What exactly is Glutathione (Reduced)?

Glutathione (reduced, GSH) is the endogenous tripeptide L‑γ‑glutamyl‑L‑cysteinylglycine (chemical formula C10H17N3O6S , molar mass 307.32 g·mol^-1) and is the most abundant low‑molecular‑weight thiol antioxidant in cells; intracellular pools are highest in liver, kidney and erythrocytes.

How does Glutathione (Reduced) work in the body?

GSH functions as the principal intracellular reducing agent: it is the substrate for glutathione peroxidases to detoxify H2O2/lipid hydroperoxides, a co‑substrate for GSTs in conjugation of electrophiles, and a regulator of redox signaling via reversible S‑glutathionylation; it is regenerated from GSSG by glutathione reductase using NADPH.

What is the optimal dosage of Glutathione (Reduced)?

Common over‑the‑counter oral dosing ranges are 250–1,000 mg/day ; for general antioxidant support 300–600 mg/day is typical; liposomal or S‑acetyl forms often use 250–500 mg/day; IV research doses vary (600–2,400 mg) and require medical supervision.

Are there side effects of Glutathione (Reduced)?

At common oral doses adverse events are usually mild: gastrointestinal complaints occur in ~ 1–5% , dermatologic reactions < 2% , and rare bronchospasm in sensitive individuals; IV forms carry infusion reaction risks.

When should I take Glutathione (Reduced)?

Timing depends on formulation: plain oral GSH may be taken on an empty stomach to reduce enzymatic competition; liposomal and S‑acetyl forms can be taken with or without food. If GI upset occurs, take with food. Co‑administration with NAC or cysteine‑rich protein can support intracellular re‑synthesis.

Which form of Glutathione (Reduced) has the best bioavailability?

Plain oral reduced GSH has low intact bioavailability ( <10% by many estimates); liposomal formulations show improved apparent absorption (~ 15–40% estimates, formulation dependent) and S‑acetyl GSH is claimed to provide higher intracellular delivery though independent human PK data are limited.

How long before I see results from Glutathione (Reduced)?

Biochemical changes in oxidative biomarkers can occur within days to weeks ; cosmetic skin effects in some studies were reported at 4–12 weeks ; sperm quality changes require at least one full spermatogenesis cycle (~ 70–90 days ); robust clinical endpoints may require months.

Can I take Glutathione (Reduced) with medications?

Some interactions are clinically important: avoid high‑dose GSH during active platinum/alkylating chemotherapy (possible reduction in cytotoxic efficacy), do not substitute GSH for NAC in acetaminophen overdose, and monitor INR if on warfarin; consult prescribers for immunosuppressants or complex regimens.

Glutathione (Reduced): Complete Science-Based Guide 2026 | DietarySupplementDB

💡Should I take Glutathione (Reduced)?

Glutathione (reduced, GSH) is a naturally occurring tripeptide antioxidant — the most abundant low‑molecular‑weight thiol in cells, typically present in the reduced form at >99% of total glutathione in healthy cells. This encyclopedia‑level guide synthesizes biochemical fundamentals, pharmacokinetics, clinical uses, formulation science and practical dosing strategies for the U.S. market. It explains why hepatic and mitochondrial pools are critical, how oral formulations are degraded by intestinal γ‑glutamyltranspeptidase (GGT), and why specialized forms (liposomal, S‑acetyl) or intravenous dosing are used to overcome bioavailability limits. The article summarizes mechanism (GPx, GST, GSR cycling), details eight evidence‑mapped clinical benefits with mechanistic context, lists common adverse events and drug interactions (notably platinum chemotherapies and acetaminophen management), and gives a U.S. consumer checklist for product quality (CoA, GMP, third‑party testing). Practical dosing recommendations, timing advice, and synergy combinations (NAC, whey, selenium, vitamins C/E) are provided to help clinicians and informed consumers choose safe, evidence‑based strategies. Sources include authoritative biochemical reviews and public databases (PubChem; NCBI Bookshelf).

✓Glutathione (reduced, GSH) is the cell’s primary low‑molecular‑weight thiol antioxidant and exists mainly in the reduced form (GSH:GSSG ratio typically >100:1 in healthy cells).

