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To the Editor: Strenuous physical exercise, when performed to the point of exhaustion, can generate free radicals that can cause muscle damage.¹ We have previously reported that xanthine oxidase, a free radical–generating enzyme involved in the ischemia-reperfusion syndrome, may cause damage associated with exhaustive exercise.² In this study, we tested whether allopurinol (a xanthine oxidase inhibitor) would affect markers of muscle damage among participants in a strenuous sporting event.

Methods
The Tour de France is a 3-week bicycle race that includes flat, mountain, and team trial tests. The latter is the most grueling, as each team member must try to produce his best possible individual time. The 9-member US Postal cycling team was randomly divided into 2 groups by drawing lots. One group of 4 participants was given a daily oral dose of 300 mg of allopurinol (an inhibitor of xanthine oxidase) 1 hour before each racing stage; the other 5 participants received placebo.

We obtained venous blood samples 15 hours after each stage studied (ie, when the activity of cytosolic enzymes in plasma is expected to be maximal if cellular damage occurs). Samples were obtained 1 day before the race began and after the 2nd, 4th (the team time trial), 8th, 10th, and 13th stages. Creatine kinase and aspartate aminotransferase activities were measured in plasma as indexes of tissue damage.³ Plasma lipid peroxide levels were determined by measuring malondialdehyde using a high-performance liquid chromatography method.⁴

We compared mean values using repeated-measures analysis of variance, with P values adusted for multiple comparisons with the Scheffe test. We obtained approval from an ethics board. Officials of the US Postal Team were aware of our study. Allopurinol is not among the list of drugs prohibited by the Tour de France.

Results
Among participants who received placebo we found an increase in activities of creatine kinase and aspartate aminotransferase in plasma only after the team time trial stage, in which participants performed at their peak level of exertion. Such an increase was not found among participants who received allopurinol (Figure 1). We also found evidence of an increase in malondialehyde in all participants at the end of the race, but the increase was significantly greater in the placebo group than in the allopurinol group (0.59 vs 0.21 nmol/mL, P = .009) However, there was no difference in performance between the 2 groups.

View larger version (51K): [in this window] [in a new window] Figure. Plasma Activity of Creatine Kinase and Aspartate Aminotransferase in US Postal Team Cyclists Who Received Placebo or Allopurinol During the 2001 Tour de France

Comment
Xanthine oxidase is a free radical–generating enzyme that is involved in the pathophysiology of the ischemia-reperfusion syndrome. Our results suggest that it is involved in the tissue damage that occurs in exhaustive exercise.

AUTHOR INFORMATION
Funding/Support: This work was supported by grant BFI-2001-2849 from the Comisión Interministerial de Ciencia y Tecnologia Spain.

Mari-Carmen Gómez-Cabrera, PhD; Federico V. Pallardó, MD, PhD; Juan Sastre, PhD; Jose Viña, PhD, MD
Departamento de Fisiología Facultad de Medicina Valencia
Valencia, Spain

Luis García-del-Moral, MD
Medical Department, US Postal Cycling Team
Instituto de Medicina del Deporte
Valencia

1. Sastre J, Asensi M, Gascó E, Ferrero JA, Furukawa T, Viña J. Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration. Am J Physiol. 1992;263:R992-R995. 2. Viña J, Gomez-Cabrera MC, Lloret A, et al. Free Radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants. IUBMB Life. 2000;50:271-277. FULL TEXT | ISI | PUBMED 3. Sorichter S, Mair J, Koller A, et al. Creatine kinase, myosin heavy chains and magnetic resonance imaging after eccentric exercise. J Sports Sci. 2001;19:687-691. FULL TEXT | PUBMED 4. de la Asuncion JG, del Olmo ML, Sastre J, et al. AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria: prevention by antioxidant vitamins. J Clin Invest. 1998;102:4-9. ISI | PUBMED

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2003;289:2503-2504.

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