A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 26362286 · doi:10.1212/WNL.0000000000002035
What was done
A 52-week multicenter, randomized, double-blind, placebo-controlled phase 2 trial evaluated the safety, tolerability, biomarker effects, and volumetric MRI changes of oral resveratrol in 119 individuals with mild to moderate Alzheimer disease. Resveratrol was initiated at 500 mg once daily and escalated by 500-mg increments every 13 weeks to a maximum of 1,000 mg twice daily. Biomarkers measured at baseline and week 52 included plasma and CSF Aβ40, Aβ42, tau, and phospho-tau 181. Pharmacokinetics were assessed in a subset of 15 participants.
What was found
Resveratrol and its major metabolites were detected in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 declined more in the placebo group than in the resveratrol group, resulting in a significant difference at week 52 (exact numerical values not reported in the abstract). Brain volume loss was greater in the resveratrol-treated group compared with placebo.
Why it matters
This trial demonstrates that oral resveratrol crosses the human blood-brain barrier and modifies central Alzheimer biomarker trajectories over one year, though paradoxical findings such as accelerated brain volume loss complicate interpretation.
Limits
The abstract does not provide numerical values, confidence intervals, or p-values for any biomarker, volumetric, or clinical outcome. Sample size was small (n = 119) and primarily designed for safety and biomarker discovery rather than clinical efficacy. The clinical significance and mechanism of increased brain volume loss remain unknown.
Cited by
- contradicts Phase 1 and Phase 2 clinical trials in Alzheimer's disease showed that resveratrol at doses of 500 mg or 1,000 mg daily reduced cerebrospinal fluid amyloid-beta 42 and improved cognitive function.