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Setria® Glutathione

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

Benefits

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.

Supported by Trial 1

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.

Supported by Trial 2, Trial 1

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.

Supported by Trial 2

Skin Health (Trends — Not Statistically Significant in Primary RCT)

RCT in 57 Thai women showed TRENDS favoring Setria for melanin index reduction over 12 weeks, but primary endpoint did NOT reach statistical significance. The Filipino trial (open-label, single-arm) showed effects but lacked placebo control. Skin lightening is a controversial cosmetic application; marketing claims often exceed peer-reviewed evidence.

Supported by Trial 2

Mechanism of action

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.

Clinical trials

1
Setria® Oral Glutathione for Blood GSH — 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. Outcomes: glutathione in whole blood, erythrocytes, plasma, lymphocytes. (Richie et al. 2015, Eur J Nutr)

54 healthy adults. 6-month intervention.

Both Setria® doses increased glutathione in whole blood (~+35%), erythrocytes, plasma, lymphocytes vs placebo. Industry-funded (Kyowa Hakko). IMPORTANT: this contradicts long-standing claim that oral glutathione is destroyed in GI tract; suggests Setria® form may have unique bioavailability characteristics.

2
Setria® for Skin Health — Weschawalit 2017 RCT
PubMed

Randomized double-blind placebo-controlled trial of 250 mg/day Setria reduced glutathione, 250 mg/day AquaGluta oxidized glutathione, or placebo for 12 weeks. Published Clinical, Cosmetic and Investigational Dermatology 2017.

57 healthy Thai female subjects, ages 20-50 (NOT Filipino — corrected from earlier database error).

Trends favored both glutathione forms for melanin index reduction and UV spots vs placebo, but primary endpoint did NOT reach statistical significance per published paper. Glutathione groups had higher skin elasticity (also non-significant). Industry-funded (Kyowa Hakko). CRITICAL CONTEXT: skin lightening is a controversial cosmetic application with cultural, ethical, and dermatological considerations. Press releases and marketing materials overstated significance vs published peer-reviewed results.

Side effects and drug interactions

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

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Frequently asked questions about Setria® Glutathione

What is Setria® Glutathione?

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.

What does Setria® Glutathione do?

Glutathione (γ-glutamyl-cysteinyl-glycine) donates electrons to neutralize hydrogen peroxide, lipid peroxides, and reactive oxygen species via glutathione peroxidase (GPx) enzymes. In clinical research, Setria® Glutathione has been studied for increased blood and tissue glutathione levels, immune system enhancement, oxidative stress reduction.

Who should take Setria® Glutathione?

Setria® Glutathione may be most relevant for people interested in antioxidant, immune support, hair, skin & nails. It has been clinically studied for increased blood and tissue glutathione levels, immune system enhancement, oxidative stress reduction. As with any supplement, consult your healthcare provider before starting, especially if you have medical conditions or take prescription medications.

How long does Setria® Glutathione take to work?

Most clinical trial effects appear over weeks of consistent use; individual response varies. Acute or same-day effects (where applicable) typically appear within hours, but most cumulative benefits — particularly those affecting biomarkers, mood, sleep quality, or chronic symptoms — require 4-12 weeks of regular use to fully assess. If you don't notice benefit after 12 weeks at the appropriate dose, it may not be your responder.

When is the best time to take Setria® Glutathione?

For anti-inflammatory and joint goals, Setria® Glutathione is typically taken with meals — fat-containing food often improves absorption for fat-soluble compounds. Daily consistency matters more than precise timing for cumulative anti-inflammatory effects. Always check product labeling and follow personalized guidance from your healthcare provider.

Is Setria® Glutathione worth taking?

Setria® Glutathione has moderate clinical evidence (Evidence Level 3/5 on NutraSmarts) — meaningful trial support exists, though results are less consistent than top-tier ingredients. Whether it's worth taking depends on your specific goals, what you've already tried, your budget, and your overall supplement strategy. The honest framing: no supplement is essential for most people, and lifestyle factors (sleep, exercise, diet, stress management) typically produce larger effects than any single supplement. Setria® Glutathione is most worth trying if its evidence-supported uses align with your specific goals.

What is the recommended dosage of Setria® Glutathione?

The clinically studied dose for Setria® Glutathione is 250–500 mg/day; 250 mg shown effective for increasing blood glutathione levels. Always follow product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Setria® Glutathione used for?

Setria® Glutathione is studied for increased blood and tissue glutathione levels, immune system enhancement, oxidative stress reduction. 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.