Effect of Caffeine on Endurance Performance in Athletes May Depend on HTR2A and CYP1A2 Genotypes

• Published in: Journal of strength and conditioning research 2022-09, Vol.36 (9), p.2486-2492
• Main Authors: Guest, Nanci S., Corey, Paul, Tyrrell, Pascal N., El-Sohemy, Ahmed
• Format: Article
• Language: English
• Subjects: Body mass; Caffeine; CYP1A2 protein; Cytochrome P450; Genotype & phenotype; Genotypes; Heterozygotes; Placebos
• ISSN: 1064-8011; 1533-4287
• DOI: 10.1519/JSC.0000000000003665

ABSTRACTGuest, NS, Corey, P, Tyrrell, PN, and El-Sohemy, A. Effect of caffeine on endurance performance in athletes may depend on HTR2A and CYP1A2 genotypes. J Strength Cond Res XX(X)000–000, 2020—This investigation determined whether variation in the HTR2A (serotonin receptor) gene modifies the ergogenic effects of caffeine on endurance and further modifies performance by the CYP1A2 genotype. Male athletes (n = 100; 25 ± 4 years) completed 10-km cycling time trials under 3 conditions as follows0, 2, or 4 mg of caffeine per kg body mass. Using a randomized, double-blinded, placebo-controlled design, data were analyzed using analysis of covariance to compare changes in cycling time between placebo (0 mg·kg) and each caffeine dose and adjusted for the placebo trial and order of treatment. A significance of ρ ≤ 0.05 was used. Subjects were genotyped for HTR2A (rs6313) and CYP1A2 (rs762551). A significant caffeine-HTR2A interaction (p = 0.003) was observed; however, after adjustment for placebo trials, the interaction was no longer significant (p = 0.37). Because of the strong caffeine-CYP1A2 interaction (p < 0.0001) previously reported in these subjects, where the 4-mg dose resulted in divergent effects (slower and faster) on the 10-km cycling time, we conducted a simplified model to examine these same factors by the HTR2A genotype. The post hoc analysis excluded HTR2A CT heterozygotes and 2-mg·kg caffeine trials. Among CYP1A2 fast metabolizers alone, a significant difference (1.7 minutes; p = 0.006) was observed when comparing (4- vs. 0-mg·kg caffeine trials) between the HTR2A CC (n = 16; 2.4 minutes) and TT (n = 7; 0.7 minutes) genotypes. Our results show that 4-mg·kg caffeine improves performance in individuals with the HTR2A CC genotype but only in those who are also CYP1A2 AA fast metabolizers. This study was registered with clinicaltrials.gov (NCT 02109783).