The effect of caffeine on cognitive performance is influenced by CYP1A2 but not ADORA2A genotype, yet neither genotype affects exercise performance in healthy adults

PURPOSE: To determine the influence of two commonly occurring genetic polymorphisms on exercise, cognitive performance, and caffeine metabolism, after caffeine ingestion. METHODS: Eighteen adults received caffeine or placebo (3 mg kg(−1)) in a randomised crossover study, with measures of endurance exercise (15-min cycling time trial; 70-min post-supplementation) and cognitive performance (psychomotor vigilance test; PVT; pre, 50 and 95-min post-supplementation). Serum caffeine and paraxanthine were measured (pre, 30 and 120-min post-supplementation), and polymorphisms in ADORA2A (rs5751876) and CYP1A2 (rs762551) genes analysed. RESULTS: Caffeine enhanced exercise performance (P < 0.001), but effects were not different between participants with ADORA2A ‘high’ (n = 11) vs. ‘low’ (n = 7) sensitivity genotype (+ 6.4 ± 5.8 vs. + 8.2 ± 6.8%), or CYP1A2 ‘fast’ (n = 10) vs. ‘slow’ (n = 8) metabolism genotype (+ 7.2 ± 5.9 vs. + 7.0 ± 6.7%, P > 0.05). Caffeine enhanced PVT performance (P < 0.01). The effect of caffeine was greater for CYP1A2 ‘fast’ vs. ‘slow’ metabolisers for reaction time during exercise (− 18 ± 9 vs. − 1.0 ± 11 ms); fastest 10% reaction time at rest (− 18 ± 11 vs. − 3 ± 15 ms) and lapses at rest (− 3.8 ± 2.7 vs. + 0.4 ± 0.9) (P < 0.05). There were no PVT differences between ADORA2A genotypes (P > 0.05). Serum caffeine and paraxanthine responses were not different between genotypes (P > 0.05). CONCLUSION: Caffeine enhanced CYP1A2 ‘fast’ metabolisers’ cognitive performance more than ‘slow’ metabolisers. No other between-genotype differences emerged for the effect of caffeine on exercise or cognitive performance, or metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00421-020-04384-8) contains supplementary material, which is available to authorized users.