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GSH:GSSG ratio

The GSH:GSSG ratio compares the amount of working, reduced glutathione (GSH) with the amount of used, oxidised glutathione (GSSG) in a cell or fluid. A lower ratio means more of the glutathione pool is oxidised, a common sign of oxidative stress.

Also called glutathione redox ratio, reduced to oxidised glutathione ratio, glutathione redox status.

Total glutathione says how much a cell has; the ratio says how much of it is still ready to work. Researchers measure both, because a cell can hold plenty of glutathione and still have a large share of it tied up as GSSG.

In healthy older adults with a mean age of 65, the ratio of reduced to oxidised glutathione was lower than in a young reference group (Lizzo 2022). Human cartilage cells from older donors showed the same imbalance from the other side, a higher ratio of GSSG to GSH (Del Carlo 2003).

The ratio moves with demand. In mouse cartilage cells a pro-oxidant challenge raised both glutathione content and the GSH:GSSG ratio, and in cow cartilage in the lab, repeated compression oxidised glutathione, which needed unloaded rest periods to recover (Zhu 2020). In a trial in healthy older adults, two weeks of glycine and NAC did not change the ratio across the whole group (Lizzo 2022), while in a six-month trial in healthy adults, oral glutathione lowered the oxidised-to-reduced ratio in whole blood (Richie 2015).

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.
  4. 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.

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