High-dose resveratrol stabilizes biomarker for Alzheimer's disease

A year-long clinical trial in people with mild to moderate Alzheimer’s disease found that high-dose resveratrol stabilized a biomarker for amyloid beta, which typically declines as Alzheimer’s disease progresses.

Resveratrol is a natural compound found in red grapes and red wine, as well as raspberries, peanuts, and dark chocolate. Previous research in mice showed that resveratrol decreased cognitive decline and Alzheimer’s disease (AD) pathology.

In this double-blind trial, published September 11, 2015 in Neurology, investigators enrolled 119 participants who were randomized to either placebo or escalating doses of pure synthetic resveratrol. The highest dose tested was 1 g by mouth twice daily—which is the equivalent to the amount of resveratrol found in about 1,000 bottles of red wine.

Investigators wanted to test resveratrol’s safety in human subjects, as well as determine its effects on biomarkers and other outcomes. They looked at several AD biomarkers, including those for amyloid beta and tau.

Their investigation showed that patients treated with resveratrol had little change in amyloid-beta40 (Abeta40) levels in blood and cerebrospinal fluid (CSF) over 12 months (from 6,574 ng/mL to 6,513 ng/mL in CSF). In contrast, Abeta40 significantly decreased during the course of the study in subjects taking a placebo (from 6,560 ng/mL to 5,622 ng/mL in CSF).

“A decrease in Abeta40 is seen as dementia worsens and Alzheimer’s disease progresses; still, we can’t conclude from this study that the effects of resveratrol treatment are beneficial,” said the study’s principal investigator, R. Scott Turner, MD, PhD, director of the Memory Disorders Program at Georgetown University Medical Center, in Washington, DC.

In terms of functional outcomes, measurements of activities of daily living (ADL) declined in both groups, but to a lesser extent in the subjects taking resveratrol than those in the placebo group, indicating less decline in ADL with treatment. Also, patients taking resveratrol lost some weight while those on placebo gained weight.

One finding of the study was particularly perplexing: Resveratrol-treated patients lost more brain volume than those in the placebo-treated group, as seen on volumetric MRI scans. This finding remained even after investigators excluded patients who had weight loss. The loss of brain volume in these participants was not associated with cognitive or functional decline, the researchers noted.

“We’re not sure how to interpret this finding. A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials,” Dr. Turner added. A working hypothesis is that the treatment may reduce inflammation found with Alzheimer’s.

Although the results are promising, this study wasn’t designed to determine whether resveratrol provided a benefit.

“Now we need to do the larger and longer, more definitive phase 3 study of resveratrol to see if it’s really effective for patients with Alzheimer’s disease,” Dr. Turner said. “I would not advise that patients start taking this now.”