Antioxidants may counteract the health benefits of physical exercise in humans. A study involving 39 healthy young men found that exercise improves insulin sensitivity, as measured by glucose infusion rates (GIR), and increases the expression of genes related to insulin sensitivity and antioxidant defense. However, when participants took vitamin C and E supplements, these benefits were significantly reduced. Exercise increased oxidative stress markers, such as thiobarbituric acid-reactive substances (TBARS), but antioxidant supplements blocked this increase. The study also showed that exercise enhanced the expression of PGC1α, PGC1β, and PPARγ, which are involved in insulin sensitivity and antioxidant defense. Antioxidants suppressed these effects. The findings suggest that oxidative stress induced by exercise may be necessary for the health benefits of physical activity, and that antioxidant supplementation may prevent these benefits. The study supports the concept of "mitohormesis," where mild oxidative stress promotes adaptive responses that improve insulin sensitivity and antioxidant defense. The results indicate that antioxidants may interfere with the beneficial effects of exercise on insulin sensitivity and antioxidant defense in humans.Antioxidants may counteract the health benefits of physical exercise in humans. A study involving 39 healthy young men found that exercise improves insulin sensitivity, as measured by glucose infusion rates (GIR), and increases the expression of genes related to insulin sensitivity and antioxidant defense. However, when participants took vitamin C and E supplements, these benefits were significantly reduced. Exercise increased oxidative stress markers, such as thiobarbituric acid-reactive substances (TBARS), but antioxidant supplements blocked this increase. The study also showed that exercise enhanced the expression of PGC1α, PGC1β, and PPARγ, which are involved in insulin sensitivity and antioxidant defense. Antioxidants suppressed these effects. The findings suggest that oxidative stress induced by exercise may be necessary for the health benefits of physical activity, and that antioxidant supplementation may prevent these benefits. The study supports the concept of "mitohormesis," where mild oxidative stress promotes adaptive responses that improve insulin sensitivity and antioxidant defense. The results indicate that antioxidants may interfere with the beneficial effects of exercise on insulin sensitivity and antioxidant defense in humans.