Glutathione

GSH, L-glutathione (reduced), γ-L-glutamyl-L-cysteinylglycine; oxidised form GSSG; liposomal glutathione; S-acetyl glutathione

Immune & bioregulators

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Note on this profile. Glutathione is a molecule every cell in the body makes. It is sold as a dietary supplement in most countries and used intravenously in some clinical settings (notably as an approved drug in Italy and Japan). Most IV "glutathione therapy" for skin lightening, detox or anti-ageing is unapproved use, and regulators have warned about it.

Summary

Class: Naturally occurring tripeptide (glutamate–cysteine–glycine), the most abundant small-molecule antioxidant inside human cells
Mechanism: Donates electrons to neutralise reactive oxygen species and detoxify compounds via glutathione-S-transferases; recycled by glutathione reductase
Routes studied: Oral (standard, liposomal, sublingual), intravenous, nebulised/inhaled, intranasal, intramuscular, topical
Dose range reported: Oral trials: 250–1,000 mg/day. IV in clinical trials: 600 mg to 1.2–2.4 g per infusion; Parkinson's trials used 1,400 mg three times weekly. Inhaled: 600 mg twice daily in cystic fibrosis trials. Community/clinic IV: 600–2,000 mg, often weekly. All as reported in studies or by the community
Half-life: Plasma half-life of IV glutathione is short, roughly 10–15 minutes; intracellular levels are what matter and are regulated by synthesis, not plasma supply
Storage: Lyophilised or powder: cool, dry, protect from light and air — oxidises readily. Reconstituted: refrigerate and use within days, not weeks; a yellowing solution has oxidised
Regulatory status: Dietary supplement (oral) in US, EU, UK, AU. Approved IV drug in Italy and Japan for specific indications †. Compounded IV use in the US is restricted after FDA action on endotoxin problems

Doses are as reported in studies or by the community — never recommendations.

1What it is

Glutathione is a three-amino-acid molecule found in millimolar concentrations in essentially every human cell, with the highest levels in the liver. It is not a drug someone invented; it is the cell's main buffer against oxidative stress and a key player in detoxifying drugs, pollutants and the by-products of normal metabolism. The body makes it from cysteine, glutamate and glycine, with cysteine availability usually being the rate-limiting step. Levels decline with age and are low in many diseases (HIV, cystic fibrosis, diabetes, liver disease, Parkinson's).

The reason this profile sits among "longevity" compounds is that low glutathione tracks with ageing and disease, and the question of whether raising it from outside helps has been studied for decades with mixed answers. The core problem is delivery: oral glutathione is largely broken down in the gut, and IV glutathione leaves the blood within minutes, so most of the interesting human data are about precursors (N-acetylcysteine, glycine) or specialised formulations rather than the peptide itself.

2How it's thought to work

Antioxidant. reduced glutathione (GSH) hands an electron to reactive species or to oxidised proteins, becoming GSSG, which the enzyme glutathione reductase recycles using NADPH.

Detoxification. glutathione-S-transferases attach GSH to drugs and toxins (including paracetamol's toxic metabolite) so they can be excreted — this is why N-acetylcysteine is the antidote for paracetamol overdose.

Redox signalling. the GSH/GSSG ratio acts as a cellular switch affecting gene expression and immune function.

Melanin. GSH shifts melanin synthesis from dark eumelanin toward lighter pheomelanin by inhibiting tyrosinase — the basis for skin-lightening use.

Mitochondria. maintains the mitochondrial GSH pool that protects the respiratory chain.

The tripeptide gives up an electron to neutralise a free radical; the two oxidised molecules pair up and are recycled by glutathione reductase.Schematic — not to scale

3What the research shows

Graded A (mixed)

Raising body glutathione with oral supplementation

A 6-month of 250 or 1,000 mg/day oral glutathione in healthy adults reported increases of 30–35% in blood, red-cell and lymphocyte GSH and improved natural-killer cell activity (Richie 2015, Eur J Nutr). An earlier 4-week RCT at 500 mg twice daily found no change in any oxidative-stress marker (Allen & Bradley 2011, J Altern Complement Med). Liposomal and sublingual formulations show better short-term bioavailability in small trials. [1][2]

Graded A (small)

Precursor approach (GlyNAC) in older adults

Supplementing glycine plus N-acetylcysteine for 16 weeks in older adults restored red-cell glutathione, reduced oxidative stress and insulin resistance, and improved several ageing markers in a 24-person RCT (Kumar 2023, J Gerontol A). This is the strongest "longevity"-flavoured human evidence and it is about precursors, not glutathione itself. [3]

Graded A (negative/neutral)

Parkinson's disease (IV and intranasal)

A randomised, placebo-controlled trial of IV glutathione 1,400 mg three times weekly for 4 weeks found no significant benefit over placebo (Hauser 2009, Mov Disord). Intranasal glutathione Phase I/IIb trials showed safety and raised brain GSH on spectroscopy but no clinical benefit beyond placebo (Mischley 2017). [4][5]

Graded A (negative on lung function)

Cystic fibrosis (inhaled)

A 6-month multicentre RCT of inhaled glutathione showed no improvement in FEV1 (Griese 2013, Am J Respir Crit Care Med). [6]

Graded A (small, short-term)

Skin lightening

Several small RCTs of oral (500 mg/day) and topical glutathione reported modest reductions in melanin index over 4–12 weeks (Arjinpathana 2012, J Dermatolog Treat; Watanabe 2014, Clin Cosmet Investig Dermatol). Effects were small and reversible; no RCT supports IV glutathione for lightening, and the Philippine FDA among others has warned against it. [7]

Non-alcoholic fatty liver disease

A 4-month open-label pilot of 300 mg/day oral glutathione reduced ALT in 34 patients (Honda 2017, BMC Gastroenterol). Uncontrolled. [8]

Graded A (older, mixed)

Chemotherapy neuropathy protection

IV glutathione alongside cisplatin or oxaliplatin reduced neurotoxicity in several small RCTs in the 1990s–2000s (Cascinu 2002, J Clin Oncol); later trials with paclitaxel/carboplatin were negative. [9]

Graded B/A (scattered)

Male infertility, peripheral artery disease, psychiatric conditions

Small or older trials, mostly with IV or glutathione, with modest or inconsistent results.

