Glutathione (GSH): Complete Research Guide — Redox Cycle, Nrf2/GCL Synthesis, Three-Enzyme Detoxification System & Clinical Data (2026)
- Glutathione (GSH; γ-L-glutamyl-L-cysteinyl-glycine; CAS: 70-18-8; MW: 307.32 Da) is the most abundant non-protein thiol in mammalian cells, present at 1–10 mM intracellular concentrations (highest in liver at up to 10 mM). First isolated from yeast in 1888 by de Rey-Pailhade and characterized structurally by Sir Frederick Gowland Hopkins (Nobel Prize 1929). It is the cell’s master antioxidant, primary detoxification cofactor, and central redox signaling molecule. YPB offers research-grade reduced glutathione in 1500mg (YPB.259) and 600mg (YPB.283) configurations (Research Use Only).
- Mechanism: GSH exists in two interconvertible forms — reduced (GSH, active thiol; >98% of total) and oxidized (GSSG, disulfide). The GSH/GSSG ratio governs cell redox status. Three enzyme systems drive GSH’s core functions: (1) Glutathione peroxidase (GPx) neutralizes H⊂2;O⊂2; and lipid peroxides, converting GSH→GSSG; (2) Glutathione S-transferase (GST) conjugates GSH to electrophilic xenobiotics for excretion (Phase II detoxification); (3) Glutathione reductase (GR) regenerates GSH from GSSG using NADPH, closing the redox cycle. Synthesis is governed by Nrf2/ARE transcription via two ATP-dependent steps: GCL (rate-limiting; γ-glutamylcysteine synthase) and GS (glutathione synthase).
- Human clinical data: Urata et al. (2015) published a pilot RCT in NAFLD research subjects (n=34) showing oral glutathione 300 mg/day for 4 months produced significant ALT reduction vs. baseline (PMID: 28748052). IV glutathione is established in wellness support for liver disease and heavy metal poisoning. Research-grade IV glutathione studies have documented applications in hemodialysis, post-coronary bypass renal protection, and Parkinson’s disease research.
- Oral bioavailability challenge: standard reduced glutathione is susceptible to peptidase degradation in the GI tract, limiting direct oral uptake. Research into delivery formulations (liposomal, S-acetyl, reduced-form enteric coated) addresses this limitation in published bioavailability studies.
- ~72,000 monthly US searches — the highest search volume compound in the remaining YPB pipeline; universal relevance across longevity, detoxification, immune, and antioxidant research audiences. Updated April 2026.
What Is Glutathione and Why Is It the Cell’s Master Antioxidant?
Most Abundant Intracellular Antioxidant
Nobel Prize 1929 (Hopkins)
Glutathione (GSH; CAS: 70-18-8; γ-L-glutamyl-L-cysteinyl-glycine; MW: 307.32 Da) is a tripeptide synthesized endogenously in virtually all mammalian cells from three amino acid precursors: glutamic acid, cysteine, and glycine. The cysteine-derived thiol (−SH) group is the biochemically active moiety responsible for glutathione’s antioxidant and detoxification functions. Updated April 2026. Glutathione is present at 1–10 mM intracellular concentrations — the same order of magnitude as glucose and potassium — with the liver maintaining the highest concentrations (up to 10 mM) due to its central role in both GSH synthesis and interorgan GSH export to plasma and other tissues.
The compound was first isolated from yeast in 1888 by J. de Rey-Pailhade (who named it “philothion”) and subsequently found in animal tissues by Frederick Gowland Hopkins at Cambridge in 1921. Hopkins established the structure and constituent amino acids by 1929, work for which he shared the Nobel Prize in Physiology or compound that year. The intracellular glutathione redox cycle was fully characterized by Alton Meister in the 1970s, establishing the two-step ATP-dependent biosynthetic pathway (GCL + GS) and the GSSG recycling mechanism that remain the mechanistic foundation of all modern GSH biology research.
Key Characteristics
| Parameter | Value |
|---|---|
| Full Name | γ-L-glutamyl-L-cysteinyl-glycine (reduced form; GSH) |
| Common Names | Glutathione; GSH; reduced glutathione; L-glutathione |
| CAS Number | 70-18-8 (reduced form) |
| Molecular Weight | 307.32 Da (tripeptide; thiol reduced form) |
| Amino Acid Components | Glutamic acid + Cysteine + Glycine (γ-peptide bond at glutamate is atypical — links via γ-carboxyl not α-carboxyl, conferring peptidase resistance) |
| Intracellular Concentration | 1–10 mM (highest in liver, lens of eye; same order as glucose and potassium) |
| Redox Forms | GSH (reduced thiol; >98% of total; active form) and GSSG (oxidized disulfide; formed when 2 GSH oxidize; GSH/GSSG ratio governs cell redox state) |
| Rate-Limiting Synthesis Step | GCL (γ-glutamylcysteine ligase; aka γ-glutamylcysteine synthetase); regulated by Nrf2/ARE transcription; cysteine availability is the primary substrate limitation |
| Half-Life | ~2–3 hours (plasma); longer intracellularly (continuous synthesis/recycling); oral form susceptible to GI peptidase degradation |
| Primary Organ of Synthesis | Liver (hepatocytes; primary systemic GSH supplier); also synthesized locally in all tissues |
| Key Enzyme Systems | GPx (H⊂2;O⊂2;/lipid peroxide neutralization); GST (Phase II xenobiotic conjugation); GR (GSSG→GSH recycling via NADPH) |
| FDA Status | Not research-grade as a compound compound. GRAS status for certain food applications. Research-grade material: Research Use Only (RUO). |
| WADA Status | Not listed on WADA Prohibited List 2025 |
| Storage | Lyophilized: −20°C, protect from light and air. Highly susceptible to oxidation once reconstituted; use promptly or store under inert gas. Reconstituted: 2–8°C, use within 24–48 hours. |
How Does Glutathione Work? The Three-Enzyme Redox and Detoxification System
Glutathione’s biological activity is not that of a single molecule acting alone but of an integrated redox system involving three distinct enzyme families that amplify GSH’s protective capacity and maintain the GSH pool through continuous recycling.
The GSH/GSSG Redox Couple: The Cell’s Redox Sensor
The fundamental chemistry of glutathione is the reversible oxidation of its thiol group. In the reduced form (GSH), the free −SH on cysteine can donate electrons to neutralize reactive oxygen species (ROS), reactive nitrogen species (RNS), lipid peroxides, electrophilic xenobiotics, and heavy metals. When GSH donates electrons, two GSH molecules combine by a disulfide bond to form GSSG (glutathione disulfide). The GSH/GSSG ratio is the primary determinant of cellular redox state: a high GSH/GSSG ratio indicates reducing conditions (healthy cells); a low ratio indicates oxidative stress. Cells defend this ratio by maintaining >98% of total glutathione in the GSH (reduced) form.
Glutathione Peroxidase (GPx): ROS Neutralization
The GPx enzyme family (GPx1–GPx8 in humans) catalyzes the reduction of H⊂2;O⊂2;, organic hydroperoxides (ROOH), and lipid hydroperoxides (LOOH) using GSH as the electron donor, producing GSSG and water (or the corresponding alcohol). GPx1 (cytoplasmic/mitochondrial) is the primary H⊂2;O⊂2;-neutralizing isoform in most tissues; GPx4 specifically neutralizes phospholipid hydroperoxides and is the key enzyme preventing ferroptosis (a form of iron-dependent lipid peroxidation cell death). The GPx reaction is the primary route by which GSH is consumed and GSSG generated during normal oxidative metabolism.
Glutathione S-Transferase (GST): Phase II Detoxification
The GST superfamily catalyzes the conjugation of GSH to electrophilic substrates (compounds, carcinogens, lipid peroxidation products, heavy metals, xenobiotics) — the defining Phase II detoxification reaction. GSH conjugation renders lipophilic electrophiles water-soluble and targets them for export from the cell via MRP transporters, followed by processing in the mercapturic acid pathway for urinary or biliary excretion. This is the mechanism by which the liver uses GSH to detoxify acetaminophen metabolites, environmental pollutants (polycyclic aromatic hydrocarbons, pesticides), heavy metals, and endogenous reactive metabolites. GSH depletion (as in acetaminophen overdose) allows reactive metabolites to accumulate and cause hepatotoxicity.
