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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

##article.authors##

  • 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 https://orcid.org/0000-0002-1613-9416
  • 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. https://orcid.org/0000-0003-0740-0683
  • 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. https://orcid.org/0000-0002-8712-4975
  • 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. https://orcid.org/0000-0001-6596-8707
  • Jozo Grgic Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia https://orcid.org/0000-0002-6929-2844
  • 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 https://orcid.org/0000-0003-0995-9077

DOI:

https://doi.org/10.51224/SRXIV.272

Keywords:

sports and exercise science, Caffeine, genetics

Abstract

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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References

Grgic, J., et al., Wake up and smell the coffee: caffeine supplementation and exercise performance-an umbrella review of 21 published meta-analyses. Br J Sports Med, 2020. 54(11): p. 681-688 DOI: 10.1136/bjsports-2018-100278.

Grgic, J. and C. Pickering, The effects of caffeine ingestion on isokinetic muscular strength: A meta-analysis. J Sci Med Sport, 2019. 22(3): p. 353-360 DOI: 10.1016/j.jsams.2018.08.016.

Doherty, M. and P.M. Smith, Effects of caffeine ingestion on exercise testing: a meta-analysis. Int J Sport Nutr Exerc Metab, 2004. 14(6): p. 626-46 DOI: 10.1123/ijsnem.14.6.626.

Daly, J.W., P. Butts-Lamb, and W. Padgett, Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cell Mol Neurobiol, 1983. 3(1): p. 69-80 DOI: 10.1007/BF00734999.

Salamone, J.D., et al., The role of adenosine in the ventral striatal circuits regulating behavioral activation and effort-related decision making: importance for normal and pathological aspects of motivation, in Adenosine. 2013, Springer. p. 493-512.

Davis, J.M., et al., Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol, 2003. 284(2): p. R399-404 DOI: 10.1152/ajpregu.00386.2002.

Southward, K., et al., The Role of Genetics in Moderating the Inter-Individual Differences in the Ergogenicity of Caffeine. Nutrients, 2018. 10(10) DOI: 10.3390/nu10101352.

Pickering, C. and J. Grgic, Caffeine and Exercise: What Next? Sports Med, 2019. 49(7): p. 1007-1030 DOI: 10.1007/s40279-019-01101-0.

Reis, C.E.G., B. Saunders, and T.H.M. da Costa, Absence of dietary control precludes solid conclusions for sport nutrition trials. J Sci Med Sport, 2021. 24(6): p. 518-519 DOI: 10.1016/j.jsams.2020.11.017.

Marticorena, F.M., et al., Nonplacebo Controls to Determine the Magnitude of Ergogenic Interventions: A Systematic Review and Meta-analysis. Med Sci Sports Exerc, 2021. 53(8): p. 1766-1777 DOI: 10.1249/MSS.0000000000002635.

Carvalho, A., et al., Can I Have My Coffee and Drink It? A Systematic Review and Meta-analysis to Determine Whether Habitual Caffeine Consumption Affects the Ergogenic Effect of Caffeine. Sports Med, 2022. 52(9): p. 2209-2220 DOI: 10.1007/s40279-022-01685-0.

Barreto, G., et al., Novel insights on caffeine supplementation, CYP1A2 genotype, physiological responses and exercise performance. Eur J Appl Physiol, 2021. 121(3): p. 749-769 DOI: 10.1007/s00421-020-04571-7.

Grgic, J., et al., CYP1A2 genotype and acute ergogenic effects of caffeine intake on exercise performance: a systematic review. Eur J Nutr, 2021. 60(3): p. 1181-1195 DOI: 10.1007/s00394-020-02427-6.

Southward, K., et al., The role of genetics in moderating the inter-individual differences in the ergogenicity of caffeine. Nutrients, 2018. 10(10): p. 1352.

Gu, L., et al., Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics, 1992. 2(2): p. 73-7 DOI: 10.1097/00008571-199204000-00004.

