Caffeine, CYP1A2 Genotype and Exercise Performance: A Systematic Review and Meta-analysis

Abstract

ABSTRACT Purpose To summarise and meta-analyse existing evidence regarding the influence of CYP1A2 genotypes on the acute effects of caffeine for exercise performance, and to investigate the interaction between genotype, dosage, and timing of caffeine supplementation. Methods Six databases were searched for studies determining the effect of caffeine (except mouth rinsing) on exercise performance between CYP1A2 genotypes. Three-level meta-analyses were performed using standardized mean differences (SMD; Hedge’s g) to determine the effect of caffeine on exercise outcomes within and between CYP1A2 genotypes (AA, AC, CC). Meta-regressions were performed for dose, timing, and for the presence of reported conflict of interests (RCOI). A meta-analysis was also performed with baseline values to assess for imbalances between genotypes. Results Thirteen studies, totalling 119 outcomes and 440 participants were included (233 AA, 175 AC, 34 CC). Caffeine improved performance for AAs (SMD = 0.30, 95%CI: 0.21; 0.39, p < .0001) and ACs (SMD = 0.16, 95%CI: 0.06; 0.25, p = 0.022), but reduced for CCs (SMD = -0.22, 95%CI: -0.44; -0.01, p < .0001). Dose affected only CCs, with greater doses generating more positive SMDs (CC*dose estimate: +0.19/1 mg/kg BM, 95%CI: 0.04; 0.33, p = 0.01). Timing influenced only CCs, with better performance with later onset of exercise after supplementation (CC*timing estimate: +0.01 /minute, 95%CI: 0.00; 0.02, p = 0.02). RCOI only affected SMDs of CCs (CC*RCOI estimate: -0.57, 95%CI: -1.02; -0.12, p = 0.01). After excluding studies with RCOI, no influence of genotype was seen (all p ≥ 0.19). Small, non-significant differences were seen in placebo between genotypes (SMDs AAs vs. CCs: -0.13; AAs vs. ACs: -0.12; ACs vs. CCs: -0.05; all p ≥ 0.26). Conclusions Caffeine improved performance for AAs and ACs, but worsened performance for CCs. Dose and timing moderated the efficacy of caffeine for CCs only. Caution is advised since baseline differences and studies with RCOI could have influenced these results.