European Journal of Nutrition

, Volume 54, Issue 2, pp 251–263 | Cite as

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

  • John P. RichieJr.Email author
  • Sailendra Nichenametla
  • Wanda Neidig
  • Ana Calcagnotto
  • Jeremy S. Haley
  • Todd D. Schell
  • Joshua E. Muscat
Original Contribution



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.


Glutathione Supplementation Antioxidant Immune function 



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.

Supplementary material

394_2014_706_MOESM1_ESM.docx (48 kb)
Supplementary material 1 (DOCX 47 kb)
394_2014_706_MOESM2_ESM.docx (14 kb)
Supplementary material 2 (DOCX 14 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • John P. RichieJr.
    • 1
    Email author
  • Sailendra Nichenametla
    • 1
    • 2
  • Wanda Neidig
    • 3
  • Ana Calcagnotto
    • 1
  • Jeremy S. Haley
    • 4
  • Todd D. Schell
    • 4
  • Joshua E. Muscat
    • 1
  1. 1.Department of Public Health Sciences, Penn State Cancer Institute, H069Penn State University College of MedicineHersheyUSA
  2. 2.Orentreich Foundation for the Advancement of ScienceCold SpringUSA
  3. 3.Penn State Hershey Cancer Institute Clinical Trials OfficePenn State University College of MedicineHersheyUSA
  4. 4.Department of Microbiology and ImmunologyPenn State University College of MedicineHersheyUSA

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