, increase the delivery of fatty acids to the liver.

Role of Alcohol in Diseases of the Nervous System

Wernicke-Korsakoff's Syndrome
Wemicke's encephalopathy is characterized by weakness of eye move-
ments, gait disturbance, and confusion, and Korsakoffs psychosis by

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amnesia, a disordered sense of time, and confabulation. The two conditions
probably represent a continuum, and they usually occur together as Wer-
nicke-Korsakoff's syndrome. In approximately one-fourth of patients, the
memory disturbance is completely reversible. In half of the cases, improve-
ment ranges from slight to significant although the memory loss can be
incapacitating, but in the remaining one-fourth of the patients, the memory
disturbance is completely irreversible (Dreyfus 1979). If Wemicke's en-
cephalopathy goes unrecognized, the chances of preventing its progression
to Korsakoff's psychosis and resolving its manifestations are reduced.

In alcoholics, Wemicke-Korsakoffs syndrome is caused more by thiamin
deficiency than by the direct toxic effect of alcohol. The eye manifestations
of Wernicke's encephalopathy respond rapidly to thiamin administration,
although the associated ataxia and confusion respond more slowly. Brain
lesions similar to those found in patients with Wemicke-Korsakoff's syn-
drome are found in the brains of animals that are deficient in thiamin
(Victor, Adams, and Collins 1971). Alcohol may directly or indirectly affect
thiamin intake, absorption, storage, metabolism, and excretion (Hoyumpa
1983). Another possible mechanism includes altered cerebral energy me-
tabolism resulting from deficiencies in the function of thiamin-dependent
enzymes; these deficits can affect energy production, diminish acet: lcho-
line neurotransmission, and impair DNA synthesis (Reuler, Girard, and
Cooney 1985). Subclinical thiamin deficiency, as measured by the activity
of the thiamin-dependent enzyme erythrocyte transketolase, may occur in
as many as one-third of alcoholics suspected of having liver disease (Cami-
lo, Morgan, and Sherlock 1981). Because alcohol inhibits active rather than
passive transport of thiamin, supplementation of the vitamin in amounts
larger than the Recommended Dietary Allowance can overcome the
thiamin malabsorption caused by alcohol (Lieber 1983).

The variations in clinical presentation and the fact that most persons with
thiamin deficiency do not have Wernicke-Korsakoffs syndrome raises the
possibility that there may be genetic variants that predispose individuals to
its development (Blass and Gibson 1977). For example, a variant of trans-
ketolase with a low affinity for the coenzyme thiamin pyrophosphate was
found in all of four patients with Wemicke-Korsakoffs syndrome but in
none of six control patients. There is considerable evidence that iso-
enzymes of human erythrocyte transketolase exist, but the significance of
such heterogeneity and its relationship to differential susceptibility to
Wernicke-Korsakoffs syndrome has not been determined (Nixon 1984).

Because the rate of long-term institutionalization for persons admitted for
Korsakoff's psychosis is 30 to 40 percent, some experts have proposed that

6.54


Alcohol Ll

thiamin be considered for addition to alcoholic beverages (Centerwall and
Criqui 1978).

Alcoholic Peripheral Neuropathy

Alcoholic peripheral neuropathy, a distal mixed motor sensory net ropathy
primarily affecting the lower extremities, is probably the most common
neurologic complication of alcoholism, and it occurs in over 80 percent of
persons with severe neurologic problems such as Wemicke's encephalopa-
thy (Victor, Adams, and Collins 1971). The predominant pathologic abnor-
mality is a "dying back" degeneration of nerve axons that affects distal
segments of the longest nerve fibers (Behse and Buchthal 1977). Recovery
from alcoholic peripheral neuropathy is slow and often incomplete.

In the early part of this century, thiamin deficiency was considered to be
the cause of alcoholic peripheral neuropathy (Shattuck 1928). That a nutri-
tional deficiency plays a role in its development is supported by many
factors: the clinical and pathologic features are similar to those seen in
beriberi, the classic thiamin deficiency disease; patients with alcoholic
peripheral neuropathy have been shown to have deficiencies of thiamin.
folic acid, and other B-complex vitamins; improvement may occur with
vitamin supplementation; and thiamin deficiency alone can cause a similar
type of peripheral neuropathy.

Some .vidence suggests that the toxic effects of alcohol alone may cause
peripheral nerve damage because some patients with alcoholic neuropathy
show no evidence of any nutritional deficiency (Behse and Buchthall977).
Other evidence suggests that both diet and alcohol toxicity are at fault. A
heavy alcohol intake and a poor diet result in acute axonal degeneration; in
persons with chronic neuropathy, a long history of alcohol intake, but a
good diet, however, there is little evidence of axonal degeneration and, in
fact, considerable evidence of nerve regeneration (Walsh and McLeod
1970). Supplementation with B-complex vitamins and an improvement in
overall nutritional status are important in the treatment of this disease, but
abstinence from alcohol may be the single most important factor.

Alcoholic Dementia

The toxic effects of alcohol on the brain have received greater attention
since the development of computed tomography (CT). In young alcoholics,
cerebral atrophy as measured by CT may be reversed with the cessation of
excessive drinking (Ron et al. 1982), but the associated cognitive dysfunc-
tion, labeled as alcoholic dementia, may be due in part to nutritional
deficiencies. In one study, pathologic examination of alcoholic persons

655


O Nutrition and Health

showed changes in the brain consistent with Wernicke's encephalopathy,
although clinical signs of the disease were absent (Torvik, Lindboe, and
Rogde 1982). The syndrome of alcoholic dementia is also probably due to a
combination of thiamin deficiency and the direct toxic effects of alcohol on
the brain (Nakada and Knight 1984).

Role of Alcohol in Cardiovascular Diseases

Alcoholic Cardiomyopathy

The adverse effects of alcohol on the heart muscle, or myocardium, have
been known since the 1700's when William Withering observed that 10
percent of the patients to whom he administered foxglove (containing
digitalis) for heart failure were excessive users of alcohol. Similar observa-
tions relating alcohol abuse to heart failure were made by other scientists,
such as Steel1 in the late 1800's and Osler in the early 1900's, but these early
observations were all but forgotten when beriberi heart disease was de-
scribed in thiamin-deficient alcoholics (Weiss and Wilkins 1937). As with
many other alcohol-associated conditions, nutritional deficiencies were
presumed to be responsible for heart failure in alcoholics, and it was not
until the early 1%0's that alcohol was recognized to have a direct toxic
effect on the myocardium (Brigden and Robinson 1944). Beriberi heart
disease and the congestive cardiomyopathy of alcoholism are now known
to be distinctly different entities.

The theory that alcoholic cardiomyopathy is caused by the direct toxic
effect of alcohol on the myocardium has strong support. The ultrastructural
changes seen in the myocardial cells of a person with alcoholic car-
diomyopathy, such as fragmentation of myofibrils, clusters of giant
mitochondria with distorted membrane folds, dilated sarcoplasmic re-
ticulum, and increased glycogen and fat deposits, are similar to those seen
in the livers of persons with alcoholic liver disease. Furthermore, thiamin
administration and other nutritional therapies alone have produced no
benefit in persons with alcoholic cardiomyopathy. The only factor shown to
affect recovery significantly is abstinence from alcohol (Demakis et al.
1974).

The manner in which alcohol produces its direct toxic effect on cardiac
muscle is unclear, although acetaldehyde, the first product of alcohol
oxidation, may induce myocardial damage (Schreiber et al. 1972) and has
been shown to diminish myocardial protein synthesis (Bing 1978). Changes
in cardiac metabolism may also be involved. Alcohol inhibits mitochondri-
al respiration and the activity of mitochondrial enzymes in the tricarboxylic

656


Alcohol 0

acid cycle in addition to interfering with mitochondrial calcium binding and
uptake. Alcoholics display blood levels of acetaldehyde high enough to
inhibit the association of the muscle proteins actin and myosin in vitro and
to interfere with mitochondrial protein synthesis (Rubin 1979).

Dysrhythmias

Another manifestation of the ability of alcohol to produce cardiac toxicity
is seen in persons with alcohol-induced dysrhythmia, dubbed "the holiday
heart syndrome" because it occurs more frequently around holidays such
as New Year's Eve when alcohol intake is generally highest (Ettinger et al.
1978). Individuals with unexplained acute atria1 fibrillation have been
shown to have a significantly higher rate of heavy alcohol consumption than
control persons (Rich, Siebold, and Campion 1985). Alcoholics with evi-
dence of myocardial dysfunction are more sensitive to the depressant
effects of alcohol on the heart and to atria1 and ventricular dysrhythmias
following the acute administration of alcohol. Serious dysrhythmias have
been observed in patients consuming as little as 7 oz of vodka (Singer and
Lundberg 1972).

Hemodynamic Effects

Acute alcohol ingestion produces complex changes in cardiovascular phys-
iology, including dilation of peripheral blood vessels and diminished blood
return to the heart. Recent studies have shown that acute alcohol ingestion
in normal subjects has a depressant effect on heart muscle action (Lang et
al. 1985), but in one group of patients with congestive heart failure, a single
intoxicating dose of alcohol significantly reduced pumping efficiency with-
out causing any significant deterioration in cardiac performance (Green-
berg et al. 1982). It is well established from both animal and human studies
that chronic alcohol use injures the heart muscle, depresses ventricular
function, and impairs cardiac performance. Over time, alcohol abuse may
lead to irreversible damage to the heart muscle and cause congestive heart
failure or cardiac arrhythmias.

Hypertension

Most studies have indicated that a self-reported average consumption of
three to four alcoholic drinks per day causes a measurable increase in both
the systolic and diastolic blood pressures. These studies suggest that as
much as 11 percent of hypertension in men may be attributable to consump-
tion of alcohol at this level (MacMahon 1986).


O Nutrition and Health

Hypertriglyceridemia

The most common lipid abnormality associated with alcohol abuse and
alcoholism is hypertriglyceridemia. In such persons, the very low density
lipoprotein (VLDL) levels are high, corresponding to what would tradition-
ally be classified as hyperlipidemia type IV. In more severely affected
individuals, there may be an accompanying elevation of chylomicrons,
which is consistent with hyperlipidemia type V. Because VLDL particles
contain some cholesterol, the serum cholesterol may also be elevated as a
result.

The effect of alcohol intake on triglyceride levels is often overlooked.
Among patients referred to lipid clinics, only diabetes is more important as
a secondary cause of hyperlipidemia. Typically, persons with alcohol-
induced hyperlipidemia do not respond to dietary or drug intervention
unless alcohol intake is limited (Janus and Lewis 1978).

Indeed, the alcohol intake of all persons with hypertriglyceridemia should
be assessed. In a light to moderate drinker especially, awareness of this
effect of alcohol may provide sufficient motivation to lower intake. In the
alcoholic person, this awareness might lead to the identification and treat-
ment of the alcoholism.

Severe hypertriglyceridemia may cause and/or result from pancreatitis
(Geokas 1984). Because pancreatitis is more common in alcoholics than in
nonalcoholics, all individuals presenting with pancreatitis or otherwise
unexplained recurrent upper abdominal pain should be evaluated for hyper-
triglyceridemia and history of alcohol use.

In alcoholics, extreme forms of hyperlipidemia have been described in
which excessive alcohol intakes were associated with jaundice, severe
hyperlipidemia, and hemolytic anemia (Zieve 1958). Liver biopsies in such
patients showed fatty infiltration with minimal to moderate portal cirrhosis.
Fortunately, this syndrome appears to be rare.

Elevated Serum Cholesterol Levels

Several population studies have suggested that light to moderate drinkers
(by self-report) have a lower risk for coronary artery disease than do
nondrinkers (Yano, Rhoads, and Kagan 1977; Blackwelder et al. 1980). The
observation that alcohol intake tends to increase high density lipoprotein
(HDL) cholesterol was originally thought to be consistent with these
epidemiologic findings, especially because HDL cholesterol appears to be
inversely related to the risk for coronary artery disease. However, more


Alcohol O

recent studies have shown that the HDL cholesterol can be subdivided into
fractions. The HDL, fraction is thought to protect against coronary artery
disease but is affected relatively little by moderate alcohol ingestion.
Alcohol elevates the HDL, fraction, which appears to have no association
with coronary artery disease. In alcoholics, however, the reports to date
regarding HDL cholesterol level have been variable and appear to depend
on a variety of factors such as level of alcohol intake. the degree of hepatic
microsomal enzyme induction, and the severity of alcoholic liver disease
(Hurt et al. 1986). Because of the association of reduced levels of apolipo-
proteins AI and AI1 (apo AI and AII) with coronary artery disease (Kottke
et al. 1986), the effect of alcohol on apo AI and AI1 is also of interest and ap-
pears to parallel its effect on HDL cholesterol. In alcoholic men, however.
the apo AI levels have been observed to be lower than in nonalcoholic con-
trols (Hurt et al. 1986). The epidemiologic findings, therefore, await further
confirmation as well as elucidation of a biologic mechanism to explain the
apparent protective effect of alcohol.

Coronary Heart Disease

Some evidence suggests that the ingestion of two to three alcoholic drinks
per day reduces the rate of nonfatal myocardial infarction and mortality
from coronary heart disease (Yano, Rhoads, and Kagan 1977; Blackwelder
et al. 1980). Whether these epidemiologic observations are mediated by
effects of alcohol on HDL levels is unknown at present (Ernst et al. 1980).
The effects at various levels of alcohol intake, the presence of liver disease,
and effects of exercise on HDL cholesterol levels in alcoholics require
further study. It appears that the benefits of consuming two to three drinks
per day do not increase in persons who drink more. On the contrary,
mortality from other diseases increases markedly when alcohol consump-
tion exceeds those levels (Blackwelder et al. 1980; Marmet et al. 198 1).

Role of Alcohol in Reproductive Disorders

The relationship between maternal alcoholism and adverse fetal effects has
been known for centuries, but interest was revived after publication of a
report on this relationship in the early 1970's (Jones et al. 1973). Fetal
alcohol syndrome is characterized by a triad of features: (1) facial malfor-
mations, (2) prenatal and postnatal growth deficiencies, and (3) central
nervous system disorders, including mental retardation, with the effect
occurring as early as the time of conception (Ernhart 1987). Although the
initial observations were made of the children of severe alcoholics with
longstanding, high-volume alcohol use, fetal abnormalities have now been
associated with lesser quantities of alcohol intake during pregnancy


O Nutrition and Health

(Streissguth et al. 1980), and there appears to be a dose-response relation-
ship in which abnormalities increase in proportion to the dose of alcohol
(AMA 1983; Emhart 1987). The observation that the fetal alcohol syn-
drome occurs in disproportionately larger numbers of American Indians, in
patients of lower socioeconomic background, and in children of older
mothers might be explained on the basis that the rate of alcohol abuse and
alcoholism is higher among these groups (Streissguth 1978).

Although most authorities view the syndrome as a direct toxic effect of
alcohol on the fetus, malnutrition may also play a role in its development.
Acute and chronic alcohol consumption in the rat can significantly reduce
the placenta1 uptake of a variety of amino acids (Henderson et al. 1982).
However, because of substantial structural differences in the placenta from
species to species, extrapolation of these results to humans must be cau-
tious. Animal studies, on the other hand, appear to support a direct
causative effect of alcohol on fetal alcohol syndrome (Randall, Taylor, and
Walker 1977). One additional study bears on this point. When pregnant
women were separated into alcoholic and nonalcoholic groups by the use of
the Michigan Alcoholism Screening Test and by an index of volume of
alcohol consumed, pregnant alcoholics were found to have lower plasma
zinc levels than nonalcoholic controls, and lower levels of zinc were ob-
served in fetal cord blood (Flynn et al. 1981).

Although this last study undoubtedly brings attention to possible nutri-
tional contributions to the fetal alcohol syndrome, the consensus at present
is that the syndrome is due to toxic effects of alcohol and is not a nutritional
deficiency syndrome. In addition, a recent study, after controlling for other
risk factors, reported lower birth weights among infants born to mothers
who consumed as little as one alcoholic drink per day during pregnancy
(Mills et al. 1984). Until further information is available, the Surgeon
General and the American Medical Association have recognized that com-
plete abstinence at the time of conception and during pregnancy is the
safest course (DHEW 1979; AMA 1983).