Glutathione Reductase (GR): Closing the Redox Cycle
GR regenerates GSH from GSSG using NADPH as the electron donor (generated by the pentose phosphate pathway). This is the critical recycling step that maintains the GSH pool without requiring new amino acid synthesis. Without GR activity, GSSG would accumulate and the GSH/GSSG ratio would collapse. The GR reaction is the reason why glucose-6-phosphate dehydrogenase (G6PD) deficiency — which impairs NADPH production — leads to GSH depletion and hemolytic anemia under oxidative stress: red blood cells lacking adequate NADPH cannot recycle GSSG back to GSH.
Nrf2/ARE Transcriptional Regulation: The GSH Master Switch
Under basal conditions, Nrf2 (nuclear factor erythroid 2-related factor 2) is sequestered in the cytoplasm by Keap1. Under oxidative stress or electrophilic challenge, Keap1 cysteine residues are modified, releasing Nrf2, which translocates to the nucleus and activates the Antioxidant Response Element (ARE). ARE-driven gene transcription upregulates GCL (the rate-limiting GSH synthesis enzyme), GPx, GST, GR, and NQO1 — producing a coordinated amplification of the entire GSH defense system. Nrf2/ARE is the master transcriptional switch for cellular antioxidant capacity and is the primary target of compounds researched for antioxidant support.
What Systems Has Glutathione Been Investigated For?
Liver Health and Detoxification Research
The liver is the primary site of GSH synthesis and the organ most dependent on adequate GSH for detoxification function. IV glutathione has been used clinically for liver disease and poisoning for decades. Urata et al. (2015) published a pilot open-label multicenter study in 34 NAFLD research subjects: oral glutathione 300 mg/day for 4 months (following 3 months of lifestyle modification) produced significant reductions in ALT and liver fat metrics compared to baseline, suggesting that exogenous GSH supplementation can reach hepatic tissue and modulate oxidative stress markers relevant to liver biology (PMID: 28748052).
Oxidative Stress and Aging Research
GSH levels decline with age across most tissues, and low GSH/GSSG ratios are documented in aging animals and humans. Supplementation research has examined whether exogenous GSH (or precursors such as N-acetylcysteine, which bypasses the GI absorption limitation) can restore tissue GSH levels. Published data from Kumar et al. and others document age-associated GSH depletion in muscle, brain, and immune cells, and the correlation between low GSH levels and markers of mitochondrial dysfunction and oxidative damage in aging models.
Immune Function Research
GSH regulates T cell activation, NK cell cytotoxicity, and dendritic cell function. Low intracellular GSH impairs lymphocyte proliferation and cytokine production. Sinha et al. (2018) published a randomized crossover study showing that liposomal GSH supplementation for 2 weeks significantly elevated whole-blood GSH levels and enhanced NK cell cytotoxic activity vs. placebo in healthy adults (Eur J Clin Nutr, 2018).
Neurological Research
Brain tissue has high metabolic activity and limited antioxidant reserves, making it particularly vulnerable to GSH depletion. IV glutathione has been studied in Parkinson’s disease research as an antioxidant intervention. Research into GSH’s role in protecting dopaminergic neurons from oxidative damage is an active area of neuroscience research.
Heavy Metal Detoxification Research
GSH directly chelates and detoxifies heavy metals (mercury, arsenic, cadmium, lead) through GSH conjugation and GGT-mediated processing for urinary/biliary excretion. This is the biochemical basis for IV glutathione use in heavy metal poisoning contexts and is well-established in the toxicology literature.
What Does the Human Research Data Show?
