Active Voice: Caffeine, Genetics and Endurance Performance

By Ahmed El-Sohemy, Ph.D., and Nanci Guest, M.Sc., R.D., CSCS

Ahmed El-Sohemy, Ph.D. Nanci Guest, M.Sc., R.D., CSCS
Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily represent positions or policies of ACSM.

Ahmed El-Sohemy, Ph.D., is a professor and Canada research chair in Nutrigenomics at the University of Toronto, Toronto, Canada. He earned his Ph.D. in nutritional sciences from the University of Toronto and completed a postdoctoral fellowship at Harvard University, Cambridge, Massachusetts. The goal of his research is to elucidate the genetic basis for variability in nutrient response on health and performance. He received the Centrum Foundation New Scientist Award for Outstanding Research by the Canadian Nutrition Society and the Mark Bieber Professional Award by the American College of Nutrition.

Nanci Guest, M.Sc., R.D., CSCS, is a registered dietitian specializing in sport, a certified personal trainer and a strength and conditioning coach. Ms. Guest is a Ph.D. candidate at the University of Toronto and currently is focusing her research training in nutrigenomics and athletic performance. Previously, she completed an M.S. in human nutrition and sport at the University of British Columbia in Vancouver, British Columbia, Canada. She is a global consultant to high performance athletes and teams and served as the head dietitian at the Vancouver 2010 Olympics and the Toronto Pan Am Games in 2015.

This commentary presents the authors’ views on the topic related to a research article that they published with other colleagues. Their journal article appears in the August 2018 issue of
Medicine & Science in Sports & Exercise® (MSSE).

The authors have disclosed the following conflict of interest: Dr. El-Sohemy is the founder and holds shares in Nutrigenomix® Inc., a business entity that provides genetic testing for personalized nutrition; Ms. Guest is a member of the Scientific Advisory Board of Nutrigenomix® Inc.

Caffeine is widely used in sport because of its reported performance-enhancing or ergogenic effects. Numerous studies have investigated the effect of supplemental caffeine on endurance performance. While most of these studies have shown performance-enhancement influences with caffeine use, there is considerable interindividual variability as to the magnitude of these effects. Due to the infrequent reporting of individual data in performance trials, it is difficult to determine the extent to which variation in caffeine response might be occurring. The variability in performance capacity of subjects participating in such studies may vary considerably and this circumstance may contribute to inconsistent findings and conclusions regarding the extent to which caffeine may enhance performance — thus, this circumstance can contribute to clouding the evidence, so that some studies show beneficial effects, while others show detrimental or no effects whatsoever. However, these inconsistencies might be due, in part, to interindividual differences in caffeine metabolism, or response to caffeine — because of genetic variation among subjects.

More than 95 percent of caffeine is metabolized by the CYP1A2 enzyme. This enzyme is encoded by the CYP1A2 gene and is involved in the demethylation of caffeine into its primary metabolites. A single nucleotide polymorphism (SNP, pronounced “snip”) is a variation that occurs at a specific position in a gene and results in changes in the activity of what that gene encodes. In our study, the rs762551 SNP has been shown to alter CYP1A2 enzyme activity and has been used to categorize individuals as ‘‘fast,’’ “slow” or ‘‘very-slow’’ metabolizers of caffeine. The rate of caffeine metabolism has been shown to alter the response to caffeine on various health outcomes and may also have implications for sports performance.

In our study, as published in the August 2018 issue of MSSE, we used a randomized, double-blinded, placebo-controlled design and sought to determine the effects of low or moderate doses of caffeine supplementation, compared to placebo, on endurance performance. We then assessed whether variation in the CYP1A2 gene modifies these effects, where athletes are categorized as having one of three possible genotypes that determines the rate of caffeine breakdown. Subjects included 101 competitive male athletes, average age 25 years, who were recruited from a variety of sports. The endurance exercise test was a stationary cycling ergometer time trial (10-kilometer distance), performed at a predetermined constant load of 65-70 percent of the individual’s aerobic capacity.

Our results indicate that, in the total population, caffeine is ergogenic to cycling performance, with an average improvement in cycling time of 3 percent at a moderate dose (four milligrams per kilogram, roughly three small cups of coffee) — a finding that is consistent with previous studies using similar doses. In addition, we found a significant caffeine–gene interaction where performance improvements with low and moderate caffeine doses reached almost 5 percent and 7 percent, respectively. However, these latter amplified benefits were seen only in the subjects with the AA genotype, i.e., those considered ‘‘fast’’ metabolizers of caffeine. Contrary to this, “very slow” caffeine metabolizers showed an impaired endurance performance of more than 13 percent with the moderate dose of caffeine (compared to placebo). We found no effect of either dose in those who have the AC genotype.

We would like the readers to keep in mind that studies on caffeine and performance generally do not explore the basis for the interindividual variation in response; the need to explore this issue, however, has been well-documented in several studies. Our study provides the strongest evidence to date that genetic differences play a role in determining an individual’s response to caffeine during exercise.

Caffeine has widespread use in athletics in the form of coffee, tablets, energy drinks and “pre-workouts,” based on the belief that athletes can train harder or compete more successfully after ingesting caffeine. However, it appears that caffeine does not benefit all athletes equally and may, in fact, impair performance in some. Our results highlight the importance of considering CYP1A2 genotype in the development of personalized sport nutrition and sport supplement protocols.