Research Use Only: This product is supplied for laboratory research and in-vitro studies. Not for human or veterinary administration.
L-Glutathione 600mg
- Master Antioxidant Tripeptide: L-γ-Glu-L-Cys-Gly sequence, ≥98% purity
- Cellular Redox Homeostasis: Primary intracellular thiol buffer (0.5-10 mM)
- Phase II Detoxification: GST-mediated conjugation and xenobiotic metabolism studies
- Mechanistic pathway studies
- In vitro receptor profiling
- HPLC verified identity and purity
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Research Overview
Glutathione (GSH, L-gamma-glutamyl-L-cysteinyl-glycine) is an endogenous tripeptide composed of glutamic acid, cysteine, and glycine. First identified by Sir Frederick Gowland Hopkins in 1921, it is the most abundant low-molecular-weight thiol in mammalian cells and the principal non-protein antioxidant synthesized intracellularly. With over 180,000 publications indexed in PubMed, glutathione occupies a central position in cellular redox homeostasis, xenobiotic detoxification, immune regulation, and signal transduction.
Intracellular GSH concentrations range from 0.5 to 10 mM in mammalian cells, with over 90% maintained in the reduced form under physiological conditions. This establishes glutathione as the primary intracellular redox buffer and the dominant non-protein thiol in animal tissues. Glutathione possesses a unique gamma-peptide bond between the gamma-carboxyl group of glutamate and the alpha-amino group of cysteine, conferring resistance to degradation by most intracellular peptidases while remaining susceptible to gamma-glutamyltransferase. The cysteine residue contains a free sulfhydryl group that serves as the molecule's reactive center, enabling nucleophilic conjugation reactions, disulfide exchange, and reduction of oxidized species.
Research interest spans oxidative stress biology, neuroscience, hepatology, immunology, oncology, and gerontology. Dysregulation of glutathione homeostasis has been implicated in neurodegenerative diseases (Parkinson's, Alzheimer's), hepatic dysfunction, chronic obstructive pulmonary disease, diabetes, and aging-related decline. Oral supplementation studies have demonstrated that GSH at 1000 mg/day increases tissue GSH levels 30-35% in erythrocytes, plasma, and lymphocytes, with natural killer cell cytotoxicity increasing more than twofold. Liposomal formulations show enhanced bioavailability, increasing whole blood GSH by 40% and natural killer cell activity by up to 400% at doses of 500-1000 mg/day.
Primary Research Applications
Mechanism of Action
Glutathione Peroxidase (GPx) Antioxidant System
Primary Enzymatic Defense — The glutathione peroxidase system represents the primary enzymatic defense against hydrogen peroxide and lipid hydroperoxides. Glutathione peroxidase-1 (GPx-1), a selenium-dependent enzyme, catalyzes the reduction of peroxides using GSH as the electron donor (2 GSH + H₂O₂ → GSSG + 2 H₂O). The resulting GSSG is recycled back to GSH by glutathione reductase in a NADPH-dependent reaction. This system is particularly critical in mitochondria, which lack catalase and depend predominantly on the GSH/GPx/glutathione reductase axis to decompose superoxide radicals generated during oxidative phosphorylation.
Glutathione S-Transferase (GST) Conjugation
Phase II Detoxification — Glutathione S-transferases (GSTs) catalyze the conjugation of the thiolate anion of GSH to electrophilic centers within diverse substrates. GSTs lower the pKa of the GSH thiol group from approximately 9.0 to 6-7, increasing the proportion of reactive thiolate anion available for nucleophilic attack. Substrates include xenobiotic electrophiles (drugs, environmental toxins, carcinogens), endogenous electrophiles (α,β-unsaturated aldehydes, quinones), and reactive intermediates from Phase I metabolism. Following conjugation, GSH-conjugated metabolites are exported via multidrug resistance-associated proteins (MRPs) and processed through the mercapturic acid pathway for renal excretion.
Protein S-Glutathionylation
Redox Signal Transduction — Protein S-glutathionylation, the reversible formation of mixed disulfides between GSH and protein cysteine residues, is a major post-translational modification involved in redox signaling. This modification regulates proteins involved in metabolism (glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase), signal transduction (protein kinases, phosphatases), transcription (NF-κB, AP-1), cytoskeletal dynamics (actin), and apoptosis (caspases). Deglutathionylation, catalyzed by glutaredoxins and sulfiredoxin, reverses this modification, enabling dynamic redox-dependent regulation of protein function.
