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Clinical Trial
. 2015 Oct 20;85(16):1383-91.
doi: 10.1212/WNL.0000000000002035. Epub 2015 Sep 11.

A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease

R Scott Turner  1 , Ronald G Thomas  2 , Suzanne Craft  2 , Christopher H van Dyck  2 , Jacobo Mintzer  2 , Brigid A Reynolds  2 , James B Brewer  2 , Robert A Rissman  2 , Rema Raman  2 , Paul S Aisen  2 ; Alzheimer's Disease Cooperative Study
Collaborators, Affiliations
Clinical Trial

A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease

R Scott Turner et al. Neurology. .

Abstract

Objective: A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes).

Methods: Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52.

Results: Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo.

Conclusions: Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood-brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment.

Classification of evidence: This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated.

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Figures

Figure 1
Figure 1. Flow diagram and disposition of the treatment groups
MMSE = Mini-Mental State Examination.
Figure 2
Figure 2. Effects of resveratrol on Aβ levels
Resveratrol altered levels of CSF Aβ40 (A) and plasma Aβ40 (B) (ng/mL, mean ± SE). Similar but nonsignificant trends were found for CSF Aβ42 (C) and plasma Aβ42 (D) (ng/mL, mean ± SE). Note difference in scales. Sample sizes are indicated.
Figure 3
Figure 3. Effects of resveratrol on brain volume
Resveratrol increased brain volume loss (A, C) (mL, mean ± SE) with a corresponding increase in ventricular volume (B, D) (mL, mean ± SE). Sample sizes are indicated.
See this image and copyright information in PMC

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