The effect of caffeine dose on caffeine and paraxanthine changes in serum and saliva and CYP1A2 enzyme activity in athletes: a randomized placebo-controlled crossover trial
Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články
PubMed
39529054
PubMed Central
PMC11555877
DOI
10.1186/s12986-024-00863-3
PII: 10.1186/s12986-024-00863-3
Knihovny.cz E-zdroje
- Klíčová slova
- Enzyme activity, Ergogenic support, High-intensity functional training, Metabolism, Sports dietetics, Supplementation,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Although caffeine (CAF) supplementation has been shown to improve exercise performance, its dose-dependent effect on CAF metabolism has not been sufficiently investigated. The aim of this study was to evaluate the effects of 3, 6 and 9 mg of CAF/kgBM on changes of CAF and paraxanthine (PRX) in the serum and saliva at four time-points. METHODS: In a randomized, double-blind, placebo-controlled crossover design, acute pre-exercise supplementation in 26 moderately-trained athletes, participating in high-intensity functional training (HIFT), was examined. The study protocol involved CAF/PRX biochemical analyses of serum and saliva with respect to CYP1A2 polymorphism and CYP1A2 enzyme activity. RESULTS: Despite significant differences between the serum and saliva levels of CAF and PRX, there was no difference in the PRX/CAF ratio. The interaction effect of dose and time-points for PRX concentration was revealed. The main effects of dose were observed for CAF and the PRX/CAF ratio. The main effect of time-points was registered only for serum CAF. CONCLUSIONS: Dose- and time-dependent effect of CAF supplementation on CAF and PRX in the serum and saliva of athletes was confirmed, but there was no effect of the CAF dose on CYP1A2 enzyme activity, nor was there an interaction of CYP1A2 with enzyme inducibility. The CAF/PRX correlation indicated the possibility of interchangeable use of serum and/or saliva analyses in exercise studies. CLINICAL TRIAL REGISTRATION: This trial was registered prospectively at ClinicalTrials.gov (NCT03822663, registration date: 30/01/2019).
Department of Human Nutrition and Dietetics Poznań University of Life Sciences Poznań Poland
Department of Pedagogy Poznan University of Physical Education Poznań Poland
Department of Sports Dietetics Poznan University of Physical Education Poznań 61 871 Poland
Zobrazit více v PubMed
Nehlig A. Interindividual differences in caffeine metabolism and factors driving caffeine consumption. Pharmacol Rev. 2018;70:384–411. PubMed DOI
Arnaud MJ. Pharmacokinetics and metabolism of natural methylxanthines in animal and man. Handb Exp Pharmacol. 2011;33–91. PubMed
Reddy VS, Shiva S, Manikantan S, et al. Pharmacology of caffeine and its effects on the human body. Eur J Med Chem Rep. 2024;10:100138.
Kamimori GH, Karyekar CS, Otterstetter R, et al. The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Int J Pharm. 2002;234:159–67. PubMed DOI
Wickham KA, Spriet LL. Administration of caffeine in alternate forms. Sports Med. 2018;48:79–91. PubMed DOI PMC
Grgic J. Effects of caffeine on resistance exercise: a review of recent research. Sports Med. 2021;51:2281–98. PubMed DOI
Guest NS, VanDusseldorp TA, Nelson MT, et al. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021;18:1. PubMed DOI PMC
Urry E, Jetter A, Landolt H-P. Assessment of CYP1A2 enzyme activity in relation to type-2 diabetes and habitual caffeine intake. Nutr Metab. 2016;13:66. PubMed DOI PMC
Saunders B, da Costa LR, de Souza RAS, Barreto G, Marticorena FM. Caffeine and sport. Adv Food Nutr Res. 2023;106:95–127. PubMed DOI
van Doude LJAE, Koopmans RP, Guchelaar H-J. Two novel methods for the determination of CYP1A2 activity using the paraxanthine/caffeine ratio. Fundam Clin Pharmacol. 2003;17:355–62. PubMed DOI
Perera V, Gross AS, McLachlan AJ. Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Biom Chromatogr. 2010;24:1136–44. PubMed DOI
Perera V, Gross AS, Xu H, McLachlan AJ. Pharmacokinetics of caffeine in plasma and saliva, and the influence of caffeine abstinence on CYP1A2 metrics. J Pharm Pharmacol. 2011;63:1161–8. PubMed DOI
Perera V, Gross AS, McLachlan AJ. Measurement of CYP1A2 activity: a focus on caffeine as a probe. Curr Drug Metab. 2012;13:667–78. PubMed DOI
Grzegorzewski J, Bartsch F, Köller A, König M. Pharmacokinetics of caffeine: a systematic analysis of reported data for application in metabolic phenotyping and liver function testing. Front Pharmacol. 2022;12:752826. PubMed DOI PMC