Immune Cell Redox Regulation
Bidirectional Immunomodulation — The immune system requires a delicately balanced intermediate level of glutathione for optimal function. GSH is essential for T-lymphocyte proliferation, phagocytic activity of neutrophils, dendritic cell function, and natural killer cell cytotoxicity. While some immune functions (DNA synthesis) are favored by high GSH levels, certain signal pathways are enhanced by oxidative conditions and lower intracellular glutathione concentrations, indicating that GSH operates as a bidirectional immunomodulator rather than a simple immunostimulant.
“Mechanistic summaries on this page are provided for laboratory reference and should be interpreted within controlled experimental settings only.”
Preclinical Research Summary
Richie et al. (2015) conducted a six-month randomized, double-blind, placebo-controlled trial in 54 healthy adults demonstrating that oral GSH at 1000 mg/day increased GSH levels 30-35% in erythrocytes, plasma, and lymphocytes and 260% in buccal cells. Natural killer cell cytotoxicity increased more than twofold in the high-dose group versus placebo at 3 months, establishing the first evidence that oral GSH supplementation effectively accumulates in body tissues. Sinha et al. (2018) showed that liposomal GSH (500-1000 mg/day) increased whole blood GSH by 40%, PBMC GSH by 100%, and natural killer cell cytotoxicity by up to 400%, with plasma 8-isoprostane (lipid peroxidation marker) decreasing by 35%, demonstrating enhanced bioavailability of the liposomal formulation.
Kalamkar et al. (2022) studied 250 diabetic and 104 non-diabetic subjects, demonstrating that 500 mg daily oral GSH significantly increased blood GSH (Cohen's d = 1.01) and decreased oxidative DNA damage marker 8-OHdG (Cohen's d = -1.07). HbA1c improved within three months and stabilized thereafter, with effects particularly pronounced in patients over 55 years. Sekhar et al. (2011) found red blood cell glutathione concentrations 46% lower in elderly subjects with fractional synthesis rates 45% slower than younger controls. Two weeks of supplementation with cysteine and glycine produced a 95% increase in glutathione concentration and 79% increase in synthesis rates, with plasma oxidative stress markers decreasing to levels comparable to younger subjects.
Safety evaluation shows oral LD50 in mice exceeds 5000 mg/kg, classifying glutathione as essentially nontoxic. A 13-week repeated-dose study of S-Acetyl Glutathione in rats established a NOAEL of 1500 mg/kg/day. In oral supplementation trials (250-1000 mg/day for up to 6 months), side effects were mild and transient, including occasional gastrointestinal symptoms. No serious adverse reactions were reported. Glutathione has received Generally Recognized as Safe (GRAS) status from the U.S. FDA for use in food products. Following high-dose IV administration (50 mg/kg), most GSH was oxidized to GSSG and cleared from circulation with a half-life of approximately 10 minutes. Oral bioavailability of unmodified GSH is limited (below 1%) due to enzymatic degradation, though liposomal and N-methylated formulations demonstrate significantly enhanced bioavailability.
Academic References
- Richie JP Jr et al. (2015). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition.
- Sinha R et al. (2018). Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. European Journal of Clinical Nutrition.
- Kalamkar S et al. (2022). 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).
- Sekhar RV et al. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. American Journal of Clinical Nutrition.
- Lubos E et al. (2011). Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxidants & Redox Signaling.
- Johnson WM et al. (2012). Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients.
- Labarrere CA and Kassab GS (2022). Glutathione: a Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation. Frontiers in Nutrition.
- Forman HJ et al. (2008). Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine.
- Aquilano K et al. (2014). Glutathione: new roles in redox signaling for an old antioxidant. Frontiers in Pharmacology.
- Droge W and Breitkreutz R (2000). Glutathione and immune function. Proceedings of the Nutrition Society.
This product is intended exclusively for in vitro laboratory research by qualified professionals. Not for human consumption. Not approved by the FDA.