Glutathione
Also known as GSH, L-Glutathione reduced, Gamma-glutamylcysteinylglycine, Tationil
Glutathione is a tripeptide of glutamate, cysteine and glycine that every cell makes as its main antioxidant. People use it by injection, IV, oral, liposomal or nebulized routes for oxidative stress, liver support, immune health and skin lightening.
Overview
Glutathione is technically a peptide, though an unusual one: the glutamate is joined through its side chain rather than the normal backbone bond, which protects it from most peptidases. It is present at high concentration in virtually every cell, where it neutralizes reactive oxygen species, recycles vitamins C and E, and helps the liver bind and excrete toxins and drug metabolites. Levels fall with age, illness, poor diet and heavy alcohol use, and low glutathione is associated with a long list of chronic conditions.
The problem with taking glutathione is getting it into cells. Standard oral glutathione is largely broken down in the gut, although a few controlled studies have shown modest increases in blood and tissue levels with sustained daily dosing. Liposomal and sublingual forms improve absorption. Intravenous glutathione delivers high plasma levels but the peptide is cleared quickly and cells still have to take up the components. N-acetylcysteine, which supplies the limiting amino acid cysteine, is a well studied way to raise glutathione from the inside.
Human evidence exists for several uses. IV glutathione is used as an approved adjunct to cisplatin chemotherapy in some countries to reduce nerve toxicity. Trials for Parkinson's disease, cystic fibrosis (nebulized) and fatty liver have shown small or inconsistent benefits. Skin lightening via IV glutathione is popular in parts of Asia but poorly supported and carries real risks from unregulated infusions. Injectable use for general wellness is common in the peptide community, usually 200 to 600 mg several times a week.
How it works
Glutathione works as a reducing agent. The thiol group on its cysteine donates electrons to neutralize free radicals and peroxides, and the enzyme glutathione peroxidase uses it to break down hydrogen peroxide and lipid peroxides. Once oxidized, two glutathione molecules join as GSSG and are recycled back by glutathione reductase using NADPH. In the liver, glutathione S-transferases attach it to toxins and drug metabolites so they can be excreted. It also keeps protein thiols in their correct state, supports mitochondrial function, and regulates the redox-sensitive signaling that controls inflammation and cell survival. Its effect on skin pigmentation comes from inhibiting tyrosinase and shifting melanin production toward the lighter pheomelanin form.
What the research shows
- human RCTSix months of oral glutathione at 250 to 1000 mg daily increased blood and tissue glutathione levels and improved natural killer cell function in healthy adults.
- human RCTIV glutathione reduced cisplatin-induced neurotoxicity in cancer patients without reducing chemotherapy efficacy.
- human pilotOral glutathione produced measurable skin lightening in small trials in Asian populations over 4 to 12 weeks.
- human RCTIntranasal or IV glutathione in Parkinson's disease showed only marginal or no clinical benefit in controlled trials.
- human RCTNebulized glutathione improved lung function measures in some cystic fibrosis trials but not others.
Evidence labels: rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
Dosing and protocol
Injectable community protocols commonly report 200 to 600 mg two to three times weekly. IV clinics use 600 mg to 2 g. Oral doses are typically 250 to 1000 mg daily.
Ongoing, or 8-12 week courses
Some people inject after workouts or before sleep. Oral liposomal is best taken away from protein meals.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 600 mg | 3 mL | 200 mg/mL | 100 units |
| 1500 mg | 5 mL | 300 mg/mL | 66.7 units |
Lyophilized: fridge, away from light and oxygen. Reconstituted: fridge 2-8C, use within 1-2 weeks; it oxidizes quickly once in solution. Discard if it discolors or smells of sulfur.
Cautions
- ▲Plain oral glutathione has poor absorption; look for liposomal or sublingual forms, or use NAC to support natural production.
- ▲IV glutathione for skin lightening is associated with reports of kidney and liver problems, skin rashes and serious reactions from unregulated clinics.
- ▲It oxidizes fast once reconstituted, so old solution may be inactive.
- ▲High dose antioxidants can blunt some of the beneficial adaptations to exercise.
- ▲People with sulfite sensitivity or asthma should be cautious with injectable forms, which can trigger bronchospasm in rare cases.
Commonly stacked with
NAD+ supports the enzyme that recycles oxidized glutathione, so the two are commonly paired in mitochondrial protocols.
SS-31 protects mitochondrial membranes from oxidative damage while glutathione handles free radicals in the rest of the cell.
Used together in longevity and metabolic protocols targeting mitochondrial health.
Frequently asked
Is glutathione really a peptide?
Yes, it is a tripeptide, though with an unusual bond that makes it resistant to normal peptide digestion. It is included in peptide databases because it is dosed and sold alongside other injectable peptides, but it is also widely available as a regular supplement.
Does oral glutathione work?
Older studies said no, but a six month randomized trial found daily oral glutathione did raise blood and cell levels. The effect is modest and slow. Liposomal formulations absorb better. If your goal is simply to raise glutathione, N-acetylcysteine plus glycine is a cheaper and well supported alternative.
Will it lighten my skin?
Oral and IV glutathione have shown lightening effects in small studies, mainly in people with darker skin tones, by shifting melanin production. The effect reverses when you stop. IV lightening treatments from unregulated providers have caused serious harm and are not recommended.
Injectable versus IV, what is the difference?
IV delivers the full dose to the blood immediately, which is why clinics use it. Subcutaneous or intramuscular injection is slower and used at home. Both give a short plasma spike. Neither route has strong evidence for general wellness use in healthy people.
References
- Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition, 2015
- Glutathione in the prevention of cisplatin-induced neurotoxicity (review of clinical trials). Annals of Oncology, 1997
- Glutathione as a skin whitening agent: facts, myths, evidence and controversies (review). Indian Journal of Dermatology, Venereology and Leprology, 2016
- Glutathione: overview of its protective roles, measurement, and biosynthesis (review). Molecular Aspects of Medicine, 2009