title: Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers.
abstract: 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.
  
  
  OBJECTIVE
  The study objectives were to determine the effect of oral GSH supplementation on biomarkers of systemic oxidative stress in human volunteers.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled clinical trial.
  
  
  METHODS
  The study was conducted at Bastyr University Research Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA.
  
  
  METHODS
  Forty (40) adult volunteers without acute or chronic disease participated in this study.
  
  
  METHODS
  Oral GSH supplementation (500 mg twice daily) was given to the volunteers for 4 weeks.
  
  
  METHODS
  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.
authors.affiliation: Bastyr University Research Institute, Kenmore, WA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Allen
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Bradley
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D019587:Dietary Supplements; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000652:urine*; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D012016:Reference Values; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione