Exercise alone does the heavy lifting
STUDY: https://doi.org/10.1186/s13195-026-02062-z
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Canadian Institute of Health Research
Background
N-acetylcysteine (NAC) is a precursor to glutathione, the brain’s main antioxidant. Oxidative stress drives vascular cognitive decline, so boosting glutathione is a plausible target — and NAC crosses the blood-brain barrier. This trial tested whether adding NAC to an exercise-based cardiac rehabilitation program could improve cognition in patients with vascular mild cognitive impairment.
The Study
- 59 adults with coronary artery disease and mild cognitive impairment
- Randomized to oral NAC (2400 mg/day, titrated over four weeks) or placebo for 24 weeks, all while enrolled in a supervised cardiac rehabilitation program.
- The primary outcome was a composite executive function score; secondary outcomes included memory, attention, and global cognition (Montreal Cognitive Assessment).
Both groups improved on executive function over time, but NAC added nothing over placebo (treatment effect B = -0.04, essentially zero). No secondary cognitive outcomes differed between groups. Both groups also improved on non-verbal memory and global cognition, with MoCA scores rising more than 2 points.
NAC was generally well-tolerated; nausea was the one adverse event significantly more common in the NAC group (about 14% during ramp-up vs. 0% on placebo).
Practice Implications
- Exercise has powerful pro-cognitive effects, so no surprise that NAC wasn’t able to add to that. Still, the evidence for NAC’s cognitive benefits is slim.
- NAC has small trials in depression, schizophrenia, and other psychiatric disorders, but their inconsistent results leave us uncertain of its role. However, there is a signal in that data. NAC works better when inflammation is high (hs-CRP ≥ 3 mg/L) or when taken for longer than 4–6 months.
Here are lab-tested products for NAC.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
