title: Glutathione supplementation suppresses muscle fatigue induced by prolonged exercise via improved aerobic metabolism.
abstract: BACKGROUND
  Glutathione is an endogenous redox couple in animal cells and plays important roles in antioxidant defense and detoxification, although it is unknown if oral glutathione supplementation affects exercise-induced physiological changes. The present study investigated the effect of glutathione intake on exercise-induced muscle metabolism and fatigue in mice and humans.
  
  
  METHODS
  ICR mice were divided into 4 groups: sedentary control, sedentary supplemented with glutathione (2.0%, 5 μL/g body weight), exercise control, and exercise supplemented with glutathione. After 2 weeks, the exercise groups ran on a treadmill at 25 m/min for 30 min. Immediately post-exercise, intermuscular pH was measured, and hind limb muscle and blood samples were collected to measure biochemical parameters. In a double-blind, cross-over study, 8 healthy men (35.9 ± 2.0 y) were administered either glutathione (1 g/d) or placebo for 2 weeks. Then, they exercised on a cycle ergometer at 40% maximal heart rate for 60 min. Psychological state and blood biochemical parameters were examined after exercise.
  
  
  RESULTS
  In the mouse experiment, post-exercise plasma non-esterified fatty acids were significantly lower in the exercise supplemented with glutathione group (820 ± 44 mEq/L) compared with the exercise control group (1152 ± 61 mEq/L). Intermuscular pH decreased with exercise (7.17 ± 0.01); however, this reduction was prevented by glutathione supplementation (7.23 ± 0.02). The peroxisome proliferator-activated receptor-γ coactivator-1α protein and mitochondrial DNA levels were significantly higher in the sedentary supplemented with glutathione group compared with the sedentary control group (25% and 53% higher, respectively). In the human study, the elevation of blood lactate was suppressed by glutathione intake (placebo, 3.4 ± 1.1 mM; glutathione, 2.9 ± 0.6 mM). Fatigue-related psychological factors were significantly decreased in the glutathione trial compared with the placebo trial.
  
  
  CONCLUSIONS
  These results suggest that glutathione supplementation improved lipid metabolism and acidification in skeletal muscles during exercise, leading to less muscle fatigue.
authors: Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522 Japan.
authors: Wataru
authors: W
authors: Aoi
authors: Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522 Japan.
authors: Yumi
authors: Y
authors: Ogaya
authors: Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522 Japan.
authors: Maki
authors: M
authors: Takami
authors: KOHJIN Life Sciences Company, Ltd., Tokyo, Japan.
authors: Toru
authors: T
authors: Konishi
authors: KOHJIN Life Sciences Company, Ltd., Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Sauchi
authors: Laboratory of Food Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.
authors: Eun Young
authors: EY
authors: Park
authors: Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522 Japan.
authors: Sayori
authors: S
authors: Wada
authors: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors: Kenji
authors: K
authors: Sato
authors: Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522 Japan.
authors: Akane
authors: A
authors: Higashi
keywords: Dkeletal muscle; Glutathione; Lipid metabolism; PGC-1α; Running exercise