CYP1A2 (Sitokrom P450 1A2) Genotiplerine (AA, AC, CC) Göre Kafein Metabolizma Hızlarının Atletik Performansa Etkileri

Öz

Kafein, psikoaktif etkileri nedeniyle uyarıcı olarak birçok insanın tercihi halini almıştır. Farklı türevleri ile birçok alan ve amaçla kullanılan kafein, egzersiz üzerindeki etkileri ile de spor bilimciler tarafından yakından takip edilmektedir. Yine, uzun yıllardır araştırılan bir konu olarak kafein ve genotip ilişkisi, ülkemiz için azınlıkta ve yeni sayılabilir. Bu çalışma, karaciğerde kafein metabolizmasından sorumlu Sitokrom P450 1A2 enzimini kodlayan CYP1A2 genotiplerine göre, kafein metabolizma hızlarının performansa etkisini incelemek amacıyla yapılmıştır. Çalışma, derleme türünde, konu ile yakından ilgili çalışmaların araştırılması, incelenmesi ve sonuçların yorumlanması oluşturulmuştur. İlgili araştırma sonuçlarına yoğun olarak, ulusal tıp kütüphanesi temelinde bilimsel araştırmalar içeren PubMed.gov sitesinden ulaşım sağlanmıştır. Kafein üzerine yapılan çalışmalarda, alım zamanı, dozu, egzersiz tipi gibi parametrelerde daha net ifadeler görülürken, sonuçların genotip ile olan ilişkisi ve nedeni ile ilgili henüz tam anlamıyla net ifadeler oluşmamıştır. Çünkü, kafein ile genotip ilişkisinde olumlu sonuçlar gösteren çalışmaların oranı kadar olumsuz sonuçlar gösteren çalışmalar da mevcuttur. Bu da çelişkiye neden olmaktadır. Şu anda, mevcut veriler, hangi genotipin kafein takviyesinden en fazla faydayı görebileceğini belirtmek için yetersiz gibi görünmektedir. AA homozigotlarının varlığını gösteren bazı kanıtlar olsa da zayıftır. Bu nedenle, CYP1A2 genotipini belirlemek için yapılan genetik testler şu anda yeterli sonuçlara ulaşma olanağı vermediğinden gerekli olup olmadığının tartışmaya açık olduğu düşünülmektedir.

Anahtar Kelimeler

• Cyp1a2
• Kafein
• Genotip
• Atletik Performans
• Egzersiz

The Effects of Caffeine Metabolism Velocity on Athletic Performance According To CYP1A2 (Citocrome P450 1A2) Genotypes (AA, AC, CC)

Abstract

Times Caffeine has become the choice of many people as a stimulant due to its psychoactive effects. Caffeine, which is used in many fields and purposes with its different derivatives, is closely followed by sports scientists with its effects on exercise. Again, as a subject that has been researched for many years, the relationship between caffeine and genotype can be considered a minority and new for our country. This study was carried out to examine the effect of caffeine metabolism rates on performance according to CYP1A2 genotypes encoding the Cytochrome P450 1A2 enzyme responsible for caffeine metabolism in the liver. The study was formed in the type of compilation, researching and examining the studies closely related to the subject and interpreting the results. The relevant research results were accessed from the PubMed.gov site, which contains scientific research on the basis of the national medical library. In studies on caffeine, clearer expressions were observed in parameters such as intake time, dose, and exercise type, but there was no clear statement yet about the relationship between the results and the genotype and the reason. Because there are studies showing negative results as well as a ratio of studies showing positive results in the relationship between caffeine and genotype. This causes a contradiction. Currently, the available data appear to be insufficient to indicate which genotype may see the most benefit from caffeine supplementation. There is some evidence for the existence of AA homozygotes, but it is weak. Therefore, it is controversial whether genetic testing to determine the CYP1A2 genotype is necessary, as it currently does not provide sufficient results.