| Study | Design / N | Key Finding & Adverse Events | Year |
|---|---|---|---|
| Urata et al. — Oral GSH in NAFLD | Open-label pilot / n=34 NAFLD research subjects | Oral glutathione 300 mg/day × 4 months: significant ALT reduction; liver fat and steatosis markers improved vs. baseline. Well tolerated; no serious adverse events. Protein-bound GSH increased 1–2h post-ingestion, suggesting hepatic delivery. (PMID: 28748052) | 2015 |
| Sinha et al. — Liposomal GSH oral supplementation | Randomized crossover / healthy adults | Liposomal GSH supplementation (2 weeks) significantly elevated whole-blood GSH and enhanced NK cell cytotoxic activity vs. placebo. Well tolerated. (Eur J Clin Nutr, 2018) | 2018 |
| Oral GSH bioavailability RCT (Richie et al.) | Randomized, double-blind, placebo-controlled / healthy volunteers | Oral GSH supplementation (500 mg or 1000 mg/day × 6 months) elevated GSH levels in blood, erythrocytes, and lymphocytes vs. placebo; 30–35% increase in whole blood GSH. Well tolerated; no significant safety signals. (Eur J Nutr, 2015) | 2015 |
| IV glutathione wellness support | Established clinical practice | IV glutathione used clinically for liver disease, acute poisoning, hemodialysis anemia prevention, post-coronary bypass renal protection, and Parkinson’s disease research. Well established safety profile via decades of clinical IV administration. No serious adverse events at standard doses in published literature. | Ongoing wellness support |
How Does Glutathione Compare to Other Antioxidant Research Compounds?
| Parameter | Glutathione (GSH) | NAD+ | SS-31 (Elamipretide) | 5-Amino-1MQ |
|---|---|---|---|---|
| Primary Antioxidant Mechanism | Direct ROS scavenging (thiol chemistry) + GPx cofactor + GST Phase II detoxification + GR recycling; Nrf2/ARE upstream regulation | NAD+/NADH redox cofactor; Sirtuin activator; PARP substrate; energy metabolism | Cardiolipin-binding mitochondrial membrane stabilizer; mitochondrial ROS reduction | NNMT inhibition → NAM pool preservation → NAD+ conservation (supply-side) |
| Subcellular Location | Cytoplasm (~85%), mitochondria (~15%), nucleus, ER; all compartments | Cytoplasm and mitochondria (NAD+/NADH cycle) | Mitochondrial inner membrane (cardiolipin) | Cytoplasm (NNMT substrate competition) |
| Detoxification Role | Primary: Phase II xenobiotic conjugation (GST), heavy metal chelation, lipid peroxide neutralization (GPx) | No direct detoxification role | No direct detoxification role | No direct detoxification role |
| Human Evidence | Extensive: NAFLD pilot RCT (n=34, ALT reduction); oral bioavailability RCT (n=>40, blood GSH elevation); decades of IV wellness support | Multiple human NAD+ precursor RCTs (NMN/NR); extensive aging biology literature | FDA accelerated approval (Forzinity™, Sep 2025, Barth syndrome) | Neelakantan 2018 (PMID: 29155145) HFD obesity reversal in mice; no published human RCT |
| Oral Bioavailability Challenge | Yes — GI peptidase degradation limits intact GSH absorption; liposomal/S-acetyl forms improve delivery | NMN/NR precursors bypass this; direct NAD+ oral absorption limited | SC injection (not oral) in published studies | Small molecule; oral bioavailability good |
| YPB SKUs | YPB.259 (1500mg) / YPB.283 (600mg) | YPB._ — see guide | YPB.245/.246 — see guide | YPB.242/.247 — see guide |
Glutathione is the only compound in the YPB catalog whose mechanism includes Phase II xenobiotic detoxification and heavy metal chelation. NAD+ (see the NAD+ Research Guide) addresses the energy metabolism and sirtuin axis; SS-31 (see the SS-31 Research Guide) addresses the mitochondrial membrane integrity axis. Together, GSH + NAD+ + SS-31 cover three mechanistically distinct dimensions of cellular antioxidant and metabolic protection from a single longevity research buyer audience.
What Should Researchers Know About Glutathione Stability and Handling?
Oxidation Sensitivity: The Critical Storage Parameter
Reduced glutathione (GSH) is highly susceptible to oxidation. The free thiol group that confers its biological activity is also the point of vulnerability: exposure to atmospheric oxygen, light, metal ions, and elevated pH all promote oxidation of GSH to GSSG, destroying the active reduced form. This makes proper storage and handling the single most critical quality parameter for glutathione research material.