Implications for Public Health Policy

Dietary Guidance

General Public
Alcohol has been identified as a dietary factor that increases the risk for
diseases of the liver, nervous system, and heart. It also contributes to the

660


Alcohol O

development of certain cancers. Although consumption of up to one to two
drinks per day has not been associated with disease among healthy male
and nonpregnant female adults, evidence that 9 percent of the total popula-
tion consumes two or more alcoholic drinks per day suggests that the risk
for alcohol-related conditions could be reduced by an overall decrease in
alcohol consumption among some segments of the general public.

Special Populations

Because studies in pregnant women have been unable to identify a thresh-
old level of safety for alcohol intake during pregnancy, and because the risk
for fetal abnormalities increases with increased alcohol intake during preg-
nancy, pregnant women-and women planning to become pregnant-
should be advised to avoid drinking alcohol.

Persons with alcohol-related liver, nervous system, and cardiovascular
conditions (e.g., elevated blood cholesterol and blood pressure levels)
should receive advice from health professionals to reduce or eliminate
alcohol intake to reverse or to prevent progression of these conditions.
Persons with diabetes should also receive counseling on the effects of
alcohol on caloric intake and blood glucose control.

Adolescents and young adults should be counseled in schools and through
the media on the relationship between alcohol intake and motor vehicle and
other accidents, suicides, and homicides. Older individuals should be
counseled on the relationship between alcohol intake, nutritional deficien-
cies, and drug interactions.

Nutrition Programs and Services

Food Labels

Evidence related to the role of alcohol in health suggests that if alcoholic
beverage containers are required to bear health warning labels, these labels
should carry information warning of hazards to the developing fetus as well
as of other health hazards associated with alcohol consumption abuse.

Food Services

Aside from the special populations noted below, evidence related to the role
of alcohol currently holds no special implications for change in policies
related to food service programs.

661


O Nutrition and Health

Food Products
There are no special implications for change in policy related to formula-
tion of food products.

Special Populations

Pregnant women, including those served by the Special Supplemental
Food Program for Women, Infants, and Children (WIG) and other maternal
and child health programs, should be provided with counseling on avoid-
ance of alcoholic beverages. Persons with alcohol-related conditions
should be provided with counseling and referrals on the benefits of absti-
nence.

Research and Suweillance

Research and surveillance issues of special priority related to the role of
alcohol and health include investigations into:
o The levels at which alcohol intake increases risk for chronic diseases
  and birth defects.

o The mechanisms by which alcohol induces fatty changes in the liver.
o The mechanisms by which alcohol increases blood pressure, blood
cholesterol, blood glucose levels, and other risk factors for chronic
disease.

o The mechanisms by which low levels of alcohol may reduce risk for
coronary heart disease.

o The mechanisms by which alcohol increases cancer risk.
o The mechanisms by which alcohol damages the nervous system.
o The mechanisms by which alcohol intake interferes with nutritional
status.

o Definition of the physiologic energy value of alcoholic beverages.
o The interaction of alcohol intake, nutritional status, socioeconomic
status, and health.

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Chapter 18

Drug-Nutrient Interactions

. . . the suffering was caused by digestion
itself. . . vitiated by so long a use of opium.
     Thomas De Quincey
Confessions of an Opium Eater (182 1)

Introduction

Drugs are chemical agents used to prevent or treat disease. They interact
with foods and nutrients in several ways. Drugs can interfere with appetite
or with nutrient digestion, absorption, metabolism, or excretion. Similarly,
both nutritional status and diet can affect the action of drugs by altering
their metabolism and function, and various dietary components can have
pharmacologic activity under certain circumstances. Such interactions
raise concerns that drugs might impair nutritional status and induce nutri-
tional deficiencies or that inappropriate dietary intake might impair or
enhance drug activity. This chapter reviews these issues. More complete
discussion of individual topics may be found in comprehensive reviews and
monographs (Hathcock and Coon 1978; Young and Blass 1982; Smith and
Bidlack 1982; Roe 1984; Roe 1985; Hathcock 1987a, 1987b).

Historical Perspective

Throughout history, treatments for injuries and diseases have often in-
cluded manipulations of the diet and the use of remedies prepared from
plants, animals, and minerals. The earliest surviving written records de-
scribe the ancient Sumerians' medicinal uses of laurel, caraway, and thyme.
The first Chinese herb book, written in 2700 B.C., listed 365 medicinal
plants and included ma-huang, the source of ephedrine. In 1000 B.C., the
Egyptians were using garlic, opium, castor oil, coriander, mint, indigo, and
other herbs as medicines, foods, and dyes (Young 1978). Hippocrates
advocated the use of a few simple herbal drugs along with fresh air, rest, and
proper diet to help the body's "life force" eliminate health problems (Lust
1974). Galen recommended large doses of drug mixtures to correct the

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imbalances that he believed caused diseases. Descriptions of the properties
and medicinal uses of about 500 plants in De Mareria Medica, compiled in
the first century A.D. by the Greek physician Dioscorides, remained an
authoritative reference until the 17th century. Some of these plants from
earlier writings are sources of modern drugs, including quinine from
cinchona bark, morphine from the opium poppy, digitalis from foxglove,
and reserpine from rauwolfia (Lust 1974).

In the 16th and 17th centuries, a school of scientists known as iatrochemists
believed that chemistry's proper function was to assist physicians to im-
prove health care (ACS 1977). Their teachings led in the 18th and 19th
centuries to the use of minerals such as arsenic, iron, and sulfur to treat
acute infections, a practice that may be said to be the beginning of chemo-
therapy. The purges and emetics of past medical practice usually were
given as short courses of therapy and were unlikely to have a lasting effect
on nutritional status. The chronic use of drugs such as opium or alcohol,
however, was more likely to impair nutritional status through reduced
nutrient intake or, in the case of alcohol, toxic effects on the digestive
system (see chapter on alcohol).

As the sciences of medicine and nutrition developed, successful therapies
tended to occur in areas associated directly or indirectly with the treatment
of acute nutrient deficiency states, such as the use of limes to prevent or
cure scurvy.

Eventually, the use of drugs evolved from an empirical art handed down
through the centuries to a rigorous science of pharmacology in which
known amounts of pure agents with specific physiologic effects are admin-
istered to treat particular conditions. The development of new drugs has
the potential for introducing new drug-nutrient interactions, some of which
may be beneficial to the patient while others may be deleterious. Thus,
present interest in drug-nutrient interactions focuses on prevention of
nutrient deficiencies in individuals who take drugs and on minimization of
diet-induced impairments of drug function (Hathcock 1987a).

Significance for Public Health

Because of individual variations in dietary intake and in the use of and
response to drug therapies, the effects of interactions between drugs and
nutrients are difficult to measure, and no direct information is available on
the incidence, prevalence, or health cost of such interactions. Drug-nu-
trient interactions are most likely to impair health or nutritional status in
persons who take multiple drugs for prolonged time periods.

612


Drug-Nutrient Interactions O

One indicator of the potential public health importance of drug-nutrient
interactions may be found in the increasing level of use of medications by
the general public. Population exposure to prescription drugs, defined as
the average per capita number of prescription doses, increased 28 percent
between 1971 and 1982. Males obtained 40 percent of the prescriptions,
females 60 percent (Baum et al. 1985). In 1984, more than 1.5 billion
prescriptions were dispensed from retail pharmacies, a 2 percent increase
over 1983 levels. The cost of these prescriptions was $18.4 billion (Anony-
mous 1986a). New prescriptions accounted for 51 percent of the total,
refills for 49 percent. The increase in prescriptions tilled between 1984 and
1985 was 1.1 percent, largely as a result of increases in refills (Anonymous
1986b), and persons over 50 purchase prescriptions at about twice the rate
of the rest of the population (Baum et al. 1985).

The proportionate share of prescription drugs taken by older persons
increases with increasing age. Persons over age 65, for example, take about
25 percent of the national total of prescribed drugs and about an equal
proportion of drugs sold over the counter although they constitute only
about IO percent of the population (Chen et al. i985). Surveys show that the
majority of elderly people take two to five different drugs daily and experi-
ence about two to three times more adverse drug effects than younger
individuals (Rikans 1986). The medications most frequently used are drugs
for cardiovascular disease, the central nervous system, and constipation,
and most of the serious reactions are from cardiovascular and psychoactive
agents (Chen et al. 1985). Older persons are thus at increased risk for
deleterious drug-nutrient interactions because they take multiple drugs
over long periods of time, are more susceptible to nutritional deficiencies
(see chapter on aging), and have reduced ability to metabolize drugs
(Rikans 1986).

Scientific Background: Methodological Issues

When interpreting the clinical significance of drug-nutrient interactions, it
should be noted that recognized, frequent, serious interactions would
result in unacceptable toxicity, and, consequently, in abandonment of the
drug before marketing (Anonymous 1986~). Therefore, many drug-nutrient
interactions will rarely be manifest clinically and can only be demonstrated
in the laboratory. In most cases, excessive or abusive use of a drug is
necessary before adverse effects become clinically apparent, and such
effects are likely to occur only in vulnerable individuals who are chron-
ically malnourished, elderly, or ill. Although it is possible that subclinical
effects on health or nutritional status may occur at the usual levels of drug
intake, especially when therapy is long term, such effects are difficult to

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assess in individuals and are not yet possible to demonstrate in the popula-
tion (Roe 1985).

The effects of drugs on human nutrition are complex and may not be
recognized during routine preclinical toxicity testing in animals. Currently,
the potential of a drug to affect adversely nutritional status is evaluated in
animals by determination of food intake, body weight gain, and serum
chemistry and hematology profiles. Although animal toxicology studies
have often revealed adverse effects of drugs on food consumption and body
weight gain, such effects are usually seen only at high drug doses and are
not thought likely to affect nutritional status at doses typically prescribed
(Gilchrist 1981). There are, however, occasions when a drug alters the
nutritional status of animals at doses near the human therapeutic range.
One such example is the inhibition of bile acids and fat-soluble vitamin
absorption in both rats and humans by bile salt sequestrants such as
cholestyramine (Harkins, Hager-man, and Sarett 1%5; Hashim, Bergen,
and Van Itallie 1%1). The addition of cholestyramine to the diet of weanling
rats at concentrations near those that are used in humans has been shown to
reduce the normal body weight gain of these animals, perhaps because of
vitamin A depletion; the inclusion of additional vitamin A in the diet was
shown to prevent the weight loss, although liver stores of vitamin A
remained low (Whiteside et al. 1965).

Many drugs have been shown to affect serum chemistries or hematologic
parameters adversely during animal toxicity studies. In most cases, these
changes are due to toxicities unrelated to nutrition. In general, the design of
animal toxicology studies rarely allows for an adequate assessment of
chronic drug effects on nutrition, but when a nutritional problem is identi-
fied in human clinical studies, animal studies can help clarify the mecha-
nism of the interaction (Gilchrist 1981). Due to limitations in the doses used,
in the number of subjects studied, and in the duration of drug administra-
tion, prospective (cohort) studies of drug safety can detect adverse effects
on nutritional status only when they occur with high frequency in the study
population. Depending on the intended use of the drug, populations at
greatest risk for adverse nutritional effectsdhildren, pregnant women,
and older persons-may not be studied at all.

Key Scientific Issues

o Effects of Drugs on Nutritional Status
0 Effects of Diet on Drug Metabolism


Drug-Nutrient Interactions 0

o Effects of Drug-Food Incompatibilities
o Effects of Drugs Used in Food Production
o Effects of Pharmacologic Doses of Nutrients

Effects of Drugs on Nutritional Status

Drugs can affect nutritional status by altering appetite, food digestion, and
nutrient absorption, metabolism, utilization, or excretion.

Appetite and Food Intake

The regulation of food intake is exceedingly complex and involves the
integration by the brain of chemical signals that convey visual, olfactory,
and gustatory information as well as many internal signals regarding the
quality, palatability, and need for food through multiple neurotransmitters
and hormones (Morley et al. 1984; Sullivan and Gruen 1985). Appetite is
stimulated, for example, by norepinephrine, opioid peptides, pancreatic
polypeptides, growth hormone releasing factor, and gamma aminobutyric
acid (GABA). Conversely, appetite is inhibited by factors such as
dopamine, epinephrine, serotonin, neurotensin, calcitonin, and cor-
ticotropin releasing factor (Leibowitz 1986) and by intestinal hormones
such as cholecystokinin, bombesin, somatostatin, and glucagon (Merely
and Levine 1985; Sullivan and Gruen 1985).

The ways in which anorectic agents might affect appetite regulatory mech-
anisms are poorly understood. Amphetamines, fenfluramine, and the over-
the-counter phenylpropanolamine (PPA) diet pills have been reported to
exert their effects by causing the release from the central nervous system of
neurotransmitters that increase feelings of satiety (Hoebel 1977). Other
nutrition-related metabolic effects, such as lowering of body weight set
points (Stunkard 1982), have been postulated but need confirmation. Al-
though some drugs have been shown to induce weight loss in experimental
animals, both the safety and efficacy of their use by humans is controver-
sial. Certain studies suggest that they induce small but significant weight
losses, but others have found them to be ineffective and possibly harmful
(Friedman, Kindy, and Reinke 1982). PPA is an example of an
amphetamine-like agent with no data on long-term benefits but well-docu-
mented side effects, including hypertension, seizures, strokes, headache,
nausea, and behavioral disturbances (Pentel 1984).

Of considerable current research interest is exploration of the use of
narcotic antagonists such as naloxone to block the appetite-stimulating

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O Nutrition and Health

effects of endogenous opioid peptides in the brain. Naloxone has been
shown to retard weight gain in experimental animals (Reid 1985). Although
it also appears to reduce food intake in humans (Cohen et al. 1985), studies
exploring its clinical use in weight reduction have been disappointing
(Levine et al. 1985).

Digestion and Absorption
A variety of commonly used drugs impair the digestion and absorption of
certain nutrients.

Laxatives decrease gastrointestinal transit time and reduce the absorption
of glucose, calcium, protein, sodium, and potassium (Frier and Scott 1977).
It has been suggested that mineral oil solubilizes and sequesters fat-soluble
vitamins and prevents their absorption (Morgan 1941; Mahle and Patton
1947), but more recent data suggest this effect may be minimal. Cellulose
can decrease absorption of calcium and magnesium (Berstad et al. 1975;
F'ak 1973).

Excessive consumption of aluminum-containing antacids can induce a
phosphate depletion syndrome when dietary phosphate combines with
aluminum hydroxide to form aluminum phosphate, which is insoluble and
hence is completely excreted (Cooke, Teitelbaum, and Avioli 1978; Insogna
et al. 1980). The risk of acute phosphate depletion is greatest when the diet
is low in phosphate (Roe 1984). Antacids have been reported to have
induced a severe copper deficiency in a patient with decreased gastric
emptying time (Anonymous 1984a). Prolonged use of aluminum-containing
antacids by patients with impaired renal or biliary excretion should be
avoided, because the absorption and accumulation of aluminum under
these conditions may impair calcium metabolism and lead to bone disease
as is seen in kidney dialysis patients (Lemboke et al. 1982; Herzog et al.
1982).

Cholestyramine and colestipol prevent intestinal reabsorption ofbile acids;
they lower blood cholesterol levels by enhancing the conversion of choles-
terol to bile acids. These drugs, however, also alter bile acid activity and
may result in malabsorption of fat, vitamins A, D, K, and B,,, and folacin
(Whiteside et al. 1965; West and Lloyd 1975). However, use of cho-
lestyramine for 7 to 9 years in the Coronary Primary Prevention Trial by
men with high blood cholesterol did not appear to cause nutrient deficien-
cies. Fat-soluble vitamins are frequently prescribed along with cho-
lestyramine to eliminate any risk of deficiency.

676


Drug-Nutrient Interactions 0

Certain antibiotics, such as neomycin, may damage the intestinal mucosa
and also precipitate bile acids, thus decreasing the absorption of vitamin K,
carotene, and vitamin A, which are dependent on bile acid action for
absorption (Levine 1967; Thompson et al. 1971; Barrowman, D'Mello, and
Herxheimer 1973). Excessive amounts of broad-spectrum antibiotics can
also destroy the natural vitamin K-producing bacterial population of the
intestine, thus inducing bleeding conditions that can be reversed, if neces-
sary, by vitamin K administration (Ansell, Kumar, and Deykin 1977; Anon-
ymous 1984b).

The anti-inflammatory agent colchicine used to treat gout may alter intes-
tinal transport mechanisms, leading to sodium, potassium, lipid, and nitro-
gen fecal loss (R&e, Paes, and Faloon 1970; Webb et al. 1968).

