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The Bitter Taste Of COI (ffee)

A Systematic Review and Meta-Analysis On CYP1A2 Genotypes, Timing, And Dose Of Caffeine On Exercise Performance


  • Gabriel Barreto Applied Physiology and Nutrition Research Group, School of Physical Education and Sport; Rheumatology Division; Faculty of Medicine FMUSP, University of SãoPaulo, São Paulo, SP
  • Gabriel P. Esteves Applied Physiology and Nutrition Research Group, School of Physical Education and Sport; Rheumatology Division; Faculty of Medicine FMUSP, University of São Paulo, São Paulo, Brazil.
  • Felipe Marticorena Applied Physiology and Nutrition Research Group, School of Physical Education and Sport; Rheumatology Division; Faculty of Medicine FMUSP, University of São Paulo, São Paulo, Brazil.
  • Tamires N. Oliveira Applied Physiology and Nutrition Research Group, School of Physical Education and Sport; Rheumatology Division; Faculty of Medicine FMUSP, University of São Paulo, São Paulo, Brazil.
  • Jozo Grgic Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia
  • Bryan Saunders Applied Physiology and Nutrition Research Group, School of Physical Education and Sport; Rheumatology Division; Faculty of Medicine FMUSP, University of SãoPaulo, São Paulo, SP



sports and exercise science, Caffeine, genetics


Introduction: The CYP1A2 -164 A>C single nucleotide polymorphism (SNP) has been identified as a possible factor influencing the exercise responses to caffeine. Methods: Six databases were searched for studies determining the effect of caffeine (except mouth rinsing) on exercise 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 conflict of interests (COI). 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 was ergolytic for CCs (SMD=-0.22, 95%CI: -0.44; -0.01, p<.0001). Dose affected only CCs, with greater doses generating larger responses (CC*dose: +0.19/1 mg/kg BM, 95%CI: 0.04; 0.33, p = 0.01). Timing influenced only CCs, with larger SMDs with later onset of exercise after supplementation (CC*timing: +0.01/minute, 95%CI: 0.00; 0.02, p = 0.02). COI only affected CCs (CC*COI: -0.57, 95%CI: -1.02; -0.12, p=0.01), and after excluding studies with COI, no influence of CYP1A2 genotype was seen (all p≥0.19). Conclusion: Caffeine improved performance for AAs and ACs, worsening performance for CCs. Dose and timing moderated the efficacy of caffeine for CCs alone. Caution is advised since studies with COI appear to heavily influence these results.


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