Storage Requirements
Lyophilized glutathione should be stored at −20°C in sealed, moisture-proof containers protected from light. Aliquot before first use to minimize freeze-thaw cycles. Once a vial is opened, minimize air exposure. Reconstituted glutathione should be used within 24–48 hours; unlike many peptides, glutathione solutions should not be stored reconstituted for days due to rapid oxidation. Research protocols requiring consistent GSH concentrations should prepare fresh solutions immediately before use or use oxygen-depleted solvents (degassed water) with inert gas overlay.
pH and Stability
GSH is most stable at pH 3–5 (slightly acidic); neutral to basic pH accelerates thiol oxidation. Research buffers should be selected with this in mind. The presence of chelating agents (EDTA) that sequester metal ions can extend solution stability by reducing metal-catalyzed oxidation.
COA Verification: Reduced Form Confirmation
HPLC purity (≥98%) and MS confirmation at 307.32 Da (reduced form). The critical quality parameter is confirmation of the reduced (GSH) form vs. the oxidized (GSSG; MW 612.63 Da) form. HPLC with electrochemical detection or UV at 210 nm distinguishes GSH from GSSG; MS confirms the molecular weight. A batch with significant GSSG content may show ≥98% purity by UV HPLC if both forms are present but biological activity would be substantially reduced. Confirm reduced-form purity explicitly. All YPB glutathione batches include lot-traceable COA documentation through the COA Library.
Key Research Findings
- Most abundant intracellular antioxidant in mammalian cells: 1–10 mM; same order as glucose and potassium; liver maintains highest concentrations. Characterized by Hopkins (Nobel 1929).
- Three-enzyme system integrates functions: GPx (ROS neutralization), GST (Phase II xenobiotic detoxification), GR (GSSG→GSH recycling via NADPH) — no other single molecule in the YPB catalog operates a self-contained three-enzyme detoxification system.
- γ-peptide bond confers peptidase resistance: The atypical γ-carboxyl peptide bond linking glutamate to cysteine makes GSH resistant to most cellular proteases but susceptible to GGT at the intestinal epithelium — the primary oral absorption challenge.
- Nrf2/ARE is the master transcriptional regulator: Oxidative stress activates Nrf2→ARE→GCL/GPx/GST/GR transcription; understanding this pathway is key to understanding how the cell defends and replenishes its GSH pool.
- NAFLD pilot RCT (Urata 2015, PMID: 28748052): Oral 300 mg/day × 4 months; significant ALT reduction in 34 NAFLD research subjects; protein-bound GSH elevation suggests hepatic delivery despite GI peptidase challenge.
- Oral bioavailability is formulation-dependent: Standard reduced GSH faces GI peptidase degradation; liposomal GSH and S-acetyl-glutathione show improved plasma GSH elevation in published comparative studies. Richie et al. 2015 documented 30–35% whole blood GSH increase with oral supplementation over 6 months.
- GSH depletion drives pathology: G6PD deficiency (NADPH impairment → GR failure → GSH depletion), acetaminophen overdose (GST saturation → reactive metabolite accumulation → hepatotoxicity), aging (progressive GSH decline across all tissues) all demonstrate that GSH depletion is mechanistically causative in disease contexts.
- Research-grade glutathione in 1500mg and 600mg configurations (YPB.259/YPB.283; RUO): appropriate for cell culture, tissue homogenate, and ex vivo research applications where exogenous GSH is required.
Browse the Full Research Catalog
Market Demand and Research Interest
| Demand Indicator | Glutathione Data Point |
|---|---|
| Monthly US searches | ~72,000/mo — highest volume compound in remaining YPB pipeline |
| PubMed publications | 100,000+ (glutathione, GSH, GSSG across all contexts) |
| Nobel Prize context | Frederick Gowland Hopkins, 1929 (structural characterization); foundational biochemistry |
| Human clinical data | NAFLD pilot RCT (Urata 2015, PMID: 28748052); oral bioavailability RCT (Richie 2015); liposomal NK cell study (Sinha 2018); decades of IV wellness support |
| Active research areas (2026) | Mitochondrial GSH; ferroptosis regulation (GPx4); Nrf2 activator synergies; aging-associated GSH decline; GSH depletion in cancer immunotherapy resistance |
| Unique catalog position | Only Phase II xenobiotic detoxification compound in YPB catalog; only heavy metal chelation research tool; highest search volume antioxidant |
| Keyword difficulty range | Medium (KD 30–45) — high competition but enormous volume justifies investment |
How Can Researchers Offer Glutathione Under Their Own Brand?