Sachse, C., et al., Functional significance of a C-->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol, 1999. 47(4): p. 445-9 DOI: 10.1046/j.1365-2125.1999.00898.x.

Womack, C.J., et al., The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. J Int Soc Sports Nutr, 2012. 9(1): p. 7 DOI: 10.1186/1550-2783-9-7.

Guest, N., et al., Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes. Med Sci Sports Exerc, 2018. 50(8): p. 1570-1578 DOI: 10.1249/MSS.0000000000001596.

Wong, O., et al., CYP1A2 Genotype Modifies the Effects of Caffeine Compared With Placebo on Muscle Strength in Competitive Male Athletes. Int J Sport Nutr Exerc Metab, 2021. 31(5): p. 420-426 DOI: 10.1123/ijsnem.2020-0395.

Sicova, M., et al., Caffeine, genetic variation and anaerobic performance in male athletes: a randomized controlled trial. Eur J Appl Physiol, 2021. 121(12): p. 3499-3513 DOI: 10.1007/s00421-021-04799-x.

Glaister, M., et al., Caffeine, exercise physiology, and time-trial performance: no effect of ADORA2A or CYP1A2 genotypes. Appl Physiol Nutr Metab, 2021. 46(6): p. 541-551 DOI: 10.1139/apnm-2020-0551.

Spineli, H., et al., Caffeine improves various aspects of athletic performance in adolescents independent of their 163 C> A CYP1A2 genotypes. Scandinavian journal of medicine & science in sports, 2020. 30(10): p. 1869-1877.

Carswell, A.T., et al., The effect of caffeine on cognitive performance is influenced by CYP1A2 but not ADORA2A genotype, yet neither genotype affects exercise performance in healthy adults. Eur J Appl Physiol, 2020. 120(7): p. 1495-1508 DOI: 10.1007/s00421-020-04384-8.

Grgic, J., et al., CYP1A2 genotype and acute effects of caffeine on resistance exercise, jumping, and sprinting performance. Journal of the International Society of Sports Nutrition, 2020. 17(1): p. 1-11.

Giersch, G.E., et al., The Effect of the CYP1A2− 163 C> a polymorphism on caffeine metabolism and subsequent cycling performance. Journal of Caffeine and Adenosine Research, 2018. 8(2): p. 65-70.

Klein, C.S., et al., The effect of caffeine on performance in collegiate tennis players. Journal of caffeine research, 2012. 2(3): p. 111-116.

Algrain, H.A., et al., The effects of a polymorphism in the cytochrome P450 CYP1A2 gene on performance enhancement with caffeine in recreational cyclists. Journal of Caffeine Research, 2016. 6(1): p. 34-39.

Salinero, J.J., et al., CYP1A2 Genotype Variations Do Not Modify the Benefits and Drawbacks of Caffeine during Exercise: A Pilot Study. Nutrients, 2017. 9(3) DOI: 10.3390/nu9030269.

Pataky, M.W., et al., Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day. Scand J Med Sci Sports, 2016. 26(6): p. 613-9 DOI: 10.1111/sms.12501.

Page, M.J., et al., The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 2021. 372: p. n71 DOI: 10.1136/bmj.n71.

Ouzzani, M., et al., Rayyan-a web and mobile app for systematic reviews. Syst Rev, 2016. 5(1): p. 210 DOI: 10.1186/s13643-016-0384-4.

Saunders, B., et al., beta-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis. Br J Sports Med, 2017. 51(8): p. 658-669 DOI: 10.1136/bjsports-2016-096396.

Rahimi, R., The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo-controlled, crossover study. Ir J Med Sci, 2019. 188(1): p. 337-345 DOI: 10.1007/s11845-018-1780-7.

Minaei, S., et al., CYP1A2 Genotype Polymorphism Influences the Effect of Caffeine on Anaerobic Performance in Trained Males. Int J Sport Nutr Exerc Metab, 2022. 32(1): p. 16-21 DOI: 10.1123/ijsnem.2021-0090.

