A phase 2, randomized, multicenter, double-blind, placebo-controlled trial of S-adenosyl methionine in participants with mild cognitive impairment or dementia due to Alzheimer&#39;s disease

Holper, S; Barnham, KJ; Churilov, L; Yates, P; Brodtmann, A; Johns, S; Li, QX; Bhalala, O; Chin, KS; Loveland, P; Yu, JJ; Masters, CL; Watson, R; Yassi, N

A phase 2, randomized, multicenter, double-blind, placebo-controlled trial of S-adenosyl methionine in participants with mild cognitive impairment or dementia due to Alzheimer's disease

Author(s): Holper, S; Barnham, KJ; Churilov, L; Yates, P; Brodtmann, A; Johns, S; Li, QX; Bhalala, O; Chin, KS; Loveland, P; Yu, JJ; Masters, CL; Watson, R; Yassi, N;
Details: Publication Year 2026-04,Volume 22,Issue #4,Page e71381
Journal Title: Alzheimer’s & Dementia
Publication Type: Apr 14
Abstract: INTRODUCTION: S-adenosyl methionine (SAMe) is a pivotal metabolite in multiple neuronal pathways, including tau dephosphorylation. Reduced SAMe availability has been reported in the Alzheimer's disease (AD) brain, prompting interest in supplementation as a potential therapeutic strategy. METHODS: This multicenter, randomized, double-blind, placebo-controlled phase 2 study recruited people (n = 63) with a clinical AD diagnosis. Participants received 180 days of SAMe (400 mg daily) or placebo. Primary outcome was change in plasma phosphorylated tau (p-tau)217 concentration. Secondary endpoints included safety, tolerability, and cognitive outcomes. RESULTS: Mean percentage change in plasma p-tau217 in the SAMe group was an increase of 53.22 (standard deviation [SD] 159.19) compared to 25.34 (SD 94.83) in the placebo group (standardized mean difference 37.58, 95% confidence interval -32.61, 107.76; p = 0.288). No significant differences were observed in safety or other secondary endpoints. DISCUSSION: SAMe did not demonstrate disease-modifying efficacy at the dose and duration studied; however it was safe and well tolerated. TRIAL REGISTRATION: ACTRN12620000506998. Registered on the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au).
Publisher: Wiley
Keywords: Humans; Double-Blind Method; *S-Adenosylmethionine/therapeutic use; Male; *Alzheimer Disease/complications/drug therapy; Female; Aged; *Cognitive Dysfunction/drug therapy/etiology/blood; tau Proteins/blood; Treatment Outcome; Middle Aged; Aged, 80 and over; Alzheimer's disease; S‐adenosyl methionine; biomarker; clinical trial; tau
Research Division(s): Genetics and Gene Regulation
PubMed ID: 41980907
Publisher's Version: https://doi.org/10.1002/alz.71381
Open Access at Publisher's Site: https://doi.org/10.1002/alz.71381.
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-04-27 03:52:44

Last Modified: 2026-04-27 03:52:54