Glutathione

Glutathione (GSH) is a tripeptide considered the master antioxidant of the body, present in millimolar concentrations in most cells and serving as the primary intracellular defense against oxidative stress. Its unusual gamma peptide bond between glutamate and cysteine protects against hydrolysis by common peptidases.

The cysteine thiol group is glutathione's active site, capable of directly reducing reactive oxygen species and serving as a substrate for glutathione peroxidase enzymes that detoxify hydrogen peroxide and lipid peroxides. Oxidized glutathione (GSSG) is recycled back to GSH by glutathione reductase, maintaining the high GSH/GSSG ratio (typically >100:1) essential for cellular redox homeostasis.

Beyond antioxidant function, glutathione participates in detoxification of xenobiotics through glutathione S-transferase conjugation reactions, protein glutathionylation that regulates enzyme activity and signaling, and maintenance of other antioxidants (vitamins C and E) in their reduced states.

Glutathione levels decline with age and in many disease states, and this depletion correlates with increased oxidative damage and mortality. Research explores oral, intravenous, and liposomal glutathione supplementation, as well as precursor supplementation (N-acetyl cysteine, glycine) to support endogenous synthesis.