Effect of Caffeine and CYP1A2/ADORA2A Genotype on Anaerobic Exercise Performance

Caffeine is a stimulant used worldwide to enhance acute physical performance, typically in endurance events. However, research shows inconsistent results regarding its effectiveness for short-term anaerobic performance. Individual variation in responses to caffeine is thought to be influenced by specific genetic factors, including the single nucleotide polymorphisms (SNPs) of the genes -163 A>C CYP1A2 (CYP1A2) and 1976 T>C ADORA2A (ADORA2A). Those with the CYP1A2 AA variant are classified as caffeine responders, while individuals with the AC or CC variants are considered caffeine non-responders. Furthermore, the ADORA2A TT variant is associated with greater sensitivity to caffeine compared to the TC and CC variants. Purpose: The purpose of this study was to determine the effect of caffeine and the genetic influence of the CYP1A2 and ADORA2A SNPs on anaerobic performance. Methods: 26 male and female athletes (age = 20.1 yrs, weight = 77.1 kg) gave written informed consent to participate in the study. Subjects performed two 30-s Wingate cycle ergometer tests (WAnT) with a flywheel resistance load of 0.075 kg•BW(kg) -1 . The tests were separated by 5-7 days, and participants were asked to abstain from caffeine and strenuous activity for 12 hours before each testing session. Each athlete was administered caffeine, 5 mg•kg -1 BW, or a placebo, maltodextrin, one hour before each trial in a double-blinded, randomized, and counterbalanced design. Peak power, W•kg -1 (PP), mean anaerobic power, W•kg -1 (MAP), total work (TW) J• kg -1 , and fatigue index (FI) were calculated for each condition. Buccal epithelial cells were obtained from each participant, and DNA was extracted via cell lysis using proteinase K. Allelic discrimination plots were generated for CYP1A2 (rs762551) and ADORA2A (rs5751876) using qPCR, run in duplicate with positive and negative controls. The data were analyzed using 2x2 ANOVAs with repeated measures for each variable (p < 0.05). Results: The main effect of CAF compared to PLA for the WAnT showed no significant difference for PP (11.67 ± 2.23 W•kg -1 vs. 11.73 ± 2.14 W•kg -1 , respectively, p = 0.63) or MAP (8.28 ± 0.90 W•kg -1 vs. 8.19 ± 0.87 W•kg -1 , respectively, p = 0.21). TW over the 30 seconds improved significantly with CAF versus PLA (42.69 ± 9.94 W•kg -1 vs. 42.07 ± 9.74 J•kg -1 , respectively, p = 0.03), and FI revealed a 2.8%, non-significant (p = 0.15) decrease in fatigue. Analysis of 5-second averages showed significant improvement in power generated with CAF versus PLA during 10-15-s (p = 0.04) and 15-20-s (p = 0.02), but not during the first or final 10 seconds. The genotype comparison showed no significant differences for comparing PP, MAP, TW, or FI for the CYP1A2 AA to AC/CC and no interaction effect for the ADORA2A variants of CC to CT/TT. Discussion: Our data suggest that caffeine has no effect on PP or MAP; however, caffeine increased total work, specifically during the middle of the 30-s sprint. In addition, variants of the CYP1A2 or ADORA2A did not influence anaerobic performance. Messiah University, Mechanicsburg PA This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.