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The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo-controlled, crossover study



The purpose of this study was to examine the effect of CYP1A2 -163C>A polymorphism on the ergogenic effects of caffeine supplementation during a resistance exercise (RE) session.


In a randomized, double-blind, placebo (PL)-controlled, crossover study, 30 resistance-trained men took part in two RE sessions (three sets to failure at 85% of one repetition maximum, 2-min rest between sets), including bench press (BP), leg press (LP), seated cable row, and shoulder press (SP) following caffeine (CAF) (6 mg kg−1) or PL (6 mg kg−1 of maltodextrin) ingestion 1 h prior to the trial. The number of repetitions was recorded after each set, along with calculation of total number of repetitions for each exercise. Genomic DNA was isolated from the whole blood samples for analyzing the CYP1A2 -163C>A polymorphism through amplification refractory mutation system–polymerase chain reaction (ARMS–PCR). Subjects were classified as either AA (n = 14) or AC/CC genotypes (n = 16).


The two-way ANOVA with repeated measures revealed differences between AAs and AC/CCs under CAF conditions for repetitions performed in sets 1, 2, and 3 of BP (F(1, 28) = 14.84, P = 0.001, ƞ2 = 0.34), LP (F(1, 28) = 8.92, P = 0.006, ƞ2 = 0.24), SR (F(1, 28) = 17.38, P = 0.0001, ƞ2 = 0.38), and SP (F(1, 28) = 3.76, P = 0.063, ƞ2 = 0.11). CAF also increased the total number of repetitions performed for all three sets in AAs versus AC/CCs for BP (F(1, 28) = 8.72, P = 0.006, ƞ2 = 0.23), LP (F(1, 28) = 4.67, P = 0.03, ƞ2 = 0.14), SR (F(1, 28) = 5.54, P = 0.02, ƞ2 = 0.16), and SP (F(1, 28) = 3.89, P = 0.058, ƞ2 = 0.12) in athletes who were homozygous carriers of the A allele, compared to the C allele carriers. Therefore, AA homozygotes were able to carry out a greater total volume of RE work under CAF but not PL conditions, compared to the C allele carriers.


In conclusion, acute ingestion of CAF significantly enhanced RE performance in resistance-trained men who were homozygous for the A allele, but not for C allele carriers. Further studies are needed to replicate the potential role of the CYP1A2 -163C>A polymorphism on the ergogenic effects of CAF in other modes of exercise and in other populations.

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  1. Kalmar J, Cafarelli E (1999) Effects of caffeine on neuromuscular function. J Appl Physiol 87(2):801–808

    Article  CAS  PubMed  Google Scholar 

  2. Davis J, Green JM (2009) Caffeine and anaerobic performance. Sports Med 39(10):813–832

    Article  CAS  PubMed  Google Scholar 

  3. Abian-Vicen J, Puente C, Salinero JJ, González-Millán C, Areces F, Muñoz G, Muñoz-Guerra J, Del Coso J (2014) A caffeinated energy drink improves jump performance in adolescent basketball players. Amino Acids 46(5):1333–1341

    Article  CAS  PubMed  Google Scholar 

  4. Lara B, Gonzalez-Millán C, Salinero JJ, Abian-Vicen J, Areces F, Barbero-Alvarez JC, Muñoz V, Portillo LJ, Gonzalez-Rave JM, Del Coso J (2014) Caffeine-containing energy drink improves physical performance in female soccer players. Amino Acids 46(5):1385–1392

    Article  CAS  PubMed  Google Scholar 

  5. Green JM, Wickwire PJ, McLester JR, Gendle S, Hudson G, Pritchett RC, Laurent CM (2007) Effects of caffeine on repetitions to failure and ratings of perceived exertion during resistance training. Int J Sports Physiol Performance 2(3):250–259

    Article  Google Scholar 

  6. Beck TW, Housh TJ, Schmidt RJ, Johnson GO, Housh DJ, Coburn JW, Malek MH (2006) The acute effects of a caffeine-containing supplement on strength, muscular endurance, and anaerobic capabilities. J Strength Cond Res 20(3):506–510

    PubMed  Google Scholar 

  7. Jacobs I, Pasternak H, Bell DG (2003) Effects of ephedrine, caffeine, and their combination on muscular endurance. Med Sci Sports Exerc 35(6):987–994

    Article  CAS  PubMed  Google Scholar 

  8. Hoffman JR, Ratamess NA, Ross R, Shanklin M, Kang J, Faigenbaum AD (2008) Effect of a pre-exercise energy supplement on the acute hormonal response to resistance exercise. J Strength Cond Res 22(3):874–882

    Article  PubMed  Google Scholar 

  9. Burke LM (2008) Caffeine and sports performance. Appl Physiol Nutr Metab 33(6):1319–1334

    Article  CAS  PubMed  Google Scholar 

  10. Wong K, Martin B, Volland L, Rohmann R, Astorino T (2008) Effect of caffeine ingestion on resistance training performance. In: Southwest ACSM Meeting

  11. Hudson GM, Green JM, Bishop PA, Richardson MT (2008) Effects of caffeine and aspirin on light resistance training performance, perceived exertion, and pain perception. J Strength Cond Res 22(6):1950–1957

    Article  PubMed  Google Scholar 

  12. Astorino TA, Rohmann RL, Firth K (2008) Effect of caffeine ingestion on one-repetition maximum muscular strength. Eur J Appl Physiol 102(2):127–132

    Article  CAS  PubMed  Google Scholar 

  13. Williams AD, Cribb PJ, Cooke MB, Hayes A (2008) The effect of ephedra and caffeine on maximal strength and power in resistance-trained athletes. J Strength Cond Res 22(2):464–470

    Article  PubMed  Google Scholar 

  14. Butler MA, Iwasaki M, Guengerich FP, Kadlubar FF (1989) Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci 86(20):7696–7700

    Article  CAS  PubMed  Google Scholar 

  15. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270(1):414–423

    CAS  PubMed  Google Scholar 

  16. Sachse C, Brockmöller J, Bauer S, Roots I (1999) Functional significance of a C→ A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 47(4):445–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Womack CJ, Saunders MJ, Bechtel MK, Bolton DJ, Martin M, Luden ND, Dunham W, Hancock M (2012) The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. J Int Soc Sports Nutr 9(1):1

    Article  CAS  Google Scholar 

  18. Daly JW, Butts-Lamb P, Padgett W (1983) Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cell Mol Neurobiol 3(1):69–80

    Article  CAS  PubMed  Google Scholar 

  19. Thomas R, Algrain H, Ryan E, Popojas A, Carrigan P, Abdulrahman A, Carrillo A (2017) Influence of a CYP1A2 polymorphism on post-exercise heart rate variability in response to caffeine intake: a double-blind, placebo-controlled trial. Irish J Med Sci (1971-) 186(2):285–291

    Article  CAS  Google Scholar 

  20. Goldstein E, Jacobs PL, Whitehurst M, Penhollow T, Antonio J (2010) Caffeine enhances upper body strength in resistance-trained women. J Int Soc Sports Nutr 7(1):1

    Article  CAS  Google Scholar 

  21. Cox GR, Desbrow B, Montgomery PG, Anderson ME, Bruce CR, Macrides TA, Martin DT, Moquin A, Roberts A, Hawley JA (2002) Effect of different protocols of caffeine intake on metabolism and endurance performance. J Appl Physiol 93(3):990–999

    Article  PubMed  Google Scholar 

  22. Mora-Rodríguez R, Pallarés JG, López-Samanes Á, Ortega JF, Fernández-Elías VE (2012) Caffeine ingestion reverses the circadian rhythm effects on neuromuscular performance in highly resistance-trained men. PLoS One 7(4):e33807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Munir KM, Chandrasekaran S, Gao F, Quon MJ (2013) Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications. Am J Physiol Endocrin Metabol 305(6):E679–E686

