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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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


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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


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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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Literature Cied

AMA. See American Medical Association.

American Medical Association, Council on Scientific Affairs. 1983. Fetal effects of maternal
alcohol use. Journal of the American Medical Association 249:2517-21.

Badawy, A.A.-B. 1978. The metabolism of alcohol. Clinics in Endocrinology and Metabolism
7~241-71.

Baker, H.; Frank, 0.; Letterman, R.K.; Rajan, K.S; ten Hove, W.; and Leevy, CM. 1975.
Inability ofchronic alcoholics with liver disease to use food as a source offolates, thiamin, and
vitamin Bg. American Journal of Clinical Nutrition 28: 1377-80.
Barnes, GM., and Russell, M. 1978. Drinking patterns in western New York State. Journal of
Studies on Alcohol 39: 1148-57.

Bebb, H.T.; Houser, H.B.; Wits&i, J.C.; Littell, A.S.; and Fuller, R.K. 1971. Calorie and
nutrient contribution of alcoholic beverages to the usual diets of 155 adults. American Journal
of Clinical Nutrition 24: 1042-52.

Behse, F., and Buchthal, F. 1977. Alcoholic neuropathy: clinical, electrophysiological, and
biopsy findings. Annals of Neurology 2:95-l 10.

Beilin, L.J., and Puddey, I.B. 1984. Alcohol and essential hypertension (editorial). Alcohol
and Alcoholism 19: 191-95.

Berkelman, R.L. ; Ralston, M. ; Hemdon, J.; Gwinn, M.; Bertolucci, D. ; and Dufour, M. 1986.
Patterns of alcohol consumption and alcohol-related morbidity and mortality. Morbidity nnd
Mortality Weekly Report 35(2SS):lS!USS.

Bing, R.J. 1978. Cardiac metabolism: its contributions to alcoholic heart disease and myocar-
dial failwe. Circulation 58:%5-70.

Blackwelder, W.C.; Yano, K.; Rhoads, G.G.; Kagan, A.; Gordon, T.; and Palesch, Y. 1980.
Alcohol and mortality: the Honolulu Heart Study. American Journal qfhfedicine 68: 164-69.

Blass, J.P., and Gibson, G.E. 1977. Abnormality of a thiamine-requiring enzyme in patients
with Wemicke-Korsakoff syndrome. New England Journal of Medicine 297: 1367-70.

Bonjour, J.P. 1979. Vitamins and alcoholism. I. Ascorbic acid. Internafional Journal for
Vitamin Nutrition Research 49~434-41.

-. 1980. Vitamins and alcoholism. II. Folate and vitamin B1z. International Journalfor
Vitamin Nutrition Research 5096-12 1.

Brigden, W., and Robinson, J. 1964. Alcoholic heart disease. British Medical Journal
2: 1283-89.

Camilo, M.E.; Morgan, M.Y.; and Sherlock, S. 1981. Erythrocyte transketolase activity in
alcoholic liver disease. Scandinavian Journal of Gastroenterology 16:273-79.

Centerwall, B.S., and Criqui, M.H. 1978. Prevention of the Wernicke-Korsakoffsyndrome: a
cost-benefit analysis. New England Journal sf Medicine 299:285-89.

Committee on Diet, Nutrition, and Cancer. 1982. Diet, nutrition, nnd cancer. Washington,
DC: National Academy Press.

Da&y, W.J. 1979. The nutrient contributions of fermented beverages. In Fermented food
beverages in nutrition, ed. C.F. Gastineau, W.J. Darby, and T.B. `Ibmer, pp. 61-79. New York:
Academic.

463


O Nutrition and Health

Demakis, J.G.; Proskey, A.; Rahimtoola, S.H.; Jam& M.; Sutton, G.C.; Rosen, K.M.;
Gunner, R.M.; and Tobin, J.R., Jr. 1984. The natural course of alcoholic cardiomyopathy.
Annals oflnternal Medicine 80:293-97.

DHEW. See U.S. Department of Health, Education, and Welfare.
DHHS. See U.S. Department of Health and Human Services.

