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Antioxidant supplements in exercise: worse than useless?

TO THE EDITOR: In a recent paper by Higashida et al. (5), the authors report that very large doses of antioxidant vitamins do not prevent the exercise-induced adaptive responses of muscle mitochondria, GLUT4, and insulin action to exercise. As clearly stated in the paper, their data disagree with those reported by three independent research groups from Germany (14), Australia (17), and Spain (4). Using a significantly different experimental protocol regarding exercise training intensity and duration, antioxidant supplementation (doses and types of antioxidants), and molecular parameters analyzed (mRNA vs. protein levels), Higashida et al. compared their data with ours and came to exactly the opposite conclusions, i.e., that antioxidant vitamin supplementation does not have an inhibitory effect on the adaptive responses of skeletal muscle to exercise. Regarding our study published in the American Journal of Clinical Nutrition (4), we found a very significant increase (186%) in endurance time in rats after training (6 wk), which was dramatically blunted when the animals were supplemented with vitamin C (26% increment). Endurance capacity is directly related to mitochondrial content, which is why we decided to determine the mitochondrial biogenesis cascade in skeletal muscle in our animals, and we found that it was significantly hampered. Although we found a dramatic effect of vitamin C on endurance time in animals, we did not find the same effect on