DNA could explain why your body reacts to caffeine in a unique way

Caffeine is used by many high-performance athletes to increase focus and energy. Its use has expanded since 2004, when it was removed from the World Anti-Doping Agency prohibited substances list. Whether it’s a strong cup of coffee, or a specialized supplement, caffeine is an important tool in the belt of pro athletes and coaches.

Will caffeine give you the added boost you need? Scientists say that this may depend on your DNA. Athletes may experience different reactions to caffeine intake. One may notice a boost in performance – a faster time or the ability to keep fatigue at bay for longer – while another may not feel these benefits at all.

Scientists studying the effect of caffeine in athletes noticed these individual differences in performance enhancement after caffeine consumption, and their observations prompted some sports research groups to explore the genetic contribution to caffeine metabolism in athletes. The genetics of caffeine metabolism has undergone significant study in a variety of settings, identifying the CYP1A2 gene, specifically the rs762551 marker, as the main gene of interest due to its role in caffeine metabolism. In athletes, researchers discovered that those with certain gene variants may react differently to caffeine intake. This genetic information, in the context of an athlete’s daily diet and caffeine intake, can help both high-performers and fitness enthusiasts capitalize on the effects of caffeine though the development of a customized diet.

The CYP1A2 gene produces one of the most important drug metabolizing enzymes, responsible for metabolizing the majority of caffeine in your liver. Certain variants of this gene may result in slower or faster caffeine metabolism, due to varying levels of gene activity.

The faster a person’s caffeine metabolism rate, the lower their sensitivity to its effects, and vice versa.

What’s the current state of research?

Recent studies have examined the effect of caffeine on performance in exercise testing. Both short-duration, high-intensity and long-distance, endurance performance was affected by caffeine intake. However, certain studies noted individual differences in the level of performance enhancement following caffeine intake.

Researchers hypothesized that these individual differences could be due to subjects’ genetic foundation – specifically, their variant of the rs762551 marker on the CYP1A2 gene, an important gene in caffeine metabolism that has been the focus of many studies investigating drug interactions, heart disease, and even psychology.

To investigate the association between genetic type and performance enhancement from caffeine, researchers took DNA from trained cyclists and put them through their paces in a standardized time-trial test. Their findings suggest that individuals with a CC or AC genotype tend to have a higher sensitivity to caffeine than those with the AA genotype.

The lower caffeine sensitivity is due to a more active form of the CYP1A2 enzyme, which breaks down caffeine at a faster rate. Slow metabolizers (AC and CC genotypes) tend to experience more pronounced and longer lasting stimulant effects from caffeine compared to fast metabolizers (AA genotype).

Athletigen reports each marker with a letter grade for scientific confidence. The confidence grade is determined by several factors: the number of studies that replicated the same findings, the population size of each study, and the ethnic diversity in which the association has been studied. The rs762551 marker of the CYP1A2 received a “B” rating as further study is needed in large, multi-ethnic populations.

How does this affect my training?

It’s important to note that too much caffeine can have a detrimental effect on your health, regardless of genotype. Adults are advised to not exceed 400mg of caffeine per day, which is about three 8 oz cups of brewed coffee.

Low Sensitivity – A low sensitivity to caffeine it means the energy boost provided by pre-workout caffeine might not last as long, or be as pronounced during training or competition. If an athlete with a low sensitivity or caffeine wants to use it as a performance aid, they may want to consider only taking it when needed or limiting their use in order to reduce caffeine tolerance and increase sensitivity.

To maintain a caffeine boost during an athletic event, an athlete can consider consuming caffeine before, and during the event, depending on its duration. Someone with a low sensitivity to caffeine may notice they avoid the jittery sensation that some people experience after ingesting caffeine.

High sensitivity – An individual with a high sensitivity to caffeine may feel the energizing effects for a longer period of time, when compared to others. An athlete with a high sensitivity to caffeine should be mindful not to consume caffeine late in the evening. This may cause trouble sleeping, which will affect an athlete’s capacity for recovery.

People who are sensitive to caffeine may experience unpleasant jitters. If an athlete feels their caffeine sensitivity is not reflected by their DNA, it could be that they have developed a reduced sensitivity from regularly consuming larger amounts of caffeine.

How could a coach use this information to optimize an athlete’s training?

If a coach intends to have their athletes use caffeine before training or a competition, it’s imperative that they know how their athletes’ bodies respond to caffeine. While DNA plays a role in how the human body metabolizes to caffeine, coaches should observe for themselves how their athletes respond to caffeine products.

Imagine an athlete whose DNA shows a high sensitivity to caffeine. They’ve been consuming 2 cups of coffee daily for three years. This athlete’s coach suggests they take a caffeine supplement before training. The coach is then unable to observe any energizing effects.

From a purely-observational standpoint, one could speculate that this athlete has a low sensitivity to caffeine. If the coach has access to the athlete’s genetic insights, they’re able to see that the athlete is highly sensitive to caffeine. The athlete has simply build up an immunity.

To take advantage of the athlete’s sensitivity, the coach could increase supplementation to ensure the athlete receives the energizing benefits while they are training. Changing when the athlete consumes caffeine could also achieve the desired effect. If the athlete is drinking coffee two hours before practice, the coach may have the athlete drink coffee an hour before.

Altering the athlete’s diet to minimize caffeine consumption will help break down their immunity. The coach can then work towards finding the proper balance of caffeine in the athlete’s diet so that their immunity isn’t too strong and the pair can capitalize on caffeine’s energizing effects.  


Hey coaches! Want to learn how to integrate DNA insights into your daily coaching practices for the development of precision training programs? Join our educational community. We offer free, virtual seminars and resources for self-guided learning. 


Castorena-Torres, F. et al. CYP1A2 phenotype and genotype in a population from the Carboniferous Region of Coahuila, Mexico. Toxicol. Lett. 156, 331–339 (2005).

Djordjevic, N., Ghotbi, R., Jankovic, S. & Aklillu, E. Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 -163C>A polymorphism. Eur. J. Clin. Pharmacol. 66, 697–703 (2010).

Han, X. M. et al. Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G- 2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics. 11, 429–435(2001).

Pataky, M. W. et al. Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day. Scand J Med Sci Sports. (2015).

Sachse, C., Brockmöller, J., Bauer, S. & Roots, I. Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 47, 445–449 (1999).

Womack, C. J. et al. The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. J Int Soc Sports Nutr. 9, 7 (2012).

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