What does N-acetylcysteine (NAC) do in cartilage?
N-acetylcysteine (NAC) is a stable source of cysteine, the building block whose supply most limits how much glutathione a cell can make (Lu 2013). In cartilage cells NAC prevented nitric oxide-induced death through glutathione (Nakagawa 2010), and given by mouth to rats it held back MMP13, type II collagen loss and osteoarthritis development (Kaneko 2019).
Why cysteine, why NAC
Cysteine supply is one of the two key controls on glutathione synthesis (Lu 2013). In human chondrocytes, taking cystine out of the culture medium was enough to drain glutathione and make the cells more vulnerable (Del Carlo 2003). NAC delivers cysteine in a form the body can use to make glutathione.
In cartilage cells
NAC protected cartilage cells from nitric oxide-induced death, stopped the rise in reactive oxygen species and blocked the cell-death signals p53 and caspase-3. When glutathione synthesis was blocked, the protection was largely lost, so NAC was working through glutathione (Nakagawa 2010). In rat patella cultures, NAC gave cartilage resistance to the inflammatory signal IL-1β (Zhu 2020).
In animals
Injected into rat knees, NAC reduced cartilage destruction and cell death (Nakagawa 2010). Given by mouth in a rat osteoarthritis model, it held back MMP13, the loss of type II collagen and chondrocyte death, and significantly slowed the disease, including on the opposite knee (Kaneko 2019). Delivered in cartilage-targeted nanoparticles, it restored glutathione under mechanical stress and protected cartilage in mice (Wang 2026).
In people
With glycine, as GlyNAC, NAC corrected glutathione deficiency in older adults in blood measurements (Kumar 2023). There are no human cartilage measurements in the studies in our library. NAC is one of the four parts of Gluthanol™.
Other questions people ask
Is NAC the same as cysteine?
NAC is cysteine with an acetyl group attached, which makes it more stable. The body removes the acetyl group to release cysteine.
Has NAC been studied against MMP13?
Yes, in rats: oral NAC held back MMP13 expression in cartilage (Kaneko 2019).
Sources
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 2003.
- Nakagawa S, Arai Y, Mazda O et al. N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis. J Orthop Res 2010.
- 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.
- Kaneko Y, Tanigawa N, Sato Y et al. Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model. Sci Rep 2019.
- Wang S, Zhang F, Zhou X et al. Chondrocyte-Targeted Nanoparticles Loaded with N-Acetylcysteine Protect Articular Cartilage and Attenuate Osteoarthritis by Inhibiting Ferroptosis via Glutathione Maintenance. Small Sci 2026.
- 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.
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GlyNAC is a combination of glycine and N-acetylcysteine (NAC), two of glutathione's building blocks, studied as a way to correct glutathione deficiency in older adults....
What is Gluthanol™?
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