Keywords

• Cyp1a2
• Caffeine
• Genotype
• Athletic Performance
• Exercise

Kaynakça

1. Ahmetov, I. I., Fedotovskaya O. N. (2015). Current progress in sports genomics. Adv Clin Chem, 70, 247–314.
2. Ahmetov, I. I., Hall, E. C. R., Semenova, E. A., Pranckevičienė, E., Ginevičienė, V. (2022). Advances in sports genomics. In: Advances in clinical chemistry. Elsevier, 107, 215-263.
3. Algrain, H. A., Thomas, R. M., Carrillo, A. E., Ryan, E. J., Kim, C. H., Robert, B., Lettan, I. I., Ryan, E. J. (2016). The effects of a polymorphism in the cytochrome P450 CYP1A2 gene on performance enhancement with caffeine in recreational cyclists. J Caffeine Res, 6, 34-39.
4. Barreto, G., Grecco, B., Merola, P., Reis, C. E. G., Gualano, B., Saunders, B. (2021). Novel insights on caffeine supplementation, CYP1A2 genotype, physiological responses and exercise performance. European Journal of Applied Physiology, 121, 749-769.
5. Barry, R. J., Rushby, JA., Wallace, MJ., Clarke, AR., Johnstone, SJ., Zlojutro, I. (2005). Caffeine effects on resting-state arousal. Clin Neurophysiol, 116(11), 2693-700.
6. Beaudoin, M. S., Graham, T. E. (2011). Methylxanthines and human health: epidemiological and experimental evidence. Handb Exp Pharmacol, 200, 509-548.
7. Begas, E., Kouvaras, E., Tsakalof, A., Papakosta, S., Asprodini, E. K. (2007). In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratios. Biomed Chromatogr, 21(2), 190-200.
8. Benowitz, N. L., Jacob, P., Mayan, H., Denaro, C. (1995). Sympathomimetic effects of paraxanthine and caffeine in humans. Clin Pharmacol Ther, 58(6), 684-691.

