Caffeinated resistance exercise may not be for everyone

The performance-enhancing effects of caffeine have been known for over 100 years^[1]. Researchers have demonstrated the efficacy of caffeine for endurance^[2] and high-intensity^[3] sport activities, along with its general ‘can-do attitude’ boost. Resistance training, on the other hand, has been demonstrated to benefit^[4] from caffeine consumption in some studies but others have found no effects^[5]. This inconsistency could be related to factors as simple as training status, intensity of exercise, and/or caffeine dose, or as complex as variability of individual responses to caffeine, which could involve genetics.

Caffeine is primarily metabolized in the liver by cytochrome P450 1A2^[6], an enzyme that processes drugs and toxins and is encoded by the CYP1A2 gene^[7]. A single nucleotide change (rs762551 is the specific reference SNP (rs) for the gene in question) in the CYP1A2_ gene sequence has demonstrated differences in caffeine metabolism^[8] depending on which alternative form of the gene, or allele, an individual has. There are three forms of the gene at this specific location: CC, CA, and AA, each designating a small difference in the gene sequence. AA genotype carriers metabolize caffeine faster than C allele carriers (CA or CC) and appear to experience greater performance enhancement when it comes to exercise.

While the exact mechanism of enhanced ergogenic action in AA genotype carriers when compared to C allele carriers is unclear, some research has suggested that the faster metabolism of caffeine increases the concentration of certain caffeine metabolites, shown in Figure 1, which may bind more strongly^[9] to adenosine receptors than caffeine itself. Regardless of the mechanism, caffeine supplementation demonstrated greater reductions in 40-kilometer cycling times^[10] in AA genotype male cyclers than C allele carriers. The rate at which one measure of heart rate variability stabilized following 15 minutes of cycling was also improved in AA genotype individuals^[11] when compared to C allele carriers.

The influence of CYP1A2 genetic variants on caffeine’s effects on resistance exercise have not been studied thoroughly. The authors of the paper under review sought to determine the effect of acute caffeine administration on resistance exercise performance and how the genetic variants of CYP1A2 may influence this relationship.

Caffeine has demonstrated its ergogenic influence on endurance and high-intensity sport performance, but there is conflicting evidence for caffeine’s effect on resistance training. One of the probable reasons is a genetic difference in the CYP1A2 gene that encodes a liver enzyme which metabolizes caffeine. Genotypes with a C allele (CA or CC) appear to metabolize caffeine more slowly than the AA genotype. Researchers wanted to investigate the impact of acute caffeine administration on resistance exercise performance and how genetic variants of CYP1A2 may influence the relationship.