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By Craig Pickering

Earlier this year, I wrote an article entitled “The Genetics of High-Performance Exercise.” It discussed the genetic components of being a sportsperson, as well as responses to exercise. The question “Can my genes determine my nutritional needs?” arose as a result. Here is a follow-up article illustrating how understanding your genes might be useful in two aspects of sports nutrition.

First off is caffeine, a well-established ergogenic aid, especially for endurance athletes. Its use is rife in all levels of sports (except for the NCAA). Caffeine can be so potent that it was banned in competition until WADA decided that policing the ban was nearly impossible.

I’ve experimented with various doses of caffeine to improve my own performance. I started by taking 80mg before a race, and then slowly increasing my dose until I got to the point that my performance was adversely affected. This point occurred at just over 200mg.

I’ve gone as high as 400mg, which was a miserable experience. I suffered from stomach cramps, my ears rang, and my peripheral vision disappeared. I simply couldn’t race. Some of my training partners, however, regularly use pre-race doses of up to 500mg without negative effects. Clearly, how people respond to caffeine reflects individual differences.

Traditional research typically compares the mean of a group exercising with no caffeine to the mean of a group using caffeine. That’s fine if you are the mean of the group. But what if you lie outside the mean? That’s why studies reporting subjects’ individual responses to caffeine are so interesting.

For example, take this study, “Ergogenic Effects of Low Doses of Caffeine on Cycling Performance.” The researchers put subjects through four 15-minute maximum cycle trials. In each trial, subjects either had a placebo or caffeine doses of 1mg/kg of bodyweight, 2mg/kg, and 3mg/kg.

The results show that caffeine supplementation pre-exercise is highly variable. For example, one subject performed worse in all the caffeine trials compared to the placebo. Another subject performed better than the placebo with 1mg caffeine/kg but worse at higher levels. A third found caffeine to be highly ergogenic, performing much better in all the trials.

What could cause these variations? My day job at DNAFit made me aware of a gene called CYP1A2. This gene creates an enzyme that handles over 95% of all caffeine metabolism in the body. A small change in this gene, called a single nucleotide polymorphism (SNP), between individuals results in two different types of people: fast caffeine metabolizers (AA homozygotes) and slow caffeine metabolizers (AC heterozygotes and CC homozygotes).

From a health standpoint, this knowledge can be important. For example, this study examined the interactions between the CYP1A2 genotype, caffeine intake, and the risk of heart attack. Over a ten-year period, researchers spent time in Costa Rica (it’s a hard life!), identifying more than 2,000 heart-attack survivors and 2,000 controls (who hadn’t had a heart attack). They questioned both groups about their coffee intake, using the responses to measure the quantity of caffeine the two groups consumed.

They found that heart attack risk slightly increases with each cup beyond the first. Then the researchers did something very interesting (to me, at least): they split the findings among fast and slow metabolizers. They found that increased risk of heart attack with higher coffee intakes essentially disappears among fast metabolizers. But among slow metabolizers, the risk becomes even greater with higher levels.

What does this research tell us about the effects on exercise performance? Unfortunately, there currently isn’t much research in this area. Because nutrigenetics is a fairly new science, the majority of funding goes to people most at risk—the highly obese, type II diabetics, etc. Understanding whether or not the CYP1A2 genotype affects exercise performance isn’t high on lists of priorities, no matter how much I selfishly wish it were.

In fact, I know of only one study looking at the effects of caffeine on exercise performance regarding the CYP1A2 genotype. “The influence of a CYP1A2 polymorphism on the genetic effects of caffeine,” Womack et al. (2012) took 35 male cyclists through two 40km time trials. In one trial, the cyclists took a placebo. In the second, they took 6mg of caffeine per kilogram of bodyweight. Both trials were double-blind—neither the people running the experiment nor the subjects knew whether they were taking the placebo or caffeine. The study found that fast metabolizers had greater performance improvements compared to the placebo than slow metabolizers. On average, the fast metabolizers improved by around 4 minutes with caffeine, compared to less than 1.5 minutes among slow metabolizers. Additionally, almost 95% of fast metabolizers improved by more than a minute compared to the placebo, while only 53% of slow metabolizers had similar improvements.

