Caffeine can be used effectively as an ergogenic aid when taken in moderate doses, such as during sports when a small increase in endurance performance can lead to significant differences in placements as athletes are often separated by small margins.

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.

Introduction Caffeine is a widely used ergogenic aid with most research suggesting it confers the greatest effects during endurance activities. Despite the growing body of literature around the use of caffeine as an ergogenic aid, there are few recent meta-analyses which quantitatively assess the effect of caffeine on endurance exercise. Objectives To summarise studies which have investigated the ergogenic effects of caffeine on endurance time-trial performance and to quantitatively analyse the results of these studies to gain a better understanding of the magnitude of caffeine's ergogenic effect on endurance time-trial performance. Methods A systematic review was carried out on randomised placebo-controlled studies investigating the effects of caffeine on endurance performance and a meta-analysis was conducted to determine the ergogenic effect of caffeine on endurance time-trial performance. Results 44 studies met the inclusion criteria and were included in the meta-analysis. Caffeine has a small but evident effect on endurance performance when taken in moderate doses (3-6 mg·kg −1 ) as well as an overall improvement following caffeine compared to placebo in mean power output (2.92 ± 2.18%; Effect Size = 0.22 ± 0.15) and time-trial completion time (2.26 ± 2.60%; Effect Size = 0.28 ± 0.12). However, differences in responses to caffeine ingestion have been shown, with two studies reporting slower time-trial performance while five studies reported lower mean power output during the timetrial. Caffeine can be used effectively as an ergogenic aid when taken in moderate doses, such as during sports when a small increase in endurance performance can lead to significant differences in placements as athletes are often separated by small margins.

In response to “Letter: are there non-responders to the ergogenic effects of caffeine ingestion on exercise performance” by Grgic [...]