Serum Bilirubin Concentrations and the Prevalence of Gilbert Syndrome in Elite Athletes
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
MH CZ-DRO-VFN64165
Ministerstvo Zdravotnictví Ceské Republiky
SVV 260156/2021
Univerzita Karlova v Praze
Progres Q25/LF1
Univerzita Karlova v Praze
PubMed
35759151
PubMed Central
PMC9237193
DOI
10.1186/s40798-022-00463-6
PII: 10.1186/s40798-022-00463-6
Knihovny.cz E-zdroje
- Klíčová slova
- Bilirubin, Elite athletes, Gene predisposition, Gilbert syndrome, Sports performance, UGT1A1 gene promoter,
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Bilirubin is a potent endogenous antioxidant and immunomodulating substance, which is also implicated in both cell signalling and various metabolic pathways. Mild elevation of systemic bilirubin concentrations provides substantial protection against many diseases of civilization. Rare published reports have suggested that serum bilirubin might also be relevant to sports performance. The purpose of the current study was to evaluate serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in elite athletes. METHODS: The study was carried out in 536 consecutive healthy elite athletes and in 2594 individuals of the Czech post-MONICA study representing the general Czech population. Serum bilirubin concentrations, the prevalence of benign hyperbilirubinemia > 17 µmol/L (1 mg/dL, a phenotypic sign of GS), and a variant of the UGT1A1 gene promoter responsible for GS manifestation in Caucasians (rs81753472) were evaluated in study subjects. RESULTS: Compared to the general Czech population, significantly higher serum bilirubin concentrations were found in elite athletes (9.6 vs. 11.6 µmol/L, p < 0.001), both in men (11.3 vs. 12.6 µmol/L, p < 0.001) and women (8.3 vs. 10.5 µmol/L, p < 0.001). Furthermore, the prevalence of GS was also significantly higher in elite athletes (9.6 vs. 22%, p < 0.001) together with the tendency to higher frequencies of the genotypes (TA)7/7 and (TA)6/7 UGT1A1. CONCLUSION: Elite athletes have significantly higher concentrations of serum bilirubin, the most potent endogenous antioxidant substance known. Simultaneously, the prevalence of GS syndrome is also much higher in elite athletes, suggesting that a mild elevation of serum bilirubin might predispose to better sports performance.
Slovak Army Sport Centre Dukla Banská Bystrica Banská Bystrica Slovak Republic
Sports Research Institute of the Czech Armed Forces Prague Czech Republic
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Ji LL. Exercise-induced modulation of antioxidant defense. Ann N Y Acad Sci. 2002;959:82–92. doi: 10.1111/j.1749-6632.2002.tb02085.x. PubMed DOI
Vargas-Mendoza N, Morales-Gonzalez A, Madrigal-Santillan EO, et al. Antioxidant and adaptative response mediated by Nrf2 during physical exercise. Antioxidants. 2019;8(6):196. doi: 10.3390/antiox8060196. PubMed DOI PMC
Radak Z, Chung HY, Koltai E, et al. Exercise, oxidative stress and hormesis. Age Res Rev. 2008;7:34–42. doi: 10.1016/j.arr.2007.04.004. PubMed DOI
Stocker R, Yamamoto Y, McDonagh AF, et al. Bilirubin is an antioxidant of possible physiological importance. Science. 1987;235:1043–1046. doi: 10.1126/science.3029864. PubMed DOI
Pettersson J, Hindorf U, Persson P, et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol. 2008;65:253–259. doi: 10.1111/j.1365-2125.2007.03001.x. PubMed DOI PMC
Gunina LM, Mylashyus K, Voitenko VL. Physiological and hereditary hyperbilirubinemia in athletes: role in reducing efficiency and correction methodology. Ukr J Med Biol Sport. 2020;5:386–393. doi: 10.26693/jmbs05.05.386. DOI
Sedlak TW, Snyder SH. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics. 2004;113:1776–1782. doi: 10.1542/peds.113.6.1776. PubMed DOI
Wu TW, Fung KP, Yang CC. Unconjugated bilirubin inhibits the oxidation of human low-density-lipoprotein better than Trolox. Life Sci. 1994;54:Pl477–Pl481. doi: 10.1016/0024-3205(94)90140-6. PubMed DOI
Baranano DE, Rao M, Ferris CD, et al. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci U S A. 2002;99:16093–16098. doi: 10.1073/pnas.252626999. PubMed DOI PMC
Jangi S, Otterbein L, Robson S. The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int J Biochem Cell Biol. 2013;45:2843–2851. doi: 10.1016/j.biocel.2013.09.014. PubMed DOI
Vitek L, Tiribelli CT. Bilirubin, intestinal integrity, the microbiome, and inflammation. New Eng J Med. 2020;383:684–686. doi: 10.1056/NEJMcibr2013250. PubMed DOI