Metabolism and Utilization

Oral Contraceptive Agents. Oral contraceptive agents are formulated from
synthetic estrogens and progesterones that can affect metabolic processes
involving essential vitamins and minerals. They are used by an estimated
10 million women in the United States (Ory, Forrest, and Lincoln 1983).
Although numerous studies have reported laboratory evidence of marginal
nutritional deficiencies among women taking these drugs, such evidence
has been inconsistent and has only rarely been confirmed by clinical
evidence. For example, blood levels of vitamin B, were found in some
studies to be reduced among 20 percent or more of women using oral
contraceptives, but other studies have failed to demonstrate such effects
(Thorp 1980). The clinical significance of these observations is uncertain
(Leklem 1986; Miller 1986). Circulating levels of zinc and release of zinc
from tissues have also been reported to be reduced among users of oral
contraceptives, but there is no evidence that such changes alter the dietary
requirement for this mineral (King 1987). As with other interactions yield-
ing minimal to moderate decreases in serum levels of micronutrients,
clinical manifestations of deficiencies are likely to be detected only when
nutritional status is below optimal levels before taking the drug.

Anticonvulsanfs. Various anticonvulsants accelerate the metabolism and
elimination of vitamin D (Harvey 1985) and have been associated with
clinical signs of rickets in children and osteomalacia in adults (Matheson et
al. 1976). Also, the anticonvulsants phenytoin, phenobarbital, and pri-
midone are capable of inducing a biochemical or clinical folate deficiency
state (Chanarin 1979; Lambie and Johnson 1985; Edeh and Toone 1985).
These drugs also interfere with metabolism of thiamin (Klein et al. 1977).

677


O Nutrition and Health

Newborn infants of mothers taking barbiturates or phenytoin are more
likely to have coagulation defects because of reduced availability of vitamin
K (Keith, Gundberg, and Gallop 1980; Keith et al. 1983). Osteomalacia
secondary to phenytoin may require replenishment of vitamin K as well as
vitamin D to restore the vitamin K-dependent proteins that are important
for normal calcium metabolism in bone. Camitine may be depleted by
therapy with the anticonvulsant valproic acid, resulting in hepatic injury
and a Reyes-like syndrome (Bohles et al. 1982; Coulter 1984; Murphy,
Marquardt, and Shug 1985).

Vitumin Antagonists. Several drugs used as cancer chemotherapeutic
agents (e.g., methotrexate), as diuretics (triamterene), or as antimalarial or
antibacterial drugs (pyrimethamine) are antagonists of folic acid (Lambie
and Johnson 1985). These drugs bind to the enzyme dihydrofolate reduc-
tase, preventing the conversion of folic acid to tetrahydrofolate, the vi-
tamin form that is required for synthesis of purines. As a result, DNA
synthesis is arrested and the cells die (Anderson, Smith, and Hutchinson
1966; Kahn, Fein, and Brodsky 1968; Lieberman and Bateman 1968;
Myatt, Hemandez, and Coatney 1953). The drug sulfasalazine, used to
treat ulcerative colitis, inhibits intestinal transport of folic acid and has
been associated with the clinical signs of deficiency of this vitamin often
seen in persons with inflammatory bowel disease (Halsted, Gandhi, and
Tamura 1981).

The vitamin K antagonists-dicumarol, phenprocoumon, and warfarin-
are used as anticoagulants; they block a specific carboxylation step in the
activation of six vitamin K-dependent clotting factors (Wessler and Gitel
1984; O'Reilly 1985). Parkinsonian patients, whose tremors are controlled
by L-dopa, may experience a precipitation of their symptoms if they ingest
large doses of vitamin B, because of an interaction between L-dopa and
pyridoxal-5 phosphate, the active form of this vitamin (Evered 1971; Mars
1974).

The antitubercular drug isoniazid binds and inactivates vitamin B,, induc-
ing pyridoxine deficiency and its resulting neuropathy (Biehl and Vilter
1954). Consequently, vitamin B, is often given to individuals receiving this
therapy. One benefit of this interaction is that overdoses of isoniazid can be
treated successfully by administration of vitamin B, (Wason, Lacouture,
and Lovejoy 1981). A similar vitamin B,-responsive neuropathy occurs in
patients taking hydralazine, a hypotensive agent (Raskin and Fishman
1965). Cycloserine, another antitubercular drug, impairs niacin synthesis
and absorption and may lead to a niacin deficiency (Heinivaara and Plava
1964).

678


Drug-Nutrient Interactions O

Vitamin B,, metabolism is also affected by a variety of drugs. For example,
the antitubercular drug paraminosalicyclic acid affects intestinal transport
mechanisms for vitamin B,, (Toskes and Deren 1972), and prolonged
exposure to nitrous oxide has been reported to produce a megaloblastosis
(Chanarin 1982) and a myeloneuropathy similar to symptoms typical of
vitamin B,, deficiency (Layzer 1978) perhaps because of binding and
inactivation of the cobalt present in that vitamin.

Antihypertensive Drugs. These drugs produce disturbances of mac-
ronutrient metabolism, resulting in glucose intolerance and hyper-
lipidemia. Beta blockers increase blood levels of triglycerides but decrease
levels of high density lipoprotein cholesterol (Helgeland 1984; Weinberger
1985). Thiazide diuretics decrease glucose tolerance (Amery et al. 1978;
Murphy et al. 1982; Perez-Stable and Caralis 1983; Helderman et al. 1983;
Ames 1984), increase serum levels of low density lipoprotein cholesterol
(Goldman et al. 1980; Grimm et al. 1981; Weinberger 1985) and decrease
losses of calcium in urine (McCarron 1985; Stier and Itskovitz 1986).
Spironolactone lowers serum levels of high density lipoprotein cholesterol
and increases serum levels of insulin (Falch and Schreiner 1983).

Excretion

Diuretics. Diuretics, such as the thiazides and furosemide, decrease the
resorption of potassium and other minerals by the kidneys, thereby in-
creasing their excretion (Dyckner and Webster 1979; Morgan,
Murkinshaw, and Davidson 1978). Patients on long-term diuretic therapy
are usually advised to consume foods rich in potassium.

In sum, drugs cause little nutrient-related difficulty for the great majority of
individuals taking medications. Adverse effects are usually limited to per-
sons who consume relatively high doses over prolonged periods, or to
persons who have clinical conditions that interfere with normal drug me-
tabolism and excretion or that make them unusually susceptible to drug-
induced nutritional deficiencies (Smith and Bidlack 1982).

Effects of Diet on Drug Metabolism

Nutritional factors affect the activity of drugs by altering their rates of
absorption, metabolism, or excretion.

Absorption
Dietary factors can decrease, delay, or enhance the absorption of drugs,
primarily by altering their availability, their solubility, or the amount of time

679


O Nutrition and Health

they spend in the stomach or intestine (Hathcock 1985). Calcium, for
example, can bind tetracycline antibiotics and form a complex that renders
both the drug and nutrient unavailable (Roe 1985). Dietary fat enhances the
absorption of fat-soluble drugs, but the absorption of drugs that bind to
fiber is reduced by high-fiber diets. Drugs such as L-dopa and penicillin G
that are metabolized or degraded in the stomach may be partially destroyed
when gastric emptying is delayed. The bioavailability of certain drugs, such
as the antibacterial nitrofurantoin, the cardiovascular drug propranolol,
and the hypotensive drug hydralazine, is enhanced when gastric emptying
is delayed and more of the agent can be dissolved in the gastric juice
(Melander 1978; Toothaker and Welling 1980). Digitalis absorption is
slowed by the presence of food in the gastrointestinal tract. Instructions to
take drugs with or between meals, or the coating of drugs to prevent
dissolution, attempt to take advantage of these gastric properties, although
it is uncertain how well patients adhere to such instructions. The acidity of
the gastrointestinal tract also affects drug disposition. A more acidic en-
vironment reduces the bioavailability of penicillin and isoniazid but in-
creases the absorption of tetracyclines (Roe 1985).

Food decreases, delays, or enhances the absorption of certain antibiotics
(Hathcock 1985). The complexity of the diet and of drug responses makes
the clinical implications of such interactions difficult to predict.

Metabolism and Utilization

The effects of drugs are modulated by their rates of metabolism by the liver
and other tissues. Drugs that are metabolized slowly do not need to be
taken as frequently or in as high doses as those that are rapidly eliminated
by the body. Drugs are metabolized by two basic processes. The first
(Phase I) metabolic step is usually an oxidation reaction that alters a
functional group in the drug. This alteration may either activate the drug or
deactivate it. The most common example of this process involves the same
mixed-function oxidase enzyme systems that metabolize many other en-
dogenous or foreign (xenobiotic) compounds. These systems contain
cytochrome P-450 and other cytochromes and employ reduced nicotina-
mide adenine dinucleotide phosphate (NADPH) and molecular oxygen in
their reactions. A second step (Phase II) conjugates the oxidized drug to an
inactive, water-soluble form that can be readily excreted (Bidlack 1982;
Meydani 1987; Hathcock 1987a). Most effects of diet on drug metabolism
affect the oxidation reactions, whereas relatively little is known about the
ways in which nutritional factors affect conjugation reactions (Hathcock
1986).

680


Drug-Nutrient Interactions O

The rate of drug metabolism by mixed-function oxidase systems can be
accelerated (induced) by the drugs themselves as well as by a variety of
dietary factors. Such factors include protein, cruciferous vegetables such
as broccoli or cabbage, and charcoal-broiled meats (Bidlack 1982). Thiamin
deficiency also increases drug metabolism-it has been shown to increase
the demethylation of mestranol, for example (Hoyumpa and Schenker
1982).

On the other hand, low-protein, high-carbohydrate diets and deficiencies of
several vitamins and minerals reduce levels of drug-metabolizing enzymes
and, consequently, the rate of drug metabolism, so that drug concentrations
may decline slowly. Thus, in many cases, the net effect of nutritional
deficiency is to increase drug potency (Hathcock 1987a). In starved individ-
uals, for example, the activities of the mixed-function oxidase enzymes are
reduced and the clearance of drugs such as chloramphenicol and sul-
fadiazine is impaired. The metabolism of other drugs is unaffected by
starvation (Bidlack 1982).

Excretion

High-fiber diets interfere with the enterohepatic circulation of drugs ex-
creted in bile (Hathcock 1985). Urinary acidity, which can be affected by
diet, also influences drug elimination. Aspirin, for example, is resorbed in
acidic urine, whereas amphetamines are resorbed under more alkaline
conditions (Welling and Tse 1983).

Effects of Drug-Food lncompetibilities

Certain drugs can interact with specific nutrients or non-nutrient compo-
nents in foods to cause acute adverse reactions. Such reactions can be
prevented by avoiding the foods when taking the medication. Examples
include interactions between monoamine oxidase inhibitors and foods
containing tyramine, and between alcohol and disulfiram, hypoglycemic
agents, and many other drugs (Taylor 1987).

Monoamine Oxidase Inhibitors

Monoamine oxidase (MAO) inhibitors are mood-elevating agents that were
formerly used with great frequency to treat severe depression. Their nutri-
tion-related problems stem from metabolism of the potentially toxic amine
tyramine. Tyramine is formed when intestinal bacteria degrade the amino
acid tyrosine; it is also found in fermented foods such as cheese, wine,

681


O Nutrition and Health

yogurt, some kinds of sausages, and beer. Under ordinary circumstances,
the enzyme MAO converts tyramine to soluble products that can be
excreted in urine. Inhibition of MAO in the presence of foods containing
tyramine permits this toxic amine to increase in blood to the point where it
causes severe-and occasionally fatal-hypertension (Asatoor, Levi, and
Mime 1963). Because the use of MAO inhibitors by people who ingest foods
containing tyramine can induce a severe hypertensive crisis, they are now
prescribed less frequently (Roe 1984).

Alcohol

Acetaldehyde-induced nausea and vomiting can occur within 15 minutes
after the consumption of alcohol by persons taking the drugs disulfiram
(Antabuse), metronidazole (Plagyl), and chlorpropamide (Diabinese). Di-
sulfiram inhibits the enzyme acetaldehyde dehydrogenase, which oxidizes
acetaldehyde, a product derived from the metabolism of alcohol (Hald and
Johnson 1948). This interaction, which is so unpleasant as to deter the use
of alcohol, is the basis for the use of Antabuse in detoxification programs
(for reviews see Roe 1984; Seitz and Simanowski 1987).

Alcohol consumption can cause hypoglycemia in persons with diabetes
who are using agents such as the sulfonylureas to lower blood sugar levels
(Harris 1971; Carulli, Manenti, and Gal10 1971). It also potentiates the
prolongation of bleeding time induced by aspirin (Deykin, Janson, and
McMahon 1982), an interaction that can have serious consequences in
alcoholic patients who suffer from gastritis, esophageal varices, or peptic
ulcers.

Acutely, alcohol inhibits the activity of drug-metabolizing enzymes by
displacing other drugs bound to cytochrome P-450, by decreasing the
availability of NADPH, or by disturbing the lipid bilayer membrane that
provides the microenvironment for drug-metabolizing enzymes (Hoyumpa
and Schenker 1982). Chronic alcohol consumption enhances oxidation and
toxicity of many substances, for example, acetominophen (Seitz and Sim-
anowski 1987). It increases the toxic side effects of analgesics, anesthetics,
anticoagulants, anticonvulsants, antihistamines, antimicrobials, tran-
quilizers, and narcotics (Anonymous 1979). Meprobamate, chloral hy-
drate, and barbiturates are also metabolized and excreted more slowly
when alcohol is taken simultaneously (Hoyumpa and Schenker 1982).
Ingestion of benzodiazepines and alcohol together results in higher plasma
concentration of the drugs and enhanced sedative effects due to decreased
hepatic clearance. The postural hypotension produced by organic nitrates
for angina is accentuated by alcohol (Needleman, Corn and Johnson 1985).

682


Drug-Nutrient Interactions 0

As a general rule, any toxic side effect of a medication will be potentiated if
alcohol is consumed along with it (Anonymous 1979; Seitz and Simanowski
1987).

Effects of Drugs Used in Food Production

Antibiotics such as tetracycline and penicillin are fed to livestock to pre-
vent infections and to promote growth. Because the genetic information
that controls some kinds of resistance to antibiotics is carried on transposa-
ble genetic elements (plasmids) that can be transferred from one organism
to another, questions have been raised as to whether subtherapeutic doses
of livestock with antibiotics (a procedure that enhances growth and feed
utilization) might encourage the proliferation of antibiotic-resistant micro-
organisms that are human pathogens or are capable of transferring antibiot-
ic resistance to human pathogens (Stallones 1982).

In 1980, a National Academy of Sciences (NAS) report concluded that the
research necessary to establish and to measure potential risks of antibiotic
use in animals had not yet been conducted (NAS 1980). Since then, human
infections with drug-resistant Salmonella have been documented, both as a
result of eating hamburger originating from cattle that had been fed sub-
therapeutic doses of tetracyclines (Holmberg et al. 1984) and from drinking
raw cow milk infected with Salmonella resistant to chloramphenicol and
several other antimicrobial agents (Tacket et al. 1985). As a result of these
studies, the Center for Veterinary Medicine of the Food and Drug Adminis-
tration, with the counsel of a new NAS committee, is reviewing the avail-
able research findings on the hazards and benefits of this use of drugs. At
issue is whether to institute procedures to suspend low-level uses of pen-
icillins and tetracyclines in animal feeds (Goodman-Malamuth 1986).

Effects of Pharmacologic Doses of Nutrients

Nutrients are sometimes used in unusually high doses for their phar-
macologic effect. Niacin, for example, is used pharmacologically to reduce
blood cholesterol levels (Grundy et al. 1981; Blankenhorn et al. 1987).
Retinoid derivatives of vitamin A have been used successfully to treat
severe acne and other conditions (Bollag 1983). All pharmacologic
therapies induce side effects (pharmacology has been described as "applied
toxicology" because even the desirable effects of drugs are obtained by
altering-poisoning-normal metabolic function), and high-dose nutri-
tional therapies are no exception. Although excess water-soluble vitamins
are excreted and usually cause little difficulty, side effects have been

683


O Nutrition and Health

reported in cases of excessively high doses (Miller and Hayes 1982). High-
dose niacin induces flushing, and neurologic symptoms have been reported
from excessive intake of vitamin B, (Schaumburg et al. 1983). Excessive
intake of fat-soluble vitamins or their derivatives is well known to induce
toxic symptoms. Excess vitamin A, for example, causes birth dkfects in
animals, and, possibly, in humans; caution has been urged in its use for
women who are pregnant or likely to become pregnant (Teratology Society
1987).

