U.S. Department of Health

& Human Services 

National Institutes of Health 

National Institute on Alcohol Abuse 

and Alcoholism 

Number 72 April 2007 

ALCOHOL METABOLISM:
 AN UPDATE

Drinking heavily puts people at risk for many adverse health 

consequences, including alcoholism, liver damage, and various cancers. But some people appear to be at greater risk 

than others for developing these problems. Why do some 

people drink more than others? And why do some people 

who drink develop problems, whereas others do not? 

Research shows that alcohol use and alcohol-related problems 

are influenced by individual variations in alcohol metabolism, 

or the way in which alcohol is broken down and eliminated 

by the body. Alcohol metabolism is controlled by genetic 

factors, such as variations in the enzymes that break down 

alcohol; and environmental factors, such as the amount of 

alcohol an individual consumes and his or her overall nutrition. Differences in alcohol metabolism may put some people 

at greater risk for alcohol problems, whereas others may be 

at least somewhat protected from alcohol’s harmful effects. 

This Alcohol Alert describes the basic process involved in the 

breakdown of alcohol, including how toxic byproducts of 

alcohol metabolism may lead to problems such as alcoholic 

liver disease, cancer, and pancreatitis. This Alert also describes 

populations who may be at particular risk for problems resulting from alcohol metabolism as well as people who may be 

genetically “protected” from these adverse effects. 

The Chemical Breakdown 

of Alcohol 

Alcohol is metabolized by several processes or pathways. The 

most common of these pathways involves two enzymes— 

alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 

(ALDH). These enzymes help break apart the alcohol mole-

“Differences in alcohol metabolism	 

may put some people at greater risk 

for alcohol problems.” 

Alcohol
 

dehydrogenase
 

Ethanol Acetaldehyde Acetate

H3C-CH2-OH H3C-CH=O H3C-COO –

Aldehyde 

Catalase dehydrogenase (peroxisomes)
 (mitochondria)
 

P4502E1 

(microsomes) 

cule, making it possible to eliminate it from the body. First, 

ADH metabolizes alcohol to acetaldehyde, a highly toxic substance and known carcinogen (1). Then, in a second step, 

acetaldehyde is further metabolized to another, less active 

byproduct called acetate (1), which then is metabolized into 

water and carbon dioxide for easy elimination (2). 

Other enzymes—The enzymes cytochrome P450 2E1 

(CYP2E1) and catalase also break down alcohol to acetaldehyde. 

However, CYP2E1 only is active after a person has consumed 

large amounts of alcohol, and catalase metabolizes only a 

small fraction of alcohol in the body (1). Small amounts 

of alcohol also are removed by interacting with fatty acids 

to form compounds called fatty acid ethyl esters (FAEEs). 

These compounds have been shown to contribute to damage 

to the liver and pancreas (3). 

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 

etabolism 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). 

bulk of alcohol m
The Chemical Breakdown of Alcohol 

ADH CH3CHO ALDH CH3COO– CH3CH2OH Acetaldehyde Acetate 

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. 

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). 

The Genetics Behind 

Metabolism 

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 alcoholrelated 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 alcoholrelated 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.

“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.” 

2
 
 

 

 

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. 

“The very genes that protect 

some people from alcoholism 

may magnify their vulnerability 

to alcohol-related cancers.”
 

Health Consequences of 

Alcohol Use 

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. 

esophagus

stomach

liver

pancreas

brain

Many heavy drinkers do not develop cancer, and some 

people who drink only moderately do develop alcoholrelated 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 

3
 
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). 

Conclusion 

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 

TRENDS IN RESEARCH
 

Investigators are studying factors that influence alcohol metabolism, such as variations in the study subjects’ gender 

and ethnicity, genetic variations in alcohol-metabolizing enzymes, and even the food subjects consumed that day. Two 

methods that are helping researchers gain a better understanding of how alcohol is metabolized are the alcohol clamp 

method, in which alcohol is given intravenously, and the use of specially grown cells. 

The alcohol clamp method. The speed at which people absorb, distribute, and metabolize alcohol varies as much as 

three or four times between individuals (1,2). The alcohol clamp is a method of administering alcohol intravenously 

to subjects, allowing researchers to circumvent variations in alcohol absorption. This technique enables researchers to 

administer precise doses of alcohol to achieve an exact breath alcohol concentration (a measure of how much alcohol 

is in the body) (3,4). The actual dose of alcohol is calculated for each individual based on his or her specific alcohol 

elimination rate, controlling for factors like gender and body mass. This allows researchers to compare the alcohol 

elimination or metabolism rates without complicating factors. For example, using the alcohol clamp method researchers 

were able to determine that male volunteers eliminated alcohol at significantly faster rates than did female volunteers (5–8). The alcohol clamp method also helps researchers study the genetics of alcohol metabolism, including 

differences in how volunteers who carry different versions of the ADH and ALDH genes metabolize alcohol (9). 

Cultured cells. Cells that are grown in the laboratory (i.e., cultured cells) are an important tool in studying how alcohol 

damages the liver on a molecular level. Cultured cells can help to clarify the processes associated with alcohol metabolism 

that damage cells by allowing researchers to investigate individual metabolic pathways; to control the cells’ exposure to 

alcohol and its byproducts; and to work with uniform, or cloned, cells (10). Additionally, because large quantities of 

cells can be cloned, researchers are able to repeat experiments many times in order to confirm findings. 

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4
 
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tools for determining who is at risk for developing alcoholrelated problems. 

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5
 
R e s o u r c e s 

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 Volume 29, Number 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 Volume 30, Number 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 http://www.niaaa.nih.gov. 

Subscriptions to Alcohol Research & Health are available from the Superintendent 

of Documents for $25.Write to New Orders, Superintendent of Documents, 

P.O. Box 371954, Pittsburgh, PA 15250–7954; or fax 202/512–2250. 

Full text of this publication is available on NIAAA’s World Wide Web site at www.niaaa.nih.gov. 

All material contained in the Alcohol Alert is in the public domain and may be used or reproduced 

without permission from NIAAA. Citation of the source is appreciated.
 

Copies of the Alcohol Alert are available free of charge from the National Institute on Alcohol Abuse and Alcoholism
 

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