National Institute on Alcohol Abuse and Alcoholism
No. 35 PH 371 January 1997
———————————————————————-
Alcohol Metabolism
Metabolism is the body’s process of converting ingested substances to
other compounds. Metabolism results in some substances becoming more, and
some less, toxic than those originally ingested. Metabolism involves a
number of processes, one of which is referred to as oxidation. Through
oxidation, alcohol is detoxified and removed from the blood, preventing
the alcohol from accumulating and destroying cells and organs. A minute
amount of alcohol escapes metabolism and is excreted unchanged in the
breath and in urine. Until all the alcohol consumed has been metabolized,
it is distributed throughout the body, affecting the brain and other
tissues (1,2). As this Alcohol Alert explains, by understanding alcohol
metabolism, we can learn how the body can dispose of alcohol and discern
some of the factors that influence this process. Studying alcohol
metabolism also can help us to understand how this process influences the
metabolism of food, hormones, and medications.
———————————————————————-
The Metabolic Process
When alcohol is consumed, it passes from the stomach and intestines
into the blood, a process referred to as absorption. Alcohol is then
metabolized by enzymes, which are body chemicals that break down other
chemicals. In the liver, an enzyme called alcohol dehydrogenase (ADH)
mediates the conversion of alcohol to acetaldehyde. Acetaldehyde is
rapidly converted to acetate by other enzymes and is eventually
metabolized to carbon dioxide and water. Alcohol also is metabolized in
the liver by the enzyme cytochrome P450IIE1 (CYP2E1), which may be
increased after chronic drinking (3). Most of the alcohol consumed is
metabolized in the liver, but the small quantity that remains
unmetabolized permits alcohol concentration to be measured in breath and
urine.
The liver can metabolize only a certain amount of alcohol per hour,
regardless of the amount that has been consumed. The rate of alcohol
metabolism depends, in part, on the amount of metabolizing enzymes in the
liver, which varies among individuals and appears to have genetic
determinants (1,4). In general, after the consumption of one standard
drink, the amount of alcohol in the drinker’s blood (blood alcohol
concentration, or BAC) peaks within 30 to 45 minutes. (A standard drink
is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of
80-proof distilled spirits, all of which contain the same amount of
alcohol.) The BAC curve, shown on the previous page, provides an estimate
of the time needed to absorb and metabolize different amounts of alcohol
(5). Alcohol is metabolized more slowly than it is absorbed. Since the
metabolism of alcohol is slow, consumption needs to be controlled to
prevent accumulation in the body and intoxication.
Factors Influencing Alcohol Absorption and
Metabolism
Food. A number of factors influence the
absorption process, including the presence of food and the type of food
in the gastrointestinal tract when alcohol is consumed (2,6). The rate at
which alcohol is absorbed depends on how quickly the stomach empties its
contents into the intestine. The higher the dietary fat content, the more
time this emptying will require and the longer the process of absorption
will take. One study found that subjects who drank alcohol after a meal
that included fat, protein, and carbohydrates absorbed the alcohol about
three times more slowly than when they consumed alcohol on an empty
stomach (7).
Gender. Women absorb and metabolize alcohol
differently from men. They have higher BAC’s after consuming the same
amount of alcohol as men and are more susceptible to alcoholic liver
disease, heart muscle damage (8), and brain damage (9). The difference in
BAC’s between women and men has been attributed to women’s smaller amount
of body water, likened to dropping the same amount of alcohol into a
smaller pail of water (10). An additional factor contributing to the
difference in BAC’s may be that women have lower activity of the alcohol
metabolizing enzyme ADH in the stomach, causing a larger proportion of
the ingested alcohol to reach the blood. The combination of these factors
may render women more vulnerable than men to alcohol-induced liver and
heart damage (11-16).
Effects of Alcohol Metabolism
Body Weight. Although alcohol has a
relatively high caloric value, 7.1 Calories per gram (as a point of
reference, 1 gram of carbohydrate contains 4.5 Calories, and 1 gram of
fat contains 9 Calories), alcohol consumption does not necessarily result
in increased body weight. An analysis of data collected from the first
National Health and Nutrition Examination Survey (NHANES I) found that
although drinkers had significantly higher intakes of total calories than
nondrinkers, drinkers were not more obese than nondrinkers. In fact,
women drinkers had significantly lower body weight than nondrinkers. As
alcohol intake among men increased, their body weight decreased (17). An
analysis of data from the second National Health and Nutrition
Examination Survey (NHANES II) and other large national studies found
similar results for women (18), although the relationship between
drinking and body weight for men is inconsistent. Although moderate doses
of alcohol added to the diets of lean men and women do not seem to lead
to weight gain, some studies have reported weight gain when alcohol is
added to the diets of overweight persons (19,20).
