title: Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.
authors.affiliation: Department of Public Health Sciences, Penn State Cancer Institute, H069, Penn State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA, jrichie@psu.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
authors.forename: Sailendra
authors.initials: S
authors.lastname: Nichenametla
authors.forename: Wanda
authors.initials: W
authors.lastname: Neidig
authors.forename: Ana
authors.initials: A
authors.lastname: Calcagnotto
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Haley
authors.forename: Todd D
authors.initials: TD
authors.lastname: Schell
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Muscat
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000378:metabolism; D007408:Intestinal Absorption; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D007155:Immunologic Factors; D005978:Glutathione