Summary

Glutathione (GSH) is a tripeptide (γ-glutamyl-cysteinyl-glycine) that serves as the body's principal intracellular antioxidant. It plays critical roles in detoxification, immune function, and redox homeostasis. Research has investigated supplemental glutathione for oxidative stress-related conditions, liver health, and skin pigmentation. Clinical evidence supports its bioavailability in oral and intravenous forms, with moderate evidence for some applications.

Mechanism

Glutathione (GSH) functions as the body's principal intracellular antioxidant through its thiol (-SH) group on the cysteine residue. It neutralises reactive oxygen species directly and serves as a cofactor for glutathione peroxidase (reducing H₂O₂ to water) and glutathione-S-transferase (conjugating electrophilic compounds for detoxification). GSH also regenerates oxidised vitamins C and E. The GSH:GSSG ratio is a key marker of cellular redox state. Additionally, glutathione inhibits tyrosinase, the rate-limiting enzyme in melanin synthesis, which underlies its skin-lightening effects.

Evidence base

Evidence Grading: Moderate

Glutathione has a substantial human clinical evidence base.

Clinical evidence:

  • Allen & Bradley (2015): Oral glutathione (250–1000 mg/day for 6 months) significantly increased GSH levels in healthy adults — landmark bioavailability trial.
  • Arjinpathana & Asawanonda (2012): Oral GSH (500 mg/day) reduced melanin index in a double-blind RCT.
  • Weschawalit et al. (2017): GSH supplementation improved skin elasticity and reduced wrinkles.
  • Pompella et al. (2003): Comprehensive review of glutathione's biological roles.

Gap: Evidence for anti-ageing and performance applications is limited. Skin-lightening evidence is modest and primarily from small trials. IV glutathione for cosmetic use carries safety concerns.

Protocols

Research-Only Protocols

No MHRA-approved dosing protocols exist for non-licensed applications.

In published clinical research:

  • Oral: 250–1000 mg daily (Allen et al., 2015)
  • Oral (skin lightening): 500 mg daily for 4 weeks (Arjinpathana & Asawanonda, 2012)
  • Intravenous: 600–2400 mg in clinical settings
  • Nebulised: Used in cystic fibrosis research

Liposomal formulations have been investigated for enhanced bioavailability.

Glutathione is not a controlled substance in the UK. It is available as a food supplement in oral form under UK food supplement regulations. Injectable glutathione is not MHRA-licensed for cosmetic skin-lightening purposes and falls into a grey area when supplied for research. IV glutathione for skin lightening has been subject to regulatory warnings. See our UK legal status guide for further detail.

Vendor notes

Oral glutathione supplements are widely available from UK retailers. Research-grade glutathione for laboratory use is available from chemical suppliers. For peptide-grade material, see the vendor vetting guide for evaluation criteria.

References

  1. Allen J, Bradley RD. "Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers." J Altern Complement Med. 2015;21(9):557-563.
  2. Arjinpathana N, Asawanonda P. "Glutathione as an oral skin-lightening agent: a double-blind, randomised, placebo-controlled study." J Dermatolog Treat. 2012;23(2):132-137.
  3. Weschawalit S, et al. "Glutathione and its anti-aging and anti-melanogenic effects." Clin Cosmet Investig Dermatol. 2017;10:147-153.
  4. Pompella A, et al. "The changing faces of glutathione, a tale of a star athlete." Biochem Pharmacol. 2003;66(8):1499-1503.