Individuals born without the genes to produce key functional enzymes may
require amounts of certain nutrients greatly in excess of those required by
most people. Such inborn metabolic errors have been identified for en-
zymes necessary for absorption, metabolism, or storage of nearly all of the
vitamins (Stanbury et al. 1985). In some cases, higher-than-normal intake
of the vitamin will restore activity. A classic example of such a vitamin-
responsive syndrome is pernicious anemia, a condition of impaired absorp-
tion of vitamin B,,. Patients with this condition must have exceedingly high
doses of the vitamin from food or supplements, or lower doses by injection.
Another example is homocystinuria, a condition that results from a defi-
ciency of the enzyme cystathione beta synthetase. Lack of this enzyme
leads to the accumulation of methionine, the appearance of homocystine in
urine, and clinical symptoms ranging from thromboses and osteoporosis to
mental retardation. About 40 percent of individuals with this condition
respond favorably to doses of vitamin B, that are 50 to 500 times higher than
levels defined by Recommended Dietary Allowances (Mudd and Levy
1983).

Acrodermatitis enteropathica, a severe skin and gastrointestinal disorder,
is caused by a deficiency in zinc absorption, but it can be overcome by zinc
administration at levels greatly in excess of those normally required (Prasad
1983). An inborn error of metabolism resulting in systemic camitine defi-
ciency, with clinical manifestations of excessive ketone production, has
been treated successfully with supplemental camitine (Wolff et al. 1986).

In other conditions, certain metabolic products cannot be degraded and,
therefore, accumulate to toxic levels. In some cases, such disorders can be
treated with carefully designed dietary preparations having a very low
content of the poorly metabolized nutrient. An example of this type of
condition is phenylketonuria, a genetic lack of the enzyme that converts
the amino acid phenylalanine to tyrosine. Patients with phenylketonuria
accumulate phenylalanine and other metabolites that, at high levels, are
toxic and cause mental retardation and other neurologic damage (Anony-

684


Drug-Nutrient Interactions O

mous 1986d). Dietary treatment is designed to reduce the phenylalanine
content of the diet to levels below those that cause symptoms. The special
infant formula product Lofenelac, for example, contains sufficient quan-
tities of all of the essential amino acids with the exception of phenylalanine
(Tourian and Sidbury 1983).

Implications for Public Health Policy

Dietary Guidance

General Public

Although drugs interact with dietary factors in many ways that impair
nutrient availability, evidence about the public health significance of such
interactions is insufficient to recommend general shifts in the pattern of use
of any particular drug on the basis of its adverse effects on nutritional
status. Nor may any implications be drawn at this time for the general
public on intake of specific nutrients with relation to nonprescription drug
interactions.

Special Populations

Studies of patients consuming multiple drugs for prolonged time periods,
especially those patients who are older, suggest that dietary intakes may
need to be adjusted to compensate for adverse interactions of specific
nutrients with medications and that information should be provided to such
patients by qualified health professionals on appropriate use of such diets.
Patients taking drugs that induce acute reactions in the presence of dietary
factors such as tyramines or alcohol should be instructed on appropriate
means to avoid those factors.

Persons with inborn metabolic errors that respond to pharmacologic doses
of nutrients or to special products designed to minimize toxic symptoms
should be advised on the safe and effective use of such therapies. Health
professionals should receive instruction about drug-nutrient interactions to
understand how best to maximize drug efficacy and minimize adverse
reactions.

Nutrition Programs and Services

Food Labels

Evidence related to the role of diet in drug interactions currently holds no
special implications for change in policy related to food labeling.

685


O Nutrition and Health

Drug Labels
Evidence related to the role of diet in drug interactions suggests that drug
manufacturers should provide information in the package insert on the
potential effects of the medication on nutritional status, and vice versa.

Food Services

Evidence related to the role of diet in drug interactions currently holds no
special implications for change in policy related to food service programs.

Food Products

Evidence related to the role of diet in drug interactions currently holds no
special implications for change in policy related to packaged food products.
Preliminary evidence relating human infections to antibiotic-resistant
micro-organisms derived from animals treated with subtherapeutic doses
of antibiotics suggests the need for close scrutiny of this practice.

Special Populations

Persons-especially older persons-who consume drugs should be pro-
vided with counseling and assistance on dietary methods to avoid adverse
drug-nutrient interactions. Persons with inborn metabolic errors requiring
therapy with pharmacologic doses of nutrients should be provided with
counseling and assistance on appropriate and safe use of such supple-
ments.

Research and Surveillance

Research and surveillance issues of special priority related to the role of
diet in drug interactions should include investigations into:
o The extent of drug taking (prescription, over the counter, and illegal)
  among the population.

o The extent of adverse drug-nutrient interactions in the population and
their clinical significance.

o Age-related changes in nutrient metabolism with special implications
for pharmaceutical use.

o Effects of medications on the nutritional status of older persons.
o Drug effects on nutrient intake, absorption, metabolism, and excre-
tion.

o Effects of diet, including alcohol, on drug absorption, metabolism, and
excretion.

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Drug-Nutrient Interactions O

o The effects of antibiotics, hormones, or other drugs in animal feeds on
human health.
0 The levels of intake of essential nutrients that induce toxic symptoms.
o The most effective means to educate health professionals and the
general public about drug-nutrient interactions.

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u Nutrition and Health

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Chapter 19

Dietary Fads and Frauds

The advertising quack . . . is the black wolf,
aye, the Bengal tiger of the profession. . . .
He is full of shrewdness and cunning, and
knows the poor weak human nature like a
           book.
     Dr. Willis P. King, 1882
  Quacks and Quackery in Missouri

Introduction

Historical Perspective

Food, an indispensable ingredient of life, has long been endowed with
metaphysical, moral, and theological meanings. The folklore and supersti-
tions of cultures throughout history have attributed healing or harmful
properties to certain foods. This tendency has not disappeared with the
advent of the sciences of nutrition and medicine. Food folklore continues
today, although in many instances it is inconsistent with scientific evidence
(Young 1978).

Contemporary food fads often make one or more of the following claims,
none of which are substantiated by available scientific evidence (Bitensky
1973; Darby 1974; Shifflett 1976; Deutsch 1977; Stare 1980; Miller 1980;
Jarvis 1983, 1984b):

0 Some foods have magical, life-promoting properties.
o Modern foods are grown on depleted soil, are overprocessed, and,
therefore, cannot provide good nutrition.
o Food supplements are always necessary to ensure good nutrition, and
megadoses of nutrients provide "supernutrition."

Definitions

Nutrition fraud is a comprehensive term used by the U.S. Food and Drug
Administration (FDA) to describe the abuses that occur as the result of the
misleading claims for traditional foods, dietary supplements, and dietary

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products and of the deceptive promotion of other food substances, proc-
esses, and devices (Nightingale 1984). Nutrition fraud has long been recog-
nized as the leading example of health fraud (Larrick 1963). Food faddism
and quackery describe two types of nutrition fraud commonly purveyed to
the public (Huenemann 1956; Todhunter 1973; Jarvis 1984a).

Food faddism is a dietary practice based upon an exaggerated belief in the
effects of food or nutrition on health and disease. Food fads derive from
three beliefs: (1) that special attributes of a particular food may cure
disease, (2) that certain foods should be eliminated from the diet because
they are harmful, and (3) that certain foods convey special health benefits
(McBean and Speckmann 1974). Unlike more transitory fads, many key
concepts associated with food faddism persist or reappear periodically.
Food faddists are those who follow a particular nutritional practice with
excessive zeal and whose claims for its benefits are substantially more than
science has substantiated. In most instances, foods praised as beneficial,
such as special products or vitamin supplements, are not as good as
faddists claim, and those foods condemned as harmful, such as white flour
or sugar, are not as bad (Jarvis 1983).

Food quackery, which involves the exploitive, entrepreneurial aspects of
food faddism, is the promotion for profit of special foods, products, proc-
esses, or appliances with false or misleading health or therapeutic claims.
A food quack is one who pretends to have medical or nutritional knowledge
and who promotes special foods, products, processes, or appliances with
false or misleading claims, usually for personal financial gain.

Factors Contributing to Nutrition Fraud
Nutrition fraud flourishes in the United States today because of the diver-
sity of cultures, the historical tradition of concern for health and the use of
natural remedies, and the introduction of advanced communication tech-
nologies. Some frauds derive from traditional folklore inherited from the
many cultures populating this country, while others are uniquely American
(Young 1978; Deutsch 1977).

Food faddism in America had its roots in Great Britain, where patent
medicines were advertised and sold by everyone from hairdressers to
goldsmiths. In the colonies, legal protection of consumers against fraudu-
lent claims was first recorded in Massachusetts Bay in 1630. A citizen,
Nicholas Knopp, was whipped and fined five pounds for selling a cure for
scurvy that had "no worth nor value" and was "solde att a very deare rate"
(Young 1961).


Dietary Fads and Frauds Cl

Food faddism was very common in 19th-century America, perhaps as a
result of the high literacy rate and the proliferation of newspapers that
provided a medium for advertising. Claims for health benefits were an
integral part of the promotion of foods and food components sold by patent
medicine men and women and popular health reformers (Whorton 1982).
One of the earliest nutrition faddists was Sylvester Graham, a "back to
nature" reformer who was suspicious of any food, such as white flour,
altered from its "natural" condition (Young 1978; Whorton 1982). His
legacy continues among those who question whether processed food of any
type can provide adequate nutrition (Deutsch 1977; Stare 1980; Miller
1980).

Popular interest in nutrition, coupled with concern about food shortages
during World War I, was fostered by the increasing promotion of the health
properties of foods in the early 20th century (Young 1%7). Vitamins, by the
very nature of their discovery, became associated with the prevention or
cure of disease (Todhunter 1973) and were soon promoted as curative
agents (Young 1967). George I? Larrick (1959), then Commissioner of Food
and Drugs, explained this trend:

In the wake of scientific advances there often follows a host of persons who
misinterpret them and exploit them for private gain. That has been true in the
field of nutrition. The nutritionist studies the long-range benefits to the public
health from new scientific findings, withholds premature endorsement, and
has confidence that future research holds great promise. . . . The promoter

  does not wait for the facts or the possibility of different findings in the
&ire. He hastens to cash in before all the facts are known. Those interested
only in profit employ clever copywriters to promote products by pseudoscien-
tific statements, using half-truths and gross exaggeration to build up a scare
psychology. . . .

Today, the traveling patent medicine man has been largely replaced by the
highly skilled and organized use of electronic means to promote fraudulent
marketing-computers, customized mailing lists, national advertisements,
WATS banks of telephone lines, and other mass media. The medium and
the details have changed, but the message and the goals remain. It is
difficult for consumers to evaluate the validity of the health claims perpe-
trated by quacks and faddists (Tiemey 1984).

Background

Regulation of Nutrition Fraud
The need for public protection from fraud was recognized over a century
ago, when Congress enacted statutes to combat mail fraud (Nelson 1984).

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The first Federal legislation, the Pure Food and Drug Act of 1906, made it
unlawful to manufacture or introduce into interstate commerce adulterated
or misbranded food or drug products (Anderson 1964). This Act was passed
in response to an intensive campaign against patent medicines and food
abuses stimulated by the work of Dr. Harvey Washington Wiley, chief
chemist at the U.S. Department of Agriculture. Because of this, it soon
became known as "Dr. Wiley's Law."

The Federal Trade Commission Act of 1914 established Federal authority
for regulation of false advertising in interstate commerce, including adver-
tising of foods for human consumption. The 1938 Federal Food, Drug, and
Cosmetic (FD&C) Act gave the FDA new and more effective authority
over health food claims. Under the FD&C Act, a food is considered a drug
if therapeutic claims are made for it, and the burden of proving claims
fraudulent is less demanding than under the earlier law (Young 1967).

Currently, numerous Government, medical, and consumer-oriented orga-
nizations are responsible for preventing and controlling fraud (U.S. Con-
gress 1984b). At the Federal level, the FDA, the U.S. Postal Service
(USPS), and the Federal Trade Commission (FTC) have authority to act
against various kinds of illicit food and health-related practices. These
agencies work cooperatively, and their antifraud activities have become
more visible in recent years (Barrett 1985). The regulatory roles of these
various Federal agencies are reviewed below.

State enforcement activities against fraud are largely the responsibility of
the State attorneys general and offrces of consumer affairs and aging.
County consumer affairs offices and metropolitan police may also become
involved in regulation.

Private agencies and organizations such as the Better Business Bureau, the
American Dietetic Association, the American Heart Association, the Ar-
thritis Foundation, the American Cancer Society, the American Medical
Association, the National Council Against Health Fraud, and other health
professional groups are also active against food fraud. These organizations
often maintain informal liaison with each other and actively cooperate with
Federal regulatory agencies.

Despite these efforts, misleading claims about foods and nutrients are
difftcult to regulate. As noted by the 1969 White House Conference on
Food, Nutrition, and Health, "No other areaof the national health probably
is as abused by deception and misinformation as nutrition. Many travesties

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Dietary Fads and Frauds O

cheat the public of enormous sums of money, and of good health as well. Yet
the American people falsely believe they are well-protected, both by Gov-
ernment and by the ethics of commerce" (White House Conference 1969).

Not only is regulation difficult because of the complexity of the science
base, the ease of exploiting the mails, and the special vulnerabilities of
people with health concerns, but in the United States, governments at all
levels are limited in what they can do about fraudulent nutrition practices
by an obligation to observe the constitutional rights to free speech and a
free press. Nutrition information, whether supported scientifically or not,
is guaranteed the same protection under the first amendment as any other
information (Stephenson 1978; Young 1%7). The right to say, write, or
publish anything one chooses is protected, as long as it is done without
intentional malice (Barrett 1977; Pennington 1984).

Regulatory Roles of Federal Agencies

Food and Drug Administration Aurhoriry. The FD&C Act empowers the
FDA to prohibit the introduction of any food, drug, device, or cosmetic
that is adulterated or misbranded. The Act does not include explicit author-
ity to address health fraud, but many of its general provisions enable
actions in these areas. Sections 702-704 authorize the gathering of informa-
tion about health fraud products and practices through inspections, collec-
tion of samples and records of interstate shipments, and gathering of
evidence such as photographs and copies of labeling. Many fraud cases are
based on misbranding charges resulting from false or misleading labeling of
products. Only factual and nonmisleading information is allowed on food
labels. Most false promotional claims, therefore, are not made on labels.
Instead, they appear in books, lectures, and mass media that are protected
by constitutional rights.

The FDA has the authority to use its food additive and drug approval
processes to control food products allowed on the market and to remove
fraudulent products. Although food products do not need to receive pre-
market approval as safe for human consumption, some food components
need either to be classified as "Generally Recognized As Safe" (GRAS) or
to have undergone the required FDA approval process for a food additive.
If one or more of a food product's ingredients are subject to these provi-
sions but is neither GRAS nor an approved additive, the product is consid-
ered adulterated and therefore illegal.

The FD&C Act defines drugs as articles that are intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of diseases in hu-

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mans. Most fraudulent food products are classified as foods, but when
therapeutic claims are made for them, they are also considered to be drugs.
The Act's provisions require drug products to have (1) an approved New
Drug Application that demonstrates both safety and efficacy for its intend-
ed uses and (2) adequate directions for use. If a food product is also
classified as a drug and is considered by the FDA to be ineffective for its
claimed use, it will not have an approved New Drug Application. For
example, if it is promoted for treating a disease that is not amenable to lay
diagnosis, it cannot have adequate directions for use and will not be
approved. Recently, the FDA proposed a new policy on the appropriate use
of health-related messages on food labels (FDA 1987).

Educating the public on health fraud is complementary to the FDA's
regulatory activities. The Agency's magazine, FDA Consumer, devotes
editorial space to health fraud and includes major articles on the subject. In
addition, FDA consumer affairs officials across the country conduct a
health fraud consumer education program covering foods as well as medi-
cal devices and drugs. The objectives of this program are to increase public
knowledge and understanding of the FDA's statutory responsibilities and
the limitations of the FDA's authority in protecting consumers from misin-
formation about foods, dietary supplements, nutrition, and other FDA
concerns. The program provides guidance to enable consumers to recog-
nize fraud, evaluate product claims, make informed decisions, and register
complaints and concerns about fraudulent products.