Durkalec-Michalski K, Kamińska J, Saunders B, Pokrywka A, Łoniewski I, Steffl M, Podgórski T. Does sodium bicarbonate based extra-cellular buffering support reduce high intensity exercise-induced fatigue and enhance short-term recovery assessed by selected blood biochemical indices? Biol Sport. 2023;41:17–27. PubMed DOI PMC
Durkalec-Michalski K, Domagalski A, Główka N, Kamińska J, Szymczak D, Podgórski T. Effect of a four-week vegan diet on performance, training efficiency and blood biochemical indices in crossfit-trained participants. Nutrients. 2022;14:894. PubMed DOI PMC
Magkos F, Kavouras SA. Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Crit Rev Food Sci Nutr. 2005;45:535–62. PubMed DOI
Nieber K. The impact of coffee on health. Planta Med. 2017;83:1256–63. PubMed DOI
Główka N, Malik J, Podgórski T, Stemplewski R, Maciaszek J, Ciążyńska J, Zawieja EE, Chmurzynska A, Nowaczyk PM, Durkalec-Michalski K. The dose-dependent effect of caffeine supplementation on performance, reaction time and postural stability in CrossFit - a randomized placebo-controlled crossover trial. J Int Soc Sports Nutr. 2024;21:2301384. PubMed DOI PMC
Durkalec-Michalski K, Zawieja EE, Zawieja BE, Podgórski T. Evaluation of the repeatability and reliability of the cross-training specific Fight Gone Bad workout and its relation to aerobic fitness. Sci Rep. 2021;11:7263. PubMed DOI PMC
Durkalec-Michalski K, Nowaczyk PM, Główka N, Grygiel A. Dose-dependent effect of caffeine supplementation on judo-specific performance and training activity: a randomized placebo-controlled crossover trial. J Int Soc Sports Nutr. 2019;16:38. PubMed DOI PMC
Durkalec-Michalski K, Zawieja EE, Podgórski T, Łoniewski I, Zawieja BE, Warzybok M, Jeszka J. The effect of chronic progressive-dose sodium bicarbonate ingestion on CrossFit-like performance: A double-blind, randomized cross-over trial. PLoS ONE. 2018;13:e0197480. PubMed DOI PMC
Zawieja E, Chmurzynska A, Anioła J, Zawieja BE, Cholewa J. The effect of caffeine supplementation on resistance and jumping exercise: the interaction with CYP1A2 and ADORA2A genotypes. Nutraceuticals. 2023;3:274–89. DOI
Fuhr U, Rost KL, Engelhardt R, Sachs M, Liermann D, Belloc C, Beaune P, Janezic S, Grant D, Meyer UA, Staib AH. Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations. Pharmacogenetics. 1996;6:159–76. PubMed DOI
Fuhr U, Rost KL. Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics. 1994;4:109–16. PubMed DOI
Spigset O, Hägg S, Söderström E, Dahlqvist R. The paraxanthine:caffeine ratio in serum or in saliva as a measure of CYP1A2 activity: when should the sample be obtained? Pharmacogenetics. 1999;9:409–12. PubMed DOI
Grgic J, Grgic I, Pickering C, 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;54:681–8. PubMed DOI
Scott NR, Chakraborty J, Marks V. Determination of caffeine, theophylline and theobromine in serum and saliva using high-performance liquid chromatography. Ann Clin Biochem. 1984;21(Pt 2):120–4. PubMed DOI
Southward K, Rutherfurd-Markwick KJ, Ali A. The effect of acute caffeine ingestion on endurance performance: a systematic review and meta-analysis. Sports Med. 2018;48:1913–28. PubMed DOI
Davenport AD, Jameson TSO, Kilroe SP, Monteyne AJ, Pavis GF, Wall BT, Dirks ML, Alamdari N, Mikus CR, Stephens FB. A randomised, placebo-controlled, crossover study investigating the optimal timing of a caffeine-containing supplement for exercise performance. Sports Med Open. 2020;6:17. PubMed DOI PMC
Graham TE, Spriet LL. Metabolic, catecholamine, and exercise performance responses to various doses of caffeine. J Appl Physiol. 1995;78:867–74. PubMed DOI
Lajin B, Schweighofer N, Goessler W, Obermayer-Pietsch B. The determination of the Paraxanthine/Caffeine ratio as a metabolic biomarker for CYP1A2 activity in various human matrices by UHPLC-ESIMS/MS. Talanta. 2021;234:122658. PubMed DOI
Jacobson AF, Cerqueira MD, Raisys V, Shattuc S. Serum caffeine levels after 24 hours of caffeine abstention: observations on clinical patients undergoing myocardial perfusion imaging with dipyridamole or adenosine. Eur J Nucl Med. 1994;21:23–6. PubMed DOI
Spriet LL. Exercise and sport performance with low doses of caffeine. Sports Med. 2014;44(Suppl 2):S175–184. PubMed DOI PMC
Blanchard J, Sawers SJ. Comparative pharmacokinetics of caffeine in young and elderly men. J Pharmacokinet Biopharm. 1983;11:109–26. PubMed DOI
