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Alcohol Metabolism

Alcohol Alert From NIAAA

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.

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).

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 Biopharmaceutics5(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.

Are your withdrawals mild, moderate or severe? Take the Alcohol Withdrawal Symptoms Quiz.

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.

References

(1) Bosron, W.F.; Ehrig, T.; & Li,T.-K. Genetic factors in alcohol metabolism and alcoholism. Seminars in Liver Disease 13(2):126-135, 1993. (2) Wallgren, H. Absorption, diffusion, distribution and elimination of ethanol: Effect on biological membranes. In: International Encyclopedia of Pharmacology and Therapeutics. Vol. 1. Oxford: Pergamon, 1970. pp. 161-188. (3) Lieber, C.S. Metabolic consequences of ethanol. The Endocrinologist 4(2):127-139, 1994. (4) Benet, L.Z.; Kroetz, D.L.; & Sheiner, L.B. Pharmacokinetics: The dynamics of drug absorption, distribution, and elimination. In: Molinoff, P.B., & Ruddon, R.W., eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill, 1996. pp. 3-27. (5) Widmark, E.M.P. Die theoretischen Grundlagen und die praktische Verwendbarkeit der gerichtlich-medizinischen Alkoholbestimmung. Berlin: Urban and Schwarzenberg, 1932. (6) Fraser, A.G.; Rosalki, S.B.; Gamble, G.D.; & Pounder, R.E. Inter-individual and intra-individual variability of ethanol concentration-time profiles: Comparison of ethanol ingestion before or after an evening meal. British Journal of Clinical Pharmacology 40:387-392, 1995. (7) Jones, A.W., & Jönsson, K.A. Food-induced lowering of blood-ethanol profiles and increased rate of elimination immediately after a meal. Journal of Forensic Sciences 39(4):1084-1093, 1994. (8) Urbano-Márquez, A.; Estruch, R.; Fernández-Solá, J.; Nicolás, J.M.; Paré, J.C.; & Rubin, E. The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men. JAMA 274(2):149-154, 1995. (9) Nixon, S.J. Cognitive deficits in alcoholic women. Alcohol Health & Research World 18(3):228-232, 1994. (10) National Institute on Alcohol Abuse and Alcoholism. Alcohol Alert: Alcohol and Women. No. 10, PH 290. Bethesda, MD: the Institute, 1990. (11) Frezza, M.; Di Padova, C.; Pozzato, G.; Terpin, M.; Baroana, E.; & Lieber, C.S. High blood alcohol levels in women: The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. The New England Journal of Medicine 322(2):95-99, 1990. (12) Ashley, M.J.; Olin, J.S.; Le Riche, W.H.; Kornaczewski, A.; Schmidt, W.; & Rankin, J.G. Morbidity in alcoholics: Evidence for accelerated development of physical disease in women. Archives of Internal Medicine 137:883-887, 1977. (13) Krasner, N.; Davis, M.; Portmann, B.; & Williams, R. Changing pattern of alcoholic liver disease in Great Britain: Relation to sex and signs of autoimmunity. British Medical Journal 1:1497-500, 1977. (14) Morgan, M.Y., & Sherlock, S. Sex-related differences among 100 patients with alcoholic liver disease. British Medical Journal1:939-941, 1977. (15) Saunders, J.B.; Davis, M.; & Williams, R. Do women develop alcoholic liver disease more readily than men? British Medical Journal 282:1140-1143, 1981. (16) Norton, R.; Batey, R.; Dwyer, T.; & MacMahon, S. Alcohol consumption and the risk of alcohol related cirrhosis in women. British Medical Journal 295:80-82, 1987. (17) Gruchow, H.W.; Sobocinski, K.A.; Barboriak, J.J.; & Scheller, J.G. Alcohol consumption, nutrient intake and relative body weight among U.S. adults. American Journal of Clinical Nutrition 