Dickson, B.J.; Delaney, C.J.; Walker, R.D.; Hutchinson, M.; and Buergel, N. 1983. Visceral
protein status of patients hospitalized for alcoholism. American Journal of Clinical Nutrition
37:216-20.

Diehl,A.M.;Boitnott, J.K.;Herlong,H.E:;Potter,J.J.;VanDuyn,M.A.;Chandler,E.;and
Mezey, E. 1985. Effect of parenteral ammo acid supplementation in alcoholic hepatitis.
Hepatology 5~57-63.

Dreyfus, P.M. 1979. Effects ofalcohol on the nervous system. In Fermentedfood beverages in
nutrition, ed. CF. Gastineau, W.J. Darby, and T.B. Turner, pp. 341-57. New York: Academic.

Eichner, E.R., and Hillman, R.S. 1971. The evolution of anemia in alcoholic patients.
American Journal of Medicine 50:218-32.

Emhart, C.B. 1987. Alcohol teratogenicity in the human: adetailed assessment of specificity,
critical period, and threshold. American Journal of Obstetrics and Gynecology 15633-39.

Ernst, N.; Fisher, M.; Smith, W.; Gordon, T.; Riflcind, B.M.; Little, J.A.; Mishkel, M.N.; and
Williams, D.D. 1980. The association of plasma high-density lipoprotein cholesterol with
dietary intake and alcohol consumption. Circulation 62(suppl. IV):41-52.

Ettinger, PO.; Wu, C.F.; De La Cruz, C., Jr.; Weisse, A.B.; Ahmed, S.S.; and Regan, T.J.
1978. Arrhythmias and the "holiday heart": alcohol associated cardiac-rhythm disorders.
American Heart Journal 95:555-62.

Flynn,A.;Martier,S.S.;Sokol,R.J.;Miller,S.I.;Golden,N.L.;andDelvillano,B.C.1981.
Zinc status of pregnant alcoholic women: a determinant of fetal outcome. Lancer i:572-74.

French, S.W. 1971. Acute and chronic toxicity of alcohol. In The biology of afcoholism.
Biochemistry, vol. I, ed. B. Kissin and H. Begleiter, pp. 437-511. New York: Plenum.

Freinkel, N . ; Arky, R. A. ; Singer, D.L. ; Cohen, A.K. ; Bleicher, S.J. ; Anderson, LB. ; Silbert,
C.K.; and Foster, A.E. 1%5. Alcohol hypoglycemia. IV. Current concepts ofitspathogenesis.
Diabetes 14:350.

Geokas, M.C. 1984. Ethanol and the pancreas. Medical Clinics of North America 68~57-75.

Ghaiioungui, P 1979. Fermented beverages in antiquity. In Fermented food beverages in
nutrition, ed. C.F. Gastineau, W.J. Darby, and T.B. Turner, pp. 3-19. New York: Academic.

Green, P.H.R. 1983. Alcohol, nutrition and malabsorption. Clinics in Gastroenterology
12:563-74.

Greenberg, B.H.; Schutz, R.; Grunkemeier, G.L.; and Griswold, H. 1982. Acute effects of
alcohol in patients with congestive heart failure. Annals of Internal Medicine 97: 171-75.

Gruchow, H.W.; Sobocinski, K.A.; Barboriak, J.J.; and Scheller, J.G. 1985. Alcoholconsump-
tion, nutrient intake and relative body weight among U.S. adults. American Journalof Clinical
Nutrition 42~289-95.

Haisted, C.H.; Robles, E.A.; and Mezey, E. 1971. Decreased jejunal uptake of labeled folic
acid (sH-PGA) in alcoholic patients: role of alcohol and nutrition. New England Journal of
Medicine 285:7016.

664


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-. 1973. Distribution of ethanol in the human gastrointestinal tract. American Journal of
Clinical Nutrition 26:831-34.

Henderson, G.I.; Patwardhan, R.V.; McLeroy, S.; and Schenker, S. 1982. Inhibition of
placental amino acid uptake in rats following acute and chronic ethanol exposure. Alcoholism:
Clinical and Experimental Research 6:495-505.

