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European journal of applied physiology
Dec, 2021;121 (12): 3499-3513.

Caffeine, genetic variation and anaerobic performance in male athletes: a randomized controlled trial.

Marc Sicova, Nanci S Guest, Pascal N Tyrrell, Ahmed El-Sohemy
Author Information
  1. Marc Sicova: Temerty Faculty of Medicine, Department of Nutritional Sciences, University of Toronto, 1 King's College Circle, Room 5326A, Toronto, ON, M5S 1A8, Canada.
  2. Nanci S Guest: Temerty Faculty of Medicine, Department of Nutritional Sciences, University of Toronto, 1 King's College Circle, Room 5326A, Toronto, ON, M5S 1A8, Canada.
  3. Pascal N Tyrrell: Faculty of Arts and Science, Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada.
  4. Ahmed El-Sohemy: Temerty Faculty of Medicine, Department of Nutritional Sciences, University of Toronto, 1 King's College Circle, Room 5326A, Toronto, ON, M5S 1A8, Canada. a.el.sohemy@utoronto.ca. ORCID
PMID: 34529114 DOI: 10.1007/s00421-021-04799-x

Abstract

PURPOSE: The effect of caffeine on anaerobic performance is unclear and may differ depending on an individual's genetics. The goal of this study was to determine whether caffeine influences anaerobic performance in a 30 s Wingate test, and if 14 single nucleotide polymorphisms (SNPs) in nine genes, associated with caffeine metabolism or response, modify caffeine's effects.
METHODS: Competitive male athletes (N = 100; 25 ± 4 years) completed the Wingate under three conditions: 0, 2, or 4 mg of caffeine per kg of body mass (mg kg), using a double-blinded, placebo-controlled design. Using saliva samples, participants were genotyped for the 14 SNPs. The outcomes were peak power (Watts [W]), average power (Watts [W]), and fatigue index (%).
RESULTS: There was no main effect of caffeine on Wingate outcomes. One significant caffeine-gene interaction was observed for CYP1A2 (rs762551, p = 0.004) on average power. However, post hoc analysis showed no difference in caffeine's effects within CYP1A2 genotypes for average power performance. No significant caffeine-gene interactions were observed for the remaining SNPs on peak power, average power and fatigue index.
CONCLUSION: caffeine had no effect on anaerobic performance and variations in several genes did not modify any effects of caffeine.
TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (NCT02109783).

