Glutathione

What Is Glutathione?

Glutathione is a tripeptide of glycine, cysteine, and glutamate that every cell synthesises, with the highest concentrations in the liver. It is the principal endogenous antioxidant: the thiol group on its cysteine residue donates an electron to neutralise reactive oxygen species, the by-products of normal metabolism and external stressors that drive oxidative damage to DNA, lipids, and proteins. On donating that electron it becomes oxidised glutathione (GSSG), and the ratio of reduced (GSH) to oxidised glutathione is one of the most direct biomarkers of cellular redox state.

Glutathione is also the obligate cofactor for Phase II hepatic detoxification, conjugating with the reactive intermediates produced by Phase I (CYP450) metabolism of drugs, alcohol, and environmental toxins to render them water-soluble for renal or biliary clearance. A separate mechanism underlies its study in dermatology: glutathione inhibits tyrosinase, the rate-limiting enzyme in melanin synthesis, and shifts melanocyte output from eumelanin toward pheomelanin. Tissue glutathione declines with age, chronic illness, alcohol exposure, acetaminophen exposure, and oxidative-stress conditions, which is why repletion has been investigated across a broad range of indications.

Bioavailability is the central pharmacological issue. Oral glutathione is largely degraded by intestinal proteases and first-pass hepatic metabolism, which is why most oral trials show null or weak effects despite the compound's clear intracellular role. Liposomal oral, intravenous, intramuscular, and subcutaneous routes bypass first-pass metabolism and reliably raise plasma and tissue glutathione in the published pharmacokinetic studies.