Alcohol Metabolism Could Be Key to Alcohol's Dangers

BAC Metabolism Chart
NIAAA

Why do some people drink more alcohol than others? Why do some drinkers develop serious health problems because of their drinking while others do not?

Heavy drinking increases the risk for a variety of negative health consequences—alcoholic liver disease and cancer, for instance. But some drinkers seem to be at a greater risk for developing these problems than others.

Researchers believe the difference may involve how the body breaks down and eliminates alcohol—which can vary widely from individual to individual, depending on a variety of factors.

How Fast Is Alcohol Metabolized?

No matter how much alcohol a person consumes, the body can only metabolize a certain amount every hour. The chart shown above shows the average time it took eight fasting adult males to return to a zero blood-alcohol content level after rapidly consuming 1 to 4 standard drinks.

The chart shows that those who drank only one drink recorded a BAC of 0.00 in just over two hours later. Those who had four drinks during the first hour did not return to a 0.00 blood alcohol concentration (BAC) until seven hours later.

That's because the body can break down so much alcohol and eliminate it from the bloodstream per hour. The times shown in the chart are averages; the time each individual takes to metabolize alcohol can vary widely. But in all cases, alcohol is metabolized more slowly than it is absorbed.

The Metabolism of Alcohol

When alcohol is consumed it is absorbed into the blood from the stomach and intestines. Then enzymes—body chemicals that break down other chemicals—begin to metabolize the alcohol.

Two liver enzymes—alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)‐begin to break apart the alcohol molecule so that it can eventually be eliminated from the body.

ADH helps convert the alcohol to acetaldehyde. The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol to acetaldehyde.

A Highly Toxic Carcinogen

Acetaldehyde is only in the body for a short time because it is rapidly converted to acetate by other enzymes. The acetate is further broken down into water and

Although acetaldehyde is present in the body a short period of time, it is highly toxic and a known carcinogen.

Most of the alcohol is metabolized by the liver as described above, but small amounts are eliminated from the body by forming fatty acid ethyl esters (FAEEs), compounds that have been found to damage the liver and pancreas.

Also, a small quantity of alcohol is not metabolized and is eliminated in the breath and urine. This is how blood-alcohol content is measured in breath and urine tests.

The Dangers of Acetaldehyde

Acetaldehyde can cause significant damage to the liver because that is where most alcohol is broken down into the toxic by-product. However, some alcohol is metabolized in the pancreas and the brain, where acetaldehyde can also damage cells and tissues.

Small amounts of alcohol are metabolized in the gastrointestinal tract, which can also be damaged by acetaldehyde.

Some researchers believe the effects of acetaldehyde go beyond the damage it can cause to tissues, but might also be responsible for some of the behavioral and physiological effects attributed to alcohol.

Is Acetaldehyde Responsible for Impairment?

When researchers administered acetaldehyde to laboratory animals it caused incoordination, memory impairment, and sleepiness.

Other researchers claim it is not possible for acetaldehyde alone to cause these effects because the brain protects itself from toxic chemicals in the blood with its unique blood-brain barrier.

However, when the enzymes catalase and CYP2E1 metabolizealcohol—which only happens when large amounts are consumed—acetaldehyde can be produced in the brain itself.

The Genetics Behind Metabolism

The size of the liver and body mass of the drinker are factors in how much alcohol a person can metabolize in an hour, so therefore the rate at which someone metabolizes alcohol can vary widely.

But, research tells us that the genetic makeup of the individual is probably the most significant factor in how efficiently or not alcohol is broken down and eliminated.

Variations of ADH and ALDH enzymes have been traced to variations in the genes that produce these enzymes. Some people have ADH and ALDH enzymes that work less efficiently than others, while some have enzymes that work more effectively.

Some People Have Less Effective Enzymes

Simply put, this means some people have enzymes that can break down alcohol to acetaldehyde, or acetaldehyde to acetate, more quickly than others.

If someone has a fast-acting ADH enzyme or a slow-acting ALDH enzyme, they can have a toxic acetaldehyde build up in the body, which can create dangerous or unpleasant effects when they drink alcohol.

This can also be a factor in whether are not the person is susceptible to developing alcohol use disorders.

For example, there is one variation of the enzymes that causes a build up of acetaldehyde to the point it causes facial flushing, nausea, and a rapid heart rate. These effects can occur with even moderate alcohol consumption.

Protected Against Developing Alcoholism

Therefore, people with this gene variant—common in people of Chinese, Japanese and Korean descent—tend to drink less because they find drinking alcohol to be an unpleasant experience. Their gene variant has a protective effect for developing alcoholism.