U.S. Postal Service Authority. The authority of the USPS to control health
fraud is based on a general congressional mandate to protect the public
from marketing schemes conducted by mail. The purchaser is particularly
vulnerable to fraudulent inducements by mail because of the inability to
observe the product before payment (U.S. Congress 1984b). Specific au-
thority to protect the mail order consumer is vested in the criminal fraud
statute (18 U.S.C. 1341), the administrative false representation statute (39
U.S.C. 3005), and the supporting injunctive statute (39 U.S.C. 3007).

The mail fraud statute provides that any use of the mails in furtherance of an
intentional scheme to defraud is punishable by a fine of $1,000 and im-
prisonment of up to 5 years. Many nutrition-related schemes are pros-
ecuted under the mail fraud statute; they typically involve cure-ails, instant
weight reduction techniques, and a variety of substances falsely described
as having the ability to cure diseases or disabilities.

The false representation statute mandates that persons offering goods or
services for sale through the mail refrain from misrepresenting their prod-

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Dietary Fads and Frauds 0

ucts in any material respect. The Mail Order Consumer Protection Amend-
ments of 1983 enhance the effectiveness of the false representation statute
and are designed to address the problems of repeat offenders and "fly by
night" promoters who advertise a product, take orders, receive payments,
and change addresses without delivering any merchandise (Nelson 1984).
This new legislation gives the USPS authority to purchase and test without
delay any products or services sold through the mail. The 1983 amend-
ments also authorize the USPS to issue cease-and-desist orders. Such
actions, however, are limited by the validity of the address given by the
manufacturer. A growing number of promoters are advertising toll-free
telephone numbers and then delivering products using private parcel deliv-
ery services that are not under the USPS jurisdiction (Debrosse 1984).

Upon showing probable cause that a scheme violates the false representa-
tion statute, Federal district courts can order the Postal Service to detain
mail. Apparent violations of the postal fraud and misrepresentation statutes
are investigated by the Postal Inspection Service. Suspected criminal
violations are referred to the appropriate U.S. attorney.

Federal Trade Commission Authority. The FTC's authority to act against
deceptive food, drug, or other health claims derives from sections 5 and 12
of the Federal Trade Commission Act. Section 5 of the Act identifies
unlawful, unfair, and deceptive acts and practices in or affecting com-
merce. Section 12 of the Act specifically prohibits the use of false adver-
tisements regarding food, drugs, devices, or cosmetics. The Commission
can act under one or both sections to halt certain food, drug, or other health
care acts or practices.

Deceptive as well as fraudulent food, drug, and health care advertising
claims that induce people to purchase ineffective cures and nostrums are
important areas of FTC enforcement activity (Crawford 1984). A special
effort has been instituted to monitor claims for health care products, many
of which may fit into the fraud category. The FTC has implemented special
programs to monitor the advertising of some types offraudulent products in
tabloid publications and health magazines directed toward nontraditional
disease treatments. The FTC also monitors radio and television networks
and major newspapers and magazines to identify targets for Commission
action. Such targets are also identified through ongoing contacts with other
State and Federal officials and private groups.

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Key Issues

o Health Consequences of Fraud
o Economic Consequences of Fraud

Purveyors of nutrition fraud capitalize on people's desire to be healthy and
on the lack of certainty in many areas of nutrition and health. Although the
public may be injured by deceptive food claims, there are no reliable
statistics on the extent of health and nutrition fraud in this country (Young
1984).

Health Consequences of Fraud

Nutrition fraud may lead to deleterious health consequences, caused by the
failure to seek legitimate medical care, by potentially toxic components of
foods and products, by nutrient toxicities and deficiencies, by diversion of
monies from essential treatments, and by interference with sound nutrition
education.

Failure to Seek Legitimate Medical Care
Public health and safety can be jeopardized by false promises that divert or
deter individuals from pursuing sound forms of medical treatment or that
encourage them to abandon beneficial therapy for a disease (McBean and
Speckmann 1974). Fraud may encourage people to reject legitimate medi-
cal advice and to practice inappropriate self-medication that is less likely to
be helpful, and more likely to be directly harmful, than medical technology
based on a sound understanding of human biology and nutrition.

The FDA's annual reports document numerous instances of fraud-induced
failure to obtain appropriate health care (Young 1985). Because early
detection and treatment improve the prognosis for many illnesses, un-
proven "nutritional" therapies may unnecessarily delay beneficial inter-
vention (Brown 1984). Some diet regimens recommended by health fad-
dists to treat cancer, for example, are so nutritionally deficient or toxic that
adherence to them has caused death or serious illness (U.S. Congress
1984b). Although evidence is increasing that a proper diet may reduce the
risk of developing some forms of cancer, no diet or supplement can yet be
guaranteed to protect against-or to treat-these conditions.

Promotions of foods designed to treat various disorders are often targeted
to vulnerable populations (U.S. Congress 1984a). The use of these food

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Dietary Fads and Frauds 0

products accomplishes little besides increasing the market share of the
company making the fraudulent claims.

Potentially Toxic Food Components

Public injury can occur when foods and unproven remedies are toxic. Just
because a substance occurs naturally in food does not mean that it is
necessarily safe (Herbert and Barrett 1981). Many of the chemicals known
to be present in herbs, for example, have never been tested for safety
(Larkin 1983). Some plant foods contain potentially unsafe, pharmacologi-
cally active ingredients such as aflatoxin, one of the most potent carcino-
gens known. Few buyers are aware of the harmful components in these
products (Anonymous 1979).

There has been a substantial increase in the use of herbal products (Siegel
1976) that may contain pharmacologically active ingredients that can possi-
bly produce undesirable effects such as an increase in blood pressure
(Brody 1978). Occasional poisonings and clinical intoxications are reported
after the use of herbal tea products (Huxtable 1980; Siegel 1976; Larkin
1983). Ginseng, one of the most popular herbs in the United States, has
been reported to produce estrogen-like effects in some people (Siegel 1979;
Greenspan 1983). From present evidence, it cannot be concluded that all
herbal products can be consumed safely over extended periods of time
(Larkin 1983).

Potentially harmful ingredients have been identified in samples of other
food supplements, such as an estrogenic hormone in commercial alfalfa
tablets (Elakovich and Hampton 1984), arsenic in kelp tablets (Walkiw and
Douglas 1975), and cadmium in dolomite (Boulos et al. 1983). Potentially
toxic amounts of lead in bonemeal and dolomite have caused the FDA to
caution against use of these products, particularly by pregnant women and
young children (FDA 1982).

Nutrient Toxicities and Deficiencies

Frauds and fads may induce nutrient toxicities or deficiencies (Henderson
1974). Many people take vitamins as self-medication for the prevention or
treatment of health problems (Levy and Schucker 1987). An estimated 40
percent of U.S. adults consume vitamins, minerals, and/or miscellaneous
dietary components as supplements. The use of these products varies with
such demographic factors as geographic region, education, income, and
race. Women are more frequent consumers than men. Intake ranges wide-
ly, extending up to 10 to 50 times the Recommended Dietary Allowance

703


CT1 Nutrition and Health

(RDA) for individual nutrients (Stewart et al. 1985). Data from the National
Health and Nutrition Examination Survey suggest that individuals with
better nutritional intake patterns are the predominant users of supple-
ments. Thus, supplement users may not be the individuals most in need of
them (Shank and Wilkening 1986).

Nutrient supplements are usually safe in amounts corresponding to the
RDA, but the RDA's are already set to provide maximum benefit consistent
with safety. Thus, there is no reason to think that larger doses will improve
health in already healthy people, and excess intake can be harmful. Mega-
dose intakes (often defined as 10 or more times recommended levels) can
have seriously harmful effects (Rudman and Williams 1983; Herbert 1980;
Dubick and Rucker 1983a). The toxicity of high dosages of vitamins A and
D is well established (DiPalma and Ritchie 1977). Although water-soluble
vitamins are relatively nontoxic, some of them also are reported to produce
toxic effects at high doses (Alhadeff, Gualtieri, and Lipton 1984). Because
the margin is narrow between a safe and a toxic dose of most trace
elements, excessive supplementation with these substances may be partic-
ularly hazardous.

Excessively restrictive dietary practices can also induce serious medical
problems or even death. Popular weight reduction products, for example,
provide very low daily calorie intakes (Newmark and Williamson 1983b).
Because such products have been associated with the deaths of some young
women, the FDA now requires warnings on labels to alert consumers of the
potential of such products (FDA 1984).

Many popular diets are potentially harmful because they eliminate food
groups or severely limit food variety (Council on Foods and Nutrition 1973;
Barrett 1981; Willis 1982). Examples include the Atkins, Stillman, and
other weight reduction diets that drastically reduce carbohydrate intake
and the Beverly Hills Diet, which advocates excessive fruit consumption.
Fad diets seldom produce long-lasting weight control (Newmark and Wil-
liamson 1983a). Highly restricted diets, such as the more extreme forms of
Zen macrobiotics, have led to nutritional deficiencies, starvation, and even
death in a few individuals (Council on Foods and Nutrition 197 1; Newmark
and Williamson 1983a). Such diets also have been associated with retarded
fetal development and childhood growth or other nutritional problems in
young children (Dwyer et al. 1983).

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Dietary Fads and Frauds O

Interference With Sound Nutrition Education

Commercial interests have capitalized on a heightened public awareness of
nutrition and health issues, but much of the public cannot evaluate the
validity of available weight reduction schemes, supplements, and services
(White and Selvey 1982). Self-appointed health and nutrition advisors have
expressed distrust of proven public health measures such as fluoridation
and pasteurization and, instead, have promoted treatment alternatives that
are not supported by accepted medical practice (Jarvis 1983). The public
also may be misled by extravagant claims of health benefits from the use of
certain foods or nutrient supplements (Council on Scientific Affairs 1979;
White and Selvey 1982).

Economic Consequences of Fraud

Impact on Consumers

People experience economic injury when purported remedies and cures do
not work, are untrue, or are greatly exaggerated or when purchased prod-
ucts are not needed. Fraudulent products are known to be extremely
profitable for those who sell them. A 1984 report by the Subcommittee on
Health and Long-Term Care of the Select Committee on Aging, for exam-
ple, stated:

. * . the practice ofquackery . . . now invades nearly every aspect of our lives,
and, at points, attracts adherents with . . . a keen sense of the vulnerability of
potential customers, the limitations ofthe law and the profitability of exploiting
both. Quackery has become big business. Twenty-five years ago, quackery
was said to cost $1-2 billion a year. Today, it probably totals at least $10 billion
(U.S. Congress 1984b).

This estimate is probably conservative because it does not include the sales
of weight reduction pills and diet cures, which alone are estimated to cost
$5 to $6 billion yearly (Halamandaris 1984).

Many fraudulent products and services can be very costly yet are promoted
as having nutritional or health benefits that have not been substantiated in
the scientific literature (Meister 1984; Dubick and Rucker 1983a, 1983b;
Herbert 1980; Larkin 1984; Anonymous 1985). Examples include:
o Superoxide dismutase (SOD) and nucleic acids (RNA and DNA) as
  antiaging remedies.

o Bee pollen as a source of youth and health and as an energy pill for
athletes.

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O Nutrition and Health

o Lecithin in combination with vinegar, kelp, and vitamin B, for the

prevention and cure of heart disease and as a diet aid.
o Spirulina and glucomannan as diet aids.
o Ginseng as a panacea for many ailments.
o Alfalfa tablets for treatment of arthritis.
o Aloe vera for treatment of an array of unrelated medical conditions.
o Para-aminobenzoic acid (PABA) as an essential or curative nutrient.
o Pangamic acid, the so-called vitamin B,,, as an essential nutrient.
o Hair analysis for determination of nutritional status.
o Oral chelation products as treatment for heart disease.

The public incurs other costs because many products labeled as "natural"
or "organic" sell for higher prices than their "regular" counterparts, al-
though their special benefits are not generally demonstrable (Gourdine,
Traiger, and Cohen 1983). "Natural" vitamins, for example, often sell at
twice the price of synthetic products even though they are chemically
identical. In some such products labeled as "natural," only a minor fraction
of the vitamin is actually derived from natural sources (Seneker 1979; FDA
1979).

Although many food supplements are of unproven benefit, the food supple-
ment industry has expanded rapidly over the past several years (Stewart et
al. 1985). Consumer spending for the entire nutritional supplement mar-
ket-which includes nonprescription vitamins, minerals, and other prod-
ucts-was estimated to approach $2.7 billion for 1983, an increase of 5.3
percent over the 1982 sales volume (Ehrlich 1985).

Impact on Responsible Industry

Nutrition fraud can also have an adverse economic impact on responsible
members of the food industry. The false claims made by food faddists and
promoters of fraudulent products cause confusion in the minds of consum-
ers and may result in a distrust of the regular food supply and its products-
a distrust that may paradoxically increase the frequency and severity of
poor nutritional practices and food quackery. Although regulatory agencies
are responsible for maintaining a fair marketing environment, the cost of
combatting fraudulent activities often exceeds the available regulatory
resources.

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Summary

In summary, nutrition fraud in its various forms is prevalent in this country.
Health professionals and other authorities consider it to be a significant
public health problem, as well as one that can affect economic well-being.
Furthermore, the use of sophisticated communication marketing tech-
niques has substantially increased public exposure to nutrition fraud.

Implications for Public Health Policy

Dietary Guidance

General Public

Running counter to-and sometimes capitalizing on-legitimate gains in
scientific understanding of the relationships between diet and health, food
faddism and nutrition fraud are increasingly prevalent in the United States.
Although most of the adverse consequences of this trend are economic,
fraud can cause significant health consequences to individuals as a result of
direct toxicity and as a result of failure to seek appropriate medical care or
to engage in genuinely healthful dietary practices. Cooperative educational
efforts by Government, health professionals, and the private sector, includ-
ing the news media, are needed to expose emerging fads and frauds before
they are widely accepted. One approach to this end is general public
education to reinforce the basic principles of sound nutrition as stated in
the Dietary Guidelines for Americans. Another approach is to direct the
public to responsible sources of nutrition information.

Special Populations

Special efforts should be directed toward older persons, who are the target
of much nutrition fraud. Cooperative educational efforts by Government
and the private sector, such as current collaborations of the FDA with the
Pharmaceutical Advertising Council and the Council of Better Business
Bureaus, can provide effective support for Government enforcement pro-
grams. People with chronic debilitating illnesses-such as cancer, coro-
nary heart disease, arthritis, or Alzheimer's disease-may be especially
susceptible to fads and frauds, and health providers should be informed
about the most common schemes in each area and should be involved in the
effort to forewarn patients.

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O Nutrition and Health

Nutrition Programs and Services

Food Labels

Food labels should contain information about nutrient content that is
provided in a straightforward, effective, and effkient way. Should a health-
claims-approved program be implemented, claims for a particular product
should be presented in a manner that is most informative, scientifically
sound, and not misleading to consumers.

Food Services

Education provided in the context of food services should emphasize
general principles of sound nutrition for the general public and inform
people about the nature of and problems associated with common nutri-
tional frauds and fads.

Food Products

The FDA is charged with ensuring that misleading claims about foods are
not presented to the public and that specific foods are not promoted as
therapeutic or preventive agents unless there is adequate documentation to
support such claims. Continued support for, and vigilence by, the FDA is
important in this regard. A cornerstone of this effort is close coordination
of regulation and enforcement activities of the various agencies at the
Federal, State, and local levels through coalitions developed against nutri-
tion fraud.

Research and Surveillance

Research and surveillance issues of special priority related to the issue of
food fads and frauds should include investigations into:
o Frequency and type of fraudulent claims and harmful effects.
o Establishment of safe levels of essential nutrients as well as other
  components in food.

o The personal and behavioral factors that enhance response to certain
unscientific claims and ways to counter them.
o The level of use of vitamin, mineral, and food components that may
induce nutrient toxicities or deficiencies by the general public.

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711


0 Nutrition and Health

Todhunter, E .N . 1973. Food habits, food faddism and nutrition. World Review of Nutrition and
Dietetics 16:286-317.

U.S., Congress, House. 1984a. Quackery: a $10 billion scandal. Hearing before the Subcom-
mittee on Health and Long-Term Care of the Select Committee on Aging. 98th Gong., 2d sess.
Washington, DC: U.S. Government Printing Office, Comm. Publication No. 98-463.