Herman, C.P., and Polivy, J. 1980. Stress-induced eating and eating-induced stress (reduc-
tion)-a response to Robbins and Fray. Appetite 1:135-39.

Hillers, V.N., and Massey, L.K. 1985. Interrelationships of moderate and high alcohol
consumption with diet and health status. American Journal ofClinical Nutrition 41:35ti2.

Hoyumpa, A.M. 1983. Alcohol and thiamine metabolism. Alcoholism: Clinical and Experi-
menral Research 7: 11-14.

Hurt, R.D.; Higgins, LA.; Nelson, R.A.; Morse, R.M.; and Dickson, E.R. 1981. Nutritional
status uf a group of alcoholics before and after admission to an alcoholism treatment unit.
American Journal of Clinical Nutrition 34:386-92.

Hurt, R.D.; Morse, R.M.; and Swenson, W.M. 1980. Diagnosis of alcoholism with a self-
administered alcoholism screening test. Mayo Clinic Proceedings 55:365-70.

Hurt,R.D.;Briones,E.R.;Offord,K.P.;~tton,J.G.;Mau,S.J.T.;Morse,R.M.;andKonke,
B.A. 1986. Plasma lipids and lipoprotein AI and AI1 levels in alcoholic patients. American
Journal of Clinical Nutrition 431521-29.

Janus, E.D., and Lewis, B. 1978. Alcohol and abnormalities of lipid metabolism. Clinics in
Endocrinology and Metabolism 7:321-32.

Jolliffe, N., and Jellinek, E.M. 1941. Vitamin deficiencies and liver cirrhosis in alcoholism.
VII. Cirrhosis of the liver. Quarterly Journal of Studies on Alcohol 2:544-83.

Jolliffe, N.; Bowman, K.M.; Rosenblum, L.A.; and Fein, H.D. 1940. Nicotinic aciddeficien-
cy encephalopathy. Journal of the American Medical Association 114:307-12.

Jones, B.R.; Barrett-Connor, E.; Criqui, M.H.; and Holdbrook, M.J. 1982. A community
study of calorie and nutrient intake in drinkers and nondrinkers of alcohol. American Journal
of Clinical Nutrition 35: 135-39.

Jones, K.L.; Smith, D.W.; Ulleland, C.N.; and Streissguth, A.F? 1973. Pattern ofmalforma-
tion in offspring of chronic alcoholic mothers. Lancer i:1267-71.

Kalant, H. 1971. Absorption. diffusion, distribution, and elimination of ethanol: effects on
biological membranes. In The biology of alcoholism. Biochemistry, vol. I, ed. B. Kissin and
H. Begleiter, pp. 142. New York: Plenum.

Kaunitz, J.D., and Lindenbaum, J. 1977. The bioavailability offolic acid added to wine. Annals
of Internal Medicine 87:542-45.

Klatskin, G. 1961. Alcohol and its relation to liver damage. Gastroenterology 41:443-51.

Kottke, B.A.; Zinsmeister, A.R. ; Holmes, D.R., Jr.; KneUer, R. W. ; Hallaway, B . J. ; and Mau,
S.J.T. 1986. Apolipoproteins and coronary artery disease. Mayo Clinic Proceedings
61:313-20.

Laforge, R.; Stinson, ES.; Freel, C.G.; and Wiiams, G. 1987. Surveillance report #7:
apparent per capita consumption: national, stafe, and regional trends, 1977-85. Rockviue,
MD: Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and
Alcoholism, September.

Landsberg, L., and Young, J.B. 1984. The role of the sympathoadrenal system in modulating
energy expenditure. Clinics in Endocrinology and Metabolism 13~475-99.

665


0 Nutrition and Health

Lang, R.M.; Borow, K.M.; Neumann, A.; and Feldman, T. 1985. Adverse cardiac effects of
acute alcohol ingestion in young adults. Annals oflnternal Medicine 102:742-47.

Larkin, E.C., and Watson-Williams, E.J. 1984. Alcohol and the blood. Medical Clinics elf
North America 68: 105-20.

