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

Eur J Appl Physiol. 2020 Jul;120(7):1495-1508. doi: 10.1007/s00421-020-04384-8. Epub 2020 Apr 30.

Abstract

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.

Keywords: Caffeine; Cognitive performance; Endurance exercise; Ergogenic; Genetics; Polymorphism.

MeSH terms

  • Adult
  • Caffeine / administration & dosage
  • Caffeine / pharmacology*
  • Cytochrome P-450 CYP1A2 / drug effects*
  • Exercise / physiology*
  • Female
  • Genotype*
  • Humans
  • Male
  • Performance-Enhancing Substances / administration & dosage
  • Performance-Enhancing Substances / pharmacology
  • Receptor, Adenosine A2A / drug effects*
  • Young Adult

Substances

  • ADORA2A protein, human
  • Performance-Enhancing Substances
  • Receptor, Adenosine A2A
  • Caffeine
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2