When chronic heavy drinkers substitute alcohol for carbohydrates in
their diets, they lose weight and weigh less than their nondrinking
counterparts (21,22). Furthermore, when chronic heavy drinkers add
alcohol to an otherwise normal diet, they do not gain weight (21).
Sex Hormones. Alcohol metabolism alters the
balance of reproductive hormones in men and women (23-28). In men,
alcohol metabolism contributes to testicular injury and impairs
testosterone synthesis and sperm production (24,29). In a study of normal
healthy men who received 220 grams of alcohol daily for 4 weeks,
testosterone levels declined after only 5 days and continued to fall
throughout the study period (30,31). Prolonged testosterone deficiency
may contribute to feminization in males, for example, breast enlargement
(32). In addition, alcohol may interfere with normal sperm structure and
movement by inhibiting the metabolism of vitamin A, which is essential
for sperm development (30,33). In women, alcohol metabolism may
contribute to increased production of a form of estrogen called estradiol
(which contributes to increased bone density and reduced risk of coronary
artery disease) and to decreased estradiol metabolism, resulting in
elevated estradiol levels (28). One research review indicates that
estradiol levels increased in premenopausal women who consumed slightly
more than enough alcohol to reach the legal limit of alcohol (BAC of 0.10
percent) acutely (28). A study of the effect of alcohol on estradiol
levels in postmenopausal women found that in women wearing estradiol skin
patches, acute alcohol consumption significantly elevated estradiol
levels over the short term (34).
Medications. Chronic heavy drinking appears
to activate the enzyme CYP2E1, which may be responsible for transforming
the over-the-counter pain reliever acetaminophen (TylenolTM) and many
others) into chemicals that can cause liver damage, even when
acetaminophen is taken in standard therapeutic doses (3,35,36). A review
of studies of liver damage resulting from acetaminophen-alcohol
interaction reported that in alcoholics, these effects may occur with as
little as 2.6 grams of acetaminophen (four to five “extra-strength”
pills) taken over the course of the day in persons consuming varying
amounts of alcohol (35,37). The damage caused by alcohol-acetaminophen
interaction is more likely to occur when acetaminophen is taken after,
rather than before, the alcohol has been metabolized. Alcohol consumption
affects the metabolism of a wide variety of other medications, increasing
the activity of some and diminishing the activity, thereby decreasing the
effectiveness, of others (35).
———————————————————————-
Alcohol Metabolism–A Commentary by
NIAAA Director Enoch Gordis, M.D.
The study of metabolism has both practical and broader scientific
implications. On the practical side, information on how the body
metabolizes alcohol permits us to calculate, for example, what our blood
alcohol concentration (BAC) is likely to be after drinking, including the
impact of food and gender differences in the rate of alcohol metabolism
on BAC. This information, of course, is important when participating in
activities for which concentration is needed, such as driving or
operating dangerous machinery.
With respect to its broader scientific application, metabolism, which
has long been studied, is emerging with new implications for the study of
alcoholism and its medical consequences. For instance, how is metabolism
related to the resistance of some individuals to alcoholism? We know that
some inherited abnormalities in metabolism (e.g., flushing reaction among
some persons of Asian descent) promote resistance to alcoholism. Recent
data from two large-scale NIAAA-supported genetics studies suggest that
alcohol dehydrogenase genes may be associated with differential
resistance and vulnerability to alcohol. These findings are important to
the study of why some people develop alcoholism and others do not.
Studies of metabolism also can identify alternate paths of alcohol
metabolism, which may help explain how alcohol speeds up the elimination
of some substances (e.g., barbiturates) and increases the toxicity of
others (e.g., acetaminophen). This information will help health care
providers in advising patients on alcohol-drug interactions that may
decrease the effectiveness of some therapeutic medications or render
others harmful.
———————————————————————-
All material contained in the Alcohol Alert is in the public
domain and may be used or reproduced without permission from National
Institute on Alcohol Abuse and Alcoholism (NIAAA). Citation of the source
is appreciated.
Copies of the Alcohol Alert are available free of charge from
the:
NIAAAPublications
P.O. Box 34443
Washington, DC 20043
Full text of this publication is available on NIAAA’s World Wide Web
site at http://www.niaaa.nih.gov
———————————————————————-
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service * National Institutes of Health