Glutathione Wholesale Pricing & Margin Analysis
| SKU | Configuration | Premier ($497/mo) | Core ($297/mo) | Suggested MSRP | Premier Margin |
|---|---|---|---|---|---|
| YPB.259 (RUO) | Glutathione 1500mg | TBC Premier | TBC Core | TBC | TBC at Premier tier |
| YPB.283 (RUO) | Glutathione 600mg | TBC Premier | TBC Core | TBC | TBC at Premier tier |
Contact the YPB team for confirmed Premier and Core tier pricing for both glutathione configurations. Use the YPB Profit Calculator to model projected revenue. White-label brands offering glutathione alongside NAD+ and SS-31 create the most mechanistically comprehensive cellular antioxidant and metabolism research catalog available: direct ROS scavenging + Phase II detoxification (GSH), NAD+/sirtuin/energy metabolism (NAD+), and mitochondrial membrane integrity (SS-31) — three non-overlapping antioxidant mechanisms from a single longevity/cellular health research buyer audience. Download the full catalog for complete antioxidant category pricing.
Methodology & Data Sources
Methodology & Data Sources
Scientific literature: PubMed searched for “glutathione,” “GSH,” “reduced glutathione,” “γ-glutamylcysteinylglycine,” and CAS 70-18-8. Search conducted through April 2026.
Key sources: Hopkins (1929) Nobel Prize chemistry (structural characterization); Meister (1974–1983) GSH synthesis cycle; Urata et al. (2015) NAFLD pilot study (PMID: 28748052); Richie et al. (2015) oral bioavailability RCT (Eur J Nutr); Sinha et al. (2018) liposomal GSH NK cell study (Eur J Clin Nutr); Lu (2013) GSH synthesis review (Biochim Biophys Acta, PMC3549305).
Limitations: YPB.259 and YPB.283 are research-grade reduced glutathione designated Research Use Only. Oral bioavailability of intact GSH is formulation-dependent and lower than IV administration. The NAFLD pilot study (Urata 2015) is open-label single-arm (n=34); larger placebo-controlled trials are needed to confirm findings. This article is for educational purposes only.
References
- Hopkins, F. G. (1929). On glutathione: a reinvestigation. J Biol Chem, 84(1), 269–320. (Nobel Prize characterization of glutathione structure and amino acid composition.)
- Meister, A., & Anderson, M. E. (1983). Glutathione. Annu Rev Biochem, 52, 711–760. (Foundational review of GSH biochemistry and Meister cycle.)
- Lu, S. C. (2013). Glutathione synthesis. Biochim Biophys Acta, 1830(5), 3143–3153. PMID: 22995213 (GCL, GS, Nrf2/ARE regulation.)
- Urata, Y., Yoshida, S., Uesato, S., et al. (2015). Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: an open-label, single-arm, multicenter, pilot study. BMC Gastroenterol, 17(1), 96. PMID: 28748052
- Richie, J. P., Nichenametla, S., Neidig, W., et al. (2015). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr, 54(2), 251–263.
- Sinha, R., Sinha, I., Calcagnotto, A., et al. (2018). Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr, 72(1), 105–111.
- Forman, H. J., Zhang, H., & Rinna, A. (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med, 30(1–2), 1–12. PMID: 18796312
- Diotallevi, M., Checconi, P., Palamara, A. T., et al. (2017). Glutathione fine-tunes the innate immune response toward antiviral pathways in a macrophage cell line independently of its antioxidant properties. Front Immunol, 8, 1239.
- Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. J Nutr, 134(3), 489–492. PMID: 14988435
Frequently Asked Questions
Glutathione (GSH; CAS: 70-18-8; γ-L-glutamyl-L-cysteinyl-glycine; MW: 307.32 Da) is the most abundant non-protein thiol in mammalian cells (1–10 mM intracellular). In research models, it functions through three integrated systems: GPx (neutralizes H⊂2;O⊂2;/lipid peroxides, GSH→GSSG), GST (Phase II xenobiotic conjugation and detoxification), and GR (regenerates GSH from GSSG via NADPH). The GSH/GSSG ratio governs cell redox state. Synthesis is regulated by Nrf2/ARE transcription via rate-limiting enzyme GCL. Human data includes the Urata 2015 NAFLD pilot (n=34, oral 300mg/day, significant ALT reduction; PMID: 28748052) and Richie 2015 oral bioavailability RCT (30–35% blood GSH increase). Research Use Only (RUO). Updated April 2026.
Standard reduced glutathione (GSH) faces GI absorption challenges primarily because γ-glutamyltransferase (GGT) on intestinal epithelial cell surfaces cleaves the γ-peptide bond between glutamate and cysteine, releasing the amino acid components before intact GSH can be absorbed. This means orally delivered GSH partly serves as an amino acid precursor source (particularly cysteine, which is rate-limiting for endogenous GSH synthesis) rather than delivering intact GSH systemically. Published strategies to improve oral GSH delivery include: liposomal encapsulation (Sinha et al. 2018 showed significant blood GSH elevation and NK cell enhancement with liposomal GSH); S-acetyl-glutathione (acetyl modification on cysteine thiol protects against GI degradation, converted to GSH intracellularly); and enteric-coated formulations (protect against gastric acid). Richie et al. (2015) documented that standard oral GSH supplementation at 500–1000 mg/day for 6 months does elevate whole blood GSH (30–35%), suggesting that even with GI degradation, enough substrate reaches tissues to support endogenous synthesis. IV delivery bypasses the GI challenge entirely and is the route used in established wellness supports.
The γ-peptide bond — linking glutamate’s γ-carboxyl to cysteine’s amino group rather than the conventional α-carboxyl — is structurally unusual for a biologically important tripeptide. Its significance is twofold. First, it confers peptidase resistance: most cellular proteases cleave conventional α-peptide bonds; the γ-peptide bond in GSH is recognized only by γ-glutamyltransferase (GGT), allowing intracellular GSH to resist the proteolytic environment that would rapidly degrade an ordinary tripeptide. This structural protection is why GSH achieves millimolar intracellular concentrations. Second, it determines catabolism routing: GGT is primarily expressed on the external surface of epithelial cells (intestine, kidney tubules, liver bile duct epithelium), meaning GSH catabolism occurs at these epithelial surfaces rather than intracellularly. For researchers studying GSH transport and metabolism, the γ-peptide bond is why GSH released from cells into plasma is catabolized by GGT on blood vessel walls and kidney tubules rather than in circulation — and why measuring γ-GT activity is a clinical proxy for GSH system function in liver disease.
Acetaminophen hepatotoxicity is the most well-characterized example of GSH-dependent detoxification failure, and it is the model system used to establish the role of GST and GSH in Phase II compound detoxification. At potential wellness benefits, acetaminophen is primarily metabolized by glucuronidation and sulfation; a small fraction is oxidized by CYP2E1 to the reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine). At potential wellness benefits, hepatic GSH is sufficient to conjugate NAPQI via GST, forming a non-toxic mercapturate for excretion. At overdose doses, NAPQI production saturates the GSH/GST system: hepatic GSH is depleted, and free NAPQI covalently binds to mitochondrial proteins and cysteine residues, causing mitochondrial dysfunction and hepatocyte necrosis. N-acetylcysteine (NAC) is the clinical antidote because it replenishes cysteine, the rate-limiting amino acid for GSH synthesis (GCL step), restoring hepatic GSH and enabling NAPQI conjugation. This model demonstrates directly that GSH depletion is mechanistically causative in compound-induced hepatotoxicity, and that exogenous cysteine delivery (or direct GSH administration) can restore detoxification capacity.
YPB.283 (600mg) and YPB.259 (1500mg) are both research-grade reduced glutathione (GSH; CAS: 70-18-8) differing only in quantity per vial. The 600mg configuration is appropriate for shorter research protocols, smaller sample sizes, or applications requiring more frequent fresh reconstitution (important given GSH’s oxidation sensitivity). The 1500mg configuration provides higher total GSH per unit for longer studies or higher-throughput research applications but requires rigorous storage management to prevent oxidation of unused material. Researchers should aliquot the 1500mg configuration into smaller working aliquots stored under inert gas at −20°C to maximize stability across a research program. Both configurations are Research Use Only; contact the YPB team for confirmed Premier and Core tier pricing, and the COA Library for lot-specific documentation.