42:289-295, 1985. (18) Colditz, G.A.; Giovannucci, E.; Rimm, E.B.; Stampfer, M.J.; Rosner, B.; Speizer, F.E.; Gordis, E.; & Willett, W.C. Alcohol intake in relation to diet and obesity in women and men. American Journal of Clinical Nutrition 54:49-55, 1991. (19) Clevidence, B.A.; Taylor, P.R.; Campbell, W.S.; & Judd, J.T. Lean and heavy women may not use energy from alcohol with equal efficiency. Journal of Nutrition 125(10):2536-2540, 1995. (20) Crouse, J.R., & Grundy, S.M. Effects of alcohol on plasma lipoproteins and cholesterol and triglyceride metabolism in man. Journal of Lipid Research 25:486-496, 1984. (21) Lieber, C.S. Perspectives: Do alcohol calories count? American Journal of Clinical Nutrition 54:976-982, 1991. (22) Reinus, J.F.; Heymsfield, S.B.; Wiskind, R.; Casper, K.; & Galambos, J.T. Ethanol: Relative fuel value and metabolic effects in vivo. Metabolism 38(2):125-135, 1989. (23) Andersson, S.; Cronholm, T.; & Sjövall, J. Redox effects of ethanol on steroid metabolism. Alcoholism: Clinical and Experimental Research 10(6)(Suppl): 55S-63S, 1986. (24) Wright, H.I.; Gavaler, J.S.; & Van Thiel, D. Effects of alcohol on the male reproductive system. Alcohol Health & Research World 15(2):110-114, 1991. (25) Cicero, T.J., & Bell, R.D. Effects of ethanol and acetaldehyde on the biosynthesis of testosterone in the rodent testes. Biochemical and Biophysical Research Communications 94(3):814-819, 1980. (26) Johnston, D.E.; Chiao, Y.B.; Gavaler, J.S.; & Van Thiel, D.H. Inhibition of testosterone synthesis by ethanol and acetaldehyde. Biochemical Pharmacology 30(13):1827-1830, 1981. (27) Chiao, Y.B., & Van Thiel, D.H. Biochemical mechanisms that contribute to alcohol-induced hypogonadism in the male. Alcoholism: Clinical and Experimental Research 7(2):131-134, 1983. (28) Mello, N.K.; Mendelson, J.H.; & Teoh, S.K. An overview of the effects of alcohol on neuroendocrine function in women. In: Zakhari, S., ed. Alcohol and the Endocrine System. National Institute on Alcohol Abuse and Alcoholism Research Monograph No. 23.NIH Publication No. 93-3533. Bethesda, MD: the Institute, 1993. pp. 139-169. (29) Van Thiel, D.H.; Gavaler, J.; &Lester, R. Ethanol inhibition of vitamin A metabolism in the testes: Possible mechanism for sterility in alcoholics. Science 186(4167):941-942, 1974. (30) National Institute on Alcohol Abuse and Alcoholism. Alcohol Alert: Alcohol and Hormones. No. 26, PH 352. Bethesda, MD: the Institute, 1994. (31) Gordon, G.G.; Altman, K.; Southren, A.L.; Rubin, E.; & Lieber, C.S. Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men. The New England Journal of Medicine 295(15):793-797, 1976. (32) Bannister, P., & Lowosky, M.S. Ethanol and hypogonadism. Alcohol & Alcoholism 22(3):213-217, 1987. (33) Leo, M.A., & Lieber, C.S. Hepatic vitamin A depletion in alcoholic liver injury. The New England Journal of Medicine 307(10):597-601, 1982. (34) Ginsburg, E.S.; Walsh, B.W.; Shea, B.F.; Gao, X.; Gleason, R.E.; & Barbieri, R.L. The effects of ethanol on the clearance of estradiol in postmenopausal women. Fertility and Sterility 63(6):1227-1230, 1995. (35) National Institute on Alcohol Abuse and Alcoholism. Alcohol Alert: Alcohol-Medication Interactions. No. 27, PH 355. Bethesda, MD: the Institute, 1995. (36) Black, M. Acetaminophen hepatotoxicity. Annual Review of Medicine 35:577-593, 1984. (37) Seeff, L.B.; Cuccherini, B.A.; Zimmerman, H.J.; Adler, E.; & Benjamin, S.B. Acetaminophen hepatotoxicity in alcoholics: A therapeutic misadventure. Annals of Internal Medicine 104(3):399-404, 1986.

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