Glutathione: Safety Profile & Research Summary
20 PubMed CitationsExpert ReviewedGMP CertifiedLast Reviewed: February 2026
Research Summary
Key Clinical Studies
| Study | Design / Population | Key Findings | Ref |
|---|---|---|---|
| Richie et al. (2015) Eur J Nutr | RCT, n=54 healthy adults; 250 mg or 1000 mg oral GSH/day, 6 months | 1000 mg/day: significant increase in GSH in erythrocytes, plasma, lymphocytes, buccal cells (p < 0.05). 250 mg: no significant difference vs placebo | [12] |
| Mischley et al. (2017) J Parkinson's Dis | Phase IIb RCT, n=45 PD patients; 300 or 600 mg/day intranasal GSH, 12 weeks | 600 mg/day: UPDRS Total improved -4.6 points (P = 0.0025); Motor sub-score improved -2.2 points (P = 0.0485) | [11] |
| Honda et al. (2017) BMC Gastroenterol | Open-label pilot, n=34 NAFLD patients; 300 mg oral GSH/day, 4 months | Significant reduction in ALT (p < 0.05); non-significant improvements in liver stiffness | [8] |
| Søndergård et al. (2021) Appl Physiol Nutr Metab | RCT, n=20 obese males ± T2DM; 1000 mg oral GSH/day, 3 weeks | Whole-body insulin sensitivity significantly increased; skeletal muscle GSH increased ~19% | [16] |
| Weschawalit et al. (2017) Clin Cosm Invest Derm | RCT, n=57 healthy females; 250 mg oral GSH or GSSG/day, 12 weeks | Significant wrinkle reduction (P = 0.006); increased skin elasticity; melanin reduction in >40 yrs subgroup | [19] |
| Cascinu et al. (1995) J Clin Oncol | RCT, advanced gastric cancer; 1.5 g/m² IV GSH before cisplatin | Neuroprotective effect; reduced cisplatin-associated neurotoxicity without compromising chemotherapy efficacy | [4] |
| Smyth et al. (1997) Ann Oncol | RCT, ovarian cancer; IV GSH with cisplatin | Reduced toxicity; improved quality of life; no reduction in antineoplastic efficacy | [15] |
| Sinha et al. (2018) Eur J Clin Nutr | RCT; liposomal GSH supplementation | Elevated body stores of GSH; enhanced markers of immune function including natural killer cell activity | [14] |
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Strutynska et al. (2023) | Aged male Wistar rats; 52 mg/kg i.p., acute | Heart GSH +40% (p=0.0027); superoxide reduced 2.5x; H2O2 reduced 2.3x; restored vasorelaxation; inhibited mPTP opening | [3] |
| Cai et al. (2003) | BALB/c mice; oral GSH; influenza A/X-31 | Decreased viral titers in both lung and trachea homogenates | [3] |
| Chinta et al. (2007) | In vivo GSH depletion in dopaminergic midbrain neurons | Inducible GSH alterations result in nigrostriatal degeneration, confirming causative role of GSH loss in PD pathology | [5] |
Dosage Summary
| Setting | Dose | Route / Duration | Notes |
|---|---|---|---|
| In Vitro | 0.5–10 mM | Cell culture | Physiological intracellular concentration range |
| Animal (Rat) | 52 mg/kg | Intraperitoneal; acute | LD50 > 5 g/kg (mice, oral) |
| Human — Oral (antioxidant) | 250–1000 mg/day | Oral capsules; 4 weeks–6 months | 1000 mg/day required for 6 months to significantly elevate body stores[12] |
| Human — Oral (skin) | 250–500 mg/day | Oral; 4–12 weeks | Significant melanin and wrinkle reduction[19][2] |
| Human — Intranasal | 200–600 mg/day | Intranasal atomization; 12 weeks | Brain GSH >200% increase within 45 min[11] |
| Human — IV | 1.5 g/m² | Intravenous; before chemotherapy | Neuroprotective adjunct to cisplatin[4] |
| Human — Topical | 2% GSSG lotion | Twice daily; 10 weeks | Significant reduction in melanin index, wrinkles, TEWL[18] |
| Human — Inhaled | 600 mg BID | Nebulized | Respiratory conditions; contraindicated in asthma[17] |
Safety Profile
| Route | Safety Assessment | Adverse Events |
|---|---|---|
| Oral | GRAS status; well-tolerated; LD50 > 5 g/kg (mice) | Mild: flatulence, loose stools, flushing, weight gain[12] |
| Topical | Generally well-tolerated | Mild erythema, pruritus; typically self-resolving[19] |
| Intranasal | Phase IIb safety established | One withdrawal (tachycardia/cardiomyopathy, resolved upon cessation)[11] |
| Intravenous | Significant safety concerns | 32% adverse event rate; hepatotoxicity, anaphylaxis, Stevens-Johnson syndrome reported |
| Inhaled | Contraindicated in asthma | Risk of bronchospasm |
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About This Research Profile
This research profile was compiled from peer-reviewed sources and publicly available scientific literature. All articles and product information provided on this website are for informational and educational purposes only. The information presented here does not constitute medical advice and should not be relied upon as a substitute for consultation with a qualified healthcare professional.
