Ethanol Metabolism Essay

I. Alcohol metabolism in a mother's body and her fetus

Alcohol consumption in any amount by pregnant women cannot be considered safe for the fetus. Although a causal linkage between the quantity and duration of alcohol consumption, phase of pregnancy, and fetotoxic effect has not yet been established, there is no room for doubt that the concept of low risk and responsible drinking does not apply to pregnant women. The fetus is safest when the mother abstains from drink. However, it is estimated that more than 10 percent of women choose to continue drinking during pregnancy.

When alcohol is consumed, it is absorbed into the bloodstream through the digestive tract, and acetaldehyde is formed mainly by the oxidation of alcohol dehydrogenase (ADH) in the liver. Then acetaldehyde dehydrogenase (ALDH) converts this acetaldehyde to acetic acid. Acetic acid undergoes several and complex routes, and is finally broken down into H2O and CO2 which are discharged to the outside of the body.

The alcohol metabolism of a pregnant woman is much depressed compared with that of a non-pregnant woman, as estrogens largely inhibit the activity of ADH and ALDH, especially estradiol, one of three principle forms of estrogens, which has the strongest effect. Moreover, the total amount of estrogens in the serum of a pregnant woman in the early stages of pregnancy will increase by 10 - 100 times compared to that of a non-pregnant woman, and in mid to late pregnancy, increase by 100 - 1000 times. This affects the alcohol metabolism of a pregnant woman, and each of the three main estrogens exhibit relatively more volatility.

In terms of the alcohol metabolism in the body, there is no feedback mechanism and the metabolic rate is stable, 7g per hour. Generally, each of one medium size of bottle of beer (500ml), one goh of Japanese sake (180ml), two glasses of wine (240ml), two fifth goh of shochu (distilled spirit, 70ml), or one double whisky or brandy (60ml) contains 20g of alcohol. Therefore, the time required for the completion of alcohol metabolism when several kinds of alcohol are consumed can be estimated by dividing the total amount of alcohol consumption (g) by 7g. For a pregnant woman, this estimated time should be multiplied by 1.5. For example, when a person drinks one medium bottle of beer and two goh of Japanese sake, total amount of alcohol consumed will be 20g + (two goh × 20g) = 60g. Thus the required time for alcohol metabolism for this person will be 60g / 7g = 8.6 hours, and in case of pregnant woman, 8.6 × 1.5 = 13 hours.

A pregnant woman is physiologically in a state of dynamic equilibrium along with the development of fetus, therefore, her condition places her at a disadvantage for the efficient metabolism of alcohol. ADH can be found in a fetal liver from the middle of the third month of pregnancy, and its activity will slightly linear increase; nonetheless, a fetus has almost no capacity to break down alcohol. In addition, a low molecular weight alcohol passes swiftly through the placenta and harms a developing fetus. Fifty percent of the alcohol crossing the placenta enters the bloodstream of the fetus, and the remaining 50% enters the circulatory system via the fetal liver. While alcohol remains in the bloodstream, the fetus, so to speak, continues being forced to consume alcohol by the mother.

II. A congenital anomaly (Fetal Alcohol Syndrome: FAS)

Forty percent of pregnant women addicted to alcohol give birth to a baby with Fetal Alcohol Syndrome (FAS). In Japan, Dr. Takashima and others presented the first case in 1978. Both FAS as well as FAE (Fetal Alcohol Effects, incomplete features of FAS) are considered to be caused mainly by the direct action of alcohol (ethanol). There are also cases of suspected FAS (potential group) without any apparent symptoms. Three main diagnostic terms are used to describe babies associated with FAS caused by prenatal exposure to alcohol: facial abnormalities, dysfunction of the central nervous system, and retardation of growth.

Dr. Rosett standardized the diagnostic criteria(1) for FAS as shown below;

  1. Prenatal and/or postnatal growth deficiency, if any one or more of weight, length, or head circumference are below the 10th percentile.

  2. Central nervous system (CNS) disorders, including at least one of the following: neurological abnormality, developmental delay, and intellectual impairment.

  3. A distinctive pattern of facial anomalies, including at least any two of microcephalia; microphthalmia and /or short palpebral fissures (eye slits); an indistinct philtrum; a thin upper lip; and an elongated, flattened midface (the zone between the nose and the mouth).

If symptoms are found in all of 1, 2, 3 categories above, the baby is suspected to have FAS, and if symptoms are found in any of 1, 2, 3 categories, then suspected to have FAE. Meanwhile, Dr. Streissguth (2000) proposed the concept of Fetal Alcohol Spectrum Disorder (FASD), a continuum of permanent birth defects caused by maternal consumption of alcohol during pregnancy.

In Japan, the estimated rate of FAS at birth was 1 per 1,000 births 30 years ago, and the current rate must be lower than 10% of that. However, this rate may vary considerably depending on the living standard of local communities.

A fetus by the 8th week of pregnancy is still called an embryo. This embryonic period is the critical time when the fetal organs are most susceptible to the development of major abnormalities caused by the fetotoxic effect of alcohol. Susceptibility to alcohol regarding whole organs or a part shows individual variability. Thalidomide, a notorious sleep-inducing drug, causes birth defects if a pregnant woman takes the drug at a certain stage of the embryonic period (34th - 50th day after the first day of the last menstrual period). In contrast, alcohol exposure can cause damage to fetus at all stages of in utero development. The effects of fetal toxicity on development of the fetal organs occur mainly at the early stage of pregnancy including the embryonic period, and on the entire growth of the fetus at the period of mid to late pregnancy. Thus, it can be said that FAS (FAE) is embryopathy and at the same time, fetopathy. FAS is not an accidental disease; this is just the tip of the iceberg, below the surface there are enormous hidden problems.

More specifically, the embryo or fetus in a pregnant woman who continues drinking will sustain fatal damage and miscarry as a process of natural selection. However, if this damage is limited and not fatal to the embryo or fetus, it will remain in the womb due to the anti-miscarriage effect of alcohol and continue to develop. Nevertheless, the development of the entire fetus will be inhibited if the mother continues drinking. As a result, some babies are born with clinically evident congenital abnormalities (FAS) and some with several suspected abnormalities but no apparent symptoms.


III. Prenatal treatment

In the light of recent advances in testing techniques and instrumentation such as an ultrasonotomography, it seems that prenatal treatment(2) has some potential for a fetus exposed to alcohol, but is still unrealizable today. For a baby born with a congenital anomaly, this means receiving appropriate child-care. A Fetal Alcohol Syndrome Screening test (FAST)(3) (Table 1) can be used for embryo screening. However, this test should be practiced to help determine risk for abnormalities of a fetus or newborn baby, but never in order to recommend an induced abortion. It is useful to refer to FAST to prepare the specific instruments for parturition in advance, because a pregnant woman who drinks alcohol quite often needs an obstetric operation during the intrapartum period.(4) FAST data can be applied as reference after childbirth as well. There is also the problem drinking screening chart for pregnant women as shown below(5) (Figure 1), a combination of the FAST method and the Kurihama Alcoholism Screening Test (KAST)(6) (Table 2) to be used at the time of pregnancy or labor.

While the problem drinking screening chart for pregnant women(5) will identify the alcoholic pregnant woman, the DSM-IV, an alcohol dependence diagnosis, defines alcohol abuse as follows (quote Higuchi's chart(7) in part).

Alcohol use with clinically significant impairment is indicated by at least three of the following seven items within any one-year period: 1. tolerance; 2. withdrawal; 3. loss of the ability to have control over drinking; 4. unsuccessful attempts or desire to reduce or control drinking; 5. great deal of time spent drinking or recovering from drinking; 6. decrease in social, occupational, or recreational activities that are not centered on drinking; 7. resistance to negative reinforcement.

