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).


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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.