Benefits
Raising the body's glutathione stores over months
In a 6-month placebo-controlled trial in 54 healthy non-smoking adults, glutathione in blood and red cells rose above baseline at 250 and 1,000 mg/day, and at the higher dose also in plasma, immune cells and cheek cells; levels fell back within a month of stopping. A single 3 g dose and a 4-week course of 1,000 mg/day showed no rise. The long trial was supported by the ingredient's maker.
Antioxidant balance and oxidative stress markers
Results are inconsistent. In the 6-month trial, the ratio of oxidized to reduced glutathione in blood fell at both doses, a sign of less oxidative stress. But a 4-week trial in 40 healthy adults found no change in urinary oxidative-damage markers, and a 3-week trial in 20 men with obesity found no change in muscle or urinary oxidation markers.
Natural killer (NK) cell activity
In a subset of the 6-month trial, natural killer cell activity (a lab measure of how well these immune cells destroy target cells) more than doubled at 1,000 mg/day versus placebo at 3 months. A 12-person liposomal pilot with no placebo group, funded by a seller, also reported higher NK activity. These are lab markers, not evidence of fewer infections.
Skin tone and melanin index (cosmetic)
In 60 Thai medical students, 500 mg/day for 4 weeks lowered a skin melanin reading more than placebo at 2 of 6 sites. A 12-week trial of 250 mg/day in 57 Thai women saw only non-significant trends overall, and a systematic review called the evidence inconclusive. Any change is small and cosmetic; oral glutathione is not a proven skin-whitening product.
Skin wrinkles and elasticity
In the 12-week trial in 57 Thai women aged 20 to 50, 250 mg/day of reduced glutathione gave lower wrinkle readings than placebo at one sun-protected arm site, and at one forearm site in women over 40. Skin elasticity trended higher but not significantly. This is a single maker-funded trial with many measurements, so chance findings are possible.
Insulin sensitivity and blood sugar markers
In 20 men with obesity (half with type 2 diabetes), 1,000 mg/day for 3 weeks was followed by a significant rise in clamp-measured insulin sensitivity in the glutathione group. In an unblinded 6-month study of 250 adults with type 2 diabetes on medication, adding 500 mg/day raised blood glutathione, but HbA1c fell only in a post hoc subgroup over age 55.
Mechanism of action
Recycled inside cells to neutralize peroxides
Cells hold glutathione at about 1 to 10 mM. Glutathione peroxidase enzymes use it to turn hydrogen peroxide into water, producing oxidized glutathione (GSSG), which glutathione reductase converts back to the reduced form. Glutathione also binds reactive foreign compounds (conjugation) so cells can export them.
Broken down in the gut, rebuilt inside cells
Enzymes in the gut and liver (gamma-glutamyltransferase) split swallowed glutathione into its amino acids, which is why a single large dose did not raise blood levels. Cells make their own glutathione from glutamate, cysteine and glycine, with cysteine usually the limiting building block; that is the rationale for precursors such as NAC and GlyNAC.
Melanin pathway (laboratory findings)
In laboratory studies glutathione inhibits tyrosinase, the enzyme that starts melanin production, directly and indirectly, and shifts pigment production from darker eumelanin toward lighter pheomelanin. The skin trials did not measure how much oral glutathione reaches pigment cells in people.
Clinical trials
Pharmacokinetic study of one oral dose of glutathione (0.15 mmol/kg, about 3 g) with plasma sampling for 270 minutes (Witschi et al. 1992, Eur J Clin Pharmacol).
7 healthy volunteers.
Plasma glutathione, cysteine and glutamate did not rise significantly after the dose. The authors attributed this to breakdown by gamma-glutamyltransferase in the gut and liver and concluded that a single dose cannot raise circulating glutathione to a meaningful extent. Repeated daily use was not tested.
Randomized, double-blind, placebo-controlled trial of oral glutathione 500 mg twice daily for 4 weeks (Allen et al. 2011, J Altern Complement Med).
40 adult volunteers without acute or chronic disease; 39 completed per protocol.
Null result. The primary outcomes, urinary F2-isoprostanes and 8-OHdG (markers of oxidative damage to fats and DNA), did not differ from placebo at week 4. Red-cell reduced and oxidized glutathione and their ratio were also unchanged.
Randomized, double-blind, placebo-controlled 6-month trial of oral reduced glutathione at 250 or 1,000 mg/day. The glutathione (Setria) and placebo were supplied by Kyowa Hakko Bio, which also gave the lead author research support (Richie et al. 2015, Eur J Nutr).
54 healthy non-smoking adults; immune markers were measured in a subset.
Blood glutathione rose versus baseline at 1, 3 and 6 months at both doses. At 6 months the high dose raised levels by 30 to 35% in red cells, plasma and lymphocytes and by 260% in cheek cells; the low dose raised whole blood by 17% and red cells by 29%. Levels returned to baseline after a 1-month washout. The oxidized-to-reduced glutathione ratio in blood fell in both dose groups, and natural killer cell activity more than doubled with the high dose versus placebo at 3 months.
Pilot study in which participants were randomly assigned to oral liposomal glutathione at 500 or 1,000 mg/day for 4 weeks, without a placebo group; funded by Researched Nutritionals, which sells a liposomal glutathione (Sinha et al. 2018, Eur J Clin Nutr).
12 healthy non-smoking adults aged 50 to 80.
Glutathione rose within 1 week, with peak increases at 2 weeks of 40% in whole blood, 25% in red cells, 28% in plasma and 100% in blood immune cells. Plasma 8-isoprostane fell 35%, and NK cell activity rose by up to 400%. The two doses did not differ, and the authors called the findings preliminary; without a placebo group, changes cannot be firmly attributed to the supplement.
Randomized crossover trial comparing a sublingual glutathione tablet (450 mg/day), swallowed glutathione capsules (450 mg/day) and NAC (200 mg/day), each for 21 days; two authors were employees of the sublingual product's maker (Schmitt et al. 2015, Redox Biol).
20 volunteers with metabolic syndrome.
Compared with the swallowed capsules, the sublingual form gave higher plasma total and reduced glutathione and a higher reduced-to-oxidized glutathione ratio, and only the sublingual period raised plasma vitamin E. The NAC comparison used a low dose. No adverse events were reported, and liver markers stayed normal.
Randomized, double-blind, placebo-controlled trial of glutathione capsules, 500 mg/day in two doses, for 4 weeks; the main outcome was melanin index at six skin sites (Arjinpathana et al. 2012, J Dermatolog Treat).
60 otherwise healthy medical students in Bangkok, Thailand; all completed.
Melanin index fell at all six sites with glutathione, but the drop was significantly larger than with placebo at only two: the right side of the face and the sun-exposed left forearm. UV spots changed in a similar way. Both glutathione and placebo were very well tolerated; the authors noted long-term safety had not been established.
Randomized, double-blind, placebo-controlled three-arm trial of reduced glutathione (Setria, 250 mg/day), oxidized glutathione (250 mg/day) or placebo for 12 weeks; funded by Kyowa Hakko Bio (Weschawalit et al. 2017, Clin Cosmet Investig Dermatol).
60 healthy Thai women aged 20 to 50 enrolled; 57 analysed (20 reduced glutathione, 18 oxidized, 19 placebo).
Mixed. The primary outcome, melanin index, tended to be lower with both forms but was not significantly different from placebo overall; in a subgroup over 40, one forearm site was significantly lower with reduced glutathione. Wrinkle readings were lower than placebo at some sites, and elasticity trended higher without significance. Two volunteers withdrew because of a temporary rise in liver enzymes; no serious adverse events occurred.
Pragmatic, unblinded study without placebo: adults with type 2 diabetes were allocated by coin toss either to continue their usual medicines alone or to also take 500 mg/day oral glutathione for 6 months (Kalamkar et al. 2022, Antioxidants (Basel)).
In India, 250 adults with type 2 diabetes on anti-diabetic treatment (125 given glutathione) plus 104 adults without diabetes for comparison; participants were aged 30 to 78.
Blood glutathione rose and the DNA-oxidation marker 8-OHdG fell within 3 months in the glutathione group. HbA1c was maintained overall and fell only in a post hoc subgroup over age 55. Without blinding or a placebo, these results are weaker than a controlled trial.