-. 1984b. Quackery: a $10 billion scandal. A report by the chairman of the Subcommit-
tee on Health and Long-Term Care of the Select Committee on Aging. 98th Cong., 2d sess.
Washington, DC: U.S. Government Printing Office, Comm. Publication No. 98-435.
Walkiw, O., and Douglas, D.E. 1975. Health food supplements prepared from kelp-a source
of urinary arsenic. Clinical Toxicology 8:325-31.
White, P.L., and Selvey, N. 1982. Nutrition and the new health awareness. Journal of Ihe
American Medical Association 247~2914-16.

White House Conference on Food, Nutrition, and Health. 1969. Final report: report of
Subpanel on Deception and Misinformation, p. 190. Washington, DC: U.S. Government
Printing Office.

Whorton, J.C. 1982. Crusaders for fitness: the history of American health reformers, p. 3.
Princeton, NJ: Princeton Univ. Press.

Willis, J. 1982. Diet books sell well but . . . . DHHS publication no. (FDA) 82-1093.
Washington, DC: U.S. Government Printing Office.
Young, F.E. 1985. Letter to editor. Consumer Reporfs (16 April).
Young, J.H. l%l. The toadstool millionaires: a social history ofparent medicines in America
before federal regulation, p. 16. Princeton, NJ: Princeton Univ. Press.

-. 1967. The medical messiahs: a social history of health quackery in twentieth century
America, p. 335. Princeton, NJ: Princeton Univ. Press.

-. 1978. The agile role of food: some historical reflections. In Nutrient and drug
interrelations (Nutrition Foundation: a monograph series), ed. J.N. Hathcock and J. Coon, pp.
l-18. New York: Academic.

-. 1984. The regulation of health quackery. Pharmacy in history. American Institute of
Ihe History of Pharmacy in Dietary Products 26: ldo.

712


Index

A

Acrodermatitis enteropathica, 684
Acute renal failure
Description of, 386, 387
Dietary management, 387-89
Protein-energy malnutrition, 387, 392
Protein role, 392
Adipose cell metabolism, 292-94
Aging population
Alzheimer's disease. 4%. 500.613-14
Caloric intake, 603-4
Dental diseases, 348-50
Dietary guidance, 614-U
Drug-nutrient interactions, 611, 673
Economic and social changes, 601
Energy and nutrient status, 603-10
Historical perspective, 596-97
Infections and immunity and, WI,
   455,612-13

Life expectancy factors, 595
Mental function and, 613
Minerals and, 6OM
Morbidity and mortality, 61 l-12
Nutritional status, 599-601
Nutritional status assessment, 601-I 1
Nutrition programs and services, 598,
  615-16

Physiological changes, 600
Policy implications, 598-99.614
Protein and, 605
Psychologic changes, 600-601
Public health significance, 597-98
Research and surveillance, 61617
Vitamins and, 608-12
Aticultural Act of 1933. 35.542
A&icultural and Consumer Protection
  Act of 1973, 33
Agricultural support policies, 33
AIDS (acquired immunodeticiency
  syndrome), 445-41,455
Alcohol
Abuse, 635
Caloric intake and, 639-41,649-5 1
Cancer and, 214, 216-17
Carbohydrates and, 64143
Cardiovascular diseases and, 656-59
Consumption, 632-34
Coronary heart disease and, 110, 123,
    659
Diabetes and, 261
Dietary guidance, 660-61
Drug interactions, 636-37, 643, 682-83
Fats and, 641,658

Fetus and, 559-X&659-60
Gastrointestinal diseases and, 420
High blood pressure and, 153, 155
Historical perspective, 629-32
Minerals and, 64749
Neurologic disorders and, 498, 501
Nutritional deficiencies and. 638-39
Nutritional status and, 649-31
Nutrition programs and services,
  661-62

Physiology of use, 635-37
Policy i&&cations, 660-62
Protein and. 638, 643, 646
Public health significance, 632-33
Recommendations and reports, 630-32
Recommendations for, 14
Reproductive disorders and, 659-60
Research and surveillance, 662
Scientific background, 633
Vitamins and, 638,64U7,654-56
Alcoholic cirrhosis, 418.420. 638. 651-52
Alcoholic hepatitis; 653
Allergies, 429,430,439,447,450-52,455,
  456

Alternative sweeteners, 26162, 363, 499,

500,526,527

Aluminum, 331,500,613,676
Alzheimer's disease, 4%, 500,613-14
Amino acids. 58. 163. 392.436.443.

523-24,529,653
Anemia
Alcohol use and, 645,647
Causes, 469-70
Definition, 465
Dietary guidance. 483
Folate-and, 482, 483
Historical perspective. 46M
Iron role, &X-&8, 470-81
Nutrition programs and services,
   483-84
Policy implications, 483-84
Public health significance, 466-69
Research and surveillance, 484
Scientific background, 469-73
Vitamin Blz, 470,482,684
Anorexia nervosa. 51&l 1. 5W22
Antabuse, 682
Antacids, 676
Antibacterial drugs, 678,680
Antibiotics, 677, 680, 683
Anticoagulants, 678
Anticonvulsants, 677-78
Antihypertensive drugs, 679


0 Nutrition and Health

Antimalarial drugs, 678
Antisocial behavior, 528-29
Antitubercular drugs, 678-79
Apoproteins, 89
Appendicitis, 418
Appetite mechanisms, 675-76
Arachidonic acid, 57-58,393,444
ArtificiaI sweeteners. See Alternative
   sweeteners

Ascorbic acid. See Vitamin C
Aspartame, 261. 499, 500. 526, 527
Aspirin, 681,682
Asthma, 439, 451
Atherogenesis, 87-88,91
Atherosclerosis, 83,84,91,99, 100,
  104-6. See also Coronary heart
  disease

B
Barbiturates, 678
Behavior
Anorexia netvosa, 510-11,519-22
Antisocial, 528-29
Bulimia, 510, 511, 522-23
Childhood hyperactivity, 525-27
Dietarv guidance. 529
Eating-b;havior determinants, 5 12-14
Food and nutrients and, 523-25
Historic significance, 509-10
Hypoglycemia and, 528
Methodoloeical issues. 51 l-12
Nutrition piogtams and services,
    529-30
Obesity, 514-19
Pica, 511, 523,555-56
Policy implications, 529-30
Public health significance, 510-l I
Research and surveillance, 530
Scientific background, 511-12
Benzodiazepines, 682
Beta blockers, 679
Beta-carotene, 60, 209-10, 213
Body mass index, 280-81
Body weight. See also Obesity
Alcohol use and, 639-41
Cancer and, 199,202-3
Diabetes and, 255-57, 262. 266. 267
Energy balance and, 54
Pregnancy and, 552-53
Recommendations for. I l-12
Reference standards, 279-8 1
Bone physiology, 314-15
Breast cancer, 194, 195, 199,216
Breastfeeding, 441,454,472,479,563,
   577
Bulimia, 5 10. 5 11, 522-23

C
Caffeine

Behavioral effects, 524-25,527,529
Fetus and, 560-61
High blood pressure. and, 163-64
Neurologic disorders and, 501
Calcioi, 61

Calcitriol, 3 lt3-23, 327
Calcium

Absorption, 316-17, 319
Aging population and, 319-20,6054
Alcohol use and, 648
Coronary heart disease and, 113-14
Dental diseases and, 362-64,366
Dietary guidance, 333-34
Drug interactions, 676, 679,680
High blood pressure and, 157-59
Infant and child health, 563,568,572
Intake estimates, 70
Kidney diseases and, 388
Peak bone mass and, 317-20
Recommendations for, 16
Retention, 317
Skeletal diseases and, 315-21
Toxicity, 321
Caloric intake

Aging population, 603-t
Alcohol and, 639-41,649-51
Cancer and, 199, 202-3
Diabetes and, 256, 262, 263,266, 267
Estimates, 68
Kidney diseases and, 388
Maternal and child health, 553. 557-58,

   561-62, 570,512
Skeletal diseases and, 328-29
Cancer

Alcohol and, 214, 216-17
Body weight and, 199, 202-3
Caloric intake, 199, 202-3
Carcinogenesis, 182-84, 213
Definition, 177
Dietary guidance, 190, 192, 224-26
Fats and, 194-95, 197-98
Fiber and, 203-4,20@
Food and color additives, 224
Gastrointestinal tract, 414-15, 420
Historical perspective, 177-78
Lifestyle factors, 179, 181-82
Methodological issues, 185-90
Nutritional support, 184-85
Nutrition programs and services, 226
Oral, 366-67
Policy implications, 224-27
Protein and, 220, 222
Public health significance, 178-79, 405
Research and surveillance. 227

714


Index 0

Salt-i&led. salt-cured. and smoked

&Is and, 222-23
Scientific background, 179
Selenium and, 219-20
Vitamin A and, 2oP-10,213-14,366
Vitamin C and. 217-18
Vitamin E and, 218-19, 367

Carbohydrates See also Fiber
Alcohol use and. 641-43
Behavioral effects, 524, 528
Cancer and, 226
Coronary heart disease and, 110-l 1
Definition, 54-56
Diabetes and, 257-58
Drug interactions, 676, 681
High blood pressure and, 161
Infant and child health and, 562.564,

568

Infections and immunity and, 438
Recommendations for. 12-l 3

Carcinogenesis, 182-84,213
Cardiomyopathy, 656-57
Cardiovascular diseases, 656-59
Camitine, 684
Carotenes, 60,61
Carotenoids, 209-10, 213
Celiac disease, 415
Cellular immunity, 433,437,438,440
Cereal product availability, 68
Cerebrovascular disease, 492,497-98
CHD. See Coronary heart disease
Chemotherapeutic agents, 678
Child Care Food Program, 543
Child nutrition

Adolescents, 551,555,571
Anemia, 467X&472,474-75,47&80,
  482
Cholesterol guidelines, 95
Coronary heart disease, 573-74
Dental diseases, 348, 349,3.58, 361,369
Dietary guidance, 577-78
Eating patterns, 571, 572
Energy and nutrient requirements,
  570-72
Goals and recommendations, 54446
Growth and development factors,
  550-51
Historical perspective, 539-40,542-46
Hypera&e behavior, 525-27
Infants. 561-64.566-70.685
Infect&s and immune hiseases, 430,
  440-41,450,451,454
Mental function, 575-76
Metabolic disorders and, 576
Nutrition programs and services,
  578-79

Obesity, 287, 300-301, 574-75
Policy implications, 577-80
Public health significance, 546-49
Research and surveillance, 579-80
Scientific background, 550-51
Skeletal diseases and, 32, 328
Child Nutrition Act of 1966, 35, 542
Children's Bureau, 34, 36, 42, 542
Chloride, 159-60
Chlorpropamide , 643, 682
Cholecalciferol. 61
Cholestasis, 570
Cholesterol
Alcohol use and, 110,658-59
Animal studies, 1046
Cancer and, 195
Carbohydrates and, 110, 111
Child health, 564, 573, 574
Clinical studies. 96-99. 115-20
Coffee and, 112     `-
Coronary heart disease, 86-87.92,
   102-6, 11620
Definition, 58
Dietary guidance, 92-95
Dietary intervention effects, 115
Drug interactions, 679
Epidemiologic studies, 99-104
Fish oil effects, 108-9
Gallbladder disease and, 418-19
Intake estimates, 68, 92
Lipoprotein metabolism and, 88-91
Protein and, 11 l-12
Recommendations, 9-l 1
Vitamins and minerals and, 113-15
Cholestyramine, 676
Choline, 4%
Chronic renal failure

Description of, 384-86
Dietary management, 387-89
Protein and, 389-91
Protein-energy malnutrition, 386-87
Chylomicrons, 88,99, 292
Cigarette smoking, 83,89,91,329,333
Cirrhosis, 418,420,638,651-52
Cocoa availability, 68
Coffee. See also Caffeine
Availability, 68
Coronary heart disease and, 112
Cognitive function. See Mental function
Colchicine, 677
Colestipol, 676
Colon, 412
Colon cancer, 194, 195, 199, 2034, 206-g.
  216,405
Color additives, 224, 525
Color Additives Amendment, 33

715


0 Nutrition and Health

Committee on Food and Nutrition, 48
Commodity Supplemental Food Program,
  543

Community health centers, 544
Complex carbohydrates. See
  Polysaccharides
Congregate Meals, 598
Constipation, 415
Conti&ng Survey of Food Intakes by
  Individuals ICSFID. 68

Contraceptives, iiT .'
Copper
Bone metabolism role, 332
Coronary heart disease and, 114
Drug interactions, 676
Infections and immunity and, 445
Intake estimates, 70
Iron intake and, 481
Coronary heart disease (CHD)
Alcohol use and, 110,659
Atherogenesis, 87*8,91
Carbohydrates and, 110-l 1
Causes,w 83-84
Children, 573-74
Cholesterol and, 86-87, 92, 102-6,
   116-20
Coffee and, 112
Definition, 83
Dietary factors in, 109-15
Dietary guidance, 91-95, 120-23
Dietary intervention effectiveness,

High blood pressure, 165-66
Kidney diseases, 389,394
Maternal and child nutrition, 577-79
Neurologic disorders, 502
Skeletal disease related, 334

Cow milk, 566-67
Crohn's disease, 416
CSFII. See Continuing Survey of Food
  Intakes by Individuals
Cyclamate, 261. See also Alternative
   sweeteners
Cycloserine, 678

D
Dairy product availability, 64
Death rate
Alcohol-related problems, 632, 633,
   644,652
Cancer, 178, 181
Coronary heart disease, 85, 101
Diabetes, 254
Gastrointestinal diseases, 40,406
Infants, 547
Kidney diseases, 386
Obesity, 287
Delaney Clause, 33
Dementia, 655-56
Dental diseases
Alternative sweeteners and, 363
Dietary guidance, 359, 368-69
Fat and. 361
Fluoride and, 3m7,349,358-60,
    3W9
Historical perspective, 345-47
Minerals and, 3W7,349,358-60,
   362-64.366.36849

  ii5-20
Fat and, 90,95-W& 116-18
Historical perspective, 84-85
Lipoprotein metabolism, 8%91,99
Minerals and. 112-15

Nutrition programs and services, 123     Nutrition programs and services,
Obesity and, 89,91,93,95, 109-10.           369-70
    121-22                   Oral cancer, 366-67
Policy implications, 12&24           Periodontal disease, 347, 349-50,
Protein and, 111-12                  355-56.36345
Public health significance, 85-86
Research and s&veillance, 123-24       Policy implications, 368-70
                         Prevention, 355, 358, 368-69
Scientific backaround. 87-95
Thrombosis, 1069              Protein and, 360-61, 365
                       Public health significance, 347-50
Vitamins and, 112-13, 117            Research and surveillance, 370
Counseling                   Residual ridge resorption, 365-66
Alcohol use and, 661,662            Scientific background, 350.352-56

Cancer, 226                  Sugar and, 346: 356-58,368, 369
Coronary heart disease, 123             Tooth decav. 345-50.354-55.356-63.

