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.
Blood alcohol concentration (BAC) after the rapid
consumption of different amounts of alcohol by eight adult fasting male
subjects.* (Adapted from Wilkinson et al., Journal of
Pharmacokinetics and Biopharmaceutics 5(3):207-224,
1977.)
100 mg% is the legal level of intoxication in most States. 50
mg% is the level at which deterioration of driving skills begins.
(JAMA 255:522-527, 1986.)
*If the same number of drinks are consumed over a longer period of time, BAC's will be lower.
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
othe rs 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.
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