What is cartilage glutathione?
Cartilage glutathione is the glutathione made and held inside chondrocytes, the cells that build and maintain joint cartilage. Glutathione is a small antioxidant the cells make for themselves from three amino acids, glutamate, cysteine and glycine. Cartilage holds more of it than the meniscus or the knee's fat pad, and it is more prone to age-related oxidation (Zhu 2020).
An antioxidant the cell makes for itself
Glutathione is the most abundant small sulphur-containing molecule that cells make, and one of their main defences against oxidative damage (Forman 2009). It is a tripeptide: three amino acids, glutamate, cysteine and glycine, joined in a chain. The working part is the sulphur group on cysteine, which gives up electrons to neutralise oxidants.
Cells do not absorb most of their glutathione ready-made. They build it inside themselves in two enzyme steps, and the supply of cysteine is one of the two main controls on how much they can make (Lu 2013).
Why cartilage leans on it
Articular cartilage, the smooth layer on the ends of bones, has no blood vessels, lymphatics or nerves. Its cells, the chondrocytes, make up only about 2% of its volume, and nutrients reach them by moving with the water that flows through the tissue as it is loaded (Sophia Fox 2009).
Those few cells have to maintain the whole tissue around them. In a 2020 study, glutathione was more plentiful in cartilage than in the meniscus or the infrapatellar fat pad, but cartilage glutathione was also more susceptible to age-related oxidation (Zhu 2020). In a 2020 study of growth-plate cartilage, glutathione made from glutamine was what kept harmful reactive oxygen species down and let the cells survive without a blood supply (Stegen 2020).
What happens when it runs low
When researchers exposed human cartilage cells to an oxidant, more than twice as many cells from donors aged 50 and over died as cells from donors aged 18 to 49. The older cells had a higher ratio of oxidised to reduced glutathione, and cells deliberately drained of glutathione, either with an enzyme blocker or by removing cystine from their culture medium, died more readily (Del Carlo 2003).
That is the core finding behind cartilage glutathione as a field: the cell's own antioxidant tracks how well it copes with stress, and the supply of cysteine matters.
Where Gluthanol™ fits
Gluthanol™ is a blend built around this pathway. Three of its four parts supply the raw materials chondrocytes make glutathione from: N-acetylcysteine for cysteine, L-glycine, and L-glutamine as a source of glutamate. The fourth, alpha-lipoic acid, has been shown in lab studies to raise cells' own glutathione by helping them take up cysteine (Han 1997).
Other questions people ask
Is cartilage glutathione different from the glutathione in blood?
It is the same molecule, measured in a different place. The cartilage studies on this site measured glutathione in cartilage cells or tissue in the lab and in animals (Del Carlo 2003; Zhu 2020). The human supplement trials measured it in blood cells (Sekhar 2011; Kumar 2023).
Is glutathione the only antioxidant in cartilage?
No. Cartilage cells also rely on enzymes such as peroxiredoxins and catalase, and on Nrf2, the switch that turns antioxidant defences up. Several of these change with age too (Collins 2016; Taylor 2023; Bolduc 2019).
Sources
- 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.
- Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health 2009.
- Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009.
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Stegen S, Rinaldi G, Loopmans S et al. Glutamine Metabolism Controls Chondrocyte Identity and Function. Dev Cell 2020.
- Han D, Handelman G, Marcocci L et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997.
- 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.
- Kumar P, Liu C, Suliburk J et al. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci 2023.
- Collins JA, Wood ST, Nelson KJ et al. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes. J Biol Chem 2016.
- Taylor EL, Collins JA, Gopalakrishnan P et al. Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes. Osteoarthritis Cartilage 2023.
- Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med 2019.
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