Evidence Level
Moderate
2 Clinical Trials
4 Documented Benefits
3/5 Evidence Score

Setria® is Kyowa Hakko's patented reduced L-glutathione (GSH) produced via fermentation — the only commercially available oral glutathione with robust human clinical evidence for meaningfully raising blood and tissue glutathione levels. As the body's master antioxidant, glutathione plays central roles in detoxification, immune function, cellular protection, and skin health.

Studied Dose 250–500 mg/day; 250 mg shown effective for increasing blood glutathione levels
Active Compound Reduced L-Glutathione (GSH) ≥98% — Setria® by Kyowa Hakko Bioindustries, fermentation-derived

Increased blood and tissue glutathione levels

A 6-month RCT demonstrated Setria (250 and 1,000 mg/day) significantly increased glutathione levels in red blood cells, plasma lymphocytes, and buccal cells vs. placebo — with 30–35% increases in whole blood GSH at 6 months. Previous skepticism about oral GSH bioavailability is now addressed by this data.

Immune system enhancement

Human clinical trial showed Setria significantly increased NK cell cytotoxicity and reduced immunosuppression markers after 3 months. Higher GSH levels in immune cells support their proliferation, activity, and resistance to oxidative damage during immune responses.

Oxidative stress reduction

Glutathione is the body's primary intracellular antioxidant — present at millimolar concentrations in most cells. Supplementing Setria reduces systemic oxidative stress markers (8-OHdG, TBARS) and protects cellular proteins, DNA, and lipids from reactive oxygen species damage.

Skin lightening and anti-aging

Setria has shown significant skin lightening effects in Asian populations through melanin synthesis inhibition — a major market application. Additionally, glutathione supports collagen synthesis, reduces UV-induced skin damage, and may slow skin aging through antioxidant mechanisms.

1

Direct cellular antioxidant activity

Glutathione (γ-glutamyl-cysteinyl-glycine) donates electrons to neutralize hydrogen peroxide, lipid peroxides, and reactive oxygen species via glutathione peroxidase (GPx) enzymes. The resulting oxidized glutathione (GSSG) is regenerated back to GSH by glutathione reductase using NADPH.

2

Phase II detoxification conjugation

Glutathione S-transferase enzymes conjugate GSH to electrophilic toxins, heavy metals, drug metabolites, and reactive compounds — neutralizing them and enabling urinary or biliary excretion. This is the liver's primary detoxification mechanism for xenobiotics.

3

Tyrosinase inhibition (skin lightening)

Glutathione inhibits tyrosinase, the rate-limiting enzyme in melanin biosynthesis, and shifts melanin production from darker eumelanin toward lighter phaeomelanin — producing the skin-lightening effects observed in clinical trials without the toxicity of chemical skin-lightening agents.

1
Oral Setria Glutathione and Blood GSH Levels — 6-Month RCT
PubMed

Randomized, double-blind, placebo-controlled trial of Setria (250 mg/day and 1,000 mg/day) vs. placebo in 54 healthy adults for 6 months.

54 healthy non-smoking adults. 6-month intervention.

Both doses significantly increased glutathione in whole blood (up to 35%), erythrocytes, plasma, and lymphocytes vs. placebo. Significant increases in NK cell cytotoxicity. No adverse effects at either dose. First human RCT confirming oral GSH bioavailability.

2
Setria Glutathione and Skin Lightening — RCT
PubMed

RCT of Setria glutathione vs. placebo in 60 healthy adults in the Philippines for 8 weeks, measuring melanin index and skin lightening.

60 healthy adults. 8-week intervention.

Setria group showed significant reduction in melanin index across all six body sites measured. Skin became progressively lighter over the 8-week study period. No adverse effects. Well tolerated.

Common Potential side effects

Very well tolerated; no significant adverse effects reported in clinical trials at 250–1,000 mg/day
Rare reports of mild GI discomfort at initiation
May reduce efficacy of certain chemotherapy agents that rely on oxidative mechanisms — consult oncologist

Important Drug interactions

Chemotherapy (cisplatin, cyclophosphamide) — may protect cancer cells from oxidative damage; avoid concurrent use without oncologist guidance
Acetaminophen — glutathione is depleted by acetaminophen overdose; supplementation may be protective at therapeutic doses
No established interactions at standard supplemental doses