Development and Scientific Rationale of a Caffeine Supplementation Protocol to Enhance Performance in Freestyle Wrestlers with CYP1A2 Genetic Polymorphisms v1

Research rationale: Physical performance is an integral component of success in combat sports, including freestyle wrestling. Consequently, methods and tools that enhance performance—including factors outside of formal training and competition, such as dietary supplements—are a high priority in this sport. Caffeine is one of the most widely consumed psychoactive stimulants globally. The impact of caffeine supplementation on physical performance has received significant attention in the scientific literature, and evidence for its ergogenic effects is well-established. Several systematic reviews and meta-analyses have demonstrated notable ergogenic benefits for athletes in combat sports (such as taekwondo, karate, and boxing). Despite these well-documented performance-enhancing effects, it is also widely recognized that there is substantial inter-individual variability in how people respond to caffeine supplementation. One potential driver of this individual variation is genetic diversity. The CYP1A2 gene encodes cytochrome P450 1A2, an enzyme responsible for up to 95% of caffeine metabolism. The rate of caffeine metabolism is influenced by a single-nucleotide polymorphism (SNP) within this gene, known as rs762551. Individuals with the AA genotype at the rs762551 locus are typically classified as "fast caffeine metabolizers," whereas those carrying the C allele (genotypes AC or CC) generally exhibit a slower rate of caffeine elimination and are therefore classified as "slow caffeine metabolizers." A significantly greater ergogenic effect of caffeine on aerobic endurance has been reported in individuals with the AA genotype compared to those carrying the C allele. It is suggested that the ergogenic response to similar doses of caffeine varies depending on an individual's CYP1A2 polymorphisms.