How caffeine could slow you down

A gene that affects how quickly you metabolise caffeine may affect whether it helps or hurts your race times.


by Alex Hutchinson
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Caffeine is the universal performance-booster: it works for all distances, all sports and all people.

At least, that’s what I used to think. But a session at the American College of Sports Medicine annual meeting earlier this month offered a surprising caveat to that blanket statement. Caffeine, it appears, works for many people but is actually counterproductive for some - and the difference depends on a gene variant that determines how quickly you metabolise it.

Data to back this claim up was presented by Nanci Guest, a sports dietitian and Ph.D. candidate at the University of Toronto. In brief, her study involved 100 athletes who completed a blinded series of 10K cycling time trials with either 0, 2, or 4mg of caffeine per kilogram of body weight.

The gene of interest in the study was one called CYP1A2 that, among other things, affects how quickly you metabolise caffeine. In the study, 49 of the athletes had the GG variant of the gene, which results in very rapid caffeine clearance; 8 had the AA variant, which results in very slow caffeine clearance; and the other 43 had the mixed variant, which also results in slow clearance (though not quite as slow as AA).

Overall, the athletes rode 3.5 percent faster on the higher dose of caffeine compared to placebo, a not-quite-statistically-significant improvement that is fairly consistent with previous studies.

But the interesting results came when you break down the results by genotype. The fast metabolisers (GG) rode 1.2 minutes faster; the intermediate/slow metabolisers (GA) rode 0.5 minutes faster (not a statistically significant change); and the slowest metabolisers (AA) rode 2.5 minutes slower.

This data was presented as part of conference talk, so I don’t have an abstract to link to. It’s always worth being cautious about conference data, which hasn’t yet been peer-reviewed.

Still, these results don’t come out of nowhere. Guest’s doctoral supervisor, Ahmed El-Sohemy, also presented a talk at the conference, covering some of the background on research into how genetic variants can affect how we respond to different foods and nutrients - everything from glucose to salt to vitamin C to high-protein diets. (It’s worth noting here that El-Sohemy has founded a company offering personalised nutritional guidance based on genetic tests.)

El-Sohemy presented some interesting data on the caffeine-processing gene, CYP1A2, that I hadn’t been aware of, though some of it is a decade old. There’s a long-running debate about whether drinking lots of coffee raises or lowers your risk of a heart attack. Overall, research suggests there’s little to worry about - but a different story emerges if you break down the results by genotype.

In essence, the picture seems to be that in fast metabolisers, a few cups of coffee a day reduces your risk of heart attack. The working theory is that some of coffee’s other beneficial ingredients, like polyphenols, lower your risks. In these people, caffeine works its mood-boosting magic in the brain and then is cleared out of the body before it can have negative effects. (Once you get up to four-plus cups a day, the caffeine dose is high enough that the apparent benefits start to reverse.)

In slow metabolisers, on the other hand, the caffeine sticks around in the body after it has done its job in the brain, and this ends up raising your heart attack risk if you’re drinking more than two cups a day. I don’t want to overstate the strength of this evidence (you can read more about it in this Washington Post article that criticised a government panel’s blanket recommendation that even five cups of coffee a day is fine for everyone), but it does suggest that the cycling results aren’t totally unexpected.

One interesting point that El-Sohemy made: as in Guest’s study, about half of the general population are fast metabolisers and half are slow (or intermediate). But there’s no apparent difference in coffee consumption between the two groups. Everyone gets a similar buzz from the initial brain response to caffeine, but whether the caffeine is then cleared quickly or slowly from the body doesn’t seem to govern how much we like coffee.

The upshot? Only eight of the 100 people in Guest’s study were in the group that had a major slowdown. Maybe if you’ve experimented with pre-race caffeine, you have a sense of whether or not it helps you - if so, be aware that it might be possible that caffeine helps most people but hurts you. And maybe, if you’re really keen, you’ll want to find out what your genotype is.


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