The typical process of becoming an alcoholic is considered as follows: first-time drinking --> occasional drinking --> habitual drinking --> wider repertoire of drinks (succumb to any kind of alcohol) --> search for alcohol (find out and drink even hidden alcohol) --> become a strong drinker --> repeat withdrawals --> drink alcohol to avoid withdrawals --> intense desire to drink --> abnormal drinking (continuous drinking).

<Figure 1>


<Table 1>

<Table 2>


1)Rosett, H.L.(1980): A clinical perspective of the fetal alcohol syndrome. Alcoholism., 4: 119

2)Yoichi Niimi (1990): Prenatal treatment for fetal alcohol syndrome - Present condition of approach to prenatal treatment, Research on medical care for alcoholic, 7:45

3)Yoichi Niimi, Taro Matsumura, et al. (1989): FAS screening test for fetus and new-born baby (FAST) by diagnostic process with an interview with the patient, Research on medical care for alcoholic, 6:207

4)Yoichi Niimi (1975): Statistical considerations in women with alcohol preference in child birth, Obstetrics and gynecology, 42:9

5)Yoichi Niimi (1994): Pregnant women and drinking alcohol, Gynecology medical treatment, 68:773

6)Saito, S., Ikegami, N. (1978): KAST (Kurihama Alcoholism Screening Test) and its applications, Japan J. Stud. Alcohol., 13:229

7)Susumu Higuchi (2003): An introduction to alcohol addiction, Separate volume, Psychiatric syndrome III, Nippon Rinsho, 405

The Chemical Breakdown of Alcohol

The chemical name for alcohol is ethanol (CH3CH2OH). The body processes and eliminates ethanol in separate steps. Chemicals called enzymes help to break apart the ethanol molecule into other compounds (or metabolites), which can be processed more easily by the body. Some of these intermediate metabolites can have harmful effects on the body.

Most of the ethanol in the body is broken down in the liver by an enzyme called alcohol dehydrogenase (ADH), which transforms ethanol into a toxic compound called acetaldehyde (CH3CHO), a known carcinogen. However, acetaldehyde is generally short-lived; it is quickly broken down to a less toxic compound called acetate (CH3COO-) by another enzyme called aldehyde dehydrogenase (ALDH). Acetate then is broken down to carbon dioxide and water, mainly in tissues other than the liver.

Acetaldehyde: a toxic byproduct—Much of the research on alcohol metabolism has focused on an intermediate byproduct that occurs early in the breakdown process—acetaldehyde. Although acetaldehyde is short lived, usually existing in the body only for a brief time before it is further broken down into acetate, it has the potential to cause significant damage. This is particularly evident in the liver, where the bulk of alcohol metabolism takes place (4). Some alcohol metabolism also occurs in other tissues, including the pancreas (3) and the brain, causing damage to cells and tissues (1). Additionally, small amounts of alcohol are metabolized to acetaldehyde in the gastrointestinal tract, exposing these tissues to acetaldehyde’s damaging effects (5).

In addition to its toxic effects, some researchers believe that acetaldehyde may be responsible for some of the behavioral and physiological effects previously attributed to alcohol (6). For example, when acetaldehyde is administered to lab animals, it leads to incoordination, memory impairment, and sleepiness, effects often associated with alcohol (7).

On the other hand, other researchers report that acetaldehyde concentrations in the brain are not high enough to produce these effects (7). This is because the brain has a unique barrier of cells (the blood–brain barrier) that help to protect it from toxic products circulating in the bloodstream. It’s possible, however, that acetaldehyde may be produced in the brain itself when alcohol is metabolized by the enzymes catalase (8,9) and CYP2E1 (10).


Regardless of how much a person consumes, the body can only metabolize a certain amount of alcohol every hour (2). That amount varies widely among individuals and depends on a range of factors, including liver size (1) and body mass.

In addition, research shows that different people carry different variations of the ADH and ALDH enzymes. These different versions can be traced to variations in the same gene. Some of these enzyme variants work more or less efficiently than others; this means that some people can break down alcohol to acetaldehyde, or acetaldehyde to acetate, more quickly than others. A fast ADH enzyme or a slow ALDH enzyme can cause toxic acetaldehyde to build up in the body, creating dangerous and unpleasant effects that also may affect an individual’s risk for various alcohol-related problems—such as developing alcoholism.

