Because the higher 40-km time in AA homozygotes was primarily driven by GSK2118436 in vivo four cyclists whose 40 k times during the placebo trial were greater than

80 minutes (see Figure 2), we removed these four subjects from the dataset for the follow-up analysis. This resulted in similar 40-km times in the placebo condition between the two groups, yet caffeine still had a significantly (p = 0.047) greater effect in AA homozygotes (caffeine = 70.5 ± 3.0 min, placebo = 73.5 ± 3.8 min) compared to the C allele carriers (caffeine = 70.9 ± 4.3 min, placebo = 72.2 ± 4.2 min). Caffeine resulted in at least a 1-minute improvement in 40 k time in all but one of the AA homozygotes; whereas only about half of C allele

carriers responded to that extent (Figure 2). Thus, our data support the contention that it is the genetic polymorphism and not the performance capabilities of the respective groups that explain our observations. Although data from the present study clearly suggest a potential role of this polymorphism in influencing the ergogenic response of caffeine in cyclists, care should be taken in extrapolating Selleck BI-D1870 these findings. It is unknown if there is a similar genetic influence for other modes of exercise and/or for short-duration high-intensity exercise. Furthermore, we used trained cyclists in the present study and our findings cannot be extrapolated to sedentary individuals. Neither can it be suggested that this polymorphism is the only source of PF-2341066 variation or even the only source of genetic variation involved. Finally, although we have outlined a potential mechanism that explains the current findings, it should be emphasized that the mechanistic causes of our findings cannot be determined from Resveratrol the present data. Future studies should determine whether these findings can be replicated using other modes of exercise and in other populations. Other candidate polymorphisms should also be identified and evaluated. Conclusions In summary, data from the present study suggest that caffeine potentiates a larger ergogenic effect for cycling performance in individuals

homozygous for the A variant of the studied CYP1A2 polymorphism. The mechanism(s) of this selective ergogenic effect are unknown and future studies should seek to establish the impact of this polymorphism on caffeine metabolism during exercise. While these findings elucidate a possible source of variance in the ergogenic effect of caffeine, other factors, including other genetic polymorphisms, may also influence caffeine responses during exercise. Acknowledgements This study was funded by an internal grant from the College of Integrated Science and Technology, James Madison University. The authors wish to thank Professor Ahmed El-Sohemy (University of Toronto, Toronto, ON) for assistance and advice in the genotyping portion of this study.