Keywords

Anaerobic Caffeine Exercise Genetics Nutrigenomics Wingate

Associated Data

ClinicalTrials.gov | NCT02109783

References

  1. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci 97(14):8104–8109 [PMID: 10884434]
  2. Aguilar-Navarro M, Muñoz G, Salinero JJ, Muñoz-Guerra J, Fernández-Álvarez M, Plata MDM, Del Coso J (2019) Urine caffeine concentration in doping control samples from 2004 to 2015. Nutrients. https://doi.org/10.3390/nu11020286 [DOI: 10.3390/nu11020286]
  3. Amin N et al (2012) Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Mol Psychiatry 17:1116–1129 [PMID: 21876539]
  4. Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW (2013) Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc 88(10):1127–1140. https://doi.org/10.1016/j.mayocp.2013.06.012 [PMID: 24079682]
  5. Bangsbo J, Graham T, Johansen L, Saltin B (1994) Muscle lactate metabolism in recovery from intense exhaustive exercise: impact of light exercise. J Appl Physiol 77:1890–1895 [PMID: 7836214]
  6. Bar-Or O (1987) The Wingate anaerobic test. An update on methodology, reliability and validity. Sports Med 4:381–394. https://doi.org/10.2165/00007256-198704060-00001 [DOI: 10.2165/00007256-198704060-00001]
  7. Baumgart D et al (1999) Augmented α-adrenergic constriction of atherosclerotic human coronary arteries. Circulation 99:2090–2097 [PMID: 10217647]
  8. Berger M, Gray JA, Roth BL (2009) The expanded biology of serotonin. Annu Rev Med 60:355–366 [PMID: 5864293]
  9. Berthou F, Flinois J-P, Ratanasavanh D, Beaune P, Riche C, Guillouzo A (1991) Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes. Drug Metab Dispos 19:561–567 [PMID: 1680620]
  10. Bhatia A, Lenchner JR, Saadabadi A (2020) Biochemistry, Dopamine Receptors. StatPearls [Internet]
  11. Black A, Yang Q, Wen SW, Lalonde AB, Guilbert E, Fisher W (2009) Contraceptive use among Canadian women of reproductive age: results of a national survey. J Obstet Gynaecol Can 31:627–640 [PMID: 19761636]
  12. Broberg S, Sahlin K (1989) Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol 67:116–122 [PMID: 2759935]
  13. Burke LM (2008) Caffeine and sports performance. Appl Physiol Nutr Metab 33:1319–1334. https://doi.org/10.1139/h08-130 [DOI: 10.1139/h08-130]
  14. Burton DA, Stokes K, Hall GM (2004) Physiological effects of exercise. Contin Edu Anaesth Crit Care Pain 4:185–188
  15. Bylund DB, Blaxall HS, Iversen LJ, Caron MG, Lefkowitz RJ, Lomasney JW (1992) Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol 42:1–5 [PMID: 1353247]
  16. Cohen J (1992) A power primer. Psychol Bull 112:155 [PMID: 19565683]
  17. Collomp K, Ahmaidi S, Audran M, Chanal JL, Préfaut C (1991) Effects of caffeine ingestion on performance and anaerobic metabolism during the Wingate test. Int J Sports Med 12:439–443. https://doi.org/10.1055/s-2007-1024710 [DOI: 10.1055/s-2007-1024710]
  18. Collomp K, Ahmaidi S, Chatard JC, Audran M, Préfaut C (1992) Benefits of caffeine ingestion on sprint performance in trained and untrained swimmers. Eur J Appl Physiol Occup Physiol 64:377–380. https://doi.org/10.1007/bf00636227 [DOI: 10.1007/bf00636227]
  19. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141 [PMID: 16522833]
  20. Costa F, Diedrich A, Johnson B, Sulur P, Farley G, Biaggioni I (2001) Adenosine, a metabolic trigger of the exercise pressor reflex in humans. Hypertension 37:917–922. https://doi.org/10.1161/01.hyp.37.3.917 [DOI: 10.1161/01.hyp.37.3.917]
  21. Daly JW (1982) Adenosine receptors: targets for future drugs. J Med Chem 25:197–207. https://doi.org/10.1021/jm00345a001 [DOI: 10.1021/jm00345a001]
  22. Day Tasevski EL, Cahill L, Garofalo F, Eny K, El-Sohemy A (2009) Beta2-adrenergic receptor (ADRB2) genotype is associated with acute effects and withdrawal symptoms of caffeine. Fed Am Soc Exp Biol J 23:725
  23. Denden S, Bouden B, Haj Khelil A, Ben Chibani J, Hamdaoui MH (2016) Gender and ethnicity modify the association between the CYP1A2 rs762551 polymorphism and habitual coffee intake: evidence from a meta-analysis. Genet Mol Res. https://doi.org/10.4238/gmr.15027487 [DOI: 10.4238/gmr.15027487]
  24. Dishy V, Sofowora GG, Xie H-G, Kim RB, Byrne DW, Stein CM, Wood AJ (2001) The effect of common polymorphisms of the β2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med 345:1030–1035 [PMID: 11586955]
  25. Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E (2008) Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur J Clin Pharmacol 64:381–385 [PMID: 18157525]
  26. Doherty M, Smith PM (2005) Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis. Scand J Med Sci Sports 15:69–78. https://doi.org/10.1111/j.1600-0838.2005.00445.x [DOI: 10.1111/j.1600-0838.2005.00445.x]