References
- Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. Journal of Alternative and Complementary Medicine, 17(9), 827-833, 2011.
- Arjinpathana N, Asawanonda P. Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study. Journal of Dermatological Treatment, 23(2), 97-102, 2012.
- Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biological Chemistry, 390(3), 191-214, 2009.
- Cascinu S, Cordella L, Del Ferro E, et al. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology, 13(1), 26-32, 1995.
- Chinta SJ, Kumar MJ, Hsu M, et al. Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degeneration. Journal of Neuroscience, 27(51), 13997-14006, 2007.
- Handog EB, Datuin MS, Singzon IA. An open-label, single-arm trial of the safety and efficacy of a novel preparation of glutathione as a skin-lightening agent in Filipino women. International Journal of Dermatology, 55(2), 153-157, 2016.
- Holmay MJ, Terpstra M, Coles LD, et al. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clinical Neuropharmacology, 36(4), 103-106, 2013.
- Honda Y, Kessoku T, Sumida Y, et al. Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study. BMC Gastroenterology, 17(1), 96, 2017.
- Kovacs-Nolan J, Rupa P, Matsui T, et al. In vitro and ex vivo uptake of glutathione (GSH) across the intestinal epithelium and fate of oral GSH after in vivo supplementation. Journal of Agricultural and Food Chemistry, 62(39), 9499-9506, 2014.
- Lenzi A, Culasso F, Gandini L, Lombardo F, Dondero F. Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Human Reproduction, 8(10), 1657-62, 1993.
- Mischley LK, Leverenz JB, Lau RC, et al. A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson's disease. Movement Disorders, 30(12), 1696-1701, 2015.
- Richie JP, Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition, 54(2), 251-263, 2015.
- Sechi G, Deledda MG, Bua G, et al. Reduced intravenous glutathione in the treatment of early Parkinson's disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 20(7), 1159-1170, 1996.
- Sinha R, Sinha I, Calcagnotto A, et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. European Journal of Clinical Nutrition, 72(1), 105-111, 2018.
- Smyth JF, Bowman A, Perren T, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Annals of Oncology, 8(6), 569-73, 1997.
- Søndergård SD, Cintin I, Kuhlman AB, et al. The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial. Applied Physiology, Nutrition, and Metabolism, 46(9), 1133-1142, 2021.
- Visca A, Bishop CT, Hilton S, Hudson VM. Oral reduced L-glutathione improves growth in pediatric cystic fibrosis patients. Journal of Pediatric Gastroenterology and Nutrition, 60(6), 802-810, 2015.
- Watanabe F, Hashizume E, Chan GP, Kamimura A. Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women. Clinical, Cosmetic and Investigational Dermatology, 7, 267-274, 2014.
- Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clinical, Cosmetic and Investigational Dermatology, 10, 147-153, 2017.
- Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. European Journal of Clinical Pharmacology, 43(6), 667-669, 1992.
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