Antioxidants prevent health-promoting effects of physical exercise in humans

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Abstract: Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C (1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic, euglycemic clamp in previously untrained (n = 19) and pretrained (n = 20) healthy young men. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P < 0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity, peroxisome-proliferator-activated receptor gamma (PPARγ), and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense (superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.

Comment: Questions are raised about the type of challenge, in that non trained athletes would typically expect to have a graded introduction into activity a longer period may have facilitated accommodation of ROS without alteration of markers. The size of the group also makes for limited extrapolation of effect and in reality the duration of effect is likely to be very short many other studies have shown that continuous exposure to ROS does not lead to these markers (PGCl-alpha, PGCl-beta, and PPAR-gamma)being raised.. Ingestion of carbohydrates post exercise are most effective in the 20minutes afterwards and some management of insulin sensitivity would be expected at this stage, but added benefit of carbohydrate uptake is lost within 2 hours post exercise. The section of just two antioxidants probably does not reflect most athletes use of multiple antioxidant combinations. The maintainance of a diet rich in phytonutrients inevitable confers additional benefits to the athlete over a poor diet and 1 or two supplements. The correct use of multiple nutrients and planned wholefood intake still represents a compelling application of science and nutrition in the management of optimal health and performance.

M. Ristow, K. Zarse, A. Oberbach, N. Kloting, M. Birringer, M. Kiehntopf, M. Stumvoll, C.R. Kahn, M. Blüher. Antioxidants prevent health-promoting effects of physical exercise in humans. Published online before print May 11, 2009, doi: 10.1073/pnas.0903485106 View Abstract View Full Paper

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