Potgieter, S., The effect of caffeine supplementation on Olympic-distance triathletes and triathlon performance in the Western Cape, South Africa. 2013, Stellenbosch: Stellenbosch University.

McGrath, M.C., The significance of CYP1A2 genotype on caffeine metabolism and exercise performance: a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Human Nutrition at Massey University, Manawatu, New Zealand. 2015, Massey University.

Puente, C., et al., The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance. PLoS One, 2018. 13(4): p. e0195943 DOI: 10.1371/journal.pone.0195943.

Zhang, Y., et al., GRADE Guidelines: 19. Assessing the certainty of evidence in the importance of outcomes or values and preferences-Risk of bias and indirectness. J Clin Epidemiol, 2019. 111: p. 94-104 DOI: 10.1016/j.jclinepi.2018.01.013.

Sterne, J.A.C., et al., RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019. 366: p. l4898 DOI: 10.1136/bmj.l4898.

Borenstein, M., et al., Multiple outcomes or time-points within a study. Introduction to meta-analysis, 2009: p. 225-238.

Sawilowsky, S.S., New effect size rules of thumb. Journal of modern applied statistical methods, 2009. 8(2): p. 26.

Barreto, G., et al., Comment on "CYP1A2 Genotype Modifies the Effects of Caffeine Compared With Placebo on Muscle Strength in Competitive Male Athletes". Int J Sport Nutr Exerc Metab, 2022. 32(1): p. 62-63 DOI: 10.1123/ijsnem.2021-0239.

Stevens, C.J. and B.J. Dascombe, The reliability and validity of protocols for the assessment of endurance sports performance: an updated review. Measurement in Physical Education and Exercise Science, 2015. 19(4): p. 177-185.

Maughan, R.J., et al., IOC Consensus Statement: Dietary Supplements and the High-Performance Athlete. Int J Sport Nutr Exerc Metab, 2018. 28(2): p. 104-125 DOI: 10.1123/ijsnem.2018-0020.

Munoz, A., et al., Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players. Genes (Basel), 2020. 11(8) DOI: 10.3390/genes11080933.

Lesser, L.I., et al., Relationship between funding source and conclusion among nutrition-related scientific articles. PLoS Med, 2007. 4(1): p. e5 DOI: 10.1371/journal.pmed.0040005.

Grgic, J., Caffeine ingestion enhances Wingate performance: a meta-analysis. Eur J Sport Sci, 2018. 18(2): p. 219-225 DOI: 10.1080/17461391.2017.1394371.

Southward, K., K.J. Rutherfurd-Markwick, and A. Ali, Correction to: The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis. Sports Med, 2018. 48(10): p. 2425-2441 DOI: 10.1007/s40279-018-0967-4.

Salinero, J.J., B. Lara, and J. Del Coso, Effects of acute ingestion of caffeine on team sports performance: a systematic review and meta-analysis. Res Sports Med, 2019. 27(2): p. 238-256 DOI: 10.1080/15438627.2018.1552146.

Ferreira, T.T., J.V.F. da Silva, and N.B. Bueno, Effects of caffeine supplementation on muscle endurance, maximum strength, and perceived exertion in adults submitted to strength training: a systematic review and meta-analyses. Crit Rev Food Sci Nutr, 2021. 61(15): p. 2587-2600 DOI: 10.1080/10408398.2020.1781051.

Djordjevic, N., et al., Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 -163C>A polymorphism. Eur J Clin Pharmacol, 2010. 66(7): p. 697-703 DOI: 10.1007/s00228-010-0823-4.

Childs, E., et al., Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology, 2008. 33(12): p. 2791-800 DOI: 10.1038/npp.2008.17.

Mendes, G.F., et al., Can the Brazilian Caffeine Expectancy Questionnaires Differentiate the CYP1A2 and ADORA2A Gene Polymorphisms?-An Exploratory Study with Brazilian Athletes. Nutrients, 2022. 14(16) DOI: 10.3390/nu14163355.

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2023-03-09