Is caffeine responsiveness in your genes?

If you’re an athlete, you might consider caffeine in order to improve your performance – at least 75% of athletes do. The effects of caffeine are different from one person to another. You might have experienced this yourself; perhaps you can drink a cup of coffee just before bed, whilst your partner can’t sleep if they consume any caffeine after midday. Recently, researchers have suggested that these effects have a genetic component.

 

Why are the responses to caffeine so individual? Well, as you can no doubt imagine, the answer is complex. The impact of caffeine, both in our daily lives and during exercise, is governed by many different factors. One such factor is the speed by which caffeine is absorbed – for example, caffeine from caffeinated gum tends to be absorbed quicker than caffeine from a sports drink because it is absorbed through the lining of the mouth, as opposed to the stomach. The contents of your stomach can further slow caffeine absorption, with a full stomach reducing absorption rates. But even the same delivery of caffeine can give varying responses between individuals because caffeine breakdown (metabolism) by our bodies differs. This will affect how long caffeine can have its positive (or, if you can’t sleep, negative) effects for. Caffeine can also be more effective when the receptors that caffeine binds to are more abundant or more available.

 

At present, variation in two genes, called CYP1A2 and ADORA2A has been shown to impact the performance enhancing effects of caffeine, although these early results have not been well replicated. These genes cause these effects through slightly different mechanisms. CYP1A2 creates an enzyme (called cytochrome P450) which is responsible for how our bodies break down caffeine, and a small change in this gene can predispose people to be “fast” or “slow” caffeine metabolisers.

 

If you’re a fast metabolizer, then you break down caffeine quicker, so the effects of caffeine should last for a shorter time – which sounds negative, but it may well be that the molecules caffeine is broken down into also improve performance, which means being a fast metaboliser could be useful. A study from 2012 found that fast metabolisers saw a greater performance enhancing effect of 6 mg/kg caffeine than slow metabolisers on a 40km cycle time-trial (1). Whilst these results have been replicated, other studies have shown no effect of this gene on performance enhancement following caffeine, so a definitive answer is not yet possible.

 

The second gene that may affect how much caffeine improves our performance is ADORA2A. This gene encodes for an adenosine receptor. When adenosine binds to this receptor it make us feel tired – not ideal for sport! One of the ways by which caffeine improves our performance is by competing with adenosine for the adenosine receptors. In other words the more caffeine that binds to these receptors, the less adenosine can. As a result, we feel less tired and lethargic. As such, variation in these adenosine receptors may alter have much caffeine improves our performance. A single study, from 2015, has examined this, finding that this gene did impact improvements in performance following caffeine use (2). Variation in this gene might also contribute to increased anxiety or poor sleep with increased caffeine intake, which could also affect sporting performance.

 

But genes aren’t everything, and differences in our environment (a collective term that refers to non-genetic factors) also contribute to the inter-individual response to caffeine use. These include smoking, vegetable intake, menstrual cycle stage, and training status. Differences in how the caffeine is consumed, such as dose, timing, source, all impact how much caffeine improves our performance. Interestingly, those that believe caffeine will enhance their performance see a greater performance enhancing effect during exercise than those who don’t (3).

 

It is therefore clear that a large number of factors impact how much caffeine improves our performance. These fit broadly into three categories; genetic, environmental (i.e. non-genetic) and epigenetic (changes in genetic expression that aren’t caused by changes to the underlying genetic code). This inter-individual variation is so clear and so well replicated – and yet we have very broad, standardized caffeine recommendations: 3-9 mg/kg, taken 60-minutes before. This means there is a mismatch between what we know – the response to caffeine is highly individualized – and what is often preached – a one-size-fits-all recommendation on how to use caffeine in sport.

 

What does this mean to you?

One day, we might be able to use genetic profiling to give us a better idea of how we might respond to caffeine. But in the meantime, it comes down to self-experimentation. If you use caffeine to improve your performance, experiment with different dosages and different timings. Try it in tablet form and as part of a drink. Monitor how it affects you – do you sleep well that night? Are you anxious? This constant self-experimentation and self-assessment carried out in training enables you to select the caffeine strategy best suited to you, as opposed to the current one-size-fits-all recommendations, which are aimed at the average person; and, as we all know, you’re not average.

 

References

  1. Womack CJ, et al. J Int Soc Sports Nutr. 2012;9(1):7.

  2. Loy B, et al. Journal of Caffeine Research 2015;5(2):73-81.

  3. Pickering C, Kiely Are the Current Guidelines on Caffeine Use in Sport Optimal for Everyone? Inter-individual Variation in Caffeine Ergogenicity, and a Move Towards Personalised Sports NutritionJ. Sports Med. 2017 (In Press).

| Craig Pickering (mysportscience)

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