Glutathione

What glutathione does in the body

Glutathione is not a vitamin but a protein made of three amino acids that the body builds itself. The label master antioxidant is less marketing than bookkeeping: no other endogenous antioxidant is present in comparable amounts.

Its tasks are well described. Glutathione S-transferases attach it to reactive foreign substances, which can then be excreted; this is phase II of xenobiotic metabolism. Glutathione peroxidase uses it as an electron donor against hydrogen peroxide and lipid hydroperoxides, and via redox cycles it returns spent vitamin C and E to their active form.

The question everything hinges on

Anyone who buys glutathione is buying an assumption: that the three-part chain survives digestion. This was called into question early on. Seven healthy volunteers received 0.15 millimoles of glutathione per kilogram of body weight orally. Over 270 minutes, none of the three measured values rose significantly, neither glutathione nor cysteine nor glutamate. The authors attributed this to cleavage by gamma-glutamyltransferase in the gut and liver.

Against this finding stands the longest available study. 54 non-smoking adults received 250 or 1,000 milligrams daily or placebo for six months, randomized and double-blind. At the end, stores in the higher-dose group were 30 to 35 percent above baseline, and 260 percent above baseline in buccal mucosa cells. After one month without intake they were back to baseline.

And then there is the study in between that finds nothing. 40 healthy adults took 500 milligrams or placebo twice daily for four weeks. The two primary endpoints, F2-isoprostanes and 8-hydroxydeoxyguanosine in urine, remained unchanged, p equal to 0.38 and p equal to 0.27. Glutathione in the erythrocytes did not move either. The difference from the six-month study may lie in duration, compartment or measurement method.

Liposomal, sublingual, oral film

This is exactly where the special formulations come in: if the gut is the problem, you bypass it. For the sublingual form there is a direct comparison. 20 people with metabolic syndrome went through three phases of 21 days each with sublingual glutathione, oral glutathione and N-acetylcysteine. The sublingual form reached higher plasma levels and a more favorable GSH-to-GSSG ratio, with p equal to 0.003.

For the liposomal form, the most cited paper is a single-arm pilot study in twelve people over one month, without a placebo group. It reports increases of 40 percent in whole blood and 100 percent in mononuclear blood cells; the most spectacular figure, too, up to 400 percent more natural killer cell activity, comes from this design. Cleaner comparisons in 14 healthy people at least show that the formulation matters: 300 milligrams of micellar glutathione achieved higher systemic availability than 500 milligrams of standard powder. What is measured is the blood level, not well-being.

Lighter skin, a field of its own

The most frequently studied visible effect is skin lightening. Glutathione inhibits tyrosinase and shifts melanin production from the darker eumelanin to the lighter pheomelanin. In a randomized, double-blind trial in 60 healthy participants, the melanin index fell at all six measurement sites on 500 milligrams daily over four weeks, significantly versus placebo at two of them, p equal to 0.021 and p equal to 0.036. A systematic review of four studies finds the same limited pattern: lightening on sun-exposed skin, none on sun-protected skin, inconclusive overall. A later study with 83 female participants over twelve weeks missed significance.

To be kept strictly separate from this is intravenous use. It is widespread in several countries and approved for this purpose nowhere. Injectable glutathione is approved in India for alcohol-related liver disease and in the Philippines as an adjunct treatment against the neurotoxicity of cisplatin chemotherapy. The Philippine drug authority publicly warned against off-label use on May 12, 2011, citing severe skin reactions up to Stevens-Johnson syndrome, thyroid and kidney dysfunction, as well as air embolism and sepsis from improper injection.

The detour via the building blocks

Because the direct route is disputed, part of the research goes via the precursors. Furthest along is the combination of glycine and N-acetylcysteine, GlyNAC for short. 24 older adults were randomized to GlyNAC or an alanine placebo for 16 weeks, twelve per group. On GlyNAC, glutathione deficiency, oxidative stress, insulin resistance, gait speed and muscle strength improved; on placebo they did not. The groups are small, and the research group is the one that developed the concept.