Leevy, C.M. 1%7. Clinical diagnosis, evaluation and treatment of liver disease in alcoholics.
Federation Proceedings 26: 1474-8I.

Leevy, C.M.; Tanribilir, A.K.; and Smith, E 1971. Biochemistry of gastrointestinal and liver
disease in alcoholism. In The biology ofalcoholism. Biochemistry, vol. I, ed. B. Kissin and H.
Begleiter, pp. 307-25. New York: Plenum.

Lelbach, W.K. 1975. Cirrhosis in the alcoholic and its relation to the volume c&alcohol abuse.
Annals of the New York Academy qf Sciences 252:85-105.
Leo, M.A., and Lieber, C.S. 1982. Hepatic vitamin A depletion in alcoholic liver injury. New
England Journal of Medicine 307:597-l.

Lieber, C.S. 1966. Hepatic and metabolic effects of alcohol. Gastroenterology 50:119-33.

-. 1983. Interactions of alcohol and nutrition-introduction to a symposium (editorial).
Alcoholism: Clinical and Experimental Research 7~2-3.

-. 1984. Metabolism and metabolic effects of alcohol. Medical Clinics oflvorth America
68:3-31.

Lieber, C.S., and DeCarli, L.M. 1974. An experimental model of alcohol feeding and liver
injury in the baboon. Journal qf Medical Primatology 3:153-63.

Lindenbaum, J. 1977. Metabolic effects of alcohol on the blood and bone marrow. In Meta-
bolic aspects of alcoholism, ed. C.S. Lieber, pp. 215-47. Lancaster, England: MTP.

Losowsky, M.S., and Leonard, P.J. 1967. Evidence of vitamin E deficiency in patients with
malabsorption or alcoholism and the effects of therapy. Gut 8:53%3.

Lucas, CC.; Ridout, J.H.; and Lumchick, G.L. 1968. Dietary protein and chronic intoxica-
tion with ethanol. Canadian Journal qf Physiology and Pharmacology 46~475-85.

MacMahon, S.W. 1986. Alcohol and hypertension: implications for prevention and treatment
(editorial). Annals oflnternal Medicine 105:12&26.

Marks, V. 1978. Alcohol and carbohydrate metabolism. Clinics in Endocrinology and Metab-
olism 7:333-49.

Marmet, M.G.; Shipley, M.J.; Rose, G.; and Thomas, B.J. 1981. Alcohol and mortality: a U-
shaped curve. Lancet i:580-83.

McClain, C.J. ; Van Thiel, D.H. ; Parker, S. ; Badzin, L.K. ; and Gilbert, H. 1979. Alterations in
zinc, vitamin A, and retinol-binding protein in chronic alcoholics: a possible mechanism for
night blindness and hypogonadism. Alcoholism: Clinical and Experimental Research
3:135-41.

McDonald, J. 1980. Alcohol and diabetes. Diabetes Care 3:62%37.

McDonald, J.T., and Margen, S. 1976. Wine versus ethanol in human nutrition. I. Nitrogen
and calorie balance. American Journal of Clinical Nutrition 29: 1093-l 103.

Mendenhall, CL.; Anderson, S.; Weesner, R.E.; Goldberg, S.J.; and Crolic, K.A. 1984.
Protein-calorie malnutrition associated with alcoholic hepatitis. American Journal qfMedi-
tine 76:21 l-22.

666


Alcohol 0

Mezey, E., and Faillace, L.A. 1971. Metabolic impairment and recovery time in acute ethanol
intoxication. Journal of Nervous and Mental Diseases 153:445-52.

Mills,J.L.;Graubard,B.I.;Harley,E.E.;Rhoads,G.G.;andBerendes,H.W.1984.Matem~
alcohol consumption and birth weight. Journal of the American Medical Association
252: 1875-79.

Moore, M.H., andGerstein, D.R., eds. 1981. Alcoholandpublicpolicy: beyond theshadowof
prohibition. Washington, DC: National Academy Press.

Moore, R.A. 1971. The prevalence of alcoholism in a community general hospital. American
Journal of Psychiatry 128:638-39.