That protective gene, ADH1B*2 is rarely found in people of European and African descent. Another variant, ADH1B*3, is found in 15-25% of African Americans and protects against alcoholism.

However, one study has found variations of the ALDH enzyme, ALDH1A1*2, and ALDH1A1*3, may be associated with alcoholism in African-American people.

It's Not All Genetic

There's no question that alcohol use disorder (AUD) frequently seems to run in families, and genetics unquestionably influences the likelihood of developing AUD. But although research shows that genes are responsible for about half of the risk for AUD, environmental factors, along with gene and environment interactions, are responsible for the remainder of the risk. In other words, environmental factors can play a significant role in the development of AUD.

For example, while research found that Japanese alcoholics who carried the protective ADH1B*2 gene version increased from 2.5 to 13 percent between 1979 and 1992, alcohol consumption in Japan increased significantly.

Furthermore, in the U.S. more Native Americans die of alcohol-related causes than any other ethnic group, but researchers found there is no difference in the enzyme patterns or alcohol metabolism rates of Native Americans and Caucasians, indicating that there are other factors at play in the development of alcohol-related problems.

Health Consequences of Alcohol Consumption

Heavy or chronic alcohol consumption has been linked to a long list of negative health consequences, but some health problems have been directly linked to how alcohol is metabolized in the body and the production of acetaldehyde.

Cancer - The toxic effects of acetaldehyde have been linked to the development of cancers of the mouth, throat, upper respiratory tract, liver, colon, and breast. Ironically, the genes that "protect" some individuals from developing alcoholism may actually increase their vulnerability to developing cancer.

Although they are less likely to drink large amounts of alcohol, these people are at greater risk for developing cancer because their bodies produce more acetaldehyde when they do drink.

Therefore, even some moderate drinkers are a greater risk of developing cancer.

Fetal Alcohol Spectrum Disorder (FASD) - Pregnant women who drink heavily are at greater risk because they may also suffer from poor nutrition. Research has shown that poor nutrition can cause the mother to metabolize alcohol more slowly.

The unborn child can be harmed by the increased exposure to alcohol due to the mother's slow metabolism, and the increased alcohol can prevent the baby from receiving necessary nutrition through the placenta, contributing to slow fetal growth.

Alcoholic Liver Disease - Because the liver is the organ that metabolizes most of the alcohol in the body and therefore where most of the acetaldehyde is produced, it is particularly vulnerable to the effects of alcohol metabolism'. More than 90% of heavy drinkers develop fatty liver.

Alcoholic Pancreatitis - Because alcohol metabolism also takes place in the pancreas, it is exposed to high levels of acetaldehyde and FAEEs. However, less than 10% of heavy drinkers develop alcoholic pancreatitis, indicating that alcohol consumption alone is not the only factor in developing the disease.

Other factors may include smoking, diet, drinking patterns and the differences in how alcohol is metabolized may play a role, but none have been definitively linked to pancreatitis.

Women and Alcohol Metabolism

Women absorb and metabolize alcohol differently from men. Research has shown that women may have less ADH enzyme activity in the stomach, allowing a larger percentage of alcohol to reach the blood before being metabolized.

This could be one factor in women drinkers being more susceptible to alcohol liver disease, heart muscle damage and brain damage than men.

Other Factors that Affect Alcohol Metabolism

Body Weight - Alcohol consumption does not necessarily lead to increased body weight, in spite of its relatively high caloric value. Although moderate alcohol consumption does not lead to weight gain in lean men or women, studies have found that alcohol added to the diets of overweight people does lead to weight gain.

Sex Hormones - In men, alcohol metabolism contributes to testicular injury and impairs testosterone synthesis and sperm production. Prolonged testosterone deficiency may contribute to feminization in males, such as breast enlargement.

In women, alcohol metabolism may cause increased production of estradiol and decreased estradiol metabolism, resulting in increased levels. Estradiol contributes to increased bone density and a reduced risk of coronary artery disease.

Medications - Alcohol consumption affects the metabolism of many different medications, increasing the activity of some and diminishing the effectiveness of others.

Chronic heavy drinking has been found to active the CYP2E1 enzyme, which can change acetaminophen into a toxic chemical that can cause liver damage even when taken in regular therapeutic doses.

Metabolism-Based Treatment of Alcoholism

National Institute on Alcohol Abuse and Alcoholism funded research continues to examine how variations in how the body metabolizes alcohol affect why some people drink more than others and why some develop serious health problems.

Researchers believe how the body breaks down and eliminates alcohol may hold the key to explaining the differences, and continued research may help in developing metabolism-based treatments for drinkers who are at risk for developing alcohol-related health problems.

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