What the studies show

Single dose, seven volunteers, no absorption

Open pharmacokinetic study in seven healthy people: 0.15 millimoles of glutathione per kilogram of body weight orally, then measurement of glutathione, cysteine and glutamate in plasma over 270 minutes. None of the three values rose significantly. The authors call the systemic availability of glutathione in humans negligible.

Six months, 54 participants, higher stores

Randomized, double-blind, placebo-controlled trial in 54 non-smoking adults over six months, 250 or 1,000 milligrams daily. The primary endpoint was glutathione stores in whole blood, erythrocytes, plasma, lymphocytes and buccal mucosa cells. After one, three and six months they were higher; after six months, in the higher-dose group by 30 to 35 percent in erythrocytes, plasma and lymphocytes and by 260 percent in buccal mucosa cells, in the lower-dose group by 17 percent in whole blood. After one month of washout, everything was back to baseline. These increases are reported relative to baseline, not relative to placebo.

Four weeks, 40 participants, no effect

Randomized, double-blind, placebo-controlled trial in 40 healthy adults; 39 were included in the analysis. 500 milligrams twice daily for four weeks. Primary endpoints were creatinine-standardized F2-isoprostanes and 8-hydroxydeoxyguanosine in urine. After four weeks, the groups did not differ, p equal to 0.38 and p equal to 0.27. Reduced and oxidized glutathione in the erythrocytes also remained unchanged. The primary endpoint was missed.

Where the data stop

The central contradiction has still not been resolved. A single dose does not arrive, six months of intake raise stores, four weeks change nothing at all. In addition, every endpoint is a surrogate: blood levels, melanin index, isoprostanes, killer cell activity. No study measures a hard clinical endpoint. The figures on the liposomal form come from a pilot study in twelve people without a control group. For detoxification, immune strengthening and anti-aging, robust human data are lacking; on the liver there is an open pilot study in 29 evaluable patients, nothing more. The claimed age-related decline does not hold without qualification either: in a healthy population aged 18 to 70 measured in a standardized way, GSH and GSSG in whole blood remained unchanged. Long-term data beyond six months are lacking.

Status, approval and legal

Glutathione is not an approved medicinal product in Germany and is sold as a food supplement. On June 8, 2017, the Federal Office of Consumer Protection and Food Safety, by general ruling under section 54 of the German Food and Feed Code, permitted capsules containing reduced L-glutathione from the EU and EEA to be brought into Germany and placed on the market here, provided that 200 milligrams per capsule at a recommended daily intake of two capsules is not exceeded. There is no authorized health claim; detoxification or immune strengthening may not be advertised. For the modified form S-acetyl glutathione, EFSA issued a positive safety opinion as a novel food in 2026. In sport, the substance is not prohibited, but the method is: infusions and injections of more than 100 milliliters within 12 hours fall under section M2 of the WADA Prohibited List.

Safety

Orally, glutathione was well tolerated in the studies; mainly mild gastrointestinal complaints were reported, and severe reactions are rare. In 2026, EFSA derived safe intakes of 190, 269 and 307 milligrams daily of S-acetyl glutathione for younger adolescents, older adolescents and adults, from a BMDL10 of 877 milligrams per kilogram of body weight per day with an uncertainty factor of 200; pregnant and breastfeeding women and children under ten are excluded. Caution applies in asthma and sulfite sensitivity: nebulized glutathione, 600 milligrams in 4 milliliters of saline over 25 minutes, triggered marked airway narrowing in eight patients with mild asthma; FEV1 fell by 19 percent, compared with 1 percent on placebo. This concerns inhalation, not the capsule, but it is the only well-documented mechanism of harm. Interactions with medicinal products have not been systematically studied for oral use.

Sources

• Witschi et al., Eur J Clin Pharmacol 1992
• Richie et al., Eur J Nutr 2015
• Allen and Bradley, J Altern Complement Med 2011
• Sinha et al., Eur J Clin Nutr 2018
• Schmitt et al., Redox Biology 2015
• Arjinpathana and Asawanonda, J Dermatolog Treat 2012
• Dilokthornsakul et al., J Cosmet Dermatol 2019
• Sonthalia et al., Dermatol Pract Concept 2018
• EFSA NDA Panel, EFSA Journal 2026
• BVL, general ruling BVL 17/01/004 of June 8, 2017