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.

中文翻译：

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咖啡因、CYP1A2 基因型和运动表现：系统评价和荟萃分析。

目的总结和荟萃分析关于 CYP1A2 基因型对咖啡因对运动表现的急性影响的影响的现有证据，并研究基因型、剂量和咖啡因补充时间之间的相互作用。方法 检索了六个数据库，查找确定咖啡因（漱口除外）对 CYP1A2 基因型之间运动表现影响的研究。使用标准化平均差（SMD；Hedge's g）进行三级荟萃分析，以确定咖啡因对 CYP1A2 基因型（AA、AC、CC）内部和之间运动结果的影响。对剂量、时间和报告的利益冲突 (RCOI) 的存在进行元回归。还使用基线值进行荟萃分析，以评估基因型之间的不平衡。结果 纳入 13 项研究，共 119 个结果，440 名受试者（233 AA，175 AC，34 CC）。咖啡因提高了 AA（SMD = 0.30，95%CI：0.21；0.39，p < .0001）和 AC（SMD = 0.16，95%CI：0.06；0.25，p = 0.022）的性能，但降低了 CC（SMD = -0.22，95%CI：-0.44；-0.01，p < .0001）。剂量仅影响 CC，剂量越大产生更多阳性 SMD（CC*剂量估计值：+0.19/1 mg/kg BM，95%CI：0.04；0.33，p = 0.01）。时间仅影响 CC，补充后开始运动较晚，表现更好（CC*时间估计：+0.01/分钟，95%CI：0.00；0.02，p = 0.02）。RCOI 仅影响 CC 的 SMD（CC*RCOI 估计值：-0.57，95%CI：-1.02；-0.12，p = 0.01）。排除 RCOI 研究后，未发现基因型的影响（所有 p ≥ 0.19）。不同基因型之间的安慰剂存在较小的非显着差异（SMD AA 与 CC：-0.13；AA 与 AC：-0.12；AC 与 CC：-0.05；所有 p ≥ 0.26）。结论 咖啡因改善了 AA 和 AC 的表现，但恶化了 CC 的表现。剂量和时间仅调节咖啡因对 CC 的功效。建议谨慎，因为基线差异和 RCOI 研究可能会影响这些结果。