Updated: Jan 7, 2020
A few years ago, researchers started to look more closely at the individual variability in response to caffeine. Every study has some more or less random scatter in its results: If the average improvement is 3 percent, some people might actually get 6 percent better, while others don’t improve at all. But not all scatter is random.
A few years ago, evidence started to emerge that some people were consistently more likely to benefit from caffeine than others, and some might actually get slower after taking caffeine, based on their genetic profile. The biggest study to date on this topic has just been published in Medicine and Science in Sports and Exercise, and the results are striking.
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. The improvement with the lower dose wasn’t statistically significant.
Here’s what those results looked like, showing the cycling time in minutes on the vertical axis:
(Photo: Medicine & Science in Sports & Exercise)
That’s where these studies usually end: Caffeine works, so go forth and get caffeinated. But in this case, the 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.
Take a look at what happens when you break down the results by genotype:
(Photo: Medicine & Science in Sports & Exercise)
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.
A ton of questions spring from these results. First of all, why the huge difference? The answer, for now, is that we don’t know. The likely explanation is that caffeine has a mix of positive and negative effects in everyone. The positive effects are likely in the brain, leading to a reduced perception of effort. The negative effects, Guest and El-Sohemy speculate, could be a result of blood vessels constricting in response to caffeine, which would impair blood flow to muscles during exercise. Everyone gets the positive boost when they ingest caffeine, but perhaps the negative effects stick around much longer in the slow metabolizers and ultimately outweigh the benefits. That raises the question of how the results might change in an event lasting, say, one minute or, at the opposite end of the spectrum, several hours. We can only be sure that the particular balance of positive and negative effects seen here applies for a duration of (on average) 18 minutes.
In the study group, 49 percent of people were in the AA group. They’re the lucky ones in terms of getting a caffeine boost. Of the rest of the group, 43 percent were AC (slow) and just 8 percent were CC (very slow). This distribution is similar to what’s seen in other studies, suggesting that it’s relatively rare to get negative effects from caffeine but quite common to have no significant effect. Interestingly, there’s apparently no link between this gene and habitual caffeine consumption levels: Your rate of caffeine metabolism isn’t what determines whether you like caffeine.
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