The type of ADH and ALDH an individual carries has been shown to influence how much he or she drinks, which in turn influences his or her risk for developing alcoholism (11). For example, high levels of acetaldehyde make drinking unpleasant, resulting in facial flushing, nausea, and a rapid heart beat. This “flushing” response can occur even when only moderate amounts of alcohol are consumed. Consequently, people who carry gene varieties for fast ADH or slow ALDH, which delay the processing of acetaldehyde in the body, may tend to drink less and are thus somewhat “protected” from alcoholism (although, as discussed later, they may be at greater risk for other health consequences when they do drink).

Genetic differences in these enzymes may help to explain why some ethnic groups have higher or lower rates of alcohol-related problems. For example, one version of the ADH enzyme, called ADH1B*2, is common in people of Chinese, Japanese, and Korean descent but rare in people of European and African descent (12). Another version of the ADH enzyme, called ADH1B*3, occurs in 15 to 25 percent of African Americans (13). These enzymes protect against alcoholism (14) by metabolizing alcohol to acetaldehyde very efficiently, leading to elevated acetaldehyde levels that make drinking unpleasant (15). On the other hand, a recent study by Spence and colleagues (16) found that two variations of the ALDH enzyme, ALDH1A1*2 and ALDH1A1*3, may be associated with alcoholism in African-American people.

Although these genetic factors influence drinking patterns, environmental factors also are important in the development of alcoholism and other alcohol-related health consequences. For example, Higuchi and colleagues (17) found that as alcohol consumption in Japan increased between 1979 and 1992, the percentage of Japanese alcoholics who carried the protective ADH1B*2 gene version increased from 2.5 to 13 percent. Additionally, despite the fact that more Native American people die of alcohol-related causes than do any other ethnic group in the United States, research shows that there is no difference in the rates of alcohol metabolism and enzyme patterns between Native Americans and Whites (18). This suggests that rates of alcoholism and alcohol-related problems are influenced by other environmental and/or genetic factors.


Alcohol metabolism and cancer—Alcohol consumption can contribute to the risk for developing different cancers, including cancers of the upper respiratory tract, liver, colon or rectum, and breast (19). This occurs in several ways, including through the toxic effects of acetaldehyde (20).

Where Alcohol Metabolism Takes Place

Alcohol is metabolized in the body mainly by the liver. The brain, pancreas, and stomach also metabolize alcohol.

Many heavy drinkers do not develop cancer, and some people who drink only moderately do develop alcohol-related cancers. Research suggests that just as some genes may protect individuals against alcoholism, genetics also may determine how vulnerable an individual is to alcohol’s carcinogenic effects (5).

Ironically, the very genes that protect some people from alcoholism may magnify their vulnerability to alcohol-related cancers. The International Agency for Research on Cancer (21) asserts that acetaldehyde should be classified as a carcinogen. Acetaldehyde promotes cancer in several ways—for example, by interfering with the copying (i.e., replication) of DNA and by inhibiting a process by which the body repairs damaged DNA (5). Studies have shown that people who are exposed to large amounts of acetaldehyde are at greater risk for developing certain cancers, such as cancers of the mouth and throat (5). Although these individuals often are less likely to consume large amounts of alcohol, Seitz and colleagues (5) suggest that when they do drink their risk for developing certain cancers is higher than drinkers who are exposed to less acetaldehyde during alcohol metabolism.

Acetaldehyde is not the only carcinogenic byproduct of alcohol metabolism. When alcohol is metabolized by CYP2E1, highly reactive, oxygen-containing molecules—or reactive oxygen species (ROS)—are produced. ROS can damage proteins and DNA or interact with other substances to create carcinogenic compounds (22).

