The effects of CYP1A2 gene polymorphisms on caffeine pharmacokinetics and exercise performance : a thesis presented in the partial fulfilment of the requirements for the degree of Master of Science in Nutrition and Dietetics, Massey University, Albany, New Zealand
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2024
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Massey University
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Background: Caffeine is one of the most popular psychoactive stimulants consumed globally. The CYP1A2 gene encodes the cytochrome P450 1A2 enzyme, found in the liver, which is predominantly responsible (~95%) for caffeine metabolism in the body. A single nucleotide polymorphism (SNP) in the non-coding region of the CYP1A2 gene (CYP1A2; rs762551) induces different expression levels of the enzyme, influencing the clearance rate of caffeine from the body. There are equivocal results as to whether the CYP1A2 genotype is a determinant of exercise performance following supplementation with caffeine. This lack of consensus may be due to differences in trial designs, including mixed exercise modes, and solely male, or mixed sex participant cohorts with most studies using a caffeine dose of between 3-6 mg·kg-¹, and commencing exercise 60-min following caffeine ingestion. Purpose: This research aimed to determine if 6 mg·kg-¹ caffeine ingested 60-min prior to commencing exercise impacts performance, and to identify if the CYP1A2 gene, and consequent caffeine metabolism rates, has a role in improving exercise performance following caffeine consumption. Methods: Thirty-eight healthy, recreationally active, male athletes were recruited for this study. All participants were classified as moderate caffeine users. Participants attended one familiarisation session, where their body composition was measured, practiced a 1-km run or 40-km cycle, and provided saliva samples for genotyping to identify their specific CYP1A2 SNP. Two follow up sessions were undertaken one week apart, with participants completing either a 10-km run or 40- km cycle following the ingestion of an anhydrous caffeine capsule (6 mg·kg-¹) or placebo (maltodextrin) following randomised, placebo-controlled double-blind protocols. Blood sampling was undertaken before, during and following exercise in the two exercise trials to measure plasma caffeine, paraxanthine and theophylline concentrations. Results: Caffeine supplementation improved exercise performance by 1.8% (p=0.05; ηp²=0.12), with greater improvements in performance seen in the second half of exercise (2.4%; p=0.02; ηp²=0.16) in comparison with the first half (1.2%). Twenty-four of the 34 participants whose data were used to analyse time to completion, showed an improvement in exercise performance with caffeine ingestion. Heart rate was higher in participants following caffeine ingestion compared to placebo (p=0.02; ηp²=0.15). Genotyping showed 50% of participants were homozygous AA allele carriers and 50% heterozygous AC allele carriers. No participants carried the CC allele polymorphism. Plasma caffeine concentrations were higher in AA allele carriers than AC allele carriers (p=0.05; ηp²=0.207). No gene-treatment interaction effects were observed in time to completion, heart rate (HR) or plasma concentrations of paraxanthine or theophylline. A significantly higher total sum of plasma caffeine was observed in the area under the concentration time curve (AUC) in AA allele carriers compared with AC allele carriers (p=0.01). Conclusion: Ingesting a dose of 6 mg·kg-¹ caffeine 60 min prior to exercise is likely to improve performance in endurance activities in recreationally trained males. Plasma caffeine concentrations were significantly higher in AA allele carriers compared to AC allele carriers, though no gene caffeine interaction was observed in time to completion, therefore the role of CYP1A2 gene polymorphisms and caffeine consumption in determining enhancements in exercise performance remains unclear.