Kidney Diseases Cl

-. 1982. Altered glomerularpermselectivity and progressive sclerosis following extreme
ablation of renal mass. Kidney International 22~112-26.

Polinsky, M.S., and Gruskin. A.B. 1984. Aluminum toxicity in children with chronic renal
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Pullman, TN.; Alving, AS.; Dem, R.J.; and Landowne, M. 1954. The influence of dietary
protein intake on speciiic renal functions in normal man. Journal oflaboruto~ and Clinical
Medicine 44:320-32.

Purkerson,M.L.; Joist, J.H.;Greenberg, J.M.; Kay, D.;Hoffsten. F!E.;and Klahr. S. 1982.
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Purkerson, M.L.; Joist, J.H.; Yates, J.; Valdes, A.; Morrison. A.: and Klahr. S. 1985.
Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with
subtotal renal ablation. Proceedings of the National Academy of Science. Medical Sciences
82: 193-97.

Rodriguez-Iturbe, B.; Garcia, R.; Rubio, L.; Cuenca, L.; Treser, Cl.: and Lange. K. 1976.
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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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Rowe, J.W.; Andres, R.; Tobin. J.D.; Norris, A.H.; and Shock, N.W. 1976. Age-adjusted
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Schmidt, R.W.; Blumenkrantz, M.; and Wiegmann, T.B. 1983. The dilemmas of patient
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Sk Kidney International 12:193-98.

401


R

u Nutrition and Health

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Zager, R.A.; Johannes, G.; Tuttle, S.E.; and Sharma, H.M. 1983. Acute amino acid
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Zucchelli, P.; Cagnoli, L.; Casanova, S.; Donini. U.; and Pasquali, S. 1983. Focal
glomerulosclerosis in patients with unilateral nephrectomy. Kidney International 24:64%55.

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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.

411


u Nutrition and Health

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

412


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).

413


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,

414


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).

420


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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