  27. Duncan MJ, Eyre E, Grgic J, Tallis J (2019) The effect of acute caffeine ingestion on upper and lower body anaerobic exercise performance. Eur J Sport Sci 19:1359–1366 [PMID: 31013204]
  28. Duncker DJ, Bache RJ (2008) Regulation of coronary blood flow during exercise. Physiol Rev 88:1009–1086 [PMID: 18626066]
  29. Dunwiddie TV (1985) The physiological role of adenosine in the central nervous system. Int Rev Neurobiol 27:63–139. https://doi.org/10.1016/s0074-7742(08)60556-5 [DOI: 10.1016/s0074-7742(08)60556-5]
  30. Englert C, Bertrams A (2012) Anxiety, ego depletion, and sports performance. J Sport Exerc Psychol 34:580–599 [PMID: 23027229]
  31. Gardner SA, Martin TD, Barras M, Jenkins GD, Hahn GA (2005) Power output demands of elite track sprint cycling. Int J Perform Anal Sport 5:149–154
  32. Gellekink H, Muntjewerff J-W, Vermeulen SHHM, Hermus ARMM, Blom HJ, Heijer Md (2007) Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk. Thromb Haemost 98:1226–1231 [PMID: 18064318]
  33. Ghotbi R, Christensen M, Roh H-K, Ingelman-Sundberg M, Aklillu E, Bertilsson L (2007) Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol 63:537–546 [PMID: 17370067]
  34. Giovannitti JA Jr, Thoms SM, Crawford JJ (2015) Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog 62:31–38 [PMID: 25849473]
  35. Grabe HJ, Spitzer C, Schwahn C, Marcinek A, Frahnow A, Barnow S, Lucht M, Freyberger HJ, John U, Wallaschofski H (2009) Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. Am J Psychiatry 166(8):926–933 [PMID: 19487392]
  36. Greer F, Morales J, Coles M (2006) Wingate performance and surface EMG frequency variables are not affected by caffeine ingestion. Appl Physiol Nutr Metab 31:597–603 [PMID: 17111014]
  37. Grgic J, Mikulic P (2020) Acute effects of caffeine supplementation on resistance exercise, jumping, and Wingate performance: no influence of habitual caffeine intake. Eur J Sport Sci 21:1–29
  38. Grgic J, Pickering C, Bishop DJ, Del Coso J, Schoenfeld BJ, Tinsley GM, Pedisic Z (2020) ADOR2A C allele carriers exhibit ergogenic responses to caffeine supplementation. Nutrients 1:2. https://doi.org/10.3390/nu12030741 [DOI: 10.3390/nu12030741]
  39. Guest N, Corey P, Vescovi J, El-Sohemy A (2018) Caffeine, CYP1A2 genotype, and endurance performance in athletes. Med Sci Sports Exerc 50:1570–1578. https://doi.org/10.1249/mss.0000000000001596 [DOI: 10.1249/mss.0000000000001596]
  40. Guest NS et al (2021) International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr 18:1–37 [PMID: 33388079]
  41. Guest NS, Corey P, Tyrrell PN, El-Sohemy A (2020) Effect of caffeine on endurance performance in athletes may depend on HTR2A and CYP1A2 genotypes. J Strength Cond Res:1–7
  42. Higgins JP, Babu KM (2013) Caffeine reduces myocardial blood flow during exercise. Am J Med 126:730.e731-738. https://doi.org/10.1016/j.amjmed.2012.12.023 [DOI: 10.1016/j.amjmed.2012.12.023]
  43. Hirvonen M, Laakso A, Någren K, Rinne J, Pohjalainen T, Hietala J (2005) Erratum: C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo. Mol psychiatry 10(9):889
  44. Hukkanen J, Jacob P III, Peng M, Dempsey D, Benowitz NL (2011) Effect of nicotine on cytochrome P450 1A2 activity. Br J Clin Pharmacol 72:836 [PMID: 21599724]
  45. Inbar O, Bar-Or O, Skinner JS (1996) The Wingate anaerobic test. John Wiley & Sons, Hoboken
  46. Insel PA (1996) Adrenergic receptors—evolving concepts and clinical implications. N Engl J Med 334:580–585 [PMID: 8569827]
  47. Josse AR, Da Costa LA, Campos H, El-Sohemy A (2012) Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumption. Am J Clin Nutr 96:665–671. https://doi.org/10.3945/ajcn.112.038794 [DOI: 10.3945/ajcn.112.038794]
  48. Kamal S, Lappin SL (2019) Biochemistry. Catecholamine Degradation. StatPearls Publishing, Treasure Island
  49. Khait VD, Huang Y-Y, Zalsman G, Oquendo MA, Brent DA, Harkavy-Friedman JM, Mann JJ (2005) Association of serotonin 5-HT 2A receptor binding and the T102C polymorphism in depressed and healthy caucasian subjects. Neuropsychopharmacology 30(1):166–172 [PMID: 15483560]
  50. Klimek V, Schenck JE, Han H, Stockmeier CA, Ordway GA (2002) Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study. Biol psychiatry 52(7):740–748 [PMID: 12372665]
  51. Latini S, Pedata F (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem 79:463–484. https://doi.org/10.1046/j.1471-4159.2001.00607.x [DOI: 10.1046/j.1471-4159.2001.00607.x]
  52. Lesch K-P, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527–1531 [PMID: 8929413]
  53. Lynch T, Price AL (2007) The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am fam physician 76(3):391–396 [PMID: 17708140]
