What is the GSH:GSSG ratio, and why does it matter for cartilage?
GSH is glutathione in its working, reduced form; GSSG is the used, oxidised form, two molecules joined. The GSH:GSSG ratio is a standard read-out of a cell's redox state: the higher it is, the more antioxidant capacity is in reserve. Cartilage cells from older donors had a higher ratio of GSSG to GSH and were more likely to die under oxidant stress (Del Carlo 2003).
Two forms of one molecule
When glutathione neutralises an oxidant, it gives up electrons from its sulphur group and pairs with a second glutathione molecule to form GSSG. Glutathione reductase turns GSSG back into two molecules of GSH (Del Carlo 2003). A cell with plenty of GSH relative to GSSG is well buffered; a cell with more GSSG has already spent much of its reserve.
What it shows in cartilage
Older human chondrocytes had a higher GSSG to GSH ratio (Del Carlo 2003). In rat knees, cartilage glutathione was more prone to age-related oxidation than meniscus or fat pad glutathione, and in cow cartilage, compressive loading shifted the balance toward oxidation until the tissue was rested (Zhu 2020).
What it shows in blood
In 114 healthy older adults, the blood ratio of free reduced to oxidised glutathione was 11.78, against 15.26 in a young reference group (Lizzo 2022). In a pilot study of liposomal glutathione, the oxidised to reduced ratio fell by 20% (Sinha 2018).
Other questions people ask
Can I get my GSH:GSSG ratio tested?
It is measured in research laboratories, usually in blood cells. It is not part of routine blood tests.
Is a higher ratio always better?
Within normal physiology, a higher ratio means more reduced glutathione is available. Cells also respond to shifts in the ratio, which is one reason the research looks at resilience: how quickly the ratio recovers after stress (Zhu 2020).
Sources
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
- 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.
- Lizzo G, Migliavacca E, Lamers D et al. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging 2022.
- Sinha R, Sinha I, Calcagnotto A et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr 2018.
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