Glutathione

Glutathione (GSH) is the body's most abundant endogenous antioxidant tripeptide, composed of glycine, cysteine, and glutamate. It is present in virtually all mammalian cells at millimolar concentrations and serves as a central hub of cellular redox regulation. GSH acts as a direct scavenger of reactive oxygen species, a cofactor for glutathione peroxidase enzymes, and a regenerator of vitamins C and E. Its depletion is associated with aging, chronic disease, and metabolic dysfunction.

Glutathione exerts antioxidant action through two main mechanisms: direct chemical quenching of reactive oxygen and nitrogen species, and enzymatic reduction of lipid hydroperoxides via glutathione peroxidase (GPx). It maintains cellular redox balance by cycling between reduced (GSH) and oxidized (GSSG) forms, with more than 90% normally in the reduced state. GSH conjugates electrophilic toxins via glutathione S-transferase for hepatic detoxification, maintains exogenous antioxidants in active states, and supports immune lymphocyte function. It also modulates apoptosis and inflammatory signaling through thiol chemistry.

Extensive basic research confirms GSH's central role in oxidative stress defense, detoxification, and immune function. Oral bioavailability is poor due to GI peptidase hydrolysis; IV administration reliably raises plasma and tissue GSH levels. A 2011 human study showed modest systemic oxidative stress reduction with oral supplementation at 250 mg/day. N-acetylcysteine (NAC) is commonly used as a GSH precursor with superior oral bioavailability. IV GSH is used clinically in some contexts as an adjunct to cancer chemotherapy to reduce oxidative side effects.

Peptides commonly paired with Glutathione for synergistic effects.