Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers

J Altern Complement Med. 2011 Sep;17(9):827-33. doi: 10.1089/acm.2010.0716.


Background: The tripeptide glutathione (GSH) is the most abundant free radical scavenger synthesized endogenously in humans. Increasing mechanistic, clinical, and epidemiological evidence demonstrates that GSH status is significant in acute and chronic diseases. Despite ease of delivery, little controlled clinical research data exist evaluating the effects of oral GSH supplementation.

Objectives: The study objectives were to determine the effect of oral GSH supplementation on biomarkers of systemic oxidative stress in human volunteers.

Design: This was a randomized, double-blind, placebo-controlled clinical trial.

Setting/location: The study was conducted at Bastyr University Research Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA.

Subjects: Forty (40) adult volunteers without acute or chronic disease participated in this study.

Intervention: Oral GSH supplementation (500 mg twice daily) was given to the volunteers for 4 weeks.

Outcome measures: Primary outcome measures included change in creatinine-standardized, urinary F2-isoprostanes (F2-isoP) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Changes in erythrocyte GSH concentrations, including total reduced glutathione (GSH), oxidized glutathione (GSSG), and their ratio (GSH:GSSG) were also measured by tandem liquid chromatography/mass spectrometry. Analysis of variance was used to evaluate differences between groups.

Results: There were no differences in oxidative stress biomarkers between treatment groups at baseline. Thirty-nine (39) participants completed the study per protocol. Changes in creatinine standardized F2-isoP (ng/mg creatinine) (0.0±0.1 versus 0.0±0.1, p=0.38) and 8-OHdG (μg/g creatinine) (-0.2±3.3 versus 1.0±3.2, p=0.27) were nonsignificant between groups at week 4. Total reduced, oxidized, and ratio measures of GSH status were also unchanged.

Conclusions: No significant changes were observed in biomarkers of oxidative stress, including glutathione status, in this clinical trial of oral glutathione supplementation in healthy adults.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Biomarkers / blood
  • Biomarkers / urine
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / urine
  • Dietary Supplements
  • Double-Blind Method
  • Erythrocytes / metabolism*
  • F2-Isoprostanes / urine*
  • Female
  • Glutathione / metabolism
  • Glutathione / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Reference Values
  • Young Adult


  • Antioxidants
  • Biomarkers
  • F2-Isoprostanes
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Glutathione