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Caffeine, CYP1A2 Genotype, and Exercise Performance: A Systematic Review and Meta-analysis
Three-level meta-analysis of caffeine versus placebo exercise trials stratified by CYP1A2 rs762551 genotype: caffeine improved pooled exercise performance in AA (fast metaboliser) and AC genotypes but statistically worsened performance in CC (slow) homozygotes at standard research doses; dose, timing, and conflict-of-interest covariates modified CC-stratum estimates in meta-regressions.
Design
- Systematic review + three-level meta-analysis of caffeine vs placebo trials reporting exercise performance by CYP1A2 rs762551 genotype (AA, AC, CC)
- Meta-regressions: dose, timing, reported conflicts of interest
Headline genotype contrasts (abstract)
- AA: performance SMD = +0.30 (95% CI 0.21–0.39; P < 0.0001)
- AC: SMD = +0.16 (95% CI 0.06–0.25; P = 0.022)
- CC: SMD = −0.22 (95% CI −0.44 to −0.01) — interpreted by authors as worse performance on caffeine versus placebo at typical study doses
- Dose / timing: meta-regressions reported dose-dependent and timing-dependent shifts primarily within the CC stratum
Evidence hygiene
- Genotyping availability and baseline placebo imbalances between genotypes are limitations flagged in the discussion—pair with Grgic umbrella (
grgic-2020-caffeine-exercise-umbrella-bjsm) for population-level ergogenic claims.
Publication
Barreto G, Esteves GP, Marticorena FM, et al. Med Sci Sports Exerc. 2023 Dec 1;55(12):2320-2330. PMID 37844569.
Outcomes
- Effect Size (Cohen's d / SMD)CYP1A2 AA genotype: caffeine improved exercise performance vs placebo (pooled SMD +0.30, 95% CI 0.21–0.39, P<0.0001). AC: SMD +0.16 (95% CI 0.06–0.25, P=0.022). CC: SMD −0.22 (95% CI −0.44 to −0.01), interpreted as impaired performance on caffeine at standard research doses (Barreto et al. 2023).