A popular supplement gets its first rigorous test in Alzheimer’s, and disappoints
STUDY: Holper S et al, Alzheimer’s & Dementia 2026;22:e71381
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: National Health and Medical Research Council; Alzheimer’s Association
Background
SAMe (S-adenosyl methionine) is depleted in the Alzheimer’s brain and plays a role in tau regulation and DNA methylation — plausible reasons to think supplementation might slow the disease. This is the first trial to test it as a standalone treatment in humans.
The Study
Sixty-three adults with mild cognitive impairment or dementia due to Alzheimer’s were randomized to SAMe 400 mg daily or placebo for 180 days across four Australian sites. The primary outcome was change in plasma phosphorylated tau (p-tau217), a validated Alzheimer’s biomarker. Secondary outcomes included cognition (RBANS) and other neurodegeneration markers.
SAMe had no effect on p-tau217, cognition scores, or other biomarkers (p-tau181, GFAP, or neurofilament light chain).
Practice Implications
- It doesn’t surprise me. SAMe also failed to improve cognition in various populations.
- SAMe probably treats depression, though the studies are mixed. It is a delicate and poorly absorbed supplement, which may be why it sometimes fails. Make sure to use a lab-tested product.
- Caution: It can cause mania.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
