Caffeine actually slows some of us down – genetically.

Outside, that paragon of high-performance science, has some interesting findings from the University of Toronto, where researchers found that caffeine regularly boosts athletic performance – except in people with a particular version of one gene, who get slowed down by it:

The study was conducted by Nanci Guest, a sports dietitian and doctoral candidate at the University of Toronto, and her supervisor Ahmed El-Sohemy, a professor of nutritional science. They put 101 well-trained male (more on that below) athletes from a variety of sports (everything from marathon running to boxing to soccer) through a series of three 10K cycling time trials. Before each one, the athletes received either a placebo, a low dose of caffeine (2 milligrams per kilogram of body weight), or a higher dose (4 mg/kg). If you weigh 150 pounds, that corresponds to either 136 or 272 mg of caffeine. (A typical cup of coffee has 100 to 160 mg of caffeine, and a single NoDoz tablet has 200 mg.)

As expected, caffeine boosted performance. The athletes cycled 3 percent faster with the high dose of caffeine compared to the placebo.

…[T]he researchers also took a spit test to determine which version of a gene called CYP1A2 each subject had. More than 95 percent of the caffeine you drink is metabolized by an enzyme encoded by this gene. People with the AA version of the gene are considered “fast” metabolizers, breaking down the caffeine rapidly. People with the AC or CC version are “slow” metabolizers, with the latter group especially slow, meaning that the caffeine they drink lingers in their bodies for much longer.

In the AA group (the fast metabolizers), caffeine is helpful, and the more the better. They get 4.8 percent faster at the low caffeine dose and 6.8 percent faster at the high caffeine dose. In the CC group (the very slow metabolizers), the pattern is the opposite: The more caffeine they get, the slower they go. At the higher dose, they’re 13.7 percent slower! In the middle AC group, it seems to be pretty much a wash, with no significant difference either way.

Another interesting wrinkle is that the effects of caffeine metabolism aren’t limited to athletic performance. In previous work, El-Sohemy and his colleagues showed that fast metabolizers have a lower risk of heart attack if they drink one to three cups of coffee a day, perhaps thanks to its antioxidants and other health-promoting elements. In contrast, slow metabolizers have a 36 percent increase in heart attack risk if they drink two to three cups of coffee a day and a 64 percent increase if they drink four cups or more.

It’s also important to note that the subjects in this study were all male. In theory, El-Sohemy says, they would expect to see similar results in female athletes, and the researchers hope to extend the findings to women in a separate study. There’s some evidence that hormonal contraceptives can affect the activity of the caffeine metabolism enzyme, which raises the possibility that there might be some subtle effects related to the female hormonal cycle.

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You can read the study over here, in Medicine and Science in Sports and Exercise.