Vitek L. Bilirubin as a signaling molecule. Med Res Rev. 2020;40:1335–1351. doi: 10.1002/med.21660. PubMed DOI
Vitek L, Tiribelli C. Bilirubin: The yellow hormone? J Hepatol. 2021;75:1485–1490. doi: 10.1016/j.jhep.2021.06.010. PubMed DOI
Vitek L. Bilirubin as a predictor of diseases of civilization. Is it time to establish decision limits for serum bilirubin concentrations? Arch Biochem Biophys. 2019;672:108062. doi: 10.1016/j.abb.2019.108062. PubMed DOI
Vitek L, Ostrow JD. Bilirubin chemistry and metabolism; harmful and protective aspects. Curr Pharm Des. 2009;15:2869–2883. doi: 10.2174/138161209789058237. PubMed DOI
Lin JP, Vitek L, Schwertner HA. Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for cardiovascular disease. Clin Chem. 2010;56:1535–1543. doi: 10.1373/clinchem.2010.151043. PubMed DOI
Vitek L, Bellarosa C, Tiribelli C. Induction of mild hyperbilirubinemia: Hype or real therapeutic opportunity? Clin Pharmacol Ther. 2019;106:568–575. doi: 10.1002/cpt.1341. PubMed DOI
Andelkovic M, Baralic I, Dordevic B, et al. Hematological and biochemical parameters in elite soccer players during a competitive half season. J Med Biochem. 2015;34:460–466. doi: 10.2478/jomb-2014-0057. PubMed DOI PMC
Zalavras A, Fatouros IG, Deli CK, et al. Age-related responses in circulating markers of redox status in healthy adolescents and adults during the course of a training macrocycle. Oxid Med Cell Long. 2015;2015:283921. doi: 10.1155/2015/283921. PubMed DOI PMC
Telford RD, Sly GJ, Hahn AG, et al. Footstrike is the major cause of hemolysis during running. J Appl Physiol. 1985;2003(94):38–42. doi: 10.1152/japplphysiol.00631.2001. PubMed DOI
Kratz A, Lewandrowski KB, Siegel AJ, et al. Effect of marathon running on hematologic and biochemical laboratory parameters, including cardiac markers. Am J Clin Pathol. 2002;118:856–863. doi: 10.1309/14TY-2TDJ-1X0Y-1V6V. PubMed DOI
Miller BJ, Pate RR, Burgess W. Foot impact force and intravascular hemolysis during distance running. Int J Sports Med. 1988;9:56–60. doi: 10.1055/s-2007-1024979. PubMed DOI
Hammouda O, Chtourou H, Chaouachi A, et al. Effect of short-term maximal exercise on biochemical markers of muscle damage, total antioxidant status, and homocysteine levels in football players. Asian J Sports Med. 2012;3:239–246. doi: 10.5812/asjsm.34544. PubMed DOI PMC
Neubauer O, Reichhold S, Nics L, et al. Antioxidant responses to an acute ultra-endurance exercise: impact on DNA stability and indications for an increased need for nutritive antioxidants in the early recovery phase. Br J Nutr. 2010;104:1129–1138. doi: 10.1017/S0007114510001856. PubMed DOI
Priest JB, Oei TO, Moorehead WR. Exercise-induced changes in common laboratory tests. Am J Clin Pathol. 1982;77:285–289. doi: 10.1093/ajcp/77.3.285. PubMed DOI
Banfi G, Colombini A, Lombardi G, et al. Metabolic markers in sports medicine. Adv Clin Chem. 2012;56:1–54. doi: 10.1016/b978-0-12-394317-0.00015-7. PubMed DOI
Eremiasova L, Hubacek JA, Danzig V, et al. Serum bilirubin in the czech population- relationship to the risk of myocardial infarction in males. Circ J. 2020;84:1779–1785. doi: 10.1253/circj.CJ-20-0192. PubMed DOI
Cifkova R, Bruthans J, Wohlfahrt P, et al. 30-year trends in major cardiovascular risk factors in the Czech population, Czech MONICA and Czech post-MONICA, 1985–2016/17. PLoS ONE. 2020;15:e0232845. doi: 10.1371/journal.pone.0232845. PubMed DOI PMC
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215. doi: 10.1093/nar/16.3.1215. PubMed DOI PMC
Jiraskova A, Lenicek M, Vitek L. Simultaneous genotyping of microsatellite variations in HMOX1 and UGT1A1 genes using multicolored capillary electrophoresis. Clin Biochem. 2010;43:697–699. doi: 10.1016/j.clinbiochem.2010.01.006. PubMed DOI
Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981;78:6858–6862. doi: 10.1073/pnas.78.11.6858. PubMed DOI PMC
Fabbrini E, Serafini M, Colic Baric I, et al. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects. Diabetes. 2014;63:976–981. doi: 10.2337/db13-1396. PubMed DOI PMC
Roche M, Rondeau P, Singh NR, et al. The antioxidant properties of serum albumin. FEBS Lett. 2008;582:1783–1787. doi: 10.1016/j.febslet.2008.04.057. PubMed DOI
Schulpis KH, Tsironi M, Skenderi K, et al. Dramatic reduction of erythrocyte glucose-6-phosphate dehydrogenase activity in athletes participating in the ultradistance foot race "Spartathlon". Scand J Clin Lab Invest. 2008;68:228–232. doi: 10.1080/00365510701604610. PubMed DOI