Dental diseases, 369,370            368..
Diabetes, 265-66               Tooth development, 350, 352-54
Diet change, 514                Tooth loss, 350, 367-68
Drug-nutrient interaction related, 686      Vitamins and, 36162, 364-65
Eating disorders, 530             Department of Health and Human
Gastrointestinal diseases, 420,421         Services (DHHS), 37,42, 544

716


Index O

Department of Health, Education, and
  Welfare (DHEW), 37. See also
  Department of Health and Human
  Services

Depression, 517-19, 522,600-601
Develonmental disorders. 575-76
DHEW. See Department of Health,
  Education, and Welfare
DHHS. See Department of Health and
  Human Services
Diabetes
Alcohol use and, 261,64243
Alternative sweeteners, 261-62
Caloric intake, 256,262,263,266,267
Carbohydrates and, 257-58
Coronary heart disease and, 89
Definition, 249-50
Dietary guidance, 263,266-67
Dietary therapy role, 262-66
Fat and, 258-59,266
Fiber and, 259-61
Historical perspective, 250-53
Nutrition programs and services,
    267-68
Obesity and, 255-57,262, 266,267
Policy implications, 266-68
Pregnancy and, 556-57
Protein and, 259
Public health significance, 253-54
Research and surveillance, 268
Dietary adequacy, 45-46
Dietary fiber. See Fiber
Dietary guidance, 42,45-46
Aging population, 614-15
Alcohol use, -1
Anemia, 483
Behavior related, 529
Cancer, 190, 192,224-26
Coronary heart disease, 91-95, 120-23
Dental diseases, 359,36869
Diabetes, 263,266-67
Drug-nutrient interactions, 685
Gastrointestinal diseases, 419-20
High blood pressure and, 141-42,
     164-65
Infections and immunity, 4X55
Kidney diseases, 394
Maternal and child nutrition, 577-78
Neurologic disorders, 501-2
Nutrition fraud, 707
Obesity, 299-301
Skeletal diseases and, 333-34
Dietary intake estimates, 68.70
Diet-induced thermogenesis, 295
Diet therapy. See also Nutritional support
Chronic renal failure, 387-89

Coronary heart disease, 122
Diabetes, 26266
Digestive system, 406,410-12.67677
Digitalis, 680
Dilantin, 500
Disaccharides, 55
Disuhiram, 682
Diuretics, 678,679
Diverticular disease, 415-16
Docosahexaenoic acid, 58
L-dopa, 501, 678
Drug-nutrient interactions

Aging population and, 611,673
Alcohol related, 636-37. 643. 682-83
Dietary guidance, 685
Drug metabolism, 679-81
Drugs in animal feeds, 683
Historical perspective, 671-72
Methodological issues, 673-74
Monoamine oxidase inhibitors, 681-82
Neurologic disorders and, 500-501
Nutritional status and, 675-79
Nutrition programs and services,
   685-86
Policy implications, 685-87
Public health significance, 672-73
Research and surveillance, 686-87
Scientific background, 673-74
Therapeutic nutrient doses, 683
Dysrhythmias, 657

E

Eating disorders. See also Obesity
Anorexia nervosa, 510-11, 51%22
Bulimia, 510, 511, 522-23
Counseling, 530
Pica, 511,523,555-56
Pregnancy and, 555-56
Public health significance, 510-11

Egg availability, 64
Eicosanoids, 393
Eicosapentaenoic acid, 58,439
Electrolyte metabolism, 445
End-stage renal disease (ESRD), 382, 385
Energy, 54. See also Caloric intake
Environmental Protection Agency, 34
Epilepsy, 492,498-500,502
ESRD. See End-stage renal disease
Estrogen, 320, 328,329, 334
Exchange lists, 264-65
Exercise

Obesity and, 296-97,300
Skeletal diseases and. 332-33

717


O Nutrition and Health

F

Fair Packaging and Labeling Act of 1966,
  34

Familial hypercholesterolemia, 90
Fats

Alcohol use and, 641,658
Cancer and, 194-95, 197-98,226
Child health, 564
Cholesterol and, 96-106, 108-9, 115-17
Coronary heart disease and, 9&109,
  116, 117

Dental diseases and, 361
Diabetes and, 258-59.266
Dietary guidance, 93-95
Drug interactions, 676,677,680
Gastrointestinal diseases and, 420
High blood pressure and, 162-63
Infant and child health, 562,564,573
Infections and immunity and, 438-39,
  444

Intake estimates, 68.92, 100
Kidney diseases and, 393, 394
Recommendations, el 1
Fats and oils availability, 64
Fat-soluble vitamins
Alcohol and, 64647
Definition, 60-61
Drug interactions, 676
Therapeutic doses, 684
Fatty acids

Cancer and, 198
Cholesterol and, %
Definition, 5658
High blood pressure and, 162
Infant and child health, 562.564
Infections and immunity and, 438-39,
  444

Intake estimates, 68
Thrombotic effects, 106-9
Fatty liver, 653

FDA. See Food and Drug Administration
Federal Emergency Relief
  Administration, 35
Federal Maternity and Infancy Act, 35
Federal Meat Inspection Act, 33
Federal Trade Commission, 34, 701
Federal Trade Commission Act of 1914,
  698, 701

Fetal alcohol syndrome, 559, 660
Fetal health, 557-61, 659-60,684
Fiber

Cancer and, 203-4, 206-8
Coronary heart disease and, 111
Definition, 55-56
Diabetes and, 259-61
Drug interactions, 680,681

Gastrointestinal diseases and, 414,
  41&20

High blood pressure. and, 161
Intake estimates, 70
Recommendations for, 12-13
Fish availabilitv. 64
Fish oils, 107-i; 163, 198
Flour availability, 68
Fluoride

Dental diseases and, 3ti7,349,

   358-60,368-69
Infant health and, 563
Recommendations for, 15
Skeletal diseases and, 330-31
Folate
Alcohol and, 644-45
Anemia and, 482,483
Dental diseases, 365
Drug interactions, 677
Maternal and child health, 554,564,
   569,572
Folic acid, 678
Food additives, 224,500,525,529
Food Additives Amendment, 33
Food allergies, 429,430,439,447,450-52,
  455,456
Food and Agriculture Act of 1977, 33,37
Food and Drug Administration (FDA), 34,
  42, 141-42,695,69p=MK), 708

Food and Nutrition Board, 48
Food assistance. 34-35.5434l
Food-associated.diseases, 415,417,
  428-30,447-54,499-500
Food availability data, 6344,68
Food consumption surveys, 68.70
Food Distribution Rogram, 35
Food, Drug, and Cosmetic Act, 33, 38,
  698-700
Food faddism, 6%, 697
Food intake monitoring, 36-37
Food labeling, 34
Alcohol and, 661
Anemia and, 484
Behavior and, 529
Cancer and, 226
Coronary heart disease and, 123
Dental diseases and, 369
Diabetes and, 267
Drug-nutrient interactions and, 685&
Gastrointestinal diseases and, 420
High blood pressure and, 140-42, 165
Infections and immunity and, 455
Kidney diseases and, 394
Neurologic disorders and, 502
Nutrition fraud and. 708
Obesity and, 301

718


Index O

Recommendations for, 18
Skeletal diseases and, 334
Food products. See also Nutrition fraud

Ag&g related, 616
Behavior disorders and, 530
Drug-nutrient interaction related, 686
Gastrointestinal diseases and, 421
Infections and immunity and, 455
Maternal and child nutrition and,
    578-79
Neurologic disorders and, 502
Nutrition fraud and, 708
Obesity and, 301
Recommendations for, 19
Skeletal diseases and, 335
Food quackery, 6%
Food safety and regulation, 33-34. See
  also Nutrition fraud
Food services. See Nutrition services
Food Stamp Act of 1%5,35
Food Stamo Program, 35,543, 598
Fortification, 34,335,479-81
Fructose, 54,55, 111,258,356
Fruit availability, 64
Furosemide, 679

G
Galactose, 54,55
Gallbladder disease. 417-18. 420
Gastrointestinal diskase
Bone loss and, 322
Cirrhosis, 418, 638, 651-52
Dietary guidance, 4 19-20
Digestive system, 406, 410-12
Fiber and, 414,416-20
Food-related, 415,417,451-54
Gallbladder disease, 417-18,420
Gastrointestinal function and, 412-14
Gastrointestinal system, 403
Historical oersoective. 403-4
Intestinal disoiders, 414-17
Malnutrition. 413
Nutrition p&rams and services,
    420-2 1
Policy implications, 419-21
Public health significance, 404
Research and surveillance, 421
Scientific background, 406,410-12
Gingivitis, 355
Glucose, 54, 55, 161, 356,557-58,676
Glucose tolerance, 642, 679
Gluten-induced enteropathy, 415
Glycemic indexes, 257
Glycogen, 55
Goat milk, 567

H
Hatch Act, 33
HDL. See High density lipoproteins
Headaches, 492,498,502
Head Start, 544
Height and weight tables. 279-80
Heme iron, 472-73
Hemochromatosis, 481
Hepatitis, 653
High blood pressure
Alcohol use and, 153, 155, 657
Blood pressure regulation, 144
Caffeine and, 163-64
Carbohydrates and, 161
Dietary guidance, 14142, 164-65
Fat and, 162-63
Fiber and, 161
Historical perspective, 14W2
Minerals and, 15541
Nutrition programs and services,
    1654
Obesity and, 140, 142, 146, 148
Overview, 13W
Policy implications, 164-66
Pregnancy and, 556
Protein and, 163
Public health sianificance. 142-44
Research and s&-veillance, 166
Scientific background, 1W
Sodium and, 140-42, 148, 150-53
Stroke and, 497
High density lipoproteins (HDL), 88-89,
  91, 110,658-59,679
Home-Delivered Meals, 598
Homocystinuria, 684
Human milk, 564, 566, 569. See also
  Breastfeeding
Humoral immunity, 433-34,437
Hydralazine, 500.678.680
Hyperactive behavior, 525-27
Hypercholesterolemia, 86-87,90, 106,

  110
Hyperlipidemia, 658,679
Hyperrnetabolism, 442-43
Hyperplastic obesity, 285-86
Hypertriglyceridemia, 658
Hypertrophic obesity, 285-86
Hypoglycemia, 528,642,643

I

ICHNR. See Interagency Committee on
  Human Nutrition Research
Imitation milk. 566
Incidence. See Prevalence and incidence
Infant feeding, 563-68, 684
Infant Formula Act of 1980, 562

719


0 Nutrition and Health

Infant formulas, 566, 569, 684
Infections and immunity
Age-related factors, WI, 612-13
Carbohydrates and, 438
Dietary guidance, 454-55
Fats and, 438-39, 444
Food allergies, 429, 430,439, 447,
   4X)-52,455,456
Food associated, 428-30, 447-54
Historical perspective, 427-29
Immune mechanisms, 433-34,437
Iron and. 478-79.481
Malnutrition and; 427-29,43 1,435-37,
   446-47
Methodological issues, 434
Minerals, 439-40,445
Nonspecific defenses, 432-33
Nutritional status effects, 441-47
Nutrition programs and services,
   455-56
Policy implications, 454-57
Protein aid, 438,443-44
Public health signiIicance, 429
Research and surveillance, 45&57
Scientific background, 431-34
Vitamins. 439. 440. 444

hfhmmato~~ bowel hisease, 416, 420
Insoluble fiber, 55, 56, 418
Interagency Committee on Human
  Nutrition Research (ICHNR), 42
Intestinal disorders, 414-17
Iodine, 494
Iron

Absorption, 471-73,480
Adverse effects, 481
Age-related factors, 474-76, 606-8
Alcohol use and, 647
Anemia and, 466-68.470
Causes of deficiency, 474
Consequences of deficiency, 477-79
Infant and child health, 563,568, 572
Infections and immunity and, 440,445
Intake estimates, 70
Predisposing factors of deficiency. 473
Pregnancy and, 554
Prevention of, 479-81
Recommendations for, 16-17
Role of, 470-7 1
Stages of deficiency, 474
Irritable bowel syndrome, 417,420
Isoniazid, 678, 680.

K

Kidney diseases
Acute renal disease, 386-89, 392
Caloric intake and, 388

Chronic renal disease, 384-91
Dietary guidance, 394
Fats, 393, 394
Historical perspectives, 381-82
Kidney function, 383
Minerals and, 38%89,392,394
Nutrition programs and services, 394
Phosphate and, 392
Policy implications, 39&%
Protein and, 381. 386-92. 394
Public health significance, 382,386
Research and surveillance, 395-%
Scientific background, 383-89
Skeletal diseases and, 324,331
Stones, 383-84, 394
Vitamins and, 389

L
Lactose, 55

Lactose intolerance, 417,420
Laxatives, 676
LDL. See Low density lipoproteins
Lead poisoning, 479
Life expectancy, 595
Linoleic acid, 57-58, 107, 162, 198, 562,

564,568

Linolenic acid, 57
Lipids, 5658. See also Fats
Lipoprotein lipase, 293
Lipoprotein metabolism, 88-91, 99, 108
Liver disease, 420, 647,651-53
Low birth we&t. 547-49. 555. 568-70.

575, 578 -
Low density lipoproteins (LDL), 87.
  89-92,94,98-99, 112,679
Lower body obesity, 286
Lung cancer, 181, 210,213,218

M
Macrocytic megaloblastic anemia, 645
Macrocytosis, 645
Macrominerals, 62
Magnesium
Alcohol use and, 648
Coronary heart disease and, 114
Drug interactions, 676
Epilepsy and, 498-99
High blood pressure and, 160
Kidney diseases and, 388
Skeletal diseases and, 331
Mail fraud. 701
Mail Order Consumer Protection
  Amendments, 701
Malnutrition, 21
Alcohol and, 638,649,650
Gastrointestinal diseases, 413

720


Index 0

Infectious diseases and, 427-29,431,
   435-37,446-47
Maltose, 55
Maternal and child nutrition programs,
  5424l
Maternal nutrition

Adolescents, 555
Alcohol use and. 559-60.659-62
Caffeine and, 5&l
Diabetes and, 55&57
Dietarv auk-lance. 577-78
Eating-disorders and, 555-56
Energy and nutrient requirements,
  552-55
Fetal requirements, 557-59
Fetal risks, 559-61,659-60,684
Goals and rcsommendations, 5W
Historical perspective, 539-46
Nutrition programs and services,
  578-79
Obesity and, 553
Policy implications, 577-80
Pregnancy and lactation factors, 549-50
Public health significance, 546-49
Research and surveillance, 579-80
Scientific background, 549-50

Meat availability,drl
Medicaid. 544
Menorrhagia, 475
Mental function
Aging and, 613
Infants and children, 575-76
Metabolic rate, 294
Metronidazole, 682
Milk
Availability, 64
Infant feeding, 564-67,569
Minerals
Alcohol use and, 64749
Coronary heart disease and, 112-15
Definition, 62-63
Dental diseases and, 346-47,349,
   358-60,362-44,366,36849
Drug interactions, 676, 677, 680
High blood pressure and, 155-61
Infections and immunity and, 439,440,
    445
Intake estimates, 70-7 1
Kidney diseases, 388-89, 392, 394
Maternal and child health, 554-55.559,
   563,568,570,572
Neurologic disorders and, 491,494,
   498-99,501,502
Skeletal diseases and, 315-21,325-28,
    330-32
Monoamine oxidase (MAO) inhibitors,
  500-501,681-82

Monosaccharides, 54-55
Monounsaturated fatty acids
Cholesterol and, 96-98
Coronary heart disease and, 87
Definition, 57
High blood pressure and, 16243
Intake estimates, 68
Thrombotic effects, 109
Mood disorders, 517-19, 522
Mot-till Act, 33
Mortality rates. See Death rate
Mouth

Cancer, 366-67
Digestive role, 406,410

N

National Cancer Institute, 190, 192
National Cholesterol Education Program
  (NCEP), 93

National Health and Nutrition
  Examination Surveys (NHANES),
  31, 37,38

National High Blood Pressure Education

Program (NHBPEP), 142
National Institutes of Health (NIH), 37,
  42

National Nutrition Monitoring System, 37
National School Lunch Act. 542
National School Lunch Program, 35,542
Nationwide Food Consumption Survey

(NFCS). 36

NCEP See National Cholesterol
  Education Program
Neurologic disorders
Alcohol related, 653
Drug-nutrient interactions, 500-501
Epilepsy, 492,498-500,502
Food additives and, 500,525, 529
Food-borne toxins, 499-500
Headache, 492,498, 502
Historical perspective, 491-92
Neurotransmitter dietary precursors,
   49s-%,523-24
Nutrition programs and services, 502
Policy implications, 501-3
Public health significance, 492
Research and surveillance, 502-3
Scientific background, 493-%
Stroke, 492,497-98, 501
Vitamin excess and, 499
Neurotransmitters. 495-%. 500,517, 518,

523-24, 529

NHANES. See National Health and
  Nutrition Examination Surveys
NHBPEP See National High Blood
  Pressure Education Program