  54. Miyagi WE, Bertuzzi RC, Nakamura FY, de Poli RAB, Zagatto AM (2018) Effects of caffeine ingestion on anaerobic capacity in a single supramaximal cycling test. Front Nutr 5:86. https://doi.org/10.3389/fnut.2018.00086 [DOI: 10.3389/fnut.2018.00086]
  55. Muszkat M et al (2010) Desensitization of vascular response in vivo: contribution of genetic variation in the [alpha]2B-adrenergic receptor subtype. J Hypertens 28:278–284 [PMID: 20051907]
  56. Nardin M, Verdoia M, Negro F, Suryapranata H, Khedi E, De Luca G (2020) Relationship between adenosine A2a receptor polymorphism rs5751876 and fractional flow reserve during percutaneous coronary intervention. Heart Vessels 35:1349–1359 [PMID: 32367186]
  57. Overgaard M et al (2012) Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain. FASEB J 26:3012–3020. https://doi.org/10.1096/fj.11-191999 [DOI: 10.1096/fj.11-191999]
  58. Palatini P et al (2009) CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27:1594–1601 [PMID: 19451835]
  59. Paton C, Costa V, Guglielmo L (2015) Effects of caffeine chewing gum on race performance and physiology in male and female cyclists. J Sports Sci 33:1076–1083. https://doi.org/10.1080/02640414.2014.984752 [DOI: 10.1080/02640414.2014.984752]
  60. Pickering C, Grgic J (2019) Caffeine and exercise: What next? Sports Med 49:1–24 [PMID: 30560423]
  61. Porras G, Di Matteo V, Fracasso C, Lucas G, De Deurwaerdère P, Caccia S, Esposito E, Spampinato U (2002) 5-HT 2A and 5-HT 2C/2B receptor subtypes modulate dopamine release induced in vivo by amphetamine and morphine in both the rat nucleus accumbens and striatum. Neuropsychopharmacology 26(3):311–324 [PMID: 11850146]
  62. Reihsaus E, Innis M, MacIntyre N, Liggett SB (1993) Mutations in the gene encoding for the 132-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 8:334–339 [PMID: 8383511]
  63. Robertson D, Frölich JC, Carr RK, Watson JT, Hollifield JW, Shand DG, Oates JA (1978) Effects of caffeine on plasma renin activity, catecholamines and blood pressure. N Engl J Med 298:181–186 [PMID: 339084]
  64. Salinero JJ et al (2017) CYP1A2 genotype variations do not modify the benefits and drawbacks of caffeine during exercise: a pilot study. Nutrients. https://doi.org/10.3390/nu9030269 [DOI: 10.3390/nu9030269]
  65. San Juan AF et al (2019) Caffeine supplementation improves anaerobic performance and neuromuscular efficiency and fatigue in olympic-level boxers. Nutrients. https://doi.org/10.3390/nu11092120 [DOI: 10.3390/nu11092120]
  66. Skinner TL, Jenkins DG, Coombes JS, Taaffe DR, Leveritt MD (2010) Dose response of caffeine on 2000-m rowing performance. Med Sci Sports Exerc 42:571–576. https://doi.org/10.1249/MSS.0b013e3181b6668b [DOI: 10.1249/MSS.0b013e3181b6668b]
  67. Smith CR, Eberly J, Steckbeck RJ, Wright MR, Shenk B, Shin M, Kieffer HS (2019) The influence of caffeine and the− 163 A> C CYP1A2 polymorphism on peak and mean power during a Wingate test. FASEB J 33:839
  68. Snyder EM, Johnson BD, Joyner MJ (2008) Genetics of β2-adrenergic receptors and the cardiopulmonary response to exercise. Exerc Sport Sci Rev 36:98 [PMID: 18362692]
  69. van Dijk R, Ties D, Kuijpers D, van der Harst P, Oudkerk M (2018) Effects of caffeine on myocardial blood flow: a systematic review. Nutrients. https://doi.org/10.3390/nu10081083 [DOI: 10.3390/nu10081083]
  70. Wilkins BW, Pike TL, Martin EA, Curry TB, Ceridon ML, Joyner MJ (2008) Exercise intensity-dependent contribution of β-adrenergic receptor-mediated vasodilatation in hypoxic humans. J Physiol 586:1195–1205 [PMID: 18048452]
  71. Wise RA (2005) Forebrain substrates of reward and motivation. J Comp Neurol 493(1):115–121 [PMID: 16254990]
  72. Womack CJ et al (2012) The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. J Int Soc Sports Nutr 9:7. https://doi.org/10.1186/1550-2783-9-7 [DOI: 10.1186/1550-2783-9-7]
  73. Woolf K, Bidwell WK, Carlson AG (2008) The effect of caffeine as an ergogenic aid in anaerobic exercise. Int J Sport Nutr Exerc Metab 18:412–429. https://doi.org/10.1123/ijsnem.18.4.412 [DOI: 10.1123/ijsnem.18.4.412]
  74. Yamada Y, Nakazato Y, Ohga A (1989) The mode of action of caffeine on catecholamine release from perfused adrenal glands of cat. Br J Pharmacol 98:351 [PMID: 2819322]
  75. Zhang G, Stackman RW Jr (2015) The role of serotonin 5-HT2A receptors in memory and cognition. Front Pharmacol 6:225 [PMID: 26500553]
  76. Zupan MF, Arata AW, Dawson LH, Wile AL, Payn TL, Hannon ME (2009) Wingate anaerobic test peak power and anaerobic capacity classifications for men and women intercollegiate athletes. J Strength Cond Res 23:2598–2604 [PMID: 19910814]

MeSH Term

Anaerobiosis
Athletes
Athletic Performance
Caffeine
Cytochrome P-450 CYP1A2
Double-Blind Method
Genetic Variation
Genotype
Humans
Male
Performance-Enhancing Substances
Polymorphism, Single Nucleotide

Chemicals

Performance-Enhancing Substances
Caffeine
CYP1A2 protein, human
Cytochrome P-450 CYP1A2
Journal Article
Article has an altmetric score of 5

Word Cloud

Created with Highcharts 10.0.0caffeinepowerperformanceanaerobicWingateaverageeffectSNPseffectsCaffeinestudy14genesmodifycaffeine'smaleoutcomespeakWatts[W]fatigueindexsignificantcaffeine-geneobservedCYP1A2PURPOSE:unclearmaydifferdependingindividual'sgeneticsgoaldeterminewhetherinfluences30 stestsinglenucleotidepolymorphismsnineassociatedmetabolismresponseMETHODS:CompetitiveathletesN = 10025 ± 4 yearscompletedthreeconditions:024 mgperkgbodymassmg kgusingdouble-blindedplacebo-controlleddesignUsingsalivasamplesparticipantsgenotyped%RESULTS:mainOneinteractionrs762551p = 0004HoweverposthocanalysisshoweddifferencewithingenotypesinteractionsremainingCONCLUSION:variationsseveralTRIALREGISTRATION:registeredclinicaltrialsgovNCT02109783geneticvariationathletes:randomizedcontrolledtrialAnaerobicExerciseGeneticsNutrigenomics

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