High-dose resveratrol intake linked to stabilised Alzheimer’s biomarker

By Nathan Gray contact

- Last updated on GMT

Very high doses of synthetic, pharmaceutical grade, resveratrol could help to stabilise certain biomarkers associated with cognitive impairment and Alzheimer's disease, according to the phase 2 clinical trial.
Very high doses of synthetic, pharmaceutical grade, resveratrol could help to stabilise certain biomarkers associated with cognitive impairment and Alzheimer's disease, according to the phase 2 clinical trial.

Related tags: Resveratrol, Clinical trial, Alzheimer

Long term intake of a high-dose resveratrol supplement or drug may help people with mild to moderate Alzheimer's disease to stabilise a biomarker that declines when the disease progresses, say researchers.

While the findings from the small-scale trial cannot definitively show that the pharmaceutical grade synthetic resveratrol is beneficial for those with Alzheimer’s disease, the results of the randomised, phase II, placebo-controlled, double blind study “are very interesting”,​ said lead investigator Dr R. Scott Turner of Georgetown University Medical Center.

Published in Neurology​, the trial data suggests Alzheimer’s patients who were treated with increasing doses of resveratrol over 12 months showed little or no change in amyloid-beta40 (Abeta40) levels in blood and cerebrospinal fluid. In contrast, those taking a placebo had a decrease in the levels of Abeta40 compared with their levels at the beginning of the study.

"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,"​ Turner explained. "It does appear that resveratrol was able to penetrate the blood brain barrier, which is an important observation. Resveratrol was measured in both blood and cerebrospinal fluid."

"Given safety and positive trends toward effectiveness in this phase 2 study, a larger phase 3 study is warranted to test whether resveratrol is effective for individuals with Alzheimer's -- or at risk for Alzheimer's,"​ he added.

Resveratrol trial

The study, funded by the National Institute on Aging and conducted with the Alzheimer's Disease Cooperative Study, began in 2012 and ended in 2014. An investigational new drug application was required by the U.S. