What it is
Glutathione is a very short peptide, a chain of just three amino acids: glutamate, cysteine and glycine. Nearly every cell makes its own supply, and it is the most abundant antioxidant the body produces. The sulfur atom in its cysteine lets it neutralize reactive oxygen molecules and lets liver enzymes tag certain drugs and toxins for removal. Doing that work oxidizes it, and enzymes then recycle it.
Glutathione is not an essential nutrient, because the body builds it from amino acids in food. It is marketed as an oral supplement and, notably in the Philippines and other parts of Asia, offered as an IV drip or injection for skin lightening. Neither the US FDA nor the Philippine FDA has approved injectable glutathione for that purpose.
Glutathione (γ-L-glutamyl-L-cysteinylglycine; C10H17N3O6S, 307.33 g/mol) has an isopeptide bond between the γ-carboxyl of glutamate and cysteine, which protects it from most peptidases. It is synthesized in two ATP-dependent steps by glutamate–cysteine ligase (rate-limiting and feedback-inhibited by glutathione) and glutathione synthetase, reaching millimolar intracellular concentrations, mostly as reduced GSH. Glutathione peroxidases use GSH to reduce hydrogen peroxide and lipid hydroperoxides, forming glutathione disulfide (GSSG), which glutathione reductase regenerates with NADPH; the GSH:GSSG ratio is a standard redox marker. Glutathione S-transferases conjugate GSH to electrophiles, including the acetaminophen metabolite NAPQI, for excretion through the mercapturic acid pathway.
Extracellular glutathione is degraded by membrane γ-glutamyltransferase, and plasma concentrations are low (6.2 µmol/L at baseline in Witschi et al., 1992). Its antioxidant and conjugation roles are enzymatic rather than receptor-mediated. The proposed skin-lightening mechanism, drawn mainly from in-vitro work, is inhibition of tyrosinase and a shift from dark eumelanin toward lighter pheomelanin; human evidence for this is limited.
Who made it and when
In 1888 the French scientist J. de Rey-Pailhade found a substance in yeast that turned sulfur into hydrogen sulfide and named it “philothion”, Greek for “sulfur-loving”. In 1921 the British biochemist Frederick Gowland Hopkins isolated the compound, called it glutathione, and thought it was made of two amino acids. Others disagreed, and in 1929 Hopkins and, independently, Edward Kendall in the US reported that it contains three. In 1935 chemists confirmed the structure by making it from scratch.
Glutathione is a natural molecule, so no company owns it. Injectable glutathione is authorized as a medicine in some countries, including the Philippines, but not in the United States, where the oxidized form appears only as one ingredient of an approved eye-surgery rinse.
De Rey-Pailhade (1888) described philothion in yeast extracts as a substance that reduces sulfur to hydrogen sulfide. Hopkins (Biochem J 1921, “On an autoxidisable constituent of the cell”) isolated it, provisionally named it glutathione, and proposed a glutamyl-cysteine dipeptide. In 1929 Hopkins (“On glutathione: a reinvestigation”, J Biol Chem) and, independently, Edward C. Kendall revised this to a tripeptide of glutamate, cysteine and glycine, and Harington and Mead reported its synthesis in 1935 (“Synthesis of glutathione”, Biochem J).
The Philippine FDA states that injectable glutathione is approved there as an adjunct treatment in cisplatin chemotherapy. In the US, the oxidized dimer glutathione disulfide (0.184 mg/mL) is one of eight listed active ingredients of BSS PLUS (Alcon; NDA 018469, approved 1981-10-28), an intraocular irrigating solution for eye surgery. Renovion’s ARINA-1, a nebulized combination of reduced glutathione and ascorbic acid, is in an FDA-regulated phase 3 trial (NCT05654922), following a phase 1 study in bilateral lung transplant recipients (NCT03226431) and a phase 2a study in non-cystic fibrosis bronchiectasis (NCT05495243). It is the only active late-stage US program containing glutathione identified for this article. No patent is listed.
What the data say
Taken by mouth: an early study found that one large oral dose did not raise glutathione in the blood, because the gut and liver break it down. A 2015 six-month trial in 54 adults found daily supplements did raise glutathione stored in blood cells, by roughly a third at the higher dose, although levels fell back within a month of stopping. A four-week trial found no change.
Skin: a small trial in 60 Thai medical students reported slightly lighter skin at two of six sites after four weeks of oral glutathione. A 2018 review found that evidence for IV glutathione for skin lightening rested on one poorly designed study.
Disease: inhaled glutathione did not improve lung function in a 153-patient cystic fibrosis trial. In Parkinson disease, IV and nasal glutathione were tolerated in small trials but did not outperform placebo.
Bioavailability: Witschi et al. (Eur J Clin Pharmacol 1992) gave 7 volunteers about 3 g orally and found no significant rise in plasma glutathione over 270 minutes, attributed to gut and liver γ-glutamyltransferase. Richie et al. (Eur J Nutr 2015) randomized 54 non-smokers to 250 or 1,000 mg/day or placebo for 6 months; at 1,000 mg, GSH rose 30–35% in erythrocytes, plasma and lymphocytes and 260% in buccal cells, returning to baseline after a 1-month washout. Allen and Bradley (2011; 500 mg twice daily for 4 weeks; n=40) found no change in oxidative-stress markers or glutathione status.
Skin: Arjinpathana and Asawanonda (2012) reported that 500 mg/day orally for 4 weeks lowered the melanin index more than placebo at 2 of 6 sites (n=60). Sonthalia et al. (2018) called the IV evidence a single, dubiously designed study.
Disease: Griese et al. (NCT00506688; AJRCCM 2013) found no FEV1 difference with 646 mg inhaled twice daily for 6 months in CF (n=153). Hauser et al. (Mov Disord 2009; 1,400 mg IV three times weekly for 4 weeks; n=21) and Mischley et al. (NCT02424708; J Parkinsons Dis 2017; 100 or 200 mg intranasally three times daily; n=45) found no significant difference from placebo.
Regulatory picture
Three separate facts. Approval: no FDA-approved drug has reduced glutathione as its active ingredient; the oxidized form is one of eight ingredients of an approved rinse used during eye surgery. An inhaled mix of glutathione and vitamin C is in a late-stage trial in lung transplant patients, which is why this page lists glutathione as investigational. Compounding: IV glutathione in the US is made by compounding pharmacies, and the FDA lists glutathione as “under evaluation” (Category 1) for its bulk-ingredient list, with no final decision. An FDA advisory committee voted 8 to 5 in 2022 to recommend adding it; that vote is not binding and the FDA has not acted on it. Enforcement and safety: the FDA warned compounders in 2019 after patients reacted to injections made with contaminated glutathione powder, and again in August 2026, when at least 30 patients became ill after IV glutathione made from a supplement-grade ingredient. The US FDA (2015) and the Philippine FDA (2019) have both said that no injectable skin-lightening product is approved.
Approval: investigational. Reduced glutathione is not an active ingredient of any FDA-approved product (BSS PLUS contains the distinct disulfide), but ARINA-1 (Renovion; 150 mg/mL reduced glutathione with 88 mg/mL ascorbic acid, 4 mL nebulized twice daily) is in a recruiting, FDA-regulated phase 3 trial for bronchiolitis obliterans syndrome after bilateral lung transplant (NCT05654922).
Compounding: glutathione is in 503A Category 1 (FDA list updated 2026-05-14) and is not on the 503A bulks list in 21 CFR 216.23. The Pharmacy Compounding Advisory Committee reviewed it on 2022-06-08 and voted 8–5 with 1 abstention in favour of inclusion; the vote is non-binding and FDA had not completed rulemaking to add it as of the 2026-05-14 list, so compounding is recorded as unknown. On 2019-02-01 FDA warned against L-glutathione distributed by Letco Medical after seven patients reacted to an injectable compounded with it at 200 mg/mL, and on 2019-06-07 it reported that all FDA-tested samples contained excessive endotoxin, some up to five times the appropriate limit. In 2026, three Texas compounders recalled glutathione products for elevated endotoxin, CDC counted more than 25 cases in at least four states, and FDA’s 2026-08-27 alert cited at least 30 patients and a dietary-supplement-grade ingredient supplied by Medisca Inc.
Cosmetic use: FDA’s 2015 consumer update on injectable skin-lightening products, which followed a 2014 seizure of injectable glutathione kits, and Philippine FDA Advisory No. 2019-182 both state that no injectable skin-lightening product is approved.