✓Oral reduced GSH has <10% intact bioavailability; liposomal and S‑acetyl forms report higher apparent absorption but data vary by formulation.

✓Clinical benefits are mechanistically strong for oxidative stress and detoxification; high‑quality large RCTs for many clinical endpoints are limited.

🎯Key Takeaways

✓Glutathione (reduced, GSH) is the cell’s primary low‑molecular‑weight thiol antioxidant and exists mainly in the reduced form (GSH:GSSG ratio typically >100:1 in healthy cells).
✓Oral reduced GSH has <10% intact bioavailability; liposomal and S‑acetyl forms report higher apparent absorption but data vary by formulation.
✓Clinical benefits are mechanistically strong for oxidative stress and detoxification; high‑quality large RCTs for many clinical endpoints are limited.
✓Avoid high‑dose antioxidant/GSH supplementation during active cytotoxic chemotherapy without oncology approval; NAC remains the standard for acetaminophen toxicity.
✓Choose supplements with batch CoAs, third‑party verification (NSF/USP/ConsumerLab) and prefer stabilized formulations for oral use when aiming to raise systemic GSH.

Everything About Glutathione (Reduced)

🧬 What is Glutathione (Reduced)? Complete Identification

Glutathione (reduced, GSH) is the endogenous tripeptide antioxidant L‑γ‑glutamyl‑L‑cysteinylglycine with molecular formula C10H17N3O6S and molar mass 307.32 g·mol^-1.

What is it? Glutathione (reduced) is an intracellular thiol tripeptide that serves as a primary redox buffer, a co‑substrate for detoxifying enzymes and a regulator of protein thiol status.

Alternative names: Glutathione (reduced), GSH, L‑γ‑glutamyl‑L‑cysteinylglycine, Reduced glutathione.

Classification: Antioxidant / thiol peptide; endogenous tripeptide antioxidant, redox cofactor and phase II detoxification co‑substrate.

Origin and production: Endogenously synthesized in virtually all aerobic cells (highest concentrations in liver, kidney, lens, erythrocytes). Commercially manufactured by chemical peptide synthesis or microbial/enzymatic fermentation; specialty stabilized forms (S‑acetyl GSH, liposomal GSH) are produced to increase oral stability and bioavailability.

📜 History and Discovery

The first chemical detection of a reducing sulfur substance related to glutathione dates to 1888 (J. de Rey‑Pailhade), and the peptide nature and physiological significance were clarified through the 20th century.

1888: First reports of a reducing sulfur compound in yeast/liver preparations.
1950s: Role in enzymatic detoxification and as substrate for glutathione S‑transferases (GSTs) and glutathione peroxidases (GPx) established.
1960s: γ‑glutamyl cycle and enzymes (γ‑glutamylcysteine synthetase; glutathione synthetase) characterized (Meister et al.).
Late 20th–21st century: Clinical/translational study of supplementation strategies including IV GSH, oral reduced GSH, S‑acetyl and liposomal forms; interest in dermatology, neurodegeneration and metabolic disease.

Traditional vs modern use: Traditional diets supplied GSH precursors via sulfur‑rich foods (garlic, crucifers, high‑protein diets). Direct supplemental GSH and engineered oral forms are modern developments (20th–21st century).

Fascinating facts:

The peptide bond between glutamate and cysteine is a γ‑linkage (γ‑glutamyl bond), unusual for peptides and a reason GSH resists many peptidases but is a substrate for γ‑glutamyltranspeptidase (GGT).
In healthy cells the reduced:oxidized ratio (GSH:GSSG) is typically >100:1; elevated GSSG or low ratio is a biomarker of oxidative stress.

⚗️ Chemistry and Biochemistry

GSH is a tri‑amino‑acid peptide composed of glutamate (γ‑linked), cysteine (thiol functional group) and glycine; the cysteine thiol (-SH) is the redox‑active center.

Molecular structure & properties

Formula: C10H17N3O6S
Molar mass: 307.32 g·mol^-1
Appearance: White/off‑white crystalline powder (reduced form)
Solubility: Freely soluble in water; sparingly soluble in organic solvents
Thiol pKa: ~8.7 (microenvironment dependent)

Physicochemical stability

Reduced GSH oxidizes to glutathione disulfide (GSSG) on exposure to air; aqueous GSH solutions can oxidize within hours to days depending on pH, temperature and trace metals.

Formulation strategies: S‑acetylation and liposomal encapsulation protect the thiol and peptide from oxidation and enzymatic degradation.
Storage: Lyophilized powder stored cold, under inert gas, extends shelf life; consumer supplements typically advise cool, dry storage.

Dosage forms

Powder (bulk)
Capsules/tablets (reduced GSH)
S‑acetyl glutathione (protected thiol)
Liposomal glutathione (encapsulated liquid/soft‑gel)
Intravenous sterile GSH (medical administration)

💊 Pharmacokinetics: The Journey in Your Body

Absorption and Bioavailability

Oral reduced GSH has low and highly variable intact bioavailability — commonly estimated at <10% for intact GSH vs. IV exposure; liposomal and S‑acetyl forms report higher apparent bioavailability in manufacturer or small studies.

Mechanism: Brush‑border and extracellular γ‑glutamyltranspeptidase (GGT) cleaves GSH to γ‑glutamyl amino acids and cysteinylglycine; cysteine and other amino acids are absorbed and used for intracellular resynthesis of GSH.

Key factors affecting absorption: intestinal GGT activity, formulation (liposomal/S‑acetyl), concurrent protein/NAC intake, GI health and microbiome, dose.
Reported comparative estimates: plain oral GSH: <10%; liposomal: ~15–40% (formulation dependent); S‑acetyl: manufacturer claims elevated intracellular delivery (independent human data limited).

Distribution and Metabolism

GSH distributes predominantly intracellularly with highest concentrations in liver, kidney, lung, erythrocytes and lens; mitochondrial GSH pools are essential and are maintained by transport across mitochondrial membranes.

BBB: Native systemic GSH crosses the blood‑brain barrier poorly; the brain relies on precursor uptake (e.g., cysteine/NAC) for intracellular synthesis.
Metabolic enzymes: GGT, GPx (uses GSH and forms GSSG), glutathione reductase (GR, NADPH‑dependent), glutathione S‑transferases (GSTs), peptidases.
Metabolites: GSSG, cysteinylglycine, γ‑glutamyl amino acids, mercapturic acid conjugates.

Elimination

Renal and biliary excretion of metabolites (mercapturic acids) is the primary elimination route; plasma half‑life of exogenous GSH is short (minutes to hours) while intracellular pool half‑lives vary by tissue (hours to ~1 day in liver under some conditions).

🔬 Molecular Mechanisms of Action

GSH acts primarily as a reducing cofactor and substrate: it fuels glutathione peroxidase to reduce peroxides, serves as co‑substrate for GST conjugation of electrophiles, and modulates redox signaling via S‑glutathionylation.

Cellular targets: Glutathione peroxidases, glutathione S‑transferases, glutaredoxins, mitochondrial antioxidant systems.
Signaling pathways: Nrf2 (antioxidant response), NF‑κB (inflammatory signaling), MAPK/JNK/ASK1 redox‑sensitive kinases.
Protein modulation: Reversible S‑glutathionylation alters enzyme and receptor activities and protects thiols from irreversible oxidation.

✨ Science-Backed Benefits

🎯 Reduction of systemic oxidative stress markers

Evidence Level: medium

Physiology: GSH directly detoxifies hydrogen peroxide/lipid hydroperoxides through GPx and regenerates other antioxidants (vitamin C/E).

Target populations: smokers, metabolic syndrome, aging adults with low GSH.

Clinical Study: Mechanistic and small human trials report measurable reductions in oxidative biomarkers (e.g., increased erythrocyte GSH, reduced plasma TBARS) within days to weeks after supplementation (see authoritative reviews: PubChem entry and NCBI Bookshelf summaries).

🎯 Hepatic detoxification and liver support

Evidence Level: medium

Physiology: Hepatocytes use GSH for GST‑mediated conjugation and protection against reactive metabolites.

Clinical relevance: GSH is mechanistically central to detox; N‑acetylcysteine (NAC) remains the evidence‑based antidote for acute acetaminophen toxicity.

Clinical Study: Controlled and observational data indicate improved biochemical markers of oxidative stress and hepatoprotection in small trials; see NCBI Bookshelf discussion and toxicology literature for quantitative values.