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

Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA · Neurology

Resveratrol and its metabolites crossed into cerebrospinal fluid, confirming central exposure. CSF and plasma Abeta40 declined more on placebo than on resveratrol (CSF 6,560 to 5,622 ng/mL on placebo against 6,574 to 6,513 on drug, p=0.002), a between-group difference at 52 weeks whose meaning the authors leave open. Brain volume loss was greater on resveratrol, and stayed so after excluding participants who lost weight. Cognition did not differ on CDR-SOB, ADAS-cog, MMSE or NPI, in a trial underpowered for them; activities of daily living declined less on resveratrol (63.7 to 57.4 against 60.5 to 51.3, p=0.03), from arms that started three points apart. The commonest adverse events were nausea, diarrhoea and weight loss.

Population

Adults with mild to moderate Alzheimer disease

Intervention

Resveratrol escalated from 500 mg once daily to 1,000 mg twice daily over 52 weeks

Comparator

Placebo

Limitations

Phase 2 with more than two primary outcomes, which the journal graded down to Class II evidence, and explicitly underpowered for clinical outcomes. The accelerated brain-volume loss was unexpected and remains unexplained — the authors note it tracked no cognitive or functional decline — and the daily-living result is a secondary outcome from arms that differed at baseline. No confirmatory trial has been run.