Glutathione (GSH / L-Glutathione / Gamma-Glutamylcysteinylglycine)

Glutathione (gamma-L-glutamyl-L-cysteinyl-glycine) is a tripeptide with CAS number 70-18-8 and molecular weight 307.32 Da. It's the most abundant intracellular antioxidant in the human body, present at 1-10 millimolar concentrations inside cells. What makes glutathione different from other antioxidants is its role as a regenerator. When vitamin C or vitamin E gets oxidized while neutralizing free radicals, glutathione reduces them back to their active forms. This makes it the central hub of the entire cellular antioxidant network. Without adequate GSH, other antioxidants can't recycle, and the whole system degrades. The bioavailability problem has historically limited oral glutathione supplementation. Plain oral GSH gets broken down by stomach acid and intestinal peptidases before it can be absorbed intact. This is where liposomal technology changed the equation. Sinha et al. (European Journal of Clinical Nutrition 2018, PMC: PMC6389332) showed that liposomal glutathione raised whole blood GSH by 40%, erythrocyte GSH by 25%, and plasma GSH by 28% within just 2 weeks. It also increased PBMC GSH by 100% and enhanced NK cell cytotoxicity. A 2025 study showed liposomal formulations achieving 6x higher plasma concentrations than plain GSH. The Parkinson's story is instructive about GSH's evidence level. Sechi et al. (1996, PMID: 8938817) gave IV GSH 600 mg twice daily to 9 early Parkinson's patients for 30 days. All showed improvement, with disability scores declining by 42%. Effects lasted 2-4 months after stopping treatment. But when Hauser et al. (Movement Disorders 2009, PMID: 19230029) ran a proper randomized, double-blind, placebo-controlled trial with IV GSH 1,400 mg 3x/week for 4 weeks, there was no efficacy difference versus placebo. The treatment was well-tolerated, but the positive open-label results didn't hold up. The GlyNAC approach (glycine + N-acetyl cysteine) has gained traction from Dr. Rajagopal Sekhar's work at Baylor College of Medicine. By providing both the rate-limiting amino acid for GSH synthesis (cysteine via NAC) and glycine (the other amino acid constituent), GlyNAC supplementation showed improvements in oxidative stress, mitochondrial function, inflammation, and body composition in elderly subjects. IV glutathione drips have become a staple at wellness clinics, typically at 1,000-2,000 mg per infusion. The plasma half-life is only about 14 minutes (Aebi et al., 1991, PMID: 1907548), so the effects of a single IV session are transient. This is why some practitioners prefer subcutaneous injection (200-400 mg, 2-3x per week) or daily liposomal oral supplementation for sustained levels. Glutathione was not affected by the FDA's peptide compounding restrictions. It's available as a dietary supplement, through IV clinics, and through compounding pharmacies. The FDA has warned against using dietary-grade glutathione for sterile injectable preparations due to impurity and endotoxin risks, so compounding pharmacies should use pharmaceutical-grade bulk substance.