The role of N-acetylcysteine and glutathione in the management of Parkinson's disease: a systematic review of oxidative biomarkers and clinical outcomes.
Level 1 - systematic review of randomized trials
Systematic review of randomized and non-randomized comparative clinical studies
PubMed 41874704 · doi:10.1007/s00726-026-03513-5
What was done
Authors searched six databases from 2003 to 2024 for randomized controlled trials and non-randomized comparative studies evaluating N-acetylcysteine (NAC) or glutathione (GSH) in Parkinson's disease versus placebo or healthy controls. Primary outcomes were motor and non-motor symptoms measured by the Unified Parkinson's Disease Rating Scale (UPDRS) interpreted using minimal clinically important difference thresholds. Secondary outcomes included blood and CSF redox markers (GSH, GSSG, GSH/GSSG ratio), magnetic resonance spectroscopy brain GSH levels, and DaTscan SPECT dopamine transporter (DAT) binding.
What was found
Nine studies involving 196 participants were included. NAC administration improved motor and non-motor UPDRS scores, increased CSF GSH levels, elevated GSH/GSSG ratios, and increased DAT binding. Intranasal GSH produced modest increases in brain GSH levels without significant improvements in clinical symptoms or oxidative stress markers. The abstract reports no numerical effect sizes or confidence intervals.
Why it matters
This review distinguishes the therapeutic potential of the glutathione precursor NAC from direct glutathione administration in Parkinson's disease, supporting further clinical trial development for NAC.
Limits
The total sample across all nine studies was very small (196 participants) with short intervention durations. Studies varied in dosing regimens and administration routes, and no pooled quantitative effect sizes or risk-of-bias details were provided in the abstract.
Cited by
- supports Supplementing with N-acetylcysteine (NAC) supports glutathione production and detoxification in the body.