4Reported side effects and interactions

Literature-reported

Oral glutathione is well tolerated; mild bloating, cramps or flatulence in some trials. IV glutathione in clinical trials was generally safe at studied doses; the main real-world harms come from compounded products and off-label clinic use — in 2019 the FDA warned about compounded IV glutathione containing high levels after reports of fever, chills, nausea and hypotension. Case reports of liver injury, kidney dysfunction and Stevens–Johnson syndrome have been linked to high-dose IV skin-lightening regimens; causality is uncertain but regulators (Philippines, US) have acted.

Community-reported

oral — digestive upset, occasional sulphur-like body odour; IV — flushing, a metallic taste, lightheadedness during infusion, infusion-site discomfort; some report transient worsening of fatigue or headache ("detox" claims are unverified).

Theoretical. zinc depletion has been raised with long-term high oral doses; high-dose antioxidants may blunt beneficial exercise adaptations (shown for vitamins C and E, not specifically GSH). In cancer, antioxidant supplementation during active treatment is controversial because tumour cells also use glutathione to resist chemotherapy.

Interactions. may reduce the effectiveness of some chemotherapy agents (and in other cases protects against their toxicity — context-specific); theoretical additive effects with other sulphur-containing antioxidants (NAC, alpha-lipoic acid). People on paracetamol in high doses are, if anything, the group where glutathione support has a mechanistic basis.

Markers researchers commonly monitor

Marker	Why it's watched
Red-cell or whole-blood glutathione (GSH, GSSG and ratio)	direct marker of whether a protocol is changing glutathione status; sampling and handling are finicky.
Liver enzymes (ALT, AST, GGT)	GGT in particular reflects glutathione turnover; ALT fell in the NAFLD pilot.
Oxidative-stress markers (F2-isoprostanes, 8-OHdG, malondialdehyde)	research-grade; used in the GlyNAC trials.
Kidney function (creatinine, eGFR)	case reports of kidney problems with high-dose IV regimens.
Zinc	theoretical depletion with long-term high oral dosing.
Melanin index or skin colorimetry	if lightening is the research question.
General baseline CBC, CMP

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Oral products need no preparation. Injectable glutathione is supplied as powder in large vials (typically 600 mg to 2 g — hundreds of times the mass of most peptides on this site) or as pre-made ampoules. It oxidises quickly once dissolved: with sterile water immediately before use, do not store the solution for weeks, discard if it turns yellow. For nebulised use, researchers used pharmacy-prepared sterile solutions. Sterility and matter more here than for most peptides because of the volumes involved.

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6Commonly studied alongside

N-acetylcysteine and glycine (precursors; the GlyNAC trials), vitamin C (often co-infused in clinics; no trial basis for the combination), alpha-lipoic acid, NAD⁺ precursors, SS-31 and MOTS-c (community "mitochondrial" protocols — no combined data).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Oral: dietary supplement. IV: not FDA-approved as a drug; in 2019 the FDA warned about compounded glutathione with high endotoxin levels, and compounding of glutathione for injection is restricted †
European Union	Oral: food supplement. Injectable: authorised medicine in Italy (e.g. for cisplatin neuropathy prevention) †; not authorised EU-wide
United Kingdom	Oral: food supplement. Injectable: not licensed
Australia	Oral: listed complementary medicine (TGA). Injectable: not approved; IV use in clinics has drawn TGA attention †
South Africa	Oral: complementary medicine. Injectable: not registered
Sport	Not prohibited by WADA. IV infusions above 100 ml per 12 hours are prohibited (M2) regardless of content

8Open questions

Does oral glutathione raise intracellular levels meaningfully, or do precursors do it better and cheaper?
Is the age-related fall in glutathione a driver of ageing or a consequence?
Are the GlyNAC results reproducible at scale?
What are the long-term risks of repeated high-dose IV glutathione, given the lack of controlled data on that use?

9References

1Richie JP et al. (2015). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. PubMed · DOI
2Allen J, Bradley RD (2011). Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med. PubMed · DOI
3Kumar P et al. (2023). Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: a randomized clinical trial. J Gerontol A Biol Sci Med Sci. PubMed · DOI
4Hauser RA et al. (2009). Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov Disord. PubMed · DOI
5Mischley LK et al. (2017). Phase IIb study of intranasal glutathione in Parkinson's disease. J Parkinsons Dis. PubMed · DOI
6Griese M et al. (2013). Inhalation treatment with glutathione in patients with cystic fibrosis: a randomized clinical trial. Am J Respir Crit Care Med. PubMed · DOI
7Arjinpathana N, Asawanonda P (2012). Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study. J Dermatolog Treat. PubMed · DOI
8Honda Y et al. (2017). Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study. BMC Gastroenterol. PubMed
9Cascinu S et al. (2002). Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. PubMed · DOI
10FDA (2019). Warning on compounded drugs containing L-glutathione with high endotoxin levels. PubMed
11Forman HJ, Zhang H, Rinna A (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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11Page history

25 Oct 2026Profile published — awaiting medical review

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