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

Abstract

Guest, 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 36(9): 2486-2492, 2022-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 5 100; 25 6 4 years) completed 10-km cycling time trials under 3 conditions as follows: 0, 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 21 ) and each caffeine dose and adjusted for the placebo trial and order of treatment. A significance of r # 0.05 was used. Subjects were genotyped for HTR2A (rs6313) and CYP1A2 (rs762551). A significant caffeine-HTR2A interaction (p 5 0.003) was observed; however, after adjustment for placebo trials, the interaction was no longer significant (p 5 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 21 caffeine trials. Among CYP1A2 fast metabolizers alone, a significant difference (1.7 minutes; p 5 0.006) was observed when comparing (4-vs. 0-mg•kg 21 caffeine trials) between the HTR2A CC (n 5 16; 2.4 minutes) and TT (n 5 7; 0.7 minutes) genotypes. Our results show that 4-mg•kg 21 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).

Prevalence and Amounts of Common Ingredients Found in Energy Drinks and Shots

“…Therefore, indiscriminate and excessive use of energy drinks and energy shots may increase the likelihood for adverse events and harmful side effects [2], which could be said for many functional beverages or dietary supplements. Moreover, recent findings suggest that certain genetic factors may influence how caffeine is metabolized, subsequently influencing its performance enhancing potential and the physiological responses post-consumption [20,41,42]. It is also important to note that the type of caffeine found in energy drinks is different to that which is extracted from coffee beans, such is the source found in brewed coffee.…”

Not Another Caffeine Effect on Sports Performance Study—Nothing New or More to Do?

“…Conversely, the ADORA2A genotype did not influence caffeine’s effect on strength and power performance in a population of professional handball players [ 108 ]. Evidently, more work is needed to explore the influence of the ADORA2A genotype on sports performance along with other promising targets such as the HTR2A genotype which has been shown to influence caffeine’s ergogenic response to aerobic cycling [ 109 ].…”

“…Beyond this, future work should examine optimising ingestion periods based on CYP1A2 genotypes, were the standardised ingestion approach used in current studies may mask the potential ergogenic effects in slow metabolisers, who may need a longer ingestion period before performance-enhancing benefits occur. Other than in the work by Guest et al [ 109 ], the focus of previous work in this area has been to evaluate the impact of a single genotype on caffeine’s ergogenic effects. Whilst this presents a considerable challenge, a substantial improvement in our understanding of the influence of genotype on caffeine’s ergogenic effect can only be made by stratifying groups by polymorphisms in multiple genes.…”

Efeito dose-resposta da utilização oral de cafeína na performance de exercícios aeróbicos: uma revisão sistemática e meta-análise

“…Embora ainda não seja totalmente claro o papel dessas alterações metabólicas no aumento da performance aeróbica de sujeitos tratados com cafeína, existem alguns estudos clínicos (randomizados e controlados por placebo) que investigaram os efeitos das diferentes dosagens de cafeína no tempo total utilizado em testes de performance contrarrelógio (DESBROW et al, 2009;DESBROW et al, 2012;GUEST et al, 2020;HANSON et al, 2019;SKINNER et al, 2010), bem como em protocolos de exercícios aeróbicos até a exaustão (GRAHAM, SPRIET, 1995;PASMAN et al, 1995) e que podem, em partes, dar direcionamentos sobre qual seria a melhor faixa de dosagem de consumo do estimulante.…”

“…Entre os estudos relacionados a performance de testes contrarrelógios distintos, foi observado uma mudança média de -0,38% a +4,2% quando o tratamento foi realizado com dosagens de 1,5 a 6 miligramas de cafeína por quilograma de peso dos participantes frente aos seus respectivos testes controles (DESBROW et al, 2009;DESBROW et al, 2012;GUEST et al, 2020;HANSON et al, 2019;SKINNER et al, 2010). A partir da comparação direta de todos os estudos dose-resposta tratados com baixas dosagens de cafeína (≤3mg.kg -1 ) vs. Moderadas dosagens de cafeína (3,1-6mg.kg -1 ), em exercícios contrarrelógios, foi constatado as maiores variações na performance com a administração de baixas dosagens de cafeína (+ 0,38% até +4,2%), quando comparado ao consumo de dosagens moderadas do estimulante (+0,30 até 3%) (DESBROW et al, 2009;DESBROW et al, 2012;GUEST et al, 2020;HANSON et al, 2019;SKINNER et al, 2010). Com ausência dos estudos que investigaram o uso de altas dosagens de cafeína (>6 mg.kg -1 ) no tempo de prova de testes contrarrelógios.…”