Research Links Enzyme to Alcohol’s Effect on Women
In a major advance toward understanding why women are more vulnerable to the effects of alcohol than men, researchers reported today that women appear to have significantly lower amounts of a stomach enzyme that breaks down some of the intoxicant before it circulates through the body.
The report, by researchers from the University School of Medicine in Trieste, Italy, and the Veterans Affairs Medical Center, Bronx, N.Y., also may help explain why women who drink heavily suffer more liver damage than men and why consumption of even small amounts of alcohol during pregnancy can cause serious birth defects.
If the results are confirmed in other studies, health and government officials may need to consider sex differences when defining safe levels of drinking for driving motor vehicles and other activities that demand high degrees of attention or coordination.
“The stomach represents a protective barrier against the penetration of alcohol into the body,” said Dr. Charles S. Lieber, director of the Alcohol Research and Treatment Center at the Bronx center and the senior author of the study, published in today’s New England Journal of Medicine.
The study of 20 men and 23 women shows “that the stomach plays a significant (protective) role in the metabolism of alcohol in men and a less significant and perhaps even negligible role in women,” said Dr. Albert L. Jones, a liver and metabolism expert at the Veterans Administration Medical Center in San Francisco.
For example, if differences in body weight are taken into account, a woman might become legally intoxicated after consuming 20% to 30% less alcohol than a man, Lieber said. If weight differences are not considered, an average-size woman might reach a given blood alcohol level after consuming about 50% less alcohol than a man.
For years, physicians have considered the liver the primary organ in the body for degrading the alcohol that enters the bloodstream. It also has been known that women have higher blood alcohol concentrations than men after drinking equivalent amounts of liquor and that alcoholic liver disease, such as cirrhosis, develops more readily in women than in men.
The greater susceptibility of women than men to the effects of a drink was usually explained by citing the smaller size of many women and a smaller volume of distribution of alcohol, because women’s bodies have relatively more fat and less water than men’s.
The new findings draw attention to an overlooked role for the lining of the stomach in reducing the amount of alcohol that enters the circulation.
Dr. Steven Schenker of the University of Texas in San Antonio, said, “We are dealing essentially with new territory. . . . That is why this is exciting.” Schenker was the co-author of a New England Journal editorial on the study. The editorial called for further study, cautioning that “firm proof” of the decreased protective role of the stomach in women “is lacking and other factors may be operative.”
Several years ago, the Bronx reseachers found that the stomach lining of men contains an enzyme called gastric alcohol dehydrogenase which breaks down alcohol. They then decided to investigate possible sex-related differences in the amount of this enzyme in the body and the effects on the enzyme of heavy alcohol use.
The 14 non-alcoholic men, six alcoholic men, 17 non-alcoholic women and six alcoholic women in the study were examined in two ways--measurement of blood alcohol concentrations and laboratory measurement of the alcohol dehydrogenase enzyme. All the subjects were Italians and none of the women were taking birth control pills, which might have influenced the results.
Lieber said the next steps were performance of similar studies on men and women of various ages, and racial and ethnic groups, as well as consideration of the potential effects of drugs and sex hormones, such as birth control pills, on the stomach’s protective barrier against the penetration of alcohol.
In 37 participants, blood alcohol concentrations were carefully determined after administering both oral and intravenous doses of ethanol. The doses were adjusted for variations in body weight; they were comparable to the amount of alcohol in about 1 1/2 drinks and were given one hour after a “standard” breakfast was eaten. (One drink is usually defined as a 12-ounce beer, a four-ounce glass of wine or a 1 1/2-ounce shot of 80 proof liquor.)
“In both the non-alcoholic and alcoholic groups, women had higher blood ethanol concentrations than men after ingesting an equivalent (weight-adjusted) dose of ethanol,” the report said. In contrast, there were no significant sex-related differences when the ethanol was given intravenously, thereby bypassing the stomach.
After oral ingestions, the alcoholic men had significantly higher blood ethanol concentrations than the non-alcoholic men. In the alcoholic women, the blood ethanol concentrations were even higher, almost identical to the values achieved after the intravenous ethanol doses, suggesting a total lack of protection by the stomach.
Alcoholism results in a “decrease” of the stomach’s protective barrier against alcohol, Lieber said, perhaps explaining the mechanism by which heavy drinkers are at greater risk for liver damage and other alcohol-related health problems. He added: “Alcoholic women have a total loss of this gastric protective mechanism. For an alcoholic woman to drink alcohol is the same thing as taking the same amount of alcohol intravenously.”
In 38 participants, specimens of apparently normal areas of the stomach lining were obtained, usually by endoscopy, a procedure in which a fiberoptic-lighted tube is inserted into the stomach through the mouth.
The activity of the gastric alcohol dehydrogenase enzyme was then measured in the laboratory. The enzyme’s activities were “70 to 80% higher in the non-alcoholic men than in the non-alcoholic women,” and considerably lower in alcoholics than non-alcoholics, the report said.
“When we recommend to the public moderation in drinking, what we should really do is introduce a gender factor,” Lieber said in a telephone interview. “The amount that is moderate in men is not moderate in women.” Lieber said the study results were “an additional reason” for pregnant women to abstain from drinking.
