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Oxidised glutathione (GSSG)

Oxidised glutathione (GSSG) is the used form of glutathione: two glutathione molecules joined through their sulphur atoms after neutralising an oxidant. The enzyme glutathione reductase turns it back into two molecules of working GSH.

Also called GSSG, glutathione disulphide.

The SS in GSSG is the disulphide bond that forms when two GSH molecules each give up a hydrogen and link together. A rise in GSSG relative to GSH is a standard readout of oxidative stress, and GSSG was higher in healthy older adults than in a young reference group (Lizzo 2022).

In human cartilage cells, those from donors aged 50 and over had a higher ratio of GSSG to GSH than cells from donors aged 18 to 49, and more than twice as many of them died under oxidant stress (Del Carlo 2003). In rats, cartilage glutathione was more prone to age-related oxidation than glutathione in nearby joint tissues (Zhu 2020).

GSSG is not waste; it is glutathione waiting to be recycled. Glutathione reductase, the principal enzyme that regenerates GSH from GSSG, lost activity when human cartilage cells were put under oxidative stress, and the authors linked this breakdown of the glutathione system to the greater vulnerability of older cells (Del Carlo 2003).

Sources

  1. 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.
  2. Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
  3. 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.

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Last reviewed 3 November 2026Every study cited here is indexed on PubMed. How we read the evidence