Morgan, M.Y. 1982. Alcohol and nutrition. British Medical Bulletin 38:21-29.
Nakada, T., and Knight, R.T. 1984. Alcohol and the central nervous system. Medical Clinics
of North America 68:121-31.

Nasrallah, SM., and Galambos, J.T. 1980. Amino acid therapy of alcoholic hepatitis. Loncet
ii:l27&77.

National Center for Health Statistics. 1986. Health, United States, 1986. DHHS publication
no. (PHS) 87-1232. Washington, DC: U.S. Government Printing Oflice.

NCHS. See National Center for Health Statistics.

Neville, J.N.; Eagles, J.A.; Samson, G.; and Olson, R.E. 1968. Nutritional status of alco-
holics. American Journal of Clinical Nutrition 21~132940.

Nixon, P.F. 1984. Is there agenetic component to the pathogenesis ofthe Wemicke-Korsakoff
syndrome? (editorial). Alcohol and Alcoholism 19:219-21.

Orten, J.M., and Sardesai, V.M. 1971. Protein, nucleotide, and porphyrin metabolism. In The
biology of alcoholism. Biochemisrry, vol. I, ed. B. Kissin and H. Begleiter, pp. 229-61. New
York: Plenum.

Passmore, R. 1979. The energy valueofalcohol. InFermentedfood beverages in nutrition, ed.
C.F. Gastineau, W.J. Darby, and T.B. nmer, pp. 213-23. New York: Academic.

Patek, A.J., Jr. 1979. Alcohol, malnutrition, and alcoholic cirrhosis. American Journal of
Clinical Nutrition 32~130442.

Patek, A.J., Jr., and Post, J. 1941. `l?eatment of cirrhosis of the liver by a nutritious diet and
supplements rich in vitamin B complex. Journal of Clinical Znvestigation 20:481-505.

Patek, A.J., Jr.; Toth, LG.; Saunders, M.G.; Castro, G.A.M.; and Engel, J.J. 1975. Alcohol
and dietary factors in cirrhosis: an epidemiological study of304 alcoholic patients. Archives of
Internal Medicine 135:1053-57.

Pennington, J.A.T. and Church, H.N. 1985. Bowes and Church's food values ofportions
commonly used. New York: Harper & Row.

Pequignot, G., and Cyralnik, F. 1970. Chronic disease due to overconsumption of alcoholic
drinks. In International encyclopedia ofpharmacology and therapeutics, vol. II, pp. 375412.
Oxford, England: Pergamon.

Pirola, R.C. 1978. Drug metabolism and alcohol. Baltimore, MD: Univ. Park Press.
Pirola, R.C., and Lieber, C.S. 1972. The energy cost of the metabolism of drugs, including
ethanol. Pharmacology 7: 185-%.

Polivy, J., and Herman, C.P. 1976a. Effects of alcohol on eating behavior: disinhibition or
sedation? Addictive Behaviors 1: 121-25.

667


O Nutrition and Health

-. 1976b. Effects of alcohol on eating behavior: influences of mood and perceived
intoxication. Journal of Abnormal Psychology 85:601.

Randall, CL.; Taylor, W.J.; and Walker, D.W. 1977. Ethanol-induced malformations in mice.
Alcoholism: Clinical and Experimental Research 1:219-24.

Ravenholt, R.T. 1984. Addiction mortality in the United States, 1980: tobacco, alcohol and
other substances. Population and Development Review 10~697-724.

Reuler, J.B.; Girard, D.E.; and Cooney, T.G. 1985. Current concepts: Wemicke's encepha-
lopathy. New England Journal of Medicine 312: 1035-39.
Rich, E.C.; Siebold, C.; and Campion, B. 1985. Alcohol-related acute atria1 fibrillation.
Archives of Internal Medicine 145:83@-33.

Roe, D.A. 1979. Alcohol and the diet. Westport, CT: AVI.

Ron, M.A.; Acker, W.; Shaw, G.K.; and Lishman, W.A. 1982. Computerized tomography of
the brain in chronic alcoholism: a survey and follow-up study. Brain 105:497-514.
Rothwell, N.J., and Stock, M.J. 1986. Diet-induced thermogenesis. Nutrition International
2(2):95-99.

