The effect of the CYP1A2 -163 C\u3eA polymorphism on the metabolism of caffeine and effect on performance

Prior studies from our laboratory suggest that the -163 C \u3e A polymorphism of the Cytochrome P450 (CYP1A2) gene influences the ergogenic effect of caffeine. Although this polymorphism has been known to influence the inducibility of hepatic CYP1A2 and the rate of caffeine metabolism, levels of caffeine and/or metabolites have never been reported in these aforementioned studies (1, 12, 16). Thus, a mechanistic link between the polymorphism and the ergogenic effect of caffeine is lacking. The purpose of this study was to determine if the CYP1A2 polymorphism affected caffeine metabolism between the genotypes (AA homozygotes and C allele carriers). Twenty male subjects were recruited for this study. Subjects participated in two 3km cycling time trials with placebo (all-purpose flour) and caffeine (6mg/kg body weight anhydrous caffeine) supplementation. “Slow metabolizers” were characterized as possessing a “C” allele on the first intron of that gene (grouped AC heterozygotes, and CC homozygotes), and “fast metabolizers” were those who were homozygous for the A allele. C allele carriers had significantly higher serum caffeine after one hour (C allele carriers = 14.2 ± 1.8 ppm, AA homozygotes = 11.7 ± 1.7 ppm). While there was a main effect for caffeine ingestion on time trial performance, there was no caffeine x genotype interaction (C allele carriers: Placebo = 297 ± 20.8 sec, Caffeine = 292 ± 20 sec; AA homozygotes: Placebo = 318.3 ± 34.5 sec; Caffeine = 307.9 ± 21.9 sec). Results from this study suggest that C allele carriers have higher serum caffeine after one hour than AA homozygotes, consistent with the assertion that C allele carriers metabolize caffeine slower. These findings do not support a genetic influence on the ergogenic effect of caffeine in a 3km cycling trial