While this is just one study, it certainly is food for thought. With more research in this area, we might develop specific guidelines for caffeine use in both fast and slow metabolizers. I’m a slow metabolizer, and my experience told me I could tolerate less total caffeine than other people (who I assume were fast metabolizers).

I also found that having caffeine 75 minutes pre-race was better than having it an hour before. This is interesting because 60 minutes is often the time frame used in research and the general recommendation from sports nutritionists. Finally, taking more caffeine between a heat and a final decreased my performance—perhaps taking me over my performance threshold. In the future, athletes may not require this costly trial and error process. Instead, looking at their genes might provide a much better starting point when it comes to caffeine metabolism.

I’d also like to discuss Vitamin D. It was the supplement de jour in 2009 and 2010, so much so that my governing body, UKAthletics, made Vitamin D testing available to its athletes. UKAthletic decided that all athletes should have blood levels above 50nmol/l of Vitamin D, and, in fact, preferred them to be closer to 100nmol/l. So, I had a Vitamin D test in September 2009. It came back with a value of 55nmol/l, very close to the insufficiency cut-off point. I took 5000iu Vitamin D per day (a pretty high dose) and was considered “cured.”

A few years later, I had another Vitamin D test. My levels had increased to 84nmol/l—higher, but still below the 100nmol/l cut-off. However, my training partners had reached and even exceeded this cut-off, even though they were taking the same supplemental doses of Vitamin D as I was.

It turns out that a whole host of genes can affect responses to Vitamin D supplementation. Didriksen et al. (2013) found that supplementation with 40,000iu of vitamin D per week caused different changes in subjects, depending on their versions of these genes. So different people may need to have higher (or lower) amounts of vitamin D supplementation for the same effect.

Is this important? It turns out that polymorphisms in the Vitamin D receptor gene (VDR) may affect stress fracture risk. In this study, the researchers used subjects in the second phase of military training, and who as such were not novice exercisers. They then got 32 stress fracture patients and 32 controls and looked to see if there was any difference in VDR genotypes between them.

They found that carriers of the GG genotype were significantly more likely to be in the control group. Conversely, A-allele carriers were significantly more likely to be in the stress fracture group. This is potentially very useful. We might be able to identify people at risk of a stress fracture, and then provide nutritional (e.g. increased Vitamin D and calcium intakes) and lifestyle interventions to reduce this risk.

So, there you go. Not only do your genes determine how you respond to exercise, they can also have a big effect on your sports nutrition practices. While the research is in its infancy, we should gain further insights into how our genes affect our nutrition needs as time goes on, as well as a response to certain nutrients.

Please share this article so others may benefit.



  • Shane says:

    Whoa, I’ve been finding that my ears can feel pretty funky while training sometimes. I wonder if this has to do with caffeine…

    On a slightly separate note, do you know of a way that a layperson can figure out if they’re a slow or a fast metabolizer?

    Great article 🙂

    • Craig says:

      Hi Shane – glad you liked it! As a general rule of thumb, fast metabolisers can have caffeine later in the day without it affecting their sleep. So, if you have caffeine after 5pm and sleep just fine, you could we be a fast metaboliser.

  • Steven says:

    Hi Craig,

    Great article! Come to think of it, I do feel better on my training runs after eating coffee chocolate truffles!

    Could you share what other supplements do athletes take other than caffeine and vitamin D?

    • Craig says:

      Athletes take just about everything, depending on which nutritionist they are working with, or who sponsors them, or their personal beliefs. I chose caffeine and vitamin D as there is a lot of research about that + genes, and because most people take them!

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