Rubin, E. 1979. Alcoholic myopathy in heart and skeletal muscle. New England Journal of
Medicine 301:28-33.

Rubin, E., and Lieber, C.S. 1968. Alcohol-induced hepatic injury in nonalcoholic volunteers.
New England Journal of Medicine 278:869-76.

Rund, D.A.; Summers, W.K.; and Levin, M. 1981. Alcohol use and psychiatric illness in
emergency patients. Journal of the American Medical Association 245: 124M1.

Russell, R.M.; Rosenberg, I.H.; Wilson, P.D.; Iber, EL.; Oaks, E.B.; Giovetti, A.C.;
Otradovec, C.L.; Karwoski, PA.; and Press, A.W. 1983. Increased urinary excretion and
prolonged turnover time of folic acid during ethanol ingestion. American Journal of Clinical
Nutrition 38:64-70.

Schreiber, S.S.; Briden, K.; Oratz, M.; and Rothschild, M.A. 1972. Ethanol, acetaldehyde,
and myocardial protein synthesis. Journal of Clinical Investigation 51:2820-26.

Shattuck, G.C. 1928. The relation of beri-beri to polyneuritis from other causes. American
Journal of Tropical Medicine 83539-43.

Shaw, S., and Lieber, C.S. 1983. Alcoholism. In Nutritional support of medicalpractice. ed.
H.A. Schneider, C.E. Anderson, and D.B. Coursin, pp. 236-59. 2d ed. Philadelphia, PA:
Harper & Row.

Sherlock, S. 1981. Diseases of the liver and biliary system, p. 334 6th ed. Oxford, England:
Blackwell.

Simko, V.; Connell, A.M.; and Banks, B. 1982. Nutritional status in alcoholics with and
without liver disease. American Journal of Clinical Nutrition 35: 197-203.

Singer, K., and Lundberg, W.B. 1972. Ventriculararrhythmiasassociated with the ingestion of
alcohol. Annals of Internal Medicine 77~247-48.

Sorrell, M.F.; Baker, H.; Barak, A.J.; and Frank, 0. 1974. Release by ethanol of vitamins into
rat liver perfusates. American Journal of Clinical Nutrition 27~743-45.

Steinkraus, K.H. 1979. Nutritionally significant indigenous foods involving an alcoholic
fermentation. In Fermentedfood beverages in nutrition, ed. C.F. Gastineau, W.J. Darby, and
T.B. `Khmer, pp. 35-59. New York: Academic.

668


Alcohol O

Streissguth, A.P. 1978. Fetal alcohol syndrome: an epidemiological perspective. American
Journal of Epidemiology 107:467-78.

Streissguth. A.P.; Barr, H.M.: Martin, D.C.; and Herman. C.S. 1980. Effects of maternal
alcohol, nicotine, and caffeine use during pregnancy on infant mental and motor development
at eight months. A/coho/ism: C/inica/ and Experimental Research 4: 1.52-64.
Sullivan, L.W., and Herbert, V. 1964. Suppression of hematopoiesis by ethanol. Jolrrnal of
Clinical Investigation 43:2048-62.

Swenson, W.M., and Morse, R.M. 1975. The use of a self-administered alcoholism screening
test (SAAST) in a medical center. Mayo Clinic Proceedings 50:204-8.

Task Force on Nomenclature and Statistics. 1980. In Diagnostic, and Jtutisrical manuul of
mental disorders, pp. 169-70. 3rd ed. Washington. DC: American Psychiatric Association.
Thomson. A.D. 1978. Alcohol and nutrition. Clinics in Endocrinology und Metabolism
71405-28.

Tomaiolo, P.P., and Kraus, V. 1980. Nutritional status of hospitalized patients. Journal of
Purenteral and Enteral Nutrition 4: l-3.

Torvik, A.; Lindboe, C.F.: and Rogde, S. 1982. Brain lesions in alcoholics: a neu-
ropathological study with clinical correlations. Journal of Neurological Scienre 56:233-48.
USDA/DHHS. See U.S. Department of Agriculture and U.S. Department of Health and
Human Services.

