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Self-Regulating Coffee Drinkers?

March-April 2015

Illustration by Wesley Bedrosian

Could genetic code determine someone’s Starbucks habit? Apparently so, according to a new study by researchers at the Harvard T.H. Chan School of Public Health (HSPH). Their data suggest that people instinctively regulate their coffee intake in order to experience the optimal effects of caffeine.

Produced with the support of the Coffee and Caffeine Genetics Consortium and published in the journal Molecular Psychiatry this past fall, the study—one of several recent HSPH investigations of the popular beverage—involved a meta-analysis of genomic data from more than 120,000 regular coffee drinkers of European and African ancestry. The researchers analyzed their subjects’ genetic makeup through DNA sequencing, and compared those results to self-reported coffee-drinking figures, in an effort to understand why some people need more of the stimulant than others to feel the same effect.

Lead author Marilyn Cornelis, a former research associate in the HSPH nutrition department who is now assistant professor in preventive medicine at Northwestern, says their findings provide insight not only on why caffeine affects people differently, but also on how these effects influence coffee-drinking behavior. One individual, for example, may need three cups of coffee to feel invigorated, while another may need only one. If that one-cup-a-day person consumes four cups instead, Cornelis explains, any jitters or other ill effects that result may discourage that level of consumption in the future.

Given coffee’s widespread consumption, its effects on health have been the subject of continuing interest and debate. The newest edition of The Diagnostic and Statistical Manual of Mental Disorders, for example, lists both caffeine intoxication and withdrawal as disorders. On the other hand, a study released in January by other investigators at HSPH found that drinking up to six cups of coffee a day showed no association with any increased risk of death (including from cancer or cardiovascular disease). “Going back several years…coffee often had a bad rap,” Cornelis says. “I hope to finally account for those genetic variants and possibly other risk factors that might modify our response to coffee or caffeine.”

Her team identified six new genetic variants associated with habitual coffee drinking, including two—POR and ABCG2—related to caffeine metabolism, and another two that may influence the psychological boost and possible physical health benefits of caffeine. The most surprising aspect of the study, Cornelis reports, was the discovery that two genes involved in glucose and lipid metabolism—GCKR and MLXIPL—are also linked for the first time to the metabolic and neurological effects of caffeine.

Another group of researchers at HSPH reported last year that coffee drinkers who increased their average consumption by more than one cup a day during a four-year period had an 11 percent lower risk of type 2 diabetes in the following four years, compared with people who did not change their intake. The study also found that those who decreased their coffee consumption by more than a cup per day increased their type 2 diabetes risk by 17 percent. “We know there’s been a link between coffee and lower risk of type 2 diabetes, as well as between unfiltered coffee and lipid levels, but whether these associations underlie the surprising associations between GCKR and MLXIPL and coffee-consumption behavior is unclear,” Cornelis says. “It’ll be very interesting to follow up on those particular genes in the future.”

A third recent HSPH-affiliated study that tracked 50,000 women for 10 years found that those who drank four or more cups of caffeinated coffee per day were 20 percent less likely to develop depression than nondrinkers. The researchers speculate that long-term coffee drinking may boost the production of “feel good” hormones such as dopamine.

“Coffee is possibly protective,” Cornelis says. Eventually, she hopes to “account for those genetic variants and possibly other risk factors that might modify our response to coffee or caffeine. We know coffee is one of the primary sources of antioxidants of the American diet. If some individuals can metabolize caffeine quickly, then they’re potentially getting rid of the adverse effects of caffeine yet still experiencing the beneficial effects of other coffee constituents.”

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