N-acetylcysteine (NAC)
N-acetylcysteine (NAC) is a form of the amino acid cysteine with an acetyl group attached, which cells can use as a source of cysteine to make glutathione. It is widely used in research as a glutathione precursor and antioxidant.
Also called NAC, acetylcysteine, N-acetyl cysteine, N-acetyl-L-cysteine.
In rabbit cartilage cells in the lab, NAC protected against cell death caused by nitric oxide, and the protection was blocked when glutathione synthesis was blocked, showing it worked through glutathione (Nakagawa 2010). Injected into rat knees in a model of osteoarthritis, it reduced cartilage destruction and cartilage-cell death (Nakagawa 2010).
Given by mouth to rats, NAC significantly slowed osteoarthritis development and held back the rise in MMP13, the loss of type II collagen and chondrocyte death (Kaneko 2019). In mice, NAC packed into nanoparticles that home in on cartilage cells restored their glutathione under mechanical stress and reduced cartilage breakdown, and the effect disappeared in mice lacking GPX4; the same study noted that free NAC breaks down quickly and does not stay long in the joint (Wang 2026).
In people, NAC has been studied with glycine as GlyNAC. In a 16-week placebo-controlled trial in older adults, GlyNAC corrected glutathione deficiency (Kumar 2023); a two-week trial in 114 healthy older adults found no rise across the whole group, only in those who started with high oxidative stress and low glutathione (Lizzo 2022). None of these trials measured glutathione in cartilage.
Sources
- 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.
- 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.
- 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.
Related terms
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