Benowitz NL, Jacob P III, Mayan H, Denaro C. Sympathomimetic effects of paraxanthine and caffeine in humans. Clin Pharmacol Ther. 1995;58:684–91. PubMed DOI
Collomp K, Anselme F, Audran M, Gay JP, Chanal JL, Prefaut C. Effects of moderate exercise on the pharmacokinetics of caffeine. Eur J Clin Pharmacol. 1991;40:279–82. PubMed DOI
Simmonds MJ, Minahan CL, Sabapathy S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur J Appl Physiol. 2010;109:287–95. PubMed DOI
Sampaio-Jorge F, Morales AP, Pereira R, Barth T, Ribeiro BG. Caffeine increases performance and leads to a cardioprotective effect during intense exercise in cyclists. Sci Rep. 2021;11:24327. PubMed DOI PMC
Stadheim HK, Kvamme B, Olsen R, Drevon CA, Ivy JL, Jensen J. Caffeine increases performance in cross-country double-poling time trial exercise. Med Sci Sports Exerc. 2013;45:2175–83. PubMed DOI
Skinner TL, Jenkins DG, Taaffe DR, Leveritt MD, Coombes JS. Coinciding exercise with peak serum caffeine does not improve cycling performance. J Sci Med Sport. 2013;16(1):54–9. PubMed DOI
Hetzler RK, Knowlton RG, Somani SM, Brown DD, Perkins RM 3rd. Effect of paraxanthine on FFA mobilization after intravenous caffeine administration in humans. J Appl Physiol (1985). 1990;68(1):44–7. PubMed DOI
Desbrow B, Barrett CM, Minahan CL, Grant GD, Leveritt MD. Caffeine, cycling performance, and exogenous CHO oxidation: a dose-response study. Med Sci Sports Exerc. 2009;41(9):1744–51. PubMed DOI
Robertson D, Frölich JC, Carr RK, Watson JT, Hollifield JW, Shand DG, Oates JA. Effects of caffeine on plasma renin activity, catecholamines and blood pressure. N Engl J Med. 1978;26(4):181–6. PubMed DOI
Mesquita RNO, Cronin NJ, Kyröläinen H, Hintikka J, Avela J. Effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise. Exp Physiol. 2020;105(4):690–706. PubMed DOI
Bell DG, McLellan TM. Exercise endurance 1, 3, and 6 h after caffeine ingestion in caffeine users and nonusers. J Appl Physiol. 2002;93:1227–34. PubMed DOI
Conway KJ, Orr R, Stannard SR. Effect of a divided caffeine dose on endurance cycling performance, postexercise urinary caffeine concentration, and plasma paraxanthine. J Appl Physiol (1985). 2003;94:1557–62. PubMed DOI
Skinner TL, Jenkins DG, Leveritt MD, McGorm A, Bolam KA, Coombes JS, Taaffe DR. Factors influencing serum caffeine concentrations following caffeine ingestion. J Sci Med Sport. 2014;17(5):516–20. PubMed DOI
Skinner TL, Jenkins DG, Folling J, Leveritt MD, Coombes JS, Taaffe DR. Influence of carbohydrate on serum caffeine concentrations following caffeine ingestion. J Sci Med Sport. 2013;16(4):343–7. PubMed DOI
Talanian JL, Spriet LL. Low and moderate doses of caffeine late in exercise improve performance in trained cyclists. Appl Physiol Nutr Metab. 2016;41:850–5. PubMed DOI
Desbrow B, Leveritt M. Awareness and use of caffeine by athletes competing at the 2005 Ironman Triathlon World Championships. Int J Sport Nutr Exerc Metab. 2006;16:545–58. PubMed DOI
Kovacs EM, Stegen JHCH, Brouns F. Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance. J Appl Physiol (1985). 1998;85:709–15. PubMed DOI
Nordmark A, Lundgren S, Cnattingius S, Rane A. Dietary caffeine as a probe agent for assessment of cytochrome P4501A2 activity in random urine samples. Br J Clin Pharmacol. 1999;47(4):397–402. PubMed DOI PMC
Han XM, Ou-Yang DS, Lu PX, Jiang CH, Shu Y, Chen XP, Tan ZR, Zhou HH. Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics. 2001;11(5):429–35. PubMed DOI
Guest N, Corey P, Vescovi J, El-Sohemy A, Caffeine. CYP1A2 genotype, and endurance performance in athletes. Med Sci Sports Exerc. 2018;50(8):1570–8. PubMed DOI
Dobrinas M, Cornuz J, Oneda B, Kohler Serra M, Puhl M, Eap CB. Impact of smoking, smoking cessation, and genetic polymorphisms on CYP1A2 activity and inducibility. Clin Pharmacol Ther. 2011;90(1):117–25. PubMed DOI
Gunes A, Dahl M-L. Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Pharmacogenomics. 2008;9:625–37. PubMed DOI
Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML. Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. Pharmacogenomics. 2009;10(5):769–78. PubMed DOI
Tian DD, Natesan S, White JR, Paine J. Effects of Common CYP1A2 Genotypes and Other Key Factors on Intraindividual Variation in the Caffeine Metabolic Ratio: An Exploratory Analysis. Clin Transl Sci. 2019;12(1):39–46. PubMed DOI PMC
ClinicalTrials.gov
NCT03822663