Alcohol Consumption Triggers Free-Radical Damage In The Body

At levels commonly seen in social drinking, alcohol prompts a sharp increase in corrosive free radical activity in the body, the Penn study demonstrates. Such an increase in oxidant stress could well contribute to the evolution of a wide array of chronic diseases, the scientists say. The experiments also show that the antioxidant vitamin C partially quells the activity of these volatile molecules, potentially limiting the injury to organs and tissues. A report on the findings appears in the September 15 issue of the Journal of Clinical Investigation.

"These findings show that drinking alcohol activates a mechanism that has been implicated in a number of illnesses, including diseases of the liver and the cardiovascular system," says Garret A. FitzGerald, MD, chairman of pharmacology and senior author on the study. "At blood alcohol levels frequently attained in social settings, although above the limit for safe driving, damaging pro-oxidant processes are set in motion."

In healthy volunteers given alcohol in an experimental setting and in abstaining patients being treated for alcohol-induced liver diseases, measures of oxidant stress due to free radicals were significantly elevated.

Ten healthy volunteers were given 0.4, 0.6, and 0.9 g/kg of a 98 percent solution of grain alcohol, which raised their blood alcohol levels, on average, to .08, .10, and .13 g/dl respectively. The volunteers experienced, on average, 69, 289, and 345 percent increases respectively in levels of a biochemical marker of oxidant stress. (For comparison, either .08 or .10 g/dl is the legal limit for driving in most states. To reach a blood alcohol level of .08 g/dl, a 170-lb. man would have to drink more than four beers in one hour, and a 137-lb. woman would have to drink three beers in one hour.)

Patients who had abused alcohol chronically over many years and developed liver cirrhosis also displayed elevations in several markers of oxidant stress. Interestingly, despite having not been exposed to alcohol for a minimum of two weeks - and in most cases longer - prior to the assessment, these patients exhibited levels of the markers that were about ten times higher than those seen in controls. And patients admitted to the emergency room with acute alcohol-induced liver disease had levels that were approximately fifty times higher than those in controls.

"Even in people who were being treated for alcohol-induced liver disease and had stopped drinking at least two weeks prior to our study, we saw elevated levels of free-radical activity," says Emma A. Meagher, MD, an assistant professor of medicine and lead author on the study. "Oxidant stress did not immediately end when the exposure to alcohol ceased. There appeared to be a residual effect of liver damage associated with the alcohol."

When patients with chronic disease were given 2,500 mg of vitamin C for 10 days, they showed roughly 50 percent drops in levels of the marker, suggesting that antioxidant vitamins or drugs may have a contribution to make in treating alcohol-related diseases.

The stable markers of oxidant stress used in the current study were developed and their utility confirmed by FitzGerald and his colleagues in earlier studies. One previous study showed that, like alcohol, cigarette smoking also fuels free radical activity in the body, giving rise to the question of whether excessive alcohol consumption and cigarette smoking - habits often seen in the same individuals - compound each other's effects in their attack on health.

In the future, the markers developed in FitzGerald's laboratory might also form the basis for clinical studies that link free-radical activity in individuals to the development of diseases in those individuals. Because innate antioxidant protections vary from person to person, the results of such studies could reveal a great deal about the underlying role of oxidant stress in alcohol-linked disorders such as high blood pressure and heart disease. The ability of antioxidants to ameliorate the disease process in individuals could also be specifically assessed.

In addition to FitzGerald and Meagher, the other Penn-based authors are Orla P. Barry, PhD, Anne Burke, MD, Michael R. Lucey, MD, and John A. Lawson, BS. Chemist Joshua Rokach, PhD, at the Florida Institute of Technology is also a coauthor. The National Institutes of Health provided primary support for the research.

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