Glutathione (GSH)
Glutathione — the "master antioxidant" and Asia's skin-whitening story: mechanism, evidence, and the IV-safety warnings

Class: peptide
Synonyms: Glutathione
GSH (reduced form)
L-glutathione
γ-glutamyl-cysteinyl-glycine
Function tags: antioxidant / detox (endogenous)
skin lightening / brightening
anti-pigmentation (melasma)
anti-aging (claimed)
Overall evidence grade: A
WADA prohibited: no
Last updated: 2026-07-13

In brief: Glutathione (GSH) is a tripeptide that serves as the body's master antioxidant — genuinely essential intracellular chemistry. Its fame, though, comes from a striking human phenomenon: across much of Asia it became the engine of a skin-whitening movement, sold as capsules and especially intravenous "gluta drips" promising lighter skin "from within," to the point that the Philippine FDA had to issue public warnings. The lightening mechanism is real in principle — glutathione inhibits tyrosinase and nudges pigment synthesis from dark eumelanin toward lighter pheomelanin — but the clinical evidence is mixed and route-dependent: oral glutathione has low bioavailability and modest, inconsistent effects; topical works only locally; and the wildly popular IV route has essentially no efficacy evidence and is unapproved, with health authorities flagging risks including liver/kidney/thyroid effects, severe skin reactions (Stevens-Johnson syndrome), infection from non-sterile injection, and a theoretical long-term skin-cancer concern (less melanin means less UV protection). So the honest picture: a truly important antioxidant and a huge cultural phenomenon — but weak, mostly-unproven evidence for the skin-lightening use it's sold for, and a genuinely risky most-popular route. Notably, it's the pigment-lightening opposite of the register's tanning peptides (Melanotan #32 / Afamelanotide #55).

## Identity a **tripeptide** (glutamate-cysteine-glycine) that, unlike the signalling peptides elsewhere here, functions as the body's principal **intracellular antioxidant and detoxifier** — maintaining redox balance, neutralizing free radicals, supporting immune function and phase-II detoxification. It's included because it's sold as a **skin-lightening / anti-aging** peptide-adjacent supplement (oral, topical, and — controversially — IV). ## Mechanism (as proposed) as the cell's **master antioxidant**, GSH cycles between reduced (GSH) and oxidized (GSSG) forms to **neutralize reactive oxygen species**, regenerate other antioxidants (vitamins C/E), and drive **detoxification**. Its **skin-lightening** action is separate: glutathione **inhibits tyrosinase** — the rate-limiting enzyme of melanin synthesis — both **directly** (binding the enzyme's copper site) and **indirectly** (via its antioxidant effect on the melanogenic pathway), and it **shifts melanocytes from producing dark eumelanin toward lighter pheomelanin**. The net effect is **reduced pigmentation** — *if* enough active glutathione actually reaches the melanocytes, which is exactly the bioavailability problem that oral use faces and that IV marketing exploits. The mechanism is real; the **delivery and the clinical magnitude are the weak links.**

## Related reading

Where glutathione's skin-lightening claims stand against the evidence-ranked pigment actives, see [best ingredients for dark spots and hyperpigmentation](/learn/best-ingredients-for-hyperpigmentation).

Evidence grades by outcome:
outcome: Endogenous antioxidant / detox role
grade: A
base: Foundational, non-controversial cell biology
caveat: Grades GSH's natural role — NOT proof that supplementation delivers cosmetic benefits
outcome: Oral glutathione — skin lightening
grade: C
base: Some RCT/clinical data (often with vitamin C); modest, inconsistent; low bioavailability
caveat: Mixed results; bioavailability doubts; effect (if any) is subtle and reversible
outcome: Topical glutathione — pigmentation
grade: C
base: Local depigmentation data
caveat: Effect limited to application site; not systemic
outcome: IV glutathione — skin lightening (the most popular use)
grade: F
base: No published trials proving efficacy; unapproved
caveat: Popular but essentially unproven; Philippine FDA: no evidence, no dosing standard
outcome: Anti-aging / wrinkles / elasticity
grade: D
base: One oral study noted possible wrinkle/elasticity benefit + good tolerance
caveat: Preliminary; not established
outcome: Safety — oral/topical
grade: B
base: GRAS; generally well-tolerated
caveat: The reassuring part: oral/topical is broadly safe
outcome: Safety — IV (the decisive warning)
base: Health-authority advisories
caveat: Renal/hepatic/thyroid dysfunction, nervous-system effects, Stevens-Johnson syndrome; infection risk (HIV/hepatitis) if non-sterile; IV+vitC → kidney-stone risk; theoretical skin-cancer risk (less eumelanin = less UV protection). Narrow effective-vs-toxic window

Legal status:
region: INT
status: See note
note: - Oral supplement — widely legal: GRAS/OTC dietary-supplement status in the US, Philippines, Japan, India and elsewhere; no prescription needed.
- Topical — used as a cosmetic ingredient (effect limited to the application site).
- ⚠ Injectable / IV — not FDA-approved for skin lightening anywhere; off-label; the Philippine FDA and dermatological societies warn against it; in the US it is legal only if prescribed by a professional and compounded by a licensed pharmacy. Online/unlicensed injectable glutathione is exactly what authorities warn against.
- Gray-market note: heavily sold (especially IV) for whitening/anti-aging. Oral/topical glutathione is a legal lane; injectable skin-lightening is not, and should never be sold.

Cosmetic claims:

Note: The "master antioxidant" — and the molecule behind Asia's skin-whitening phenomenon. Glutathione's human story is one of the most vivid in the register: a critical cellular antioxidant that became a massive cosmetic movement for lighter skin — sold as IV "gluta drips" across the Philippines, Thailand, India and beyond — despite thin efficacy evidence and real safety warnings. Three threads: (1) endogenously it's a genuinely essential master antioxidant; (2) its fame rests on skin-lightening via tyrosinase inhibition — a real mechanism but weak, route-dependent clinical proof; (3) the popular IV route is unapproved, unproven for lightening, and flagged by health authorities for serious harms. Big real biology, big cultural phenomenon, small honest evidence for the thing it's sold for.
Status note: watch: better-bioavailability oral forms (liposomal/acetyl) with real RCTs; IV skin-lightening remains unapproved and risk-flagged

Sources:
Sonthalia S, et al. Glutathione as a skin whitening agent: facts, myths, evidence and controversies. Indian J Dermatol Venereol Leprol. 2016 (mechanism, evidence, Philippine FDA warning).
Glutathione for skin lightening: a regnant myth or evidence-based verity? (PMC5808366) — oral GRAS status, low bioavailability, IV controversy.
Philippine FDA Advisory No. 2019-182 (unsafe use of glutathione for skin lightening; approved only as cisplatin-chemo adjunct); Philippine DOH/FDA statements (SJS, organ toxicity, kidney-stone risk with IV vit C).
Cosmoderma 2025 review (IV adverse effects: renal/thyroid/dermatologic); US-FDA has not approved glutathione for skin lightening by any route. (Oral/topical modest and generally safe; IV unproven and risk-flagged.)