The role of genetic polymorphisms in the effect of caffein supplementation on exercise performance: A systematic review and meta-analysis

Caffeine, which has been shown by many studies to contribute to exercise performance, may show different effects between individuals. One of the individual factors that cause these differences is single nucleotide polymorphisms in certain genes. The aim of this systematic review and meta-analysis was to investigate the effect of caffeine on aerobic and anaerobic performance according to CYP1A2 rs762551 and ADORA2A rs5751876 gene polymorphisms. This study included randomised, placebo-controlled, English- or Turkish-language publications conducted in individuals aged 18 years and over, in which 2-6 mg/kg caffeine was supplemented 30-60 minutes before exercise, caffeine was given in capsule, tablet, powder, etc., Wingate anaerobic power performance, countermovement jump performance or time-trial performance was tested, and CYP1A2 rs762551 or ADORA2A rs5751876 polymorphisms of the participants were analysed. Studies in which caffeine was administered with another substance with an ergogenic effect, and in a form such as chewing gum, gel or in coffee were excluded. Eight databases were included in the study. Pubmed/MEDLINE, Scopus, Web of Science and ERIC database were searched on 10 June 2023, SPORTDiscus, Academic Search Ultimate, ProQuest Dissertations & Theses Global and Open Dissertations were searched on 11 June 2023. The last check of the databases was carried out on 10 September 2023. Additional references were obtained through manual searches for reference lists, cited references, relevant reviews and potentially relevant journals. The quality of the included publications was assessed using the PEDro scale. Eleven publications were included in the study. The caffeine dose of the included publications was 6 mg/kg in four, 3 mg/kg in four, 2 and 4 mg/kg in three, and in most of them caffeine was administered 60 minutes before exercise. Five of the studies assessed Wingate anaerobic power performance (n = 178), four assessed countermovement jump performance (n = 170), and four assessed time-trial performance (n = 170). The difference between caffeine and placebo groups is reported as the Hedges' g standardised mean difference (effect size (ES)). When there was no heterogeneity between the studies included in the meta-analysis, analyses were performed using a fixed-effects model; when there was heterogeneity, analyses were performed using a random-effects model. Caffeine supplementation improved Wingate peak power output and time-trial performance in the CYP1A2 AA genotype (ES: 0.214; confidence interval (CI): 0.034-0.395; ES: -1.602, CI: -2.848-(-0.356)). Counter movement jump height was increased in both AA genotype and C allele carriers (ES: 0.200, CI: 0.075-0.325; ES: 0.155, CI: 0.075-0.235, respectively). According to the ADORA2A gene polymorphisms, Wingate power output and countermovement jump height were positively influenced by caffeine supplementation in C allele carriers. However, further studies are needed to determine the role of ADORA2A gene polymorphisms. Reviewing studies in the literature, it is noted that those with AA genotype according to CYP1A2 rs762551 polymorphism have a higher tendency to ergogenic effects than those with C allele.