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Healthnotes Newswire (February 22, 2001)—Genes can determine who benefits the most from drinking alcohol, according to a new Physicians’ Health Study report in today’s New England Journal of Medicine.¹

Benefits of alcohol? While consumption of alcohol increases the risk of vehicular accidents, liver disease, and various cancers, and can lead to alcoholism in some people and increased blood pressure in others, most research shows that light drinkers, on average, live longer than teetotalers. The reason is that consumption of alcohol reduces the risk of heart disease—the most common cause of death in Americans. This protection occurs at least in part because alcohol is a blood thinner and increases the level of HDL—the “good” cholesterol. Until today’s report, however, scientists did not understand why light drinking seemed to protect some people but not others.

The researchers looked at people with three variations of genes that regulate formation of alcohol dehydrogenase type 3 (ADH3), an enzyme needed by the body to process alcohol. People with one particular genetic variation who drank at least one alcoholic beverage per day, were found to have an 86% lower risk of suffering a heart attack compared with those who consumed less alcohol. Of the three genetic variations studied, the most protective variation was the least common (seen in only 15% of the people studied). Nonetheless, consumption of at least one drink per day in both of the other groups with more common variations of this gene was associated with approximately a one-third reduction in the risk of heart attacks compared with people consuming less alcohol.

These findings make sense to researchers, because the genes in question—ADH3 γ₁ and γ₂ (pronounced “gamma-one” and “gamma-two”)—affect how quickly the ADH3 enzyme processes alcohol. People with the genetic variant associated with the greatest protection—ADH3 γ_2, γ₂—process alcohol slower than do other people, allowing alcohol to work its protective effects within the body for a longer period of time. At least part of this special protection resulted from the fact that light drinkers with this genetic variation had the highest levels of HDL cholesterol of any group studied.

The findings of the new report advance scientists a major step forward in understanding the relationship between light consumption of alcohol and prevention of heart disease. Some researchers had previously suggested that the often-found association between light drinking and a reduced risk of heart disease might be due to something other than the alcohol itself—for example, alcohol consumption might only be a marker for socioeconomic or lifestyle factors truly responsible for the reduced risk of heart disease. The findings of the new report strongly suggest that alcohol itself causes a reduction in the risk of heart disease, because people who maintain alcohol blood levels for the longest period of time are the ones who experience the greatest level of protection.

Despite the dramatic reduction in the risk of heart attacks experienced by people with the ADH3 γ_2, γ₂ variant who had at least one drink per day, the take-home message from this report remains unclear for two reasons: first, most laboratories do not perform the genetic test needed to determine which group a person is in; second, while the protective effects of light alcohol consumption were dramatic in one group, they were impressive in all groups. Therefore, even in the absence of genetic testing, people at risk of heart disease should talk with their doctor or a cardiologist about the pros and cons of drinking alcohol.

Heart disease risk is elevated in overweight people and in people with a family history of heart disease, diabetes, elevated cholesterol levels, a history of smoking, or in people who have had a previous heart attack. Even among these people, however, many should probably not drink—particularly those with hypertension, liver disease, a personal or family history of alcoholism, or a high risk of breast or gastrointestinal cancers.