U.S. Department of Agriculture and U.S. Department of Health and Human Services. 1985.
Nutrition and your health: dietary guidelines for Americans. Home and Garden Bulletin no.
232. Washington, DC: U.S. Government Printing Gffice.

U.S. Department of Health, Education, and Welfare. 1979. Healthy people: the Surgeon
General's report on health promotion and disease prevention. Stock No. 017-001-00416-2.
Washington, DC: U.S. Government Printing G&e.
U.S. Department of Health and Human Services. 1980. Promoting health/preventing disease:
objectives for the nation. Washington, DC: U.S. Government Printing Office.

-. 1983. Promoting health/preventing disease: Public Health Service implementation
plans for attaining the objectives for the nation. Public Health Reports 98(5, suppl.).

-. 1985 Report of the Secretary's Task Force on Biack and Minority Health. Vol. I:
Executive Summary. Washington, DC: U.S. Government Printing Gf?ice.

-. 1986. The 1990 health objectivesfor the nation: a midcourse review. Public Health
Service. DHHS publication no. 87-4753. Washington, DC: U.S. Government Printing GfJice.

-. 1987. Sixrh special report to the U.S. Congress on alcohol and health from the
Secretary of Health and Human Services. DHHS publication no. (ADM) 87-1519. Washing-
ton, DC: U.S. Government Printing GfBce.

Vestal, R.E.; McGuire. E.A.; Tobin, J.D.; Andres, R.; Norris, A.H.; and Mezey, E. 1977.
Aging and ethanol metabolism. Clinical Pharmacology and Therapeutics 21:343-54.

Victor, M.; Adams, R.D.; and Collins, G.H. 1971. The Wernicke-Korsakoffsyndrome. Phila-
delphia, PA: Davis.

Walsh, J.C., and McLeod, J.G. 1970. Alcoholic neuropathy: an electrophysiological and
histological study. Journal of Neurological Science 10:457-69.

Wechsler, H.; Demone, H.W.; and Gottleib, N. 1978. Drinking patterns of greater Boston
adults. Journal of Studies on Alcohol 39: 1158-65.


Cl Nutrition and Health

Weiss, S., and Wilkins, R.W. 1937. The nature of the cardiovascular disturbances in nutri-
tional deficiency states (beriberi). Annals oflnfernal Medicine 11:104-48.

Wheeler,P.G.;Smith,T.;Gollindano,C.;Alam,A.N.;Willrinson,S.P.;Edmonds,C.J.;and
W-s, R. 1977. Potassium and magnesium depletion in patients with cirrhosis on mainte-
nance diuretic regimens. Gu? 18683-87.

Wharton, J.C. 1982. Crusaders forfitness: the history ofAmerican he&h reformers. Prince-
ton, NJ: Princeton Univ. Press.

Wickramsinghe, S.N.; Gardner, B.; and Barden, G. 1987. Circulating cytotoxic protein
generated after ethanol consumption: identification and mechanism of reaction with cells.
Lancer ii: 122-26.

Williams, H.E. 1984. Alcoholic hypoglycemia and ketoacidosis. Medical Clinics of North
America 68333-38.

Williamson, D.F.; Forman, M.R.; Binkin, N.J.; Gentry, EM.; Remington, P.L.; and
Ttowbridge, FL. 1987. Alcohol and body weight in United States adults. AmericanJournalof
Public Health 71:1324-30.

World, M.J.; Ryle, P.R.; Pratt, O.E.; and Thomson, A.D. 1984. Alcohol and body weight
(editorial). Alcohol and Alcoholism 19: l-6.

Yano, K.; Rhoads, G.G.; and Kagan, A. 1977. Coffee, alcohol and risk of coronary heart
disease among Japanese men living in Hawaii. New England Journal of Medicine 297:405-9.

Zieve, L. 1958. Jaundice, hyperlipemia and hemolytic anemia: a heretofore unrecognized
syndrome associated with alcoholic fatty liver and cirrhosis. Annals of Internal Medicine
48:471-96.

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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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