Glutathione
A tripeptide of glutamate, cysteine and glycine, and the body's most abundant endogenous antioxidant. The central question for supplementation is whether swallowing it actually raises body stores — and trials disagree. One RCT reported higher blood levels after six months at 1,000 mg/day; another found no change over four weeks at the same dose. It is not the same thing as its precursor NAC, and the two follow different routes in the body.
An ingredient with still-limited research
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Effects reported in research
Blood glutathione rose over six months of supplementation — 30–35% in erythrocytes, plasma and lymphocytes (Richie et al., 2015). A four-week trial at the same dose found no change (Allen & Bradley, 2011)
A lower whole-blood oxidised-to-reduced (GSSG/GSH) ratio has been reported (Richie et al., 2015). But when direct oxidative-stress markers — urinary F2-isoprostanes and 8-OHdG — were the primary endpoints, no significant difference emerged (Allen & Bradley, 2011)
In healthy medical students over four weeks, melanin index fell more than placebo at two of six measured sites (Arjinpathana & Asawanonda, 2012); the other four showed no significant difference
Dosage & timing
- Trials have used 250–1,000 mg/day.
- The study that found higher blood levels ran 1,000 mg/day for six months; another found nothing over four weeks, so a short trial period tells you little.
- Levels returned to baseline a month after stopping.
- Studies suggesting liposomal forms absorb better exist, but all are small (around 12 people), open-label, single-dose comparisons — none show a difference in body stores under sustained use.
Cautions
- •Trials disagree on oral absorption and efficacy, and individual responses vary.
- •Findings from IV administration cannot be carried over to oral use.
- •The longest intervention we could find ran six months; we found no trial testing longer durations or higher doses for safety.
- •Consult a physician if pregnant, breastfeeding, or taking immunosuppressants.
- •This information is for educational purposes and does not constitute medical advice.
Supporting research
Randomized controlled trial of oral glutathione supplementation on body stores of glutathione
European Journal of Nutrition, 2015
A double-blind, placebo-controlled trial in 54 non-smoking adults taking 250 or 1,000 mg/day of oral glutathione for six months. Blood glutathione rose above baseline at 1, 3 and 6 months on both doses; at six months the high-dose group showed 30–35% increases in erythrocytes, plasma and lymphocytes and 260% in buccal cells. Levels returned to baseline one month after stopping. A decrease in the whole-blood oxidised-to-reduced (GSSG/GSH) ratio was also reported, which the authors take as an indirect sign of reduced oxidative stress.
Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers
Journal of Alternative and Complementary Medicine, 2011
A double-blind, placebo-controlled trial in 40 adults free of acute or chronic disease taking 500 mg of oral glutathione twice daily (1,000 mg/day) for four weeks. The primary endpoints — urinary F2-isoprostanes and 8-OHdG — did not differ from placebo, and erythrocyte total, oxidized and ratio measures of glutathione were unchanged.
Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study
Journal of Dermatological Treatment, 2012
A double-blind, placebo-controlled trial in 60 healthy medical students taking 500 mg/day of oral glutathione (split dose) for four weeks. Reductions in melanin index were significantly greater than placebo at only two of six measured sites — the right cheek and the sun-exposed left forearm. The authors note that long-term safety has not been established.
Similar supplements
NAC (N-Acetyl Cysteine)
Confidence: ModerateN-Acetyl-L-Cysteine
An amino acid derivative widely studied as a glutathione precursor. Used medically for detoxification (acetaminophen overdose) and mucolysis; also taken as a supplement for antioxidant and anti-inflammatory purposes.
L-Cysteine
Confidence: LowL-Cysteine
The rate-limiting amino acid for glutathione synthesis (the body's primary antioxidant). A simpler precursor form to NAC, studied for oxidative stress reduction and detoxification pathways.
Sulforaphane
Confidence: ModerateSulforaphane (from glucoraphanin in broccoli sprout extract)
An isothiocyanate produced when glucoraphanin (abundant in broccoli sprouts) reacts with myrosinase. Activates the Nrf2 pathway to induce production of detoxification and antioxidant enzymes.
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