L-Glutathione
Also known as: L-Glutathione, Glutathione, GSH, 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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Mechanism of Action
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.
- Half-life
- Exogenous glutathione is cleared from plasma within minutes, since gamma-glutamyl transpeptidase degrades it extracellularly; what matters clinically is the intracellular pool, which the 6-month oral RCT showed rises over weeks and returns to baseline within about a month of stopping.
- Administration Routes
- oral, topical, intravenous, subcutaneous
- Research Status
- Clinical
Reported Benefits
- Oral supplementation measurably raises body glutathione stores (6-month RCT, n=54)
- Central to phase II detoxification and to buffering oxidative stress
- Oral and topical forms reduce melanin index in randomized trials
- Natural killer cell cytotoxicity more than doubled at the high oral dose in one RCT
- Regenerates oxidized vitamins C and E, extending their antioxidant capacity
Potential Side Effects
- IV glutathione for skin lightening is judged CONTRAINDICATED by a 2025 systematic review, for lack of efficacy and for side effects
- Several national regulators have issued bans or advisories against parenteral use for skin lightening
- Skin-lightening effects are reversible and not sustained after stopping
- Body stores returned to baseline within a one-month washout in the oral RCT
- Oral and topical routes were well tolerated in the trials reviewed
Common Dosing
For research use only and not personal medical advice. The human evidence sits at modest ORAL doses: the body-stores RCT used 250 or 1,000 mg/day for 6 months, and the skin-lightening trials used 250 mg once or twice daily, or 500 mg once daily. Topical work used 0.5% preparations. Note the mismatch with how this compound is commonly sold: a large lyophilized vial intended for injection is the one route the current systematic review advises against, and parenteral glutathione is approved only for narrow indications (severe liver disorders, prevention of chemotherapy-associated neurotoxicity) in the jurisdictions that approve it at all.
The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.
Contraindications
- Parenteral use for cosmetic skin lightening (explicitly advised against)
- Pregnancy or breastfeeding
- Concurrent chemotherapy without oncologist supervision -- antioxidant interference is a live question
- Not a substitute for medical evaluation of hyperpigmentation, which can have treatable causes
NAD+
NAD+ is an essential coenzyme central to cellular energy production and DNA repair whose levels decline with age. It is studied and supplemented for longevity, mitochondrial function, and metabolic health. Note: NAD+ is a coenzyme, not a peptide, commonly sold alongside longevity research compounds.
NMN
NMN is a direct biosynthetic precursor of NAD+ used to raise cellular NAD+ levels. It is studied for longevity, metabolic health, and mitochondrial function. Note: NMN is a small-molecule NAD+ precursor, not a peptide, but is catalogued with longevity research compounds.
SS-31 (Elamipretide)
SS-31 (elamipretide) is a mitochondria-targeted tetrapeptide studied for protecting mitochondrial function in conditions involving oxidative stress and energy failure. It has been investigated clinically for mitochondrial myopathy and heart and kidney disease.
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Randomized controlled trial of oral glutathione supplementation on body stores of glutathione
2015
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Glutathione as a skin-lightening agent and in melasma: a systematic review
2025
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Glutathione for skin lightening: a regnant myth or evidence-based verity?
2018
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Combination of topical and oral glutathione as a skin-whitening agent: a double-blind randomized controlled clinical trial
2021