Allopurinol does not reduce exercise induced muscle damage in ultra-marathon runners.
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1 Allopurinol does not reduce exercise induced muscle damage in ultra-marathon runners. DR PAUL R. MASON MBBS (HONS), B. PHYSIO, MASTERS OCC. HEALTH DR JONATHAN KING FACSEP, FRACGP, MSC SPORT SCIENCE
2 Exercise induced muscle damage. novel or unaccustomed exercise soreness and swelling reduced power reduces ability to perform subsequent bouts of exercise
3 Mechanisms of exercise induced muscle damage. Mechanical muscle contraction shock impulses Reactive oxygen species unbalanced valence shell oxidise amino acids oxidise cell membrane damage of DNA / RNA
4 Biopsy findings in exercise induced muscle damage. Structural changes Cell necrosis
5 Serology of exercise induced muscle damage. released intra-cellular elements Creatine Kinase Lactate Dehydrogenase Aspartate Aminotransferase oxidised cell membranes Lipid peroxidation Produces malondialdehyde
6 Production of reactive oxygen species (1/2) ~2% of oxygen in ETC forms ROS by-product of oxygen metabolism
7 Production of reactive oxygen species (2/2) Xanthine oxidase activity Purine metabolism Produces ROS Found in many tissues liver intestines endothelium lungs relative hypoxia increases activity
8 Active metabolite oxypurinol Inhibits xanthine oxidase Half life /- 6.0 hours Reduces ROS production Allopurinol
9
10 Past research
11 Allopurinol and Markers of Muscle Damage Among Participants in the Tour de France Significant differences (placebo vs allopurinol) CK (P=0.03) AST (P=0.02) Malondialdehyde (P=0.009) Gómez-Cabrera, M.-C., Pallardó, F. V., Sastre, J., Viña, J., & García-del-Moral, L. (2003). JAMA, 289(19),
12 Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players. Significant differences (placebo vs allopurinol) CK LDH AST Myoglobin Malondialdehyde (P<0.05) (P<0.05) (P<0.05) (P<0.05) (P<0.05) Sanchis-Gomar, F., Pareja-Galeano, H., Gomez-Cabrera, M. C., Candel, J., Lippi, G., Salvagno, G. L., Viña, J. (2015). Scandinavian Journal of Medicine & Science in Sports, 25(1), e
13 Oxidative stress in marathon runners: interest of antioxidant supplementation. Placebo: increase in malondialdehyde (P<0.05) Allopurinol: no significant change in malondialdehyde Between group: no significant difference Gomez-Cabrera, M.-C., Martínez, A., Santangelo, G., Pallardó, F. V., Sastre, J., & Viña, J. (2006). The British Journal of Nutrition, 96 Suppl 1, S31 33.
14 Hypothesis Prophylactic allopurinol may lead to reduced exercise induced muscle damage by reducing oxidative stress in ultramarathon runners.
15 Ultra-marathons >42km Often extreme conditions >3,000 ultra-marathons annually globally
16 Great North Walk 100 s km 3,800m ascent/descent 22 hour limit km 6,200m ascent/descent 36 hour limit Check points ~25km apart (eat, drink and rest)
17 Methodology Recruitment via 13 runners (8 male, 5 female) Pre-event blood test baseline renal/hepatic function baseline uric acid levels Test dose 300mg allopurinol/placebo Dose night before event (300mg) Dose on morning of event (300mg) Post event blood test 48 hours post event
18
19 Results (1/2) Sex Distance (km) Time Group CK (pre) CK (post) LDH (pre) LDH (post) AST (pre) AST (post) Male :57:00 allopurinol Male :37:00 allopurinol Male :07:00 allopurinol Male :19:00 allopurinol Female :41:00 allopurinol Female :15:00 allopurinol Male :04:00 placebo Male 85 15:00:00 placebo Male :42:00 placebo Male :15:00 placebo Female :02:00 placebo Female :42:00 placebo
20 Results (2/2) Control (n = 6) Allopurinol (n = 6) Allopurinol vs. Control Pre Post Pre Post Betweencondition changes (Cohen s d) % Chances Benefical/ Trivial/Harmful CK (U/L) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 24/15/62 LDH (U/L) ( ) ( ) 71.8 ( ) ( ) ( ) 89.8 ( ) 0.43 ( ) 56/10/34 AST (U/L) 22.5 ( ) 58.3 ( ) 35.8 (5-66.6) 23.7 ( ) 55.8 ( ) 32.2 ( ) ( ) 36/6/58
21 Discussion Shock impulses vs muscle contraction Running vs. skiing Event duration vs oxypurinol half life 4 runners >30 hours Re-analysis did not change results
22 Conclusion Premature to discount benefits of prophylactic allopurinol in reducing oxidative stress Malondialdehyde useful to assess oxidative stress directly Future research should focus on Low impact activities Event duration <17 hours
23 Questions.
24 Assumpção, C. de O., Lima, L. C. R., Oliveira, F. B. D., Greco, C. C., & Denadai, B. S. (2013). Exercise-Induced Muscle Damage and Running Economy in Humans. The Scientific World Journal, Brancaccio, P., Lippi, G., & Maffulli, N. (2010). Biochemical markers of muscular damage. Clinical Chemistry and Laboratory Medicine, 48(6), Day, R. O., Graham, G. G., Hicks, M., McLachlan, A. J., Stocker, S. L., & Williams, K. M. (2007). Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clinical Pharmacokinetics, 46(8), Gomez-Cabrera, M.-C., Martínez, A., Santangelo, G., Pallardó, F. V., Sastre, J., & Viña, J. (2006). Oxidative stress in marathon runners: interest of antioxidant supplementation. The British Journal of Nutrition, 96 Suppl 1, S Gómez-Cabrera, M.-C., Pallardó, F. V., Sastre, J., Viña, J., & García-del-Moral, L. (2003). Allopurinol and markers of muscle damage among participants in the Tour de France. JAMA, 289(19), Grobler, L. A., Collins, M., Lambert, M. I., Sinclair-Smith, C., Derman, W., St Clair Gibson, A., & Noakes, T. D. (2004). Skeletal muscle pathology in endurance athletes with acquired training intolerance. British Journal of Sports Medicine, 38(6), Hill, J. A., Howatson, G., van Someren, K. A., Walshe, I., & Pedlar, C. R. (2014). Influence of compression garments on recovery after marathon running. Journal of Strength and Conditioning Research / National Strength & Conditioning Association, 28(8), Hopkins, W. G., Marshall, S. W., Batterham, A. M., & Hanin, J. (2009). Progressive statistics for studies in sports medicine and exercise science. Medicine and Science in Sports and Exercise, 41(1), Sanchis-Gomar, F., Pareja-Galeano, H., Gomez-Cabrera, M. C., Candel, J., Lippi, G., Salvagno, G. L., Viña, J. (2015). Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players. Scandinavian Journal of Medicine & Science in Sports, 25(1), e Sastre, J., Asensi, M., Gascó, E., Pallardó, F. V., Ferrero, J. A., Furukawa, T., & Viña, J. (1992). Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration. The American Journal of Physiology, 263(5 Pt 2), R Worldwide Ultramarathon Calendar. (2016, November 4). Retrieved April 11, 2016, from
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