Resveratrol for Alzheimer Disease
Jennifer Rose V. Molano, MD reviewing Turner RS et al. Neurology 2015 Sep 11.
Resveratrol was safe and well tolerated in patients with mild-to-moderate AD, but effects on biomarkers and clinical significance remain to be clarified.
Resveratrol, a polyphenol with potential antioxidant properties, has been associated with decreasing Alzheimer disease (AD) pathology in animal models. Data are limited in humans. In this randomized, double-blind, placebo-controlled, phase 2 clinical trial, researchers investigated the safety and efficacy of resveratrol in mild-to-moderate AD. Primary outcomes also included AD biomarkers, including plasma and cerebrospinal fluid (CSF) amyloid-beta 40 (Aβ40) and amyloid-beta 42 (Aβ42) levels, CSF tau and phospho-tau 181 levels, and volumetric magnetic resonance imaging (MRI) rates of change in the whole brain, ventricles, hippocampi, and entorhinal cortex.
Participants were randomized to receive resveratrol or placebo for 52 weeks, with follow-up every 6 to 7 weeks. The resveratrol group started on a dose of 500 mg daily and increased by 500 mg every 13 weeks, to a maximum dose of 1000 mg twice a day.
Fifty-six resveratrol recipients and 48 placebo recipients completed the study. Of 77 participants with CSF data at both baseline and 52 weeks, significantly greater decreases were seen in the placebo group versus the resveratrol group in plasma Aβ40 levels (from 165 to 132 ng/mL vs. from 163 to 153 ng/mL) and CSF Aβ40 levels (6560 to 5622 ng/mL vs. 6574 to 6513 ng/mL). There were no significant differences in other CSF outcomes, including Aβ42 levels. On MRI, the resveratrol group had greater rates of whole brain volume loss (866 to 839 mL vs. 850 to 840 mL; P = 0.025) and increase in ventricular volume (55 to 81 mL vs. 56 to 76 mL; P = 0.05) than the placebo group. There were no serious drug-related adverse effects; the most common adverse effects were nausea, diarrhea, and weight loss. The study was underpowered to fully assess clinical and functional outcomes.
Citation(s):
Turner RS et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 2015 Sep 11; [e-pub].
