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Also known as: Glutathione, GSH, L-Glutathione, Reduced Glutathione, gamma-Glutamylcysteinylglycine
The body's principal intracellular antioxidant, a tripeptide with genuine human trial data behind oral and topical use -- and a 2025 systematic review concluding that the injectable route sold for skin lightening is contraindicated for lack of efficacy and side effects.
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Glutathione is the tripeptide gamma-L-glutamyl-L-cysteinyl-glycine. Its defining structural feature is the gamma linkage: the glutamate joins via its side-chain carboxyl rather than the usual alpha-carboxyl, which is why standard peptidases cannot cleave it and why gamma-glutamyl transpeptidase is required to break it down. It is synthesized inside cells in two ATP-dependent steps -- glutamate-cysteine ligase, the rate-limiting enzyme, followed by glutathione synthetase -- and cysteine availability is normally the limiting factor, which is the rationale behind using N-acetylcysteine as a precursor rather than glutathione itself. Functionally it is the cell's main redox buffer: the reduced-to-oxidized (GSH/GSSG) ratio sets intracellular redox tone, it serves as the electron donor for glutathione peroxidases that reduce hydrogen peroxide and lipid peroxides, it is the conjugating substrate for the glutathione S-transferases that carry out phase II detoxification, and it helps regenerate oxidized vitamins C and E. In skin, its anti-melanogenic effect is attributed to inhibition of tyrosinase and a shift in melanogenesis away from darker eumelanin toward pheomelanin.