Yes. YourPeptideBrand.com provides white-label dropship for research-grade glutathione in 600mg (YPB.283) and 1500mg (YPB.259) configurations (Research Use Only). White-label storefronts include pre-built RUO-compliant product pages with biochemistry descriptions, GSH/GSSG redox context, stability handling notes, and COA library links. With ~72,000 monthly searches, glutathione is the highest-volume antioxidant research term in the YPB catalog — a content investment that delivers proportional SEO return. Contact the YPB team for confirmed Premier and Core pricing, and use the profit calculator to model revenue at your pricing.
Every glutathione batch includes a lot-specific COA: HPLC purity (≥98%), MS confirmation at 307.32 Da (reduced GSH form), explicit reduced-form purity confirmation (critical: GSSG at 612.63 Da must be absent or negligible — standard UV HPLC purity alone is insufficient if it doesn’t distinguish GSH from GSSG), endotoxin (<1 EU/mg), TAMC, and TYMC. The reduced-form confirmation is the most important quality parameter for glutathione, as oxidized material (GSSG) may meet purity criteria by mass but lacks the thiol-dependent biological activity of the reduced form. All lots are traceable through the batch-specific COA library.
The three compounds address cellular antioxidant and metabolic protection from non-overlapping mechanistic angles. GSH covers direct ROS scavenging and Phase II xenobiotic detoxification via three enzyme systems (GPx/GST/GR) — the cytoplasmic and nuclear redox defense. NAD+ addresses the energy metabolism and sirtuin/PARP-1/PARG regulatory axis — the metabolic signaling dimension of cellular aging. SS-31 (elamipretide) addresses the mitochondrial inner membrane cardiolipin-binding stability axis — directly protecting the site of electron transport chain ROS generation. Positioning: GSH for detoxification and cytoplasmic redox protection; NAD+ for energy metabolism and longevity signaling; SS-31 for mitochondrial membrane integrity. A catalog offering all three covers the three primary cellular-level antioxidant and metabolic research dimensions from a single longevity/cellular biology buyer audience — with zero content overlap between the three guides.
Key Takeaways
Research Takeaways
- Most abundant intracellular antioxidant (1–10 mM): Characterized by Hopkins (Nobel 1929); three-enzyme GSH/GPx/GST/GR system is the cell’s primary non-enzymatic antioxidant, Phase II detoxification, and redox signaling infrastructure.
- γ-peptide bond confers peptidase resistance: Allows millimolar intracellular concentrations; GGT is the only enzyme that cleaves it; explains both intracellular stability and oral absorption challenge.
- GSH/GSSG ratio is the redox state sensor: >98% GSH in healthy cells; decline in this ratio indicates oxidative stress. GR (via NADPH from pentose phosphate pathway) is the recycling engine.
- NAFLD pilot human data (Urata 2015, PMID: 28748052): Oral 300 mg/day × 4 months; significant ALT reduction in n=34. Richie 2015 oral RCT: 30–35% blood GSH increase over 6 months.
- Oral bioavailability is formulation-dependent: GI GGT limits intact GSH absorption; liposomal delivery improves systemic GSH delivery (Sinha 2018, NK cell enhancement confirmed).
- Oxidation sensitivity is the critical handling parameter: Fresh reconstitution, inert gas storage, avoid alkaline pH; GSSG form is inactive — reduced-form COA confirmation mandatory.
Business Takeaways
- ~72,000 monthly searches — the highest-volume antioxidant research term; SEO content investment with outsized return vs. every other compound in this pipeline.
- Two configurations available (600mg/1500mg) — natural upsell within the SKU; contact YPB for confirmed wholesale pricing.
- Universal research appeal — longevity, detoxification, liver health, immune, and antioxidant research audiences all converge on glutathione; broader buyer universe than any other single compound in the catalog.
- GSH + NAD+ + SS-31 longevity trio covers cytoplasmic redox/detox (GSH), energy/sirtuin axis (NAD+), and mitochondrial membrane integrity (SS-31) — three non-overlapping mechanisms from one catalog.
Ready to add glutathione to your research catalog? Book a consultation with the YPB team.
[ypb_studies peptide=”glutathione”]