Abstract
PurposeTo determine the influence of two commonly occurring genetic polymorphisms on exercise, cognitive performance, and caffeine metabolism, after caffeine ingestion.MethodsEighteen 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.ResultsCaffeine 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).ConclusionCaffeine 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.
Highlights
Caffeine is used globally by shift workers, military personnel, athletes, and others who need to overcome fatigue or prolong their capacity to complete occupational activities (Burke 2008)
For the rs5751876 single-nucleotide polymorphism (SNP) in the ADORA2A gene, 11 participants were homozygous for the T allele (TT, i.e., ‘high’ sensitivity); 6 participants were homozygous for the C allele (CC, i.e., ‘low’ sensitivity); and 1 participant was heterozygous (CT, i.e., ‘low’ sensitivity)
For the rs762551 SNP in the CYP1A2 gene, 10 participants were homozygous for the A allele (AA, i.e., ‘fast’ metabolisers); 7 participants were heterozygous carriers of the C allele (AC, i.e., ‘slow’ metabolisers); and 1 participant was homozygous for the C allele (CC, i.e., ‘slow’ metaboliser)
Summary
Caffeine is used globally by shift workers, military personnel, athletes, and others who need to overcome fatigue or prolong their capacity to complete occupational activities (Burke 2008). Despite generally beneficial effects of caffeine on exercise and cognitive performance, sizeable inter-individual variations have been reported, including an absence of a positive effect in some individuals (Ganio et al 2009; Grgic et al 2018, 2019; Jenkins et al 2008; McLellan et al 2016; Southward et al 2018). The rs5751876 single-nucleotide polymorphism (SNP) in the ADORA2A gene which encodes for the adenosine A2A receptor has been used to categorise individuals as having a ‘high’ (TT genotype) or ‘low’ (CT or CC genotype) sensitivity to caffeine, and may account, in part, for some of this variability (Nehlig 2018). The rs762551 SNP can affect CYP1A2 enzyme activity and has been used to identify individuals as ‘fast’ (AA genotype) or ‘slow’ (AC or CC genotype) caffeine metabolisers (Nehlig 2018)
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