N-acetyl-cysteine (NAC) is an antioxidant and precursor to glutathione, a critical intracellular antioxidant. Its use in peripheral neuropathy is based on its potential to counteract oxidative stress and inflammation, both of which are implicated in nerve damage associated with conditions like diabetes and chemotherapy-induced neuropathy. Scientific interest in NAC for this indication stems from preclinical studies showing neuroprotective effects in animal models of neuropathy, where NAC supplementation reduced nerve damage and improved nerve function.

In human studies, the evidence is limited but promising. A handful of small randomized controlled trials and pilot studies have investigated NAC in patients with diabetic neuropathy or chemotherapy-induced peripheral neuropathy. Some of these studies demonstrate modest improvements in neuropathic symptoms, such as pain and sensory disturbances, especially when NAC is used as an adjunct to standard treatments. The proposed mechanisms include reduction of oxidative stress, inhibition of inflammatory pathways, and preservation of mitochondrial function in peripheral nerves.

However, the overall quality and quantity of the clinical evidence remain low, with methodological limitations, small sample sizes, and short follow-up periods. As a result, while there is a scientific rationale and some early clinical data supporting NAC’s use in peripheral neuropathy, its efficacy has not been definitively established. Larger, well-designed clinical trials are needed to provide more conclusive evidence.