N-acetylcysteine in the treatment of ischaemic stroke: A systematic review

Abstract

BACKGROUND/OBJECTIVES: Current ischaemic stroke treatment protocols do not include the use of neuroprotective agents such as N-Acetyl Cysteine (NAC). Preclinical studies suggest that NAC may offer neuroprotection through its antioxidant, antiinflammatory and excitotoxicity-mediating effects. This systematic review aimed to evaluate the safety and efficacy of NAC in the treatment of ischaemic stroke. METHODS: A systematic review was conducted in accordance with PRISMA guidelines and was registered (CRD42025632702). PubMed, Medline, EMBASE, Cochrane and SCOPUS were searched for publications until December 30, 2024. Primary outcomes included a reduction in National Institutes of Health Stroke Scale (NIHSS) at various time points and functional outcomes as measured by the modified Rankin Scale (mRS). RESULTS: Three randomised controlled trials (182 ischaemic stroke patients) were included. Heterogeneity in the study design, population and reported outcomes precluded metaanalysis. While all 3 trials showed NIHSS score improvement with NAC, the effect was inconsistent across follow-up periods. One study showed a significant improvement in mRS score at 90 days, while another found no difference. Two studies identified significant biomarker changes. No severe adverse effects were observed. CONCLUSIONS: NAC shows potential as a safe adjunctive therapy in the treatment of ischaemic stroke, with evidence supporting improvements in neurological outcomes and biomarkers related to oxidative stress and inflammation. However, variability in study methodology and small sample size limit definitive conclusions. Larger, well-powered clinical trials are needed to determine NAC's clinical efficacy, optimal dosing strategies and long-term outcomes.