Banfi G, Di Gaetano N, Lopez RS, et al. Decreased mean sphered cell volume values in top-level rugby players are related to the intravascular hemolysis induced by exercise. Lab Hematol. 2007;13:103–107. doi: 10.1532/LH96.07012. PubMed DOI
Reinke S, Karhausen T, Doehner W, et al. The influence of recovery and training phases on body composition, peripheral vascular function and immune system of professional soccer players. PLoS ONE. 2009;4:e4910. doi: 10.1371/journal.pone.0004910. PubMed DOI PMC
Cazzola R, Russo-Volpe S, Cervato G, et al. Biochemical assessments of oxidative stress, erythrocyte membrane fluidity and antioxidant status in professional soccer players and sedentary controls. Eur J Clin Invest. 2003;33:924–930. doi: 10.1046/j.1365-2362.2003.01227.x. PubMed DOI
Andersson C, Weeke P, Fosbol EL, et al. Acute effect of weight loss on levels of total bilirubin in obese, cardiovascular high-risk patients: an analysis from the lead-in period of the Sibutramine cardiovascular outcome trial. Metabolism. 2009;58:1109–1115. doi: 10.1016/j.metabol.2009.04.003. PubMed DOI
Seyed Khoei N, Grindel A, Wallner M, et al. Mild hyperbilirubinaemia as an endogenous mitigator of overweight and obesity: implications for improved metabolic health. Atherosclerosis. 2018;269:306–311. doi: 10.1016/j.atherosclerosis.2017.12.021. PubMed DOI
Pietrocola F, Bravo-San Pedro JM. Targeting autophagy to counteract obesity-associated oxidative stress. Antioxidants. 2021;10(1):102. doi: 10.3390/antiox10010102. PubMed DOI PMC
Hinds TD, Jr, Creeden JF, Gordon DM, et al. Rats genetically selected for high aerobic exercise capacity have elevated plasma bilirubin by upregulation of hepatic biliverdin reductase-A (BVRA) and suppression of UGT1A1. Antioxidants. 2020;9(9):889. doi: 10.3390/antiox9090889. PubMed DOI PMC
Swift DL, Johannsen NM, Earnest CP, et al. Effect of different doses of aerobic exercise training on total bilirubin levels. Med Sci Sports Exer. 2012;44:569–574. doi: 10.1249/MSS.0b013e3182357dd4. PubMed DOI PMC
Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the US population: gender effect and inverse correlation with colorectal cancer. Hepatology. 2004;40:827–835. doi: 10.1002/hep.20407. PubMed DOI
Fallon KE. The clinical utility of screening of biochemical parameters in elite athletes: analysis of 100 cases. Br J Sports Med. 2008;42:334–337. doi: 10.1136/bjsm.2007.041137. PubMed DOI
Witek K, Scislowska J, Turowski D, et al. Total bilirubin in athletes, determination of reference range. Biol Sport. 2017;34:45–48. doi: 10.5114/biolsport.2017.63732. PubMed DOI PMC
Kapitonova AN, Kruglova IV, Chadina AB. Hyperbilirubinemia in the sport of higher achievement. Sovr Vop Biomed. 2018;2:16–22.
Makarova GA, Kholyavko YA, Verlina GV. Clinical laboratory examination of top class athletes: basic lines of improvement. Lecheb Fizkult Sport Med. 2013;115:4–13.
Michailidis Y, Karagounis LG, Terzis G, et al. Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. Am J Clin Nutr. 2013;98:233–245. doi: 10.3945/ajcn.112.049163. PubMed DOI
Bogdanis GC, Stavrinou P, Fatouros IG, et al. Short-term high-intensity interval exercise training attenuates oxidative stress responses and improves antioxidant status in healthy humans. Food Chem Toxicol. 2013;61:171–177. doi: 10.1016/j.fct.2013.05.046. PubMed DOI
Fatouros IG, Jamurtas AZ, Villiotou V, et al. Oxidative stress responses in older men during endurance training and detraining. Med Sci Sports Exer. 2004;36:2065–2072. doi: 10.1249/01.Mss.0000147632.17450.Ff. PubMed DOI
Varamenti E, Tod D, Pullinger SA. Redox homeostasis and inflammation responses to training in adolescent athletes: a systematic review and meta-analysis. Sports Med Open. 2020;6:34. doi: 10.1186/s40798-020-00262-x. PubMed DOI PMC
Margaritelis NV, Paschalis V, Theodorou AA, et al. Redox basis of exercise physiology. Redox Biol. 2020;35:101499. doi: 10.1016/j.redox.2020.101499. PubMed DOI PMC
Hinds TD, Jr, Stec DE. Bilirubin, a cardiometabolic signaling molecule. Hypertension. 2018;72:788–795. doi: 10.1161/HYPERTENSIONAHA.118.11130. PubMed DOI PMC
Vitek L. Bilirubin and atherosclerotic diseases. Physiol Res. 2017;66(Suppl 1):S11–20. doi: 10.33549/physiolres.933581. PubMed DOI
The physiology of bilirubin: health and disease equilibrium
Cutting edge concepts: Does bilirubin enhance exercise performance?