The Role of Genetics in Moderating the Inter-Individual Differences in the Ergogenicity of Caffeine

Abstract

Caffeine use is widespread among athletes following its removal from the World Anti-Doping Agency banned list, with approximately 75% of competitive athletes using caffeine. While literature supports that caffeine has a small positive ergogenic effect for most forms of sports and exercise, there exists a significant amount of inter-individual difference in the response to caffeine ingestion and the subsequent effect on exercise performance. In this narrative review, we discuss some of the potential mechanisms and focus on the role that genetics has in these differences. CYP1A2 and ADORA2A are two of the genes which are thought to have the largest impact on the ergogenicity of caffeine. CYP1A2 is responsible for the majority of the metabolism of caffeine, and ADORA2A has been linked to caffeine-induced anxiety. The effects of CYP1A2 and ADORA2A genes on responses to caffeine will be discussed in detail and an overview of the current literature will be presented. The role of these two genes may explain a large portion of the inter-individual variance reported by studies following caffeine ingestion. Elucidating the extent to which these genes moderate responses to caffeine during exercise will ensure caffeine supplementation programs can be tailored to individual athletes in order to maximize the potential ergogenic effect.

Response to “Are There Non-Responders to the Ergogenic 3 Effects of Caffeine Ingestion on Exercise Performance?”

“…We agree with the sentiment that responders and non-responders are misleading to readers and thus avoided using these terms in our publication [2] as much as possible. As stated by Grgic [1], an individual may perform well in one test and not another following caffeine ingestion, likewise the individual may perform better or worse on different days given the same caffeine supplementation due to multiple external factors (as mentioned in our paper [2]) and variation in performance.…”

“…In response to “Letter: are there non-responders to the ergogenic effects of caffeine ingestion on exercise performance” by Grgic [1], we welcome the additional context that this letter provides to our paper [2]. We agree with the sentiment that responders and non-responders are misleading to readers and thus avoided using these terms in our publication [2] as much as possible.…”

Effects of Caffeine on Time Trial Performance and Associated Physiological Responses: A Meta-Analysis

“…3 There is also some evidence that the effect of caffeine on time trial performance may be influenced by a genetic factor. 28,34,35,51,[65][66][67] Research to date has focused on the CYP1A2 gene that influences the rate at which the liver metabolizes caffeine, and the ADORA2A gene that, through its influence on A2A receptor binding characteristics, influences dopaminergic neurotransmission. 65,67 Results so far have been equivocal, possibly due to methodological inconsistencies.…”

“…28,34,35,51,[65][66][67] Research to date has focused on the CYP1A2 gene that influences the rate at which the liver metabolizes caffeine, and the ADORA2A gene that, through its influence on A2A receptor binding characteristics, influences dopaminergic neurotransmission. 65,67 Results so far have been equivocal, possibly due to methodological inconsistencies. 65,67 Moreover, given that the ergogenic effects of caffeine happen in advance its metabolism, and during both long and relatively short time trials, it is difficult to rec-oncile the role of the CYP1A2 gene in the ergogenic effect of caffeine.…”

“…65,67 Results so far have been equivocal, possibly due to methodological inconsistencies. 65,67 Moreover, given that the ergogenic effects of caffeine happen in advance its metabolism, and during both long and relatively short time trials, it is difficult to rec-oncile the role of the CYP1A2 gene in the ergogenic effect of caffeine. Indeed, recent reviews into the role of genetics on the ergogenic effects of caffeine have highlighted that more work in the area is warranted, including replication of previous studies and an expansion of the number of biologically plausible genes.…”