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

2026-03-27
International journal of molecular sciences 27(7)
- Robert Mîndreanu
- Irina Camelia Chiș
- Alexandra Sevastre-Berghian
- Cezar Login
- Adina Stan
- Teodora Stan
- Simona Clichici
- Șoimița Suciu

PubMed: 41977262
DOI: 10.3390/ijms27073076

Study Design

Type: Systematic Review
Population: patients across seven neurological disorders: 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)
Methods: Systematic review of PubMed and Cochrane Library for studies published between 1 January 1995 and 31 December 2025

Rigorous Journal

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.

Research Insights

N-Acetyl Cysteine→Improved Cognitive Stabilization
In AD, nutraceutical formulations including NAC and other active compounds showed trends toward cognitive stabilization
Effect
Beneficial
Effect size
Moderate
N-Acetyl Cysteine→Improved Dopamine Transporter Binding
for PD, where combined intravenous/oral NAC improved dopamine transporter binding
Effect
Beneficial
Effect size
Moderate
N-Acetyl Cysteine→Improved Oxidative Stress Biomarker
only eight of 23 assessed oxidative stress biomarkers
Effect
Neutral
Effect size
Small
N-Acetyl Cysteine→Improved Symptom Resolution
The strongest evidence emerged for acute mild TBI, where early NAC administration significantly improved symptom resolution
Effect
Beneficial
Effect size
Moderate

Adverse Events Reported

N-Acetyl Cysteine→Overall tolerability
NAC demonstrated a favorable safety profile across all conditions.
Finding
Reported