Glutathione
Glutathione is a tripeptide, a small molecule built from three amino acids (glutamate, cysteine and glycine), that cells make for themselves to defend against oxidative stress. It is the most abundant non-protein thiol in mammalian tissues.
Also called GSH, L-glutathione, gamma-glutamylcysteinylglycine.
Its working part is the sulphur-containing thiol group of cysteine, which can give up electrons to neutralise an oxidant. Cells assemble it in the cytosol, the fluid inside the cell, in two enzyme steps, and the two key controls on how much they make are the supply of cysteine and the activity of the first enzyme, glutamate cysteine ligase (Lu 2013). Besides reducing oxidants, it binds foreign reactive chemicals so they can be cleared, and it helps keep the cell's redox balance (Forman 2009).
Cartilage leans on it. In rats, glutathione was more plentiful in cartilage than in the meniscus or the knee's fat pad, although cartilage glutathione was also more prone to oxidation with age (Zhu 2020). In human cartilage cells, those from donors aged 50 and over held more of their glutathione in the used, oxidised form, and cells drained of glutathione died more readily under oxidant stress (Del Carlo 2003).
Swallowed glutathione is broken down by enzymes in the gut and liver, and a single dose did not raise blood glutathione in healthy volunteers (Witschi 1992), though six months of daily dosing did raise blood levels in a later trial (Richie 2015). The other route is to supply its building blocks, the precursors, so cells make more of their own: in older adults, two weeks of cysteine and glycine raised red-cell glutathione (Sekhar 2011).
Sources
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009.
- Zhu S, Makosa D, Miller B et al. Glutathione as a mediator of cartilage oxidative stress resistance and resilience during aging and osteoarthritis. Connect Tissue Res 2020.
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
- Witschi A, Reddy S, Stofer B et al. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992.
- Richie JP Jr, Nichenametla S, Neidig W et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr 2015.
- Sekhar RV, Patel SG, Guthikonda AP et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 2011.
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