9. Burke, L. M. (2008). Caffeine and sports performance. Appl Physiol Nutr Metab, 33, 1319-1334.
10. Carswell, A. T., Howland, K., Martinez-Gonzalez, B., Baron, P., Davison, G. (2020). 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, 120, 1495-1508.
11. Charney, D. S., Heninger, G. R., Jatlow, P. I. (1985). Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry, 42(3), 233-43.
12. Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K., Hannia Campos, H. (2006). Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA, 295(10), 1135-41.
13. Davenport, A. D., Jameson, T. S. O., Kilroe, S. P., Monteyne, A. J., Pavis, G. F., Wall, B. T., Dirks, M. L., Alamdari, N., Mikus, C. R., Stephens, F. B. (2020). A randomised, placebo-controlled, crossover study investigating the optimal timing of a caffeine-containing supplement for exercise performance. Sports Med Open, 6(1), 17.
14. Davis, J. M., Zhao, Z., Stock, H. S., Mehl, K. A., Buggy, J., Hand, G. A. (2003) Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol, 284(2), R399-404.
15. Del Coso, J., Munoz, G., Munoz-Guerra, J. (2011). Prevalence of caffeine use in elite athletes following its removal from the World Anti-Doping Agency list of banned substances. Appl Physiol Nutr Metab, 36, 555-561.
16. 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(4), 381-5.
17. Drake, C., Roehrs, T., Shambroom, J., Roth, T. (2013). Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med, 9(11), 1195-200.
18. Dunican, I. C., Higgins, C. C., Jones, M. J., Clarke, M. W., Murray, K., Dawson, B., John A Caldwell, J. A., Halson, S. L., Eastwood, P. R. (2018). Caffeine use in a Super Rugby game and its relationship to post-game sleep. Eur J Sport Sci, 18(4), 513-23.
19. Ganio, M. S., Klau, J. F., Casa, D. J., Armstrong, L. E., Maresh, C. M. (2009). Effect of caffeine on sport-specific endurance performance: a systematic review. J Strength Cond Res, 23, 315-324.
20. Ghotbi, R., Christensen, M., Roh, HR., Ingelman-Sundberg, M., Aklillu, E., Leif Bertilsson, L. (2007). Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol, 63(6), 537-46.
21. Giersch, G. E. W., Boyett, J. C., Hargens, T. A., Luden, N. D., Saunders, M. J., Daley, H., Hughey, C. A., El-Sohemy, A., Womack, C. J. (2018). The effect of the CYP1A2-163 C>A polymorphism on caffeine metabolism and subsequent cycling performance. J Caffeine Adenosine Res, 8, 65-70.
22. Grgic, J., Grgic, I., Pickering, C., Schoenfeld, B. J., Bishop, D. J., Pedisic, Z. (2020). Wake up and smell the coffee: caffeine supplementation and exercise performance-an umbrella review of 21 published meta-analyses. Br J Sports Med, 54, 681-688.
23. Grgic, J., Pickering, C., Bishop, D. J., Schoenfeld, B. J., Mikulic, P., Pedisic, Z. (2020). CYP1A2 genotype and acute effects of caffeine on resistance exercise, jumping, and sprinting performance. J Int Soc Sports Nutr, 17, 21.
24. Grgic, J., Mikulic, P., Schoenfeld, B. J., Bishop, D. J., Pedisic, Z. (2019). The influence of caffeine supplementation on resistance exercise: a review. Sports Med, 49, 17-30.
25. Grgic, J., Trexler, E. T., Lazinica, B., Pedisic, Z. (2018). Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr, 15, 11.
26. Guest, N., Corey, P., Vescovi, J., El-Sohemy, A. (2018). Caffeine, CYP1A2 genotype, and endurance performance in athletes. Med Sci Sports Exerc, 50(8), 1570-8.
27. Han, X. X., Bonen, A. (1998). Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle. Am J Physiol, 274(4), E700-707.
28. Hill, A. V. (1925). The physiological basis of athletic records1. Nature, 116(2919), 544-548.
29. Jenkins, N. T., Trilk, J. L., Singhal, A., O’Connor, P. J., Cureton, K. J. (2008). Ergogenic effects of low doses of caffeine on cycling performance. Int J Sport Nutr Exerc Metab, 18, 328-342.
30. Koonrungsesomboon, N., Khatsri, R., Wongchompoo, P., Teekachunhatean, S. (2018). The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. The Pharmacogenomics Journal, 18(6), 760-768.
31. Laurent, D., Schneider, K. E., Prusaczyk, W. K., Franklin, C., Vogel, S. M., Krssak, M., Petersen, K. F., Goforth, H. W., Shulman, G. I. (2000). Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise. J Clin Endocrinol Metab, 85(6), 2170-2175.
32. Lopes-Silva, J. P., Silva Santos, J. F., Branco, B. H., Abad, C. C., Oliveira, L. F., Loturco, I., Franchini, E. (2015). Caffeine ingestion increases estimated glycolytic metabolism during taekwondo combat simulation but does not improve performance or parasympathetic reactivation. PLoS ONE, 10(11), e0142078.
33. Loureiro, L. M., Reis, C. E., da Costa, T. H. (2018). Effects of coffee components on muscle glycogen recovery: a systematic review. Int J Sport Nutr Exerc Metab, 28(3), 284-93.
34. McLellan, T. M., Caldwell, J. A., Lieberman, H. R. (2016). A review of caffeine’s effects on cognitive, physical and occupational performance. Neurosci Biobehav Rev, 71, 294-312.
35. Meeusen, R., Roelands, B., Spriet, L. L. (2013). Caffeine, exercise and the brain. Nestle Nutr Inst Workshop Ser, 76, 1-12.
36. Mitchell, D. C., Knight, C. A., Hockenberry, J., Teplansky, R., Hartman, T. J. (2014). Beverage caffeine intakes in the U.S. Food Chem Toxicol, 63, 136-142.
37. Muñoz, A., López-Samanes, Á., Aguilar-Navarro, M., Varillas-Delgado, D., Rivilla-García, J., Moreno-Pérez, V., Del Coso, J. (2020). Effects of CYP1A2 and ADORA2A genotypes on the ergogenic response to caffeine in professional handball players. Genes, 11(8), 933.
