Differential effects of vitamin C or protandim on skeletal muscle adaptation to exercise

J Appl Physiol (1985). 2018 Aug 1;125(2):661-671. doi: 10.1152/japplphysiol.00277.2018. Epub 2018 Jun 1.


Maintaining proteostasis is a key mechanism for preserving cell function. Exercise-stimulated proteostasis is regulated, in part, by redox-sensitive signaling. Several studies suggest that supplementation with exogenous antioxidants blunts exercise-induced cellular adaptations, although this conclusion lacks consensus. Our group uses a fundamentally different approach to maintain redox balance by treatment with bioactive phytochemicals to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 and downstream endogenous antioxidant pathways. We hypothesized that vitamin C (VitC) would interfere with redox-sensitive proteostatic mechanisms in skeletal muscle, whereas phytochemical treatment would permit proteostatic maintenance. We measured protein and DNA synthesis in skeletal muscle from high-volume voluntary wheel-running rats. Whereas phytochemical treatment permitted mitochondrial and other proteostatic adaptations to exercise, VitC treatment did not. During an in vitro oxidative challenge, phytochemical treatment helped maintain proteostasis, including the mitochondrial fraction while VitC did not. Our findings support the conclusion that VitC can blunt some of the beneficial adaptations to exercise. We propose that regulation of endogenous antioxidants represents a novel approach to maintain redox balance while still permitting redox-sensitive proteostatic adaptations. NEW & NOTEWORTHY Whether vitamin C blocks aerobic exercise adaptions lacks consensus, perhaps because of approaches that only assess markers of mitochondrial biogenesis. By directly measuring mitochondrial biogenesis, we demonstrate that vitamin C blunts exercise-induced adaptations. Furthermore, we show that treatment with Protandim, a purported nuclear factor (erythroid-derived 2)-like 2 activator that upregulates endogenous antioxidants, permits mitochondrial biogenesis. We confirm that vitamin C blunts aerobic exercise adaptions, whereas Protandim does not, suggesting targeting the endogenous antioxidant network facilitates adaptations to exercise.

Keywords: deuterium oxide; mitochondrial biogenesis; proteostasis; redox.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological / drug effects*
  • Animals
  • Antioxidants / metabolism
  • Ascorbic Acid / pharmacology*
  • Dietary Supplements
  • Drugs, Chinese Herbal / pharmacology*
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Organelle Biogenesis
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Physical Conditioning, Animal / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects


  • Antioxidants
  • Drugs, Chinese Herbal
  • Protandim
  • Ascorbic Acid