Randomized controlled trial of oral glutathione supplementation on body stores of glutathione

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Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oral GSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults.


A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers.


GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30–35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.


These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.

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We thank Ashley Knipe for her technical assistance with sample processing and Nate Sheaffer in the Penn State Hershey Flow Cytometry Core Facility. We thank Mr. Yoichiro Sugimura (deceased) and Ms. Erika Hashizume for their support in the design and implementation of this trial. This work was supported by Kyowa Hakko Bio Co., Ltd (JR). Glutathione (Setria®) supplements and placebo were provided by Kyowa Hakko Bio Co., Ltd. Kyowa Hakko Bio Co., Ltd had no role in the conduct, collection, management, analysis and interpretation of the data, or writing of the manuscript. Immunological analyses were supported in part by the Penn State Hershey Cancer Institute through the Clinical Correlative Immunology Laboratory (TS and JH).

Conflict of interest

JPR received research support for this study and travel funds to present previous research findings from Kyowa Hakko Bio Co., Ltd. Kyowa Hakko Bio Co., Ltd is a biotechnology and fermentation company that provides glutathione (Setria®). None of the other authors have any conflicts of interest to disclose.

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Correspondence to John P. Richie Jr..

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Richie, J.P., Nichenametla, S., Neidig, W. et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr 54, 251–263 (2015). https://doi.org/10.1007/s00394-014-0706-z

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  • Glutathione
  • Supplementation
  • Antioxidant
  • Immune function