Glutathione

Also known as: GSH, L-Glutathione, Reduced glutathione, γ-L-glutamyl-L-cysteinyl-glycine

Evidence: Clinical

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Overview

Endogenous tripeptide (Glu-Cys-Gly) and the main intracellular antioxidant, central to phase II detoxification and cellular redox defence.

Glutathione is the endogenous tripeptide gamma-Glu-Cys-Gly (PubChem CID 124886), the main intracellular thiol antioxidant. The human trial record is mixed and route-dependent. Oral dosing at 250 or 1000 mg/day for 6 months raised glutathione in blood, erythrocytes, plasma, lymphocytes and buccal cells in 54 adults, with stores returning to baseline a month after stopping (Richie 2015). Oral 500 mg/day for 4 weeks lowered melanin index at 2 of 6 measured sites in 60 subjects (Arjinpathana 2012). By injection the picture is worse: a randomized trial of intravenous glutathione 1400 mg three times weekly for 4 weeks in 21 Parkinson patients found no significant UPDRS difference (Hauser 2009), and intranasal dosing was not superior to placebo (Mischley 2017). No parenteral glutathione product is approved for any systemic or cosmetic indication.

Benefits

Raised blood, erythrocyte and lymphocyte glutathione stores and lowered the oxidized to reduced ratio at 250 to 1000 mg/day oral for 6 months (human RCT, n=54), lower melanin index at 500 mg/day oral for 4 weeks (human RCT, n=60), phase II detoxification cofactor (biochemistry, not a trial)

Dosing reference

Research dose: 200 to 600 mg by injection: clinic and community range. Published intravenous doses were higher: 1400 mg three times weekly (Hauser 2009) and 600 mg twice daily for 30 days (Sechi 1996)
Range: 200000 to 600000 mcg, 1-3x weekly
Reconstitution: 5 mL bacteriostatic water
Common vial sizes: 200 mg, 600 mg

Intravenous or subcutaneous in research and clinic use. Published human doses, verbatim: 1400 mg intravenously three times a week for 4 weeks, randomized and placebo-controlled, no significant effect (Hauser 2009); 600 mg intravenously twice daily for 30 days, open label, 42% decline in disability (Sechi 1996); 100 or 200 mg intranasally three times daily for 3 months, not superior to placebo (Mischley 2017); 250 to 1000 mg/day orally for 6 months, which raised body stores (Richie 2015). No parenteral product is approved for a cosmetic indication anywhere, and compounded sterility is a documented problem.

Mechanism

Glutathione cycles between its reduced (GSH) and oxidized (GSSG) forms, serves as the cofactor for glutathione peroxidases, and is conjugated to electrophiles by glutathione-S-transferases for phase II elimination. The skin-lightening rationale is inhibition of tyrosinase and a shift from eumelanin to pheomelanin, which is in vitro pharmacology rather than a demonstrated mechanism in treated skin (Dlova 2026). One mechanistic claim in the old record is wrong in the other direction: parenteral dosing is justified by poor oral absorption, yet the one long randomized oral trial raised body stores at 250 and 1000 mg/day (Richie 2015), and liposomal oral dosing raised stores and natural killer activity (Sinha 2018). Direct cellular uptake of intact glutathione is limited; the gamma-glutamyl cycle normally breaks it down extracellularly and reassembles it inside cells.

Evidence

Clinical: at least one published human trial or an approved drug

Oral glutathione at 250 or 1000 mg/day for 6 months raised glutathione in blood, erythrocytes, plasma, lymphocytes and buccal cells in 54 adults, lowered the oxidized to reduced ratio, and more than doubled natural killer cytotoxicity in the high-dose group; levels returned to baseline after a 1-month washout (Richie et al., 2015)
Oral 500 mg/day for 4 weeks lowered melanin index at all six measured sites in 60 healthy subjects, reaching significance versus placebo at two sites (Arjinpathana et al., 2012)
Intravenous glutathione 1400 mg three times weekly for 4 weeks in 21 Parkinson patients was well tolerated but produced no significant UPDRS difference; a 2.8-unit mean improvement did not reach significance and reversed during follow-up (Hauser et al., 2009)
An earlier open-label series of 9 untreated early Parkinson patients given 600 mg intravenously twice daily for 30 days reported a 42% decline in disability lasting 2 to 4 months after stopping, with no control group (Sechi et al., 1996)
Intranasal glutathione at 100 or 200 mg three times daily for 3 months in 45 Parkinson patients improved UPDRS scores, but so did placebo, and neither dose separated from it; one high-dose participant developed cardiomyopathy (Mischley et al., 2017)
Human-trial status: the positive randomized evidence is oral. No randomized trial of injected glutathione has shown benefit for any indication, and a 2026 scoping review of systemic glutathione for skin lightening found the intravenous evidence base inadequate. The only US-approved product containing glutathione is an intraocular irrigating solution, BSS PLUS (NDA 018469)

References

Side effects

In the randomized trials glutathione was well tolerated: adverse events matched placebo at 1400 mg intravenously three times weekly (Hauser 2009) and at 250 to 1000 mg/day orally for 6 months (Richie 2015). Serious harms are documented in case reports and reviews of cosmetic use rather than in trials: toxic epidermal necrolysis after glutathione whitening pills, confirmed by ELISpot and mass spectrometry (Chottawornsak 2022), systemic inflammatory response syndrome after a high-dose intravenous glutathione revitalizing solution, reported as a single case in 2025, and one cardiomyopathy case in the intranasal trial. A 2026 scoping review concludes that the systemic skin-lightening evidence does not support the practice.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: Not reported in the published human trials. Oral dosing at 250 to 1000 mg/day for 6 months raised body stores, which returned to baseline within a 1-month washout (Richie 2015)
Bioavailability: Oral: absolute bioavailability has not been measured, but 250 to 1000 mg/day for 6 months raised blood, erythrocyte, plasma and lymphocyte stores (Richie 2015), and liposomal oral dosing raised stores and immune markers (Sinha 2018). Injection: no bioavailability or exposure data from the published trials
Molecular weight: 307.33 Da
Sequence: γ-Glu-Cys-Gly (γ-glutamyl bond, not standard peptide bond)