38. Namdar, M., Schepis, T., Koepfli, P., Gaemperli, O., Siegrist, P. T., Grathwohl, R., Valenta, I., Delaloye, R., Klainguti, M., Wyss, C. A., Lüscher, T. F., Kaufmann, P. A. (2009). Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controls. PLoS ONE, 4(5), e5665.
39. Nehlig, A. (2018). Interindividual differences in caffeine metabolism and factors driving caffeine consumption. Pharmacol Rev, 70, 384-411.
40. Nehlig, A., Daval, J. L., Debry, G. (1992). Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev, 17(2), 139-170.
41. Palatini, P., Benetti, E., Mos, L., Garavelli, G., Mazzer, A., Cozzio, S., Fania, C., Casiglia, E. (2015). Association of coffee consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive patients. Eur J Epidemiol, 30(3), 209-17.
42. Palatini, P., Ceolotto, G., Ragazzo, F., Dorigatti, F., Saladini, F., Papparella, I., Mos, L., Zanata, G., Massimo Santonastaso, M. (2009). CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens, 27(8), 1594-601.
43. Pataky, M.W., Womack, C. J., Saunders, M. J., Goffe, J. L., D'Lugos, A. C., El-Sohemy, A., Luden, N. D. (2016). Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day. Scand J Med Sci Sports, 26(6), 613-9.
44. Pickering, C., Kiely, J. (2018). Are the current guidelines on caffeine use in sport optimal for everyone? Inter-individual variation in caffeine ergogenicity, and a move towards personalised sports nutrition. Sports Med, 48(1), 7-16.
45. Poole, D. C., Burnley, M., Vanhatalo, A., Rossiter, H. B., Jones, A. M. (2016). Critical power: an important fatigue threshold in exercise physiology. Med Sci Sports Exerc, 48(11), 2320-2334.
46. Puente, C., Abian-Vicen, J., Del Coso, J., Lara, B., Salinero, J. J. (2018). The CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performance. PLoS ONE, 13(4), e0195943.
47. Rahimi, R. (2019). 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.
48. Retey, J. V., Adam, M., Khatami, R., Luhmann, U. F., Jung, H. H., Berger, W., Landolt, H. P. (2007). A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther, 81, 692-698.
49. Rivers, W. H., Webber, H. N. (1907). The action of caffeine on the capacity for muscular work. J Physiol, 36, 33-47.
50. Ruiz-Moreno, C., Gutierrez-Hellin, J., Amaro-Gahete, F. J., Gonzalez-Garcia, J., Giraldez-Costas, V., Perez-Garcia, V., Del Coso, J. (2021). Caffeine increases whole-body fat oxidation during 1 h of cycling at Fatmax. Eur J Nutr. 60(4), 2077-2085.
51. Sabol, F., Grgic, J., Mikulic, P. (2019). The effects of 3 different doses of caffeine on jumping and throwing performance: a randomized, double-blind, crossover study. Int J Sports Physiol Perform, 14, 1170-1177.
52. 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, 445-9.
53. Salinero, J. J., Lara, B., Ruiz-Vicente, D., Areces, F., Puente-Torres, C., Gallo-Salazar, C., Pascual, T., Coso, J. D. (2017). CYP1A2 genotype variations do not modify the benefits and drawbacks of caffeine during exercise: A pilot study. Nutrients, 9(3), 269.
54. Santos Rde, A., Kiss, M. A., Silva-Cavalcante, M. D., Correia-Oliveira, C. R., Bertuzzi, R., Bishop, D. J., Lima-Silva, A. E. (2013). Caffeine alters anaerobic distribution and pacing during a 4000-m cycling time trial. PLoS ONE, 8(9), e75399.
55. Silva-Cavalcante, M. D., Correia-Oliveira, C. R., Santos, R. A., Lopes-Silva, J. P., Lima, H. M., Bertuzzi, R., Duarte, M., Bishop, D. J., Lima-Silva, A. E. (2013). Caffeine increases anaerobic work and restores cycling performance following a protocol designed to lower endogenous carbohydrate availability. PLoS ONE, 8(8), e72025.
56. Southward, K., Rutherfurd-Markwick, K. J., Ali, A. (2018). The effect of acute caffeine ingestion on endurance performance: a systematic review and meta-analysis. Sports Med, 48, 1913-1928.
57. Spineli, H., Pinto, M. P., Dos Santos, B. P., Lima-Silva, A. E., Bertuzzi, R., Gitaí, D. L. G., de Araujo, G. G. (2020). Caffeine improves various aspects of athletic performance in adolescents independent of their 163 C>A CYP1A2 genotypes. Scand J Med Sci Sports, 30(10), 1869-1877.
58. Tarnopolsky, M. A., Atkinson, S. A., MacDougall, J. D., Sale, D. G., Sutton, J. R. (1989). Physiological responses to caffeine during endurance running in habitual caffeine users. Med Sci Sports Exerc, 21(4), 418-424.
59. Varillas Delgado, D., Telleria Orriols, J. J., Monge Martin, D., Del Coso, J. (2020). Genotype scores in energy and iron-metabolising genes are higher in elite endurance athletes than in nonathlete controls. Appl Physiol Nutr Metab, 45(11), 1225-1231.
60. Varillas Delgado, D., Telleria Orriols, J. J., Saborido, C. M. (2019). Liver-metabolizing genes and their relationship to the performance of elite Spanish male endurance athletes; a prospective transversal study. Sports Med Open, 5(1), 50.
61. Varillas-Delgado, D., Telleria Orriols, J. J., Del Coso, J. (2021). Genetic profile in genes associated with cardiorespiratory fitness in elite spanish male endurance athletes. Genes, 12(8), 1230.
62. Vinetti, G., Taboni, A., Bruseghini, P., Camelio, S., D’Elia, M., Fagoni, N., Moia, C., Ferretti, G. (2019). Experimental validation of the 3-parameter critical power model in cycling. Eur J Appl Physiol, 119(4), 941-949.
63. Womack, C. J., Saunders, M. J., Bechtel, M. K., Bolton, D. J., Martin, M., Luden, N. D., Dunham, W., Hancock, M. (2012). The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine. J Int Soc Sports Nutr, 9(1), 7.