Novel insights on caffeine supplementation, CYP1A2 genotype, physiological responses and exercise performance

Caffeine is a popular ergogenic aid due to its primary physiological effects that occur through antagonism of adenosine receptors in the central nervous system. This leads to a cascade of physiological reactions which increases focus and volition, and reduces perception of effort and pain, contributing to improved exercise performance. Substantial variability in the physiological and performance response to acute caffeine consumption is apparent, and a growing number of studies are implicating a single-nucleotide polymorphism in the CYP1A2 gene, responsible for caffeine metabolism, as a key factor that influences the acute responses to caffeine ingestion. However, existing literature regarding the influence of this polymorphism on the ergogenic effects of caffeine is controversial. Fast caffeine metabolisers (AA homozygotes) appear most likely to benefit from caffeine supplementation, although over half of studies showed no differences in the responses to caffeine between CYP1A2 genotypes, while others even showed either a possible advantage or disadvantage for C-allele carriers. Contrasting data are limited by weak study designs and small samples sizes, which did not allow separation of C-allele carriers into their sub-groups (AC and CC), and insufficient mechanistic evidence to elucidate findings. Mixed results prevent practical recommendations based upon genotype while genetic testing for CYP1A2 is also currently unwarranted. More mechanistic and applied research is required to elucidate how the CYP1A2 polymorphism might alter caffeine’s ergogenic effect and the magnitude thereof, and whether CYP1A2 genotyping prior to caffeine supplementation is necessary.