Glutathione (GSH)

Technical data

INN name

Glutathione

CAS

70-18-8

Molecular formula

C10H17N3O6S

Molecular weight

307.32 g/mol

Identity and composition

El glutathione (GSH) is an endogenous thiol tripeptide present in practically all cells and considered the main non-protein intracellular antioxidant. It is offered as a material for research in a presentation of 1500 mg. Its chemical identity corresponds to the CAS 70-18-8, molecular formula C10H17N3O6S, molecular weight 307.32 g/mol and sequence γ-L-Glutamyl-L-cysteinyl-glycine (γ-Glu-Cys-Gly).

It is also known as reduced L-glutathione, GSH, reduced glutathione o reduced glutathione. The thiol group (-SH) of its cysteine residue is the center of its redox activity and of its participation in the cell's enzymatic detoxification systems.

Mechanism of action

Glutathione functions as the main intracellular redox buffer. The thiol group (-SH) of its cysteine neutralizes reactive oxygen species and electrophiles, and serves as a substrate or cofactor for three key enzymatic systems:

• Glutathione peroxidase: reduces peroxides using GSH as an electron donor.
• Glutathione S-transferase: catalyzes the conjugation of GSH with xenobiotics for their detoxification.
• Glutathione reductase: regenerates GSH from its oxidized form (GSSG) using NADPH.

The redox state of the cell is reflected in the ratio GSH:GSSG. Its chemical identity —formula C10H17N3O6S and IUPAC name (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid— is confirmed in reference databases (PubChem CID 124886).

Pharmacokinetics

The oral bioavailability of standard glutathione is described as low, attributed to degradation by γ-glutamyltranspeptidase and intestinal peptidases. For this reason improved formulations (liposomal, micellar) have been investigated, which in a randomized crossover trial showed a several-fold increase in incremental plasma exposure (iAUC) and in Cmax compared to standard GSH (PMID 41897500).

No well-established value is available in the open sources for human plasma half-life for native GSH; for transparency, this datum is omitted rather than estimated. Data from N-methylated analogues in rats showed increases in half-life, but they are not extrapolable to human glutathione.

Scientific evidence

The human clinical evidence is limited and focuses mainly on bioavailability and on the elevation of the body's GSH reserves; it must be interpreted as preliminary.

In a controlled trial with liposomal glutathione (500 and 1000 mg/day for 4 weeks), increases in GSH stores were observed (up to ~40% in whole blood and ~200% in PBMC), together with changes in immune-function markers (NK cell cytotoxicity, lymphocyte proliferation) and a reduction in oxidative-stress markers (PMID 28853742). A more recent randomized crossover trial evaluated the bioavailability of different oral formulations (PMID 41897500).

The relevance for longevity and aging remains preliminary and inconclusive; larger studies with long-term outcomes are required.

Research applications

Product for research use.

Ideal for:

• In vitro and redox biochemistry studies focused on the GSH/GSSG system and associated enzymes (peroxidase, S-transferase, reductase).
• Research on the bioavailability of different formulations (standard versus liposomal or micellar) in experimental models.
• Reference work on the analytical characterization of the tripeptide.

Not applicable for:

• Any form of clinical, food, therapeutic or diagnostic use.
• Directly extrapolating results to clinical longevity outcomes, given that the available evidence is preliminary.

Research protocols

The cited protocols correspond to published studies and are described for informational purposes, not as a usage guideline.

• Glutathione liposomal at 500 and 1000 mg/day for 4 weeks in a human trial (PMID 28853742). - Oral formulations compared in a crossover trial: standard 500 mg, liposomal 300 mg and micellar 300 mg (PMID 41897500). - Formulation micellar at 600 mg/day for 30 days in the safety evaluation arm (PMID 41897500).

The doses in these studies are lower than the 1500 mg presentation; there is no protocol in the consulted literature that specifically supports that amount, so equivalence should not be assumed.

Reconstitution

As a general laboratory-handling guide: lyophilized materials are usually reconstituted with bacteriostatic water (sterile water with ~0.9% benzyl alcohol) or with the diluent indicated by the experimental protocol.

• Add the diluent, letting it run slowly down the wall of the vial, without directing the stream directly onto the powder.
• Do not shake forcefully; gently swirl the vial (circular motion) until fully dissolved.
• Calculate the diluent volume according to the target concentration of your assay.

This guidance is of general technique and does not constitute a dosing recommendation.

Stability and storage

As a standard handling practice:

• Lyophilized (powder): keep in a cool, dry place protected from light; for prolonged storage, refrigeration or freezing according to the protocol is usually preferred. Glutathione is a thiol sensitive to oxidation, so it is advisable to minimize exposure to air and humidity.
• Reconstituted: keep refrigerated and use in the short term; to store it longer it can be aliquoted and frozen, avoiding repeated freeze-thaw cycles.

These ranges are for general laboratory reference and must be adjusted to the validated conditions of each study.

Safety profile

In the reviewed trials, oral supplementation was described as well tolerated. With the micellar formulation at 600 mg/day for 30 days, no significant changes were reported in clinical markers (ALT, AST, ALP, creatinine); mild gastrointestinal symptoms were recorded (bloating, nausea) that improved when taken with food (PMID 41897500).

As an endogenous molecule, GSH showed a favorable safety profile at the doses studied; however, long-term safety data are lacking. As a research product, it must be handled with standard laboratory precautions and is not intended for clinical use.

Comparative context

Unlike exogenous small-molecule antioxidants such as vitamin C or vitamin E, glutathione is a endogenous thiol enzymatically regenerable and occupies a central position in the intracellular redox system through the GSH:GSSG ratio.

Its main disadvantage compared to other oral antioxidants is the low bioavailability of native GSH, which has motivated the development of liposomal and micellar formulations, as well as the use of precursors such as N-acetylcysteine (NAC), which provide cysteine for the endogenous synthesis of glutathione. Thus, while NAC acts as a precursor donor, GSH represents the already-assembled active molecule.

History and development

Glutathione is a compound endogenous present in practically all cells, widely studied within the biochemistry of oxidative stress, immune function, and aging. Its chemical identity is consolidated in reference databases such as PubChem (CID 124886).

The most recent interest in its development as a research material has been oriented toward overcoming the low bioavailability of the native tripeptide, giving rise to improved formulations (liposomal and micellar) evaluated in bioavailability and body-store GSH trials (PMID 28853742; PMID 41897500).

FAQ

Customer reviews

Average rating: 4.9 out of 5, based on 16 customer ratings.

Scientific references (4)

Peer-reviewed literature on Glutathione (GSH), with its PubMed identifier where available:

• Glutathione: Overview of its protective roles (Forman HJ, et al. · Molecular Aspects of Medicine · 2009) — Comprehensive review of the protective role of glutathione as the master antioxidant. PMID 18796312.
• Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers (Allen, et al. · Journal of Alternative and Complementary Medicine · 2011) PMID 21875351.
• Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function (Sinha, et al. · European Journal of Clinical Nutrition · 2018) PMID 28853742.
• The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial (Søndergård, et al. · Applied Physiology, Nutrition, and Metabolism · 2021) PMID 33740389.

Other related research peptides

• Humanin
• N-Acetyl Epitalon Amidate
• NAD+
• Pinealon
• PNC 27
• SS-31
• Epitalon
• FOXO4-DRI