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HIGHLIGHTED TOPICS
Oxygen Sensing in Health and Disease

Antioxidant intervention does not affect the response of plasma erythropoietin to short-term normobaric hypoxia in humans

¹Medical Clinic and Polyclinic, Department of Sports Medicine, University of Tuebingen, D-72074 Tuebingen; ²Department of Rehabilitative and Preventive Sports Medicine, Center of Internal Medicine, University of Freiburg, D-79106 Freiburg; ³Department of Transfusion Medicine, University of Tuebingen, D-72076 Tuebingen; and ⁴Department of Experimental Anesthesiology, Department of Anesthesiology, University of Ulm, D-89077 Ulm, Germany

Submitted 30 July 2003 ; accepted in final form 19 November 2003

Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac--tocopherol (800 mg/day for 3 wk) and -lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum -tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary PO₂ declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.

-tocopherol; -lipoic acid; lipid peroxides; erythropoesis; oxidative stress