Ristow · Proceedings of the National Academy of Sciences of the United States of America 2009 · Controlled clinical trial · n=39

Antioxidants prevent health-promoting effects of physical exercise in humans.

Cited 1570 times in the scientific literature.

Level 2 - randomized trial

Individual controlled clinical trial with physiological and molecular endpoints

PubMed 19433800 · doi:10.1073/pnas.0903485106 · record verified 2026-08-26

What was done

Researchers evaluated the effect of combined vitamin C (1,000 mg/day) and vitamin E (400 IU/day) supplementation during a 4-week physical exercise training program in 39 healthy young men (19 previously untrained, 20 pretrained). Before and after the 4-week intervention, insulin sensitivity was measured via glucose infusion rates (GIR) during a hyperinsulinemic-euglycemic clamp. Muscle biopsies were taken for gene expression analysis (PPARgamma, PGC1alpha, PGC1beta, SOD1, SOD2, and glutathione peroxidase), and plasma samples were analyzed for adiponectin.

What was found

Physical exercise increased parameters of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidant supplementation in both untrained (P < 0.001) and pretrained (P < 0.001) men. Exercise-induced upregulation of ROS-sensitive transcriptional regulators (PPARgamma, PGC1alpha, and PGC1beta) also occurred only without antioxidants (P < 0.001 for all). Furthermore, molecular mediators of endogenous antioxidant defense (superoxide dismutases 1 and 2, and glutathione peroxidase) were induced by exercise, but this induction was completely blocked by antioxidant supplementation.

Why it matters

This study provides human evidence for mitohormesis, demonstrating that exercise-induced reactive oxygen species are necessary signaling molecules for improving insulin sensitivity and stimulating endogenous antioxidant defenses.

Limits

The sample size was small (n = 39) and restricted to healthy young men, limiting generalizability to women, older adults, or individuals with existing type 2 diabetes. The intervention was relatively short (4 weeks), and specific high doses of vitamins C and E were tested together, leaving the effects of lower doses or other antioxidant compounds unaddressed.

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