721


O Nutrition and Health

Niacin
Alcohol and, 644
Coronary heart disease and, 113, 117
Drug interactions. 678
Neurologic disorders, 493
Therapeutic doses, 683,684
NIH. See National Institutes of Health
Nitrofurantoin, 680
Nonheme iron, 471-72
Non-nutritive sweeteners, 261, 262, 363
Nonspecific host defenses, 432-33
Nontropical sprue, 415
Nursing bottle caries, 358
Nutrition
Conclusion on, 2
Dietary patterns, 63-64, 68. 70-71
Findings and recommendations, 8-17
Health problems and, 2,4-6
Policy development, 29, 33-42, 454
Recommendations for, 3
Report organization, 23-24
Requirements. 46-48, 53-63
Science development, 24, 27-29
Scientific judgment criteria, 6-8. 71-75
Status of.il-22
Nutritional rehabilitation. 447
Nutritional requirements
Carbohydrates, 54-56
Energy, 54
Infants and children, 561-63, 570-72
Lipids, 56-58
Minerals, 62
Pregnancy and. 554. 555
Principles of, 4647
Protein, 58-59
Recommended Dietary Allowances, 48,
    53
Vitamins. 59-62
Nutritional science, 24, 27-29
Nutritional status
Aging population. 599-611
Alcohol use and. 649-51
Drug-nutrient interactions and. 675-79
Monitoring, 36-37
Nutritional support
AIDS. 44W7. 455
Alcoholic hepatitis. 653
Cancer. 184-85
Kidney diseases, 389. 392
Low birth weight infants. 568
Nutrition education, 42, 4546
Diabetes, 264-66
Eating behavior change, 514
Nutrition fraud, 700, 705, 707
Nutrition fraud
Definitions. 695-96
Dietary guidance, 707

Economic consequences, 705-7
Federal agency roles, 699-701
Health consequences, 702-5
Historical perspective, 695-97
Nutrition programs and services, 708
Policy implications, 707-8
Regulation of, 697-99
Research and surveillance, 708
Nutrition Program for Older Americans,
  598

Nutrition Program for the Elderly, 35, 598
Nutrition services, 35-36
Aging populations and, 598, 615-16
Alcohol use and, 661-62
Anemia and, 483-84
Behavior related, 529-30
Cancer related, 226
Coronary heart disease and, 123
Dental diseases and, 369-70
Diabetes and, 267-68
Drug-nutrient interaction related,

685-86

Gastrointestinal diseases and, 420-21
High blood pressure and, 165-66
Infections and immunity, 455-56
Kidney diseases and, 394
Maternal and child nutrition and,

578-79

Neurologic disorders and, 502
Nutrition fraud and, 708
Obesity and, 301
Recommendations for, 18-19
Skeletal diseases and, 334-35
Nutrition training. 18, 36,578
Nutritive sweeteners, 261, 262

0
Obesity

Adipose cell metabolism and, 292-94
Aging population and. 604, 605
Alcohol use and. 639, 641
Behavioral aspects, 51619
Causes, 290-97
Children and. 287, 300-301, 574-75
Coronary heart disease and, 89.91.93,

  95. 109-10. 121-22
Definition. 275, 279-81, 285-87
Diabetes and, 255-57,262,266,267
Dietary guidance, 299-301
Exercise and, 296-97
Genetic causes, 290-91
Health effects, 287-89
High blood pressure and, 140, 142, 146,
  148
Historical perspective, 275-76
Medications and, 297
Nutrition programs and services, 301

722


Index 0

Overeating and, 29192
Policy implications, 299-302
Pregnancy and.553
Public health significance. 277-78
Recommendations for, 1 l-12
Reference body weight standards.
  279-81
Research and surveillance, 301-2
Thermogenesis and, 294-96
Treatment of, 297-99
Tvpes, 285-87

Older Americans Act, 35
Oleic acid. 57, 107. 162-63. 198
Omega fatty acids, 57-58, 107-8. 163. 198
Oral cancer, 366+7
Oral contraceptives. 677
Osteomalacia, 311, 313-14. 323-26. 331.
  677,678
Osteoporosis, 312-13, 319,322-23,
  330-33

P
Paraminosalicyclic acid, 679
Parenteral nutrition. See Nutritional
  support
Parkinson's disease, 4%
Peak bone mass, 314, 317-20
Penicillin. 680, 683
Periodontal disease
Diet and, 363-65
Process of, 355-56
Public health significance, 347, 349-50
Peripheral neuropathy, 655
Pernicious anemia, 684
Phenobarbital, 677
Phenylketonuria, 576, 684-85
Phenytoin, 677,678
Phosphate, 363, 388, 392. 394
Phosphatidylcholine. 4%
Phospholipids, 56
Phosphorus, 70. 325-28,568, 648
Pica, 511, 523, 555-56
Policy issues
Aging population, 598-99. 614
Alcohol related, 66CL662
Anemia, 483-84
Behavior related. 529-30
Cancer, 224-27
Coronary heart disease, 12&24
Dental diseases, 368-70
Diabetes, 266-68
Drug-nutrient interactions, 685-87
Gastrointestinal diseases, 419-21
High blood pressure, 164-66
Historical perspective. 29. 33-42.45-46
Infections and immunity. 454-57
Kidney diseases, 394-96

Maternal and child nutrition, 577-80
Neurologic disorders. 501-3
Nutrition. 17-20
Nutrition fraud, 707-8
Obesity. 299-302
Skeletal diseases. 333-36
Polysaccharides. 12. 55
Polyunsaturated fatty acids
Cancer and. 198
Cholesterol and. 9699. I IS-17
Coronary heart disease and. 90. 102.
    103. 116-18
Definition. 57
Dietary guidance. 93. 95
High blood pressure and. I62
Infections and immunity and. 438-39
Intake estimates. 68
Thrombotic effects. IO9
Potassium
Drug interactions. 676, 677. 679
High blood pressure and. 155-57
Intake estimates. 70
Neurologic disorders, 498
Poultry availability, 64
Pregnancy. See Maternal nutrition
Prevalence and incidence
Age-related disorders, 597. 613
Alcohol-related problems, 632
Anemia, 467. 468
Behavioral disorders, 510-I 1
Cancer, 178-79, 181-82
Coronary heart disease, 86, 100-101
Dental diseases, 347-49
Diabetes, 253
Food allergies, 430
Gastrointestinal diseases, 404-6. 415
High blood pressure and, 142
Infections, 429-30. 453-54
Kidney diseases. 382
Neurologic disorders and. 492
Obesity, 277-78
Skeletal diseases, 313
Primidone. 677
Propranolol. 680
Prostaglandins, 393
Prostate cancer, 194
Protein
Aging. population and, 605

- -. .

Alcohol and, 638. 643,646
Behavioral effects. 523-24
Cancer and, 220, 222
Cholesterol and, 99
Coronarv heart disease and. I I l-12
Definition. 58-59
Dental diseases and. 360-61. 365
Diabetes and. 259
Drug interactions. 676. 681. 682

723


O Nutrition and Health

Protein (continued)
High blood pressure and, 163
Infections and immunity and, 438,
   441-44
Intake estimates, 68
Kidney diseases and, 381,386-92,394
Maternal and child health, 554,558,
   562,564,568,570
Metabolism, 443-44
Skeletal diseases and, 329
Public health issues
Aging population, 597-98
Alcohol use, 632-33
Anemia, 466-69
Behavior related, 510-I 1
Cancer, 178-79, 405
Coronary heart disease, 85-86
Dental diseases, 347-50
Diabetes, 253-54
Drug-nutrient interactions, 672-73
Gastrointestinal diseases, 404
High blood pressure. 1424
Infections &d immunity, 429
Kidney diseases, 382, 386
Maternal and child nutrition, 546-49
Neurologic disorders, 492
Obesity, 277-78
Skeletal diseases, 312-14
Public Health Service, 45
Pure Food and Drug Act of 1906,33,34,
  698
Pyridoxine. 499. See also Vitamin B6

R
Recommended Dietary Allowances
  (RDA's), 45,48,49-51,53
Reference body weight standards, 279-81
Reflux esophagitis, 418-19
Relative weight, 280
Renal diseases. See Kidney diseases
Reproductive disorders, 65W, 684
Research and surveillance
Aging, 616-17
Alcohol use, 662
Anemia, 484
Behavior related, 530
Cancer, 227
Coronary heart disease, 123-24
Dental diseases, 370
Diabetes, 268
Drug-nutrient interaction related,
    686-87
Gastrointestinal diseases, 421
High blood pressure, 166
Historical perspective, 37.42
Infections and immunity, 45657

Kidney diseases, 395-%
Maternal and child nutrition, 579-80
Neurologic disorders, 502-3
Nutrition, 19-20
Nutrition fraud, 708
Obesity, 301-2
Residual ridge resorption, 36W
Retinol, 60,209-10, 213,646
Riboflavin, 644
Rickets, 311-14, 323, 325, 326,677

S
Saccharin, 261
Salt-cured foods, 223
Salt-pickled foods, 223
Saturated fat
Cholesterol and, 87,90,96-99, 100,
   102, 115
Coronary heart disease and, 87,90,92,
   100, 102, 103, 117
Definition, 59
Dietary guidelines, 93-95
Intake estimates, 68, 92, 100-103
Thrombotic effects, 106, 107
School Breakfast Program, 35,543
School Lunch Program, 35,543
Selenium, 114-15, 219-20
Serotonin, 59, 518, 524, 526
Set points, 294
Simple carbohydrates, 54-55
Sinemet, 501
Skeletal diseases
Alcohol and, 330
Bone physiology, 314-15
Calcium and, 315-21
Calorie intake and, 328-29
Dietary guidance, 333-34
Exercise and, 332-33
Historical perspective, 31 l-12
Minerals and, 315-21, 325-28,330-32
Nutrition moerams and services,

334-3-S -
Osteomalacia, 311, 313-14, 323-26,
  33 I, 677,678
Osteoporosis, 312-13, 319,322-23,

   33&33
Phosphorus and, 325-28
Policy implications, 333-36
Protein and, 329
Public health significance, 312-14
Research and surveillance, 335-36
Rickets, 311-14, 323, 325. 326,677
Scientific background, 314-15
Vitamins and, 312, 321-25, 332-33
Skinfold thickness measurement, 281
Smoked foods, 222-23

724


Index 0

Social Security Act of 1935. 35, 542
Sodium

Dietary guidance, 14142
Drug interactions, 676, 677
High blood pressure and, 140-42. 148.

15cL53

Intake, 70, 148, I50
Neurologic disorders and. 501, 502
Recommendations for. 13
Skeletal diseases and. 331-32
Soluble fiber. 55. 56, 260, 261. 418
Special Milk Program, 35, 543
Special populations
Aging, 615. 616
Alcohol users. 661. 662
Anemia. 483,484
Behavior related. 529. 530
Cancer. 226
Coronary heart disease. 122. 123
Dental disease and, 369, 370
Diabetes, 267. 268
Drug-nutrient interaction related. 685.

686

Gastrointestinal diseases, 420. 421
High blood pressure, 165
infections and immunitv. 44U1. 455.

456

Maternal and child nutrition, 577-79
Neurologic disorders, 501-6
Nutrition related, 17-18
Obesity, 300-301
Skeletal disease, 334, 335
Special Supplemental Food Program for
  Women. Infants, and Children IWICL
  35, 468,480-81, 543
Spironolactone, 679
Starch, 55, 110-l 1, 356
Stomach

Cancer, 181, 223
Digestive role, 411
Stroke, 492, 497-98, 501
Sucrose, 55, 11 I, 161,257~58, 356, 357
Sugars

Availability, 68
Behavioral effects, 526-27
Coronary heart disease and, I1 I
Definition, 54-55
Recommendations for, 15-16
Tooth decay and, 346, 35658,368,369
Sulfasalazine, 678
Summer Food Service Program, 543
Supplements

Aging population and, 610-12
Calcium, 316, 319-22, 334
Children and. 570-71
Fiber, 260

Fluoride. 3.59. 369. 563
Folate. 564
Iron, 480, 554, 555, 568
Market growth, 706
Maternal nutrition, 576
Phosphate, 363
Therapeutic doses, 684
Thiamin. 654, 655
Use of. 70-7 I. 7034
Vitamin D. 322-24. 563, 564.610
Vitamin E. 568
Vitamin K. 564
Surplus Commodities Corporation. 35
Sweetener availability. 68

T
Tea availability, 68
Tetracycline. 680, 683
Thermogenesis, 294-%
Thiamin
Alcohol and, 643.654-56
Coronary heart disease and. 113
Drug interactions, 677, 681
Neurologic disorders and, 493

Thiazide diuretics, 679
Thrombosis, 106-9
Title V Maternal and Child Health
  Program, 544
Tooth decay
Diet and, 356-63
Dietary guidance, 368
Historical perspective, 34547
Process of, 354-55
Public health significance, 347-50
Tooth development, 350, 352-54
Tooth loss, 350, 367-68
Trace elements. See also Fluoride; Iron;
  Zinc
Cancer and.21920
Coronary heart disease and, 114-15
Definition, 62
Dental diseases and, 363
Drug interactions, 676
High blood pressure and, 161
infections and immunity and, 445
Intake estimates, 70,481
Kidney diseases and, 389
Neurologic disorders and, 494
Skeletal diseases and, 332
Tram fatty acids, %
Triglycerides, 56, 88,91, lIl,292,444,
  564,658,679
Tryptophan, 59,4%, 524
Tumor necrosis factor, 442
Tyramine, 682
Tyrosine, 496, 500, 524

125


O Nutrition and Health

U

Ulcerative colitis, 416
Ulcers, 419, 420

Unsaturated fatty acids, 106. See also
  Monounsaturated fatty acids;
  Polyunsaturated fatty acids
Upper body obesity, 286
U:s. Depaitment df Agriculture (USDA),
  33-37.42. 45.63. 543. 544

U.S. Postal Service, iO0

V
Valproic acid, 678
Vegetable availability, 64
Very low density lipoproteins (VLDL),
  87,91,99, 111,658
Vitamin A
Aging population and, 609
  - -. .
Alcohol use and, 646
Cancer and. 209-10. 213-14. 366
Definition, &O-61
Dental diseases and, 361-62
Drug interactions, 676
Fetus and, 558
Intake estimates, 70
Neurologic disorders and, 499
Skeletal diseases and, 332
Therapeutic doses, 683,684
Vitamin antagonists, 678-79
Vitamin B complex
Aging population and, 608
Alcohol and, 638,643-45,654-56
Anemia and, 470.482,483
Coronary heart disease and, 113, 117
Definition, 61
Dental diseases and, 365
Drug interactions, 676-79
Intake estimates, 70
Maternal and child health and, 554. 564.
   569. 572
Neurologic disorders and. 493-94.499
Therapeutic doses. 683-84
Vitamin Bh
Alcohol and, 644
Drug interactions, 677, 678
Therapeuric doses, 684
Vitamin BII,
Alcohol and, 644,645
Anemia and. 470. 482, 483
Drug interactions, 676, 679
Infant health and, 564
Neurologic disorders and, 493
Vitamin C
Aging population and, 608-9.611-12
Alcohol use and, 645
Cancer and, 217-18

Coronary heart disease and, 113
Definition, 61
Dental diseases and, 364-65
Infections and immunity and, 440
Intake estimates, 70
Iron absorption and, 480
Skeletal diseases and, 332
Supplement use, 71
Vitamin D
Aging population and, 609-10
Alcohol use and, 646
Dental diseases and, 362
Drug interactions, 676-78
Infants and, 563,564, 568
Skeletal diseases and, 312,321-25
Toxicity, 325
Vitamin D3, 61
Vitamin E
Aging population and, 610
Alcohol use and, 647
Cancer and, 218-19, 367
Coronary heart disease and, 113
Definition, 61
Infant and child health, 568-69
Intake estimates, 70
Neurolotic disorders and. 494

Vitamin K-

Alcohol use and, 647
Definition, 61

Drug interactions, 676-78
Infants and, 563, 564
Skeletal diseases and. 332
Vitamins

Alcohol and. 638,643-47,654-56
Cancer and, 209-10, 213-14, 217-19,
  367

Coronary heart disease and, 112-13
Definition, 59-62
Dental diseases and, 361-62, 364-65
Drug interactions, 676-79, 681
Infections and immunity and, 439,440,
  444

Kidney diseases and, 389
Maternal and child health and, 554, 558,
  563,564,568-72
Neurologic disorders and, 493-94,499
Skeletal diseases and, 312, 321-25,
  332-33

Supplement use, 70-71
Therapeutic doses, 683-84
VLDL. See Very low density lipoproteins

W

Water intake, 562
Water-soluble fiber, 61-62, 1 Il. 260
Water-soluble vitamins, 64-5, 683-84

726


Index 13

Wemicke-Korsakoffs syndrome, 653-55
WIC See Special Supplemental Food
Program for Women, Infants, and
  Children

n

A
Zinc

Alcohol use and, 648
Bone metabolism role, 332
Coronary heart disease and, 114
Drug interactions, 677
Infections and immunity and, 439-40,

445

Intake estimates, 70
Iron intake and, 481
Maternal and child health and, 555, 572
Therapeutic doses, 684

4U.S.G.P.O.  1966 221-483/90196

121