Fetal Alcohol Spectrum Disorder (FASD)—Pregnant women who drink heavily are at even greater risk for problems. Poor nutrition may cause the mother to metabolize alcohol more slowly, exposing the fetus to high levels of alcohol for longer periods of time (23). Increased exposure to alcohol also can prevent the fetus from receiving necessary nutrition through the placenta (24). In rats, maternal malnutrition has been shown to contribute to slow fetal growth, one of the features of FASD, a spectrum of birth defects associated with drinking during pregnancy (23). These findings suggest that managing nutrition in pregnant women who drink may help to reduce the severity of FASD (25).

Alcoholic liver disease—As the chief organ responsible for the breakdown of alcohol, the liver is particularly vulnerable to alcohol metabolism’s effects. More than 90 percent of people who drink heavily develop fatty liver, a type of liver disease. Yet only 20 percent will go on to develop the more severe alcoholic liver disease and liver cirrhosis (26).

Alcoholic pancreatitis—Alcohol metabolism also occurs in the pancreas, exposing this organ to high levels of toxic byproducts such as acetaldehyde and FAEEs (3). Still, less than 10 percent of heavy alcohol users develop alcoholic pancreatitis—a disease that irreversibly destroys the pancreas— suggesting that alcohol consumption alone is not enough to cause the disease. Researchers speculate that environmental factors such as smoking and the amount and pattern of drinking and dietary habits, as well as genetic differences in the way alcohol is metabolized, also contribute to the development of alcoholic pancreatitis, although none of these factors has been definitively linked to the disease (27).


Researchers continue to investigate the reasons why some people drink more than others and why some develop serious health problems because of their drinking. Variations in the way the body breaks down and eliminates alcohol may hold the key to explaining these differences. New information will aid researchers in developing metabolism-based treatments and give treatment professionals better tools for determining who is at risk for developing alcohol-related problems.


