The brains of chronically heavy drinkers have twice the capacity of those of light drinkers to consume a chemical that may add to impairment and some other effects of alcohol, Yale School of Medicine researchers have found. This added capacity may also increase the vulnerability to alcohol dependence, according to the study, which appears in the Journal of Clinical Investigation.
Researchers studied 14 drinkers. Half of them were what would be considered heavy drinkers, many of them “binge drinkers.” They regularly consumed at least eight drinks a week, and at least four drinks on one of those days. The rest were light drinkers, who consumed less than two drinks per week.
All 14 subjects were given the chemical acetic acid (also called acetate). Normally the body has very little acetate, but when we drink, the liver converts the alcohol to acetate, The chemical is released into the blood and reaches the brain, which uses it for fuel.
The researchers found that the brains of the heavy drinkers were twice as able as those of the light drinkers to consume the acetate, creating a situation where heavy drinkers may adapt to the use of the acetate and have a harder time reducing drinking or quitting.
Normally, the brain relies on blood sugar for fuel, but it can also use other things like acetate. Binge drinking on an empty stomach can drop a person’s blood sugar acutely, and the acetic acid can fill in for the missing fuel, which creates more incentive to keep drinking. Habitual heavy drinkers have an even greater ability to get that extra energy. The acetate effects of binge drinking on the brain may promote dependence, because if people stop drinking, they lose not only the alcohol, but also the acetate. If the brain has adapted to having that chemical around, the drinker may suffer withdrawal symptoms, explain the researchers.
Senior author Graeme Mason, professor of diagnostic radiology and psychiatry at Yale School of Medicine, says that this sets up a dangerous situation. “Acetate as fuel for the brain may sound like a good thing, but heavy drinkers’ brains may adapt to that supply of energy and so have a harder time reducing or quitting drinking. This is consistent with previous research that has shown that the acetate from alcohol can even displace some sugar consumption by the brain.”
“Another potential adaptation also provides a danger for dependence,” Mason added. “When the brain uses acetate for fuel, it creates another chemical called adenosine, which causes drowsiness. Adaptation to that extra adenosine may also make it more difficult to stop drinking.”
Mason says that this new understanding of the cycle of tolerance and withdrawal may provide valuable insight not just into addiction, but into possible therapeutic interventions that can facilitate detoxification. “There may be ways to support early sobriety with acetate or drugs that mimic some effects of acetate, and we need to investigate that with respect to effectiveness, safety, cost, and practicality,” said the Yale scientist. “For the foreseeable future, nothing is going to make it easy to stop drinking. My hope is that we can add to the current measures to make it safer and less uncomfortable to get sober.”
Other authors are Lihong Jiang, Barbara Gulanski, Henk DeFeyter, Stuart Weinzimer, Brian Pittman, Elizabeth Guidone, Julia Koretski, Susan Harman, Ismene Petrakis, and John Krystal of Yale School of Medicine.
The study was supported by grants from the National Institutes of Health (R21 AA018210, R21 AA019803, R01 DA021785); The Yale Clinical and Translational Science Award Grant (UL1 RR024139) from the National Center for Research Resources and the National Center for Advancing Translational Science; and components of the National Institutes of Health and NIH roadmap for Medical Research.
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