    Article  CAS  Google Scholar 

  24. Baechle TR, Earle RW (2008) Essentials of strength and conditioning. In: Baechle TR, Earle RW (eds) Resistance training and spotting techniques

  25. Medrano RFV, de Oliveira CA (2014) Guidelines for the tetra-primer ARMS–PCR technique development. Mol Biotechnol 56(7):599–608

    CAS  PubMed  Google Scholar 

  26. Davis J, Green JM, Laurent CM (2012) Effects of caffeine on resistance training performance on repetitions to failure. J Caffeine Res 2(1):31–37

    Article  CAS  Google Scholar 

  27. Duncan MJ, Stanley M, Parkhouse N, Cook K, Smith M (2013) Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise. Eur J Sport Sci 13(4):392–399

    Article  PubMed  Google Scholar 

  28. Astorino TA, Martin BJ, Schachtsiek L, Wong K, Ng K (2011) Minimal effect of acute caffeine ingestion on intense resistance training performance. J Strength Cond Res 25(6):1752–1758

    Article  PubMed  Google Scholar 

  29. Duncan MJ, Oxford SW (2011) The effect of caffeine ingestion on mood state and bench press performance to failure. J Strength Cond Res 25(1):178–185

    Article  PubMed  Google Scholar 

  30. Duncan MJ, Lyons M, Hankey J (2009) Placebo effect of caffeine on short-term resistance exercise to failure. Int J Sports Physiol Performance 4:244–253

    Article  Google Scholar 

  31. Zając A, Chalimoniuk M, Gołaś A, Lngfort J, Maszczyk A (2015) Central and peripheral fatigue during resistance exercise—a critical review. J Hum Kinetics 49(1):159–169

    Article  Google Scholar 

  32. Davis J, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA (2003) Central nervous system effects of caffeine and adenosine on fatigue. Am J Phys Regul Integr Comp Phys 284(2):R399–R404

    CAS  Google Scholar 

  33. Bockman EL, Berne RM, Rubio R (1975) Release of adenosine and lack of release of ATP from contracting skeletal muscle. Pflugers Arch 355(3):229–241

    Article  CAS  PubMed  Google Scholar 

  34. Cazeneuve C, Pons G, Rey E, Treluyer J, Cresteil T, Thiroux G, d'Athis P, Olive G (1994) Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults. Br J Clin Pharmacol 37(5):405–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Górska A, Gołembiowska K (2015) The role of adenosine A1 and A2A receptors in the caffeine effect on MDMA-induced DA and 5-HT release in the mouse striatum. Neurotox Res 27(3):229–245

    Article  CAS  PubMed  Google Scholar 

  36. Karcz-Kubicha M, Antoniou K, Terasmaa A, Quarta D, Solinas M, Justinova Z, Pezzola A, Reggio R, Müller CE, Fuxe K (2003) Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Neuropsychopharmacology 28(7):1281–1291

    Article  CAS  PubMed  Google Scholar 

  37. Solinas M, Ferré S, You Z-B, Karcz-Kubicha M, Popoli P, Goldberg SR (2002) Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. J Neurosci 22(15):6321–6324

    Article  CAS  PubMed  Google Scholar 

  38. Hendrix CR, Housh TJ, Mielke M, Zuniga JM, Camic CL, Johnson GO, Schmidt RJ, Housh DJ (2010) Acute effects of a caffeine-containing supplement on bench press and leg extension strength and time to exhaustion during cycle ergometry. J Strength Cond Res 24(3):859–865

    Article  PubMed  Google Scholar 

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The author wishes to thank the subjects who volunteered for the study.


This research project was funded by the University of Kurdistan (grant number 14/20137; Monday, 13 July 2015).

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Correspondence to Rahman Rahimi.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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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 188, 337–345 (2019).

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  • Caffeine
  • CYP1A2 -163C>A polymorphism
  • Resistance exercise