Two novel types of antioxidant effects

Antioxidants are actually more properly termed “redox-active agents.”

The two new effects of redox-active agents are:

  1. Inhibit mitochondrial biogenesis and presumably mitochondrial respiration.
  2. Stimulate mitochondrial biogenesis and presumably mitochondrial respiration.

Until recently, no one considered the effect of so-called antioxidants on mitochondrial biogenesis and still no one is considering whether even stimulating mitochondrial biogenesis is bad when it is not needed.

Here are two references:

  1. Am J Clin Nutr. 2008 Jan;87(1):142-9.

    Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance.

    Author information

    • 1Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain.



    Exercise practitioners often take vitamin C supplements because intense muscular contractile activity can result in oxidative stress, as indicated by altered muscle and blood glutathione concentrations and increases in protein, DNA, and lipid peroxidation. There is, however, considerable debate regarding the beneficial health effects of vitamin C supplementation.


    This study was designed to study the effect of vitamin C on training efficiency in rats and in humans.


    The human study was double-blind and randomized. Fourteen men (27-36 y old) were trained for 8 wk. Five of the men were supplemented daily with an oral dose of 1 g vitamin C. In the animal study, 24 male Wistar rats were exercised under 2 different protocols for 3 and 6 wk. Twelve of the rats were treated with a daily dose of vitamin C (0.24 mg/cm2 body surface area).


    The administration of vitamin C significantly (P=0.014) hampered endurance capacity. The adverse effects of vitamin C may result from its capacity to reduce the exercise-induced expression of key transcription factors involved in mitochondrial biogenesis. These factors are peroxisome proliferator-activated receptor co-activator 1, nuclear respiratory factor 1, and mitochondrial transcription factor A. Vitamin C also prevented the exercise-induced expression of cytochrome C (a marker of mitochondrial content) and of the antioxidant enzymes superoxide dismutase and glutathione peroxidase.


    Vitamin C supplementation decreases training efficiency because it prevents some cellular adaptations to exercise.



    Scand J Med Sci Sports. 2012 Dec;22(6):764-75. doi: 10.1111/j.1600-0838.2011.01314.x. Epub 2011 Apr 21.

    Mitochondrial nutrients stimulate performance and mitochondrial biogenesis in exhaustively exercised rats.

    Author information

    • 1Key Laboratory of General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai, China.


    The aim of this study was to investigate the effects of a combination of nutrients on physical performance, oxidative stress and mitochondrial biogenesis in rats subjected to exhaustive exercise. Rats were divided into sedentary control (SC), exhaustive exercise (EC) and exhaustive exercise with nutrient supplementation (EN). The nutrients include (mg/kg/day): R-α-lipoic acid 50, acetyl-L-carnitine 100, biotin 0.1, nicotinamide 15, riboflavin 6, pyridoxine 6, creatine 50, CoQ10 5, resveratrol 5 and taurine 100. Examination of running distances over the 4-week period revealed that EN rats ran significantly longer throughout the entire duration of the exhaustive exercise period compared with the EC rats. Nutrient supplementation significantly inhibited the increase in activities of alanine transaminase, lactate dehydrogenase and creatine kinase, reversed increases in malondialdehyde, inhibited decreases in glutathione S-transferase and total antioxidant capacity in plasma, and suppressed the elevation of reactive oxygen species and apoptosis in splenic lymphocytes. Nutrient supplementation increased the protein expression of mitochondrial complexes I, II and III, mtDNA number and transcription factors involved in mitochondrial biogenesis and fusion in skeletal muscle. These findings suggest that mitochondrial nutrient supplementation can reduce exhaustive exercise-induced oxidative damage and mitochondrial dysfunction, thus leading to enhancement of physical performance and of fatigue recovery.


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