N-Acetylcysteine in Neurological Disorders: A Systematic Review of Clinical and Translational Evidence Across Seven Disorders

N-acetylcysteine (NAC) is a glutathione precursor with established antioxidant and anti-inflammatory properties that has been investigated as a neuroprotective agent across multiple neurological conditions. This systematic review systematically mapped the clinical evidence for NAC across seven neurological disorders. PubMed and Cochrane Library were searched for studies published between 1 January 1995 and 31 December 2025. Twenty-three studies were included: traumatic brain injury (TBI, n = 6), Alzheimer’s disease (AD, n = 5), Parkinson’s disease (PD, n = 5), multiple sclerosis (n = 4), amyotrophic lateral sclerosis (n = 2), and migraine (n = 1); no eligible epilepsy studies were identified. The strongest evidence emerged for acute mild TBI, where early NAC administration significantly improved symptom resolution, and for PD, where combined intravenous/oral NAC improved dopamine transporter binding. In AD, nutraceutical formulations including NAC and other active compounds showed trends toward cognitive stabilization. Most included studies had a high or serious risk of bias, and only eight of 23 assessed oxidative stress biomarkers. NAC demonstrated a favorable safety profile across all conditions. Despite fragmented and heterogeneous evidence, the encouraging signals identified warrant large-scale randomized controlled trials with a standardized biomarker assessment.

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Publication Details

Journal
International Journal of Molecular Sciences
Published
2026-03-27
DOI
https://doi.org/10.3390/ijms27073076
Primary Topic
Sulfur Compounds in Biology
Type
article
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article

N-Acetylcysteine in Neurological Disorders: A Systematic Review of Clinical and Translational Evidence Across Seven Disorders

International Journal of Molecular Sciences
Sulfur Compounds in Biology
article

N-Acetylcysteine in Neurological Disorders: A Systematic Review of Clinical and Translational Evidence Across Seven Disorders

article en

Abstract

N-acetylcysteine (NAC) is a glutathione precursor with established antioxidant and anti-inflammatory properties that has been investigated as a neuroprotective agent across multiple neurological conditions. This systematic review systematically mapped the clinical evidence for NAC across seven neurological disorders. PubMed and Cochrane Library were searched for studies published between 1 January 1995 and 31 December 2025. Twenty-three studies were included: traumatic brain injury (TBI, n = 6), Alzheimer’s disease (AD, n = 5), Parkinson’s disease (PD, n = 5), multiple sclerosis (n = 4), amyotrophic lateral sclerosis (n = 2), and migraine (n = 1); no eligible epilepsy studies were identified. The strongest evidence emerged for acute mild TBI, where early NAC administration significantly improved symptom resolution, and for PD, where combined intravenous/oral NAC improved dopamine transporter binding. In AD, nutraceutical formulations including NAC and other active compounds showed trends toward cognitive stabilization. Most included studies had a high or serious risk of bias, and only eight of 23 assessed oxidative stress biomarkers. NAC demonstrated a favorable safety profile across all conditions. Despite fragmented and heterogeneous evidence, the encouraging signals identified warrant large-scale randomized controlled trials with a standardized biomarker assessment.

International Journal of Molecular SciencesVol. 27(7)
Iuliu Hațieganu University of Medicine and Pharmacy (RO)
Good health and well-being
Openalex Percentile: Top 5%
Sulfur Compounds in Biology
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N-Acetylcysteine in Neurological Disorders: A Systematic Review of Clinical and Translational Evidence Across Seven Disorders · International Journal of Molecular Sciences (2026) | TGRS Research Map | TGRS