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Glutathione (GSH) is the most prevalent low-molecular-weight thiol in mammalian cells and is crucial for antioxidant defense, nutrient metabolism, and the regulation of pathways essential for whole body homeostasis. GSH transport systems have been identified in the membranes of various tissues and organs, including the small intestine. However, little is known regarding GSH transport across intestinal epithelial cells. The current in vitro and ex vivo uptake study of GSH demonstrated that intact GSH can be transported across intestinal epithelial cells, suggesting that GSH uptake is not proton-dependent. It would appear that the initial uptake of GSH into cells is a rapid process. Furthermore, the visualized GSH after 60 min of transport by MALDI-MS imaging showed localization of intact GSH inside the intestinal wall. In vivo study found that ingested (13)C-GSH was rapidly converted to GSSG and accumulated in red blood cells and liver, but was little present in plasma. The ingested GSH has potent nutraceutical benefits for human health to improve oxidative stress and defense in human.

The present study examined the impact of the supplementation of glutathione (GSH), γ-L-glutamyl-L-cysteinyl-glycine, on human blood GSH levels. Healthy human volunteers were orally supplemented with GSH (50 mg/kg body weight). Venous blood was collected from the cubital vein before and after ingestion. Plasma was mixed with 3 volumes of ethanol. The supernatant and precipitate were used for the deproteinized and protein fractions of plasma, respectively. Blood cell and plasma fractions were pretreated with 5% trichloroacetic acid-2% 2-mercaptoethanol to reduce the oxidized form of GSH and liberate protein-bound GSH. The 2-mercaptoethanol-pretreated GSH was determined by precolumn derivatization with 6-aminoquinolyl-N-hydroxy succinimidyl carbamate and liquid chromatography-tandem mass spectrometry. There was no significant difference in GSH contents in the deproteinized fraction of plasma and blood cell fraction after GSH ingestion. However, the GSH contents in the protein-bound fraction of plasma significantly (P<0.01) increased from 60 to 120 min after GSH supplementation.

BackgroundsGlutathione 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.MethodsICR 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.ResultsIn 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.ConclusionsThese results suggest that glutathione supplementation improved lipid metabolism and acidification in skeletal muscles during exercise, leading to less muscle fatigue.Electronic supplementary materialThe online version of this article (doi:10.1186/s12970-015-0067-x) contains supplementary material, which is available to authorized users.

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