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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 Clinical Trial

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. (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

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.

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 is Setria Glutathione used for?

Setria Glutathione is researched primarily for Antioxidant, Immune Support, and Hair, Skin & Nails. 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.

What is the recommended dosage of Setria Glutathione?

The clinically studied dose is 250–500 mg/day; 250 mg shown effective for increasing blood glutathione levels Always follow the product label and check with a healthcare provider for personal advice.

Is Setria Glutathione safe, and does it have side effects?

For most healthy adults, Setria Glutathione is well tolerated at studied doses. Reported effects can include: 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 It may also interact with some medications. Setria Glutathione is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Setria Glutathione interact with any medications?

Possible interactions include: 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 If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Setria Glutathione?

NutraSmarts rates the evidence for Setria Glutathione as Moderate (3 out of 5). It is backed by 2 clinical trials and 8 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(8 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Lomaestro BM, Malone M. Glutathione in health and disease: pharmacotherapeutic issues. Ann Pharmacother. 1995;29(12):1263-73. doi: 10.1177/106002809502901213.PubMedUsed to support: Classic pharmacotherapeutic review of glutathione: mechanisms (antioxidant, detoxification, redox homeostasis), conditions where GSH is depleted, and rationale for supplementation. Establishes the long-standing pharmacological framing for why GSH supplementation became a clinical research priority.
  2. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30(1-2):1-12. doi: 10.1016/j.mam.2008.08.006.PubMedUsed to support: Comprehensive mechanism review of glutathione as the most abundant low-molecular-weight thiol in cells, with millimolar intracellular concentrations. Covers protective roles against oxidative damage and xenobiotic electrophiles, redox homeostasis, biosynthesis (γ-glutamylcysteine synthetase rate-limiting step), and methods for measurement. Backs the page's framing of GSH as the body's master antioxidant.
  3. Pizzorno J. Glutathione! Integr Med (Encinitas). 2014;13(1):8-12.PubMedUsed to support: Integrative medicine overview discussing the critical role of adequate glutathione for detoxification, mitochondrial function, immune support, and healthy aging — with attention to lifestyle, nutrient, and supplementation strategies to maintain GSH status. Supports the page's positioning of GSH as foundational to detoxification and cellular protection.
  4. Richie JP Jr, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54(2):251-63. doi: 10.1007/s00394-014-0706-z.PubMedUsed to support: 6-month double-blind placebo-controlled RCT in 54 non-smoking adults: Setria oral L-glutathione (250 mg/day and 1,000 mg/day) significantly increased glutathione in whole blood, erythrocytes, plasma, lymphocytes, and exfoliated buccal cells vs placebo (whole-blood GSH ~30-35% increase). Industry-funded (Kyowa Hakko) but landmark trial overturning the long-held claim that oral GSH is destroyed in the GI tract. Directly matches the page's trial card #1.
  5. Schmitt B, Vicenzi M, Garrel C, Denis FM. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biol. 2015;6:198-205. doi: 10.1016/j.redox.2015.07.012.PubMedUsed to support: Comparative crossover study evaluating NAC vs oral GSH vs a sublingual GSH form: sublingual GSH achieved superior bioavailability and greater improvements in oxidative stress markers than oral GSH or NAC. Provides important context for evaluating Setria's oral-only delivery against alternative GSH-raising strategies.
  6. Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clin Cosmet Investig Dermatol. 2017;10:147-153. doi: 10.2147/CCID.S128339.PubMedUsed to support: 12-week randomized double-blind placebo-controlled three-arm trial in healthy Thai females: oral reduced GSH (250 mg/d, the Setria form) and oxidized GSSG (250 mg/d) showed trends favoring melanin index reduction and UV spot improvement vs placebo, but the primary endpoint did not reach statistical significance. Industry-funded (Kyowa Hakko). Directly matches the page's trial card #2 and its honest 'not statistically significant in primary RCT' framing on benefit #4.
  7. Sinha R, Sinha I, Calcagnotto A, Trushin N, Haley JS, Schell TD, Richie JP Jr. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018;72(1):105-111. doi: 10.1038/ejcn.2017.132.PubMedUsed to support: 1-month pilot RCT in healthy adults: oral liposomal GSH (500 mg/day and 1,000 mg/day) elevated body GSH stores and increased NK-cell cytotoxicity and reduced biomarkers of oxidative stress vs baseline. Companion to the Richie 2015 Setria trial from the same Penn State lab — supports the page's immune-enhancement benefit and frames GSH bioavailability as a delivery-form-dependent issue, not a categorical impossibility.
  8. Kalamkar S, Acharya J, Madathil AK, Gajjar V, Divate U, Karandikar-Iyer S, Goel P, Ghaskadbi S. Randomized Clinical Trial of How Long-Term Glutathione Supplementation Offers Protection from Oxidative Damage and Improves HbA1c in Elderly Type 2 Diabetic Patients. Antioxidants (Basel). 2022;11(5):1026. doi: 10.3390/antiox11051026.PubMedUsed to support: 6-month randomized clinical trial in elderly T2DM patients: oral GSH supplementation reduced oxidative damage markers and improved HbA1c vs control. Modern, non-industry-funded trial demonstrating that sustained oral GSH supplementation can improve clinically meaningful metabolic outcomes — extending the page's framing beyond skin/immune to metabolic health.