(1) Edenberg, H.J. The genetics of alcohol metabolism: Role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Research & Health 30(1):5–13, 2007. (2) National Institute on Alcohol Abuse and Alcoholism.Alcohol Alert: Alcohol Metabolism. No. 35, PH 371. Bethesda, MD: the Institute, 1997 (3) Vonlaufen, A.; Wilson, J.S.; Pirola, R.C.; and Apte, M.V. Role of alcohol metabolism in chronic pancreatitis. Alcohol Research & Health 30(1):48–54, 2007. (4) Zakhari, S. Overview: How is alcohol metabolized by the body? Alcohol Research & Health 29(4):245–254, 2006. (5) Seitz, H.K., and Becker, P. Alcohol metabolism and cancer risk. Alcohol Research & Health 30(1):38–47, 2007. (6) Deitrich, R., Zimatkin, S., and Pronko S. Oxidation of ethanol in the brain and its consequences. Alcohol Research & Health 29(4):266–273, 2006. (7) Quertemont, E., and Didone, V. Role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol. Alcohol Research & Health 29(4):258–265, 2006. (8) Aragon, C.M.; Rogan, F.; and Amit, Z. Ethanol metabolism in rat brain homogenates by a catalase–H2O2 system. Biochemical Pharmacology 44:93–98, 1992. PMID: 1632841 (9) Gill, K.; Menez, J.F.; Lucas, D.; and Deitrich, R.A. Enzymatic production of acetaldehyde from ethanol in rat brain tissue. Alcoholism: Clinical and Experimental Research 16:910–915, 1992. PMID: 1443429(10) Warner, M., and Gustafsson, J.A. Effect of ethanol on cytochrome P450 in the rat brain. Proceedings of the National Academy of Sciences of the United States of America 91:1019–1023, 1994. PMID: 8302826(11) Hurley, T.D.; Edenberg, H.J.; Li, T.-K. The Pharmacogenomics of alcoholism. In: Pharmacogenomics: The Search for Individualized Therapies. Weinheim, Germany: Wiley–VCH, 2002, pp. 417–441. (12) Oota, H.; Pakstis, A.J.; and Bonne-Tamir, B. The evolution and population genetics of the ALDH2 locus: Random genetic drift, selection, and low levels of recombination. Annals of Human Genetics 68(Pt. 2):93–109, 2004. PMID: 15008789(13) Bosron, W.F., and Li, T.-K. Catalytic properties of human liver alcohol dehydrogenase isoenzymes. Enzyme 37:19–28, 1987. PMID: 3569190(14) Ehlers, C.L.; Gilder, D.A.; Harris L.; and Carr L. Association of the ADH2*3 allele with a negative family history of alcoholism in African American young adults. Alcoholism: Clinical and Experimental Research 25:1773–1777, 2001. PMID: 11781511(15) Crabb, D.W. Ethanol oxidizing enzymes: Roles in alcohol metabolism and alcoholic liver disease. Progress in Liver Disease 13:151–172, 1995. PMID: 9224501(16) Spence, J.P.; Liang, T.; Eriksson, C.J.; et al. Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations. Alcoholism: Clinical and Experimental Research 27:1389–1394, 2003. PMID: 14506398(17) Higuchi, S.; Matsushita, S.; Imazeki, H.; et al. Aldehyde dehydrogenase genotypes in Japanese alcoholics. Lancet 343:741–742, 1994. PMID: 7907720(18) Bennion, L.J., and Li, T.-K. Alcohol metabolism in American Indians and whites: Lack of racial differences in metabolic rate and liver alcohol dehydrogenase. New England Journal of Medicine 294:9–13, 1976. PMID: 1244489(19) Bagnardi, V.; Blangiardo, M.; La Vecchia, C.; and Corrao, G. Alcohol consumption and the risk of cancer: A meta-analysis. Alcohol Research & Health 25(4):263–270, 2001. PMID: 11910703 (20) Koop, D.R. Alcohol metabolism’s damaging effects on the cell: A focus on reactive oxygen generation by the enzyme cytochrome P450 2E1. Alcohol Research & Health 29(4):274–280, 2006. (21) International Agency for Research on Cancer (IARC). Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. In: Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Acetaldehyde No. 77. Lyon, France: IARC, 1999, pp. 319–335. (22) Seitz, H.K., and Stickel, F. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biological Chemistry 387:349–360, 2006. PMID: 16606331(23) Shankar, K.; Hidestrand, M.; Liu, X.; et al. Physiologic and genomic analyses of nutrition-ethanol interactions during gestation: Implications for fetal ethanol toxicity. Experimental Biology and Medicine 231:1379–1397, 2006. PMID: 16946407(24) Dreosti, I.E. Nutritional factors underlying the expression of the fetal alcohol syndrome. Annals of the New York Academy of Sciences 678:193–204, 1993. PMID: 8494262(25) Shankar, K.; Ronis, M.J.J.; Badger, T.M. Effects of pregnancy and nutritional status on alcohol metabolism. Alcohol Research & Health 30(1):55–59, 2007. (26) McCullough, A.J., and O’Connor, J.F. Alcoholic liver disease: Proposed recommendations for the American College of Gastroenterology. American Journal of Gastroenterology 93(11): 2022–2036, 1998. PMID: 9820369 (27) Ammann, R.W. The natural history of alcoholic chronic pancreatitis. Internal Medicine 40(5):368–375, 2001. PMID: 1393404



Source material for this Alcohol Alert originally appeared in a special two-part series of Alcohol Research & Health that examines the topic of alcohol metabolism.

  • Alcohol Research & Health, Vol. 29, No. 4, 2006: This issue describes alcohol’s metabolic pathways, their genetic variation, and the effects of certain byproducts, such as acetaldehyde, on a range of organs and tissues.

  • Alcohol Research & Health, Vol. 30, No. 1, 2007. This issue examines how differences in metabolism may lead to increased or reduced risk among individuals and ethnic groups for alcohol-related problems such as alcohol dependence, cancer, fetal alcohol effects, and pancreatitis.

  • Full-text articles from each issue of Alcohol Research & Health are available on the NIAAA Web site at

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