Top

European Journal of Applied Physiology

Published in:

01-12-2021 | Original Article

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

Authors: Marc Sicova, Nanci S. Guest, Pascal N. Tyrrell, Ahmed El-Sohemy

Published in: European Journal of Applied Physiology | Issue 12/2021

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⁻¹), 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).

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):8104–8109PubMedPubMedCentral

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/nu11020286CrossRefPubMedPubMedCentral

Amin N et al (2012) Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Mol Psychiatry 17:1116–1129PubMed

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.2013.06.012PubMed

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 77:1890–1895PubMed

Bar-Or O (1987) The Wingate anaerobic test. An update on methodology, reliability and validity. Sports Med 4:381–394. https://doi.org/10.2165/00007256-198704060-00001CrossRefPubMed

Baumgart D et al (1999) Augmented α-adrenergic constriction of atherosclerotic human coronary arteries. Circulation 99:2090–2097PubMed

Berger M, Gray JA, Roth BL (2009) The expanded biology of serotonin. Annu Rev Med 60:355–366PubMedPubMedCentral

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 19:561–567PubMed

Bhatia A, Lenchner JR, Saadabadi A (2020) Biochemistry, Dopamine Receptors. StatPearls [Internet]

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 31:627–640PubMed

Broberg S, Sahlin K (1989) Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol 67:116–122PubMed

Burke LM (2008) Caffeine and sports performance. Appl Physiol Nutr Metab 33:1319–1334. https://doi.org/10.1139/h08-130CrossRefPubMed

Burton DA, Stokes K, Hall GM (2004) Physiological effects of exercise. Contin Edu Anaesth Crit Care Pain 4:185–188

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 42:1–5PubMed

Cohen J (1992) A power primer. Psychol Bull 112:155PubMed

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-2007-1024710CrossRefPubMed

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/bf00636227CrossRefPubMed

Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141PubMed

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.37.3.917CrossRefPubMed

Daly JW (1982) Adenosine receptors: targets for future drugs. J Med Chem 25:197–207. https://doi.org/10.1021/jm00345a001CrossRefPubMed

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

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.15027487CrossRefPubMed

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 345:1030–1035PubMed

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 64:381–385PubMed

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.xCrossRefPubMed

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 19:1359–1366PubMed

Duncker DJ, Bache RJ (2008) Regulation of coronary blood flow during exercise. Physiol Rev 88:1009–1086PubMed

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)60556-5CrossRefPubMed

Englert C, Bertrams A (2012) Anxiety, ego depletion, and sports performance. J Sport Exerc Psychol 34:580–599PubMed

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

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 98:1226–1231PubMed

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 63:537–546PubMed

Giovannitti JA Jr, Thoms SM, Crawford JJ (2015) Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog 62:31–38PubMedPubMedCentral

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):926–933PubMed

Greer F, Morales J, Coles M (2006) Wingate performance and surface EMG frequency variables are not affected by caffeine ingestion. Appl Physiol Nutr Metab 31:597–603PubMed

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

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/nu12030741CrossRef

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.0000000000001596CrossRefPubMed

Guest NS et al (2021) International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr 18:1–37PubMedPubMedCentral

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

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.2012.12.023CrossRef

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

Hukkanen J, Jacob P III, Peng M, Dempsey D, Benowitz NL (2011) Effect of nicotine on cytochrome P450 1A2 activity. Br J Clin Pharmacol 72:836PubMedPubMedCentral

Inbar O, Bar-Or O, Skinner JS (1996) The Wingate anaerobic test. John Wiley & Sons, Hoboken

Insel PA (1996) Adrenergic receptors—evolving concepts and clinical implications. N Engl J Med 334:580–585PubMed

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.112.038794CrossRefPubMed

Kamal S, Lappin SL (2019) Biochemistry. Catecholamine Degradation. StatPearls Publishing, Treasure Island

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):166–172PubMed

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):740–748PubMed

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.xCrossRefPubMed

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):1527–1531PubMed

Lynch T, Price AL (2007) The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am fam physician 76(3):391–396PubMed

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.2018.00086CrossRefPubMedPubMedCentral

Muszkat M et al (2010) Desensitization of vascular response in vivo: contribution of genetic variation in the [alpha]2B-adrenergic receptor subtype. J Hypertens 28:278–284PubMedPubMedCentral

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 35:1349–1359PubMed

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.11-191999CrossRefPubMed

Palatini P et al (2009) CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27:1594–1601PubMed

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/10.1080/02640414.2014.984752CrossRefPubMed

Pickering C, Grgic J (2019) Caffeine and exercise: What next? Sports Med 49:1–24PubMed

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):311–324PubMed

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 8:334–339PubMed

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 298:181–186PubMed

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/nu9030269CrossRefPubMedPubMedCentral

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/nu11092120CrossRefPubMedPubMedCentral

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.0b013e3181b6668bCrossRefPubMed

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

Snyder EM, Johnson BD, Joyner MJ (2008) Genetics of β2-adrenergic receptors and the cardiopulmonary response to exercise. Exerc Sport Sci Rev 36:98PubMedPubMedCentral

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/nu10081083CrossRefPubMedPubMedCentral

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 586:1195–1205PubMed

Wise RA (2005) Forebrain substrates of reward and motivation. J Comp Neurol 493(1):115–121PubMedPubMedCentral

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/10.1186/1550-2783-9-7CrossRefPubMedPubMedCentral

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.18.4.412CrossRefPubMed

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 98:351PubMedPubMedCentral

Zhang G, Stackman RW Jr (2015) The role of serotonin 5-HT2A receptors in memory and cognition. Front Pharmacol 6:225PubMedPubMedCentral

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 23:2598–2604PubMed

Title: Caffeine, genetic variation and anaerobic performance in male athletes: a randomized controlled trial
Authors: Marc Sicova
Nanci S. Guest
Pascal N. Tyrrell
Ahmed El-Sohemy
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Applied Physiology / Issue 12/2021
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-021-04799-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Trial registration

Please log in to get access to this content

Other articles of this Issue 12/2021

A critical review of citrulline malate supplementation and exercise performance

Influence of the MCT1-T1470A polymorphism (rs1049434) on repeated sprint ability and blood lactate accumulation in elite football players: a pilot study

Sex differences in cardiovascular adaptations in recreational marathon runners

Bolus intravenous 0.9% saline leads to interstitial permeability pulmonary edema in healthy volunteers

Contralateral strength training attenuates muscle performance loss following anterior cruciate ligament (ACL) reconstruction: a randomised-controlled trial

Negligible epimuscular myofascial force transmission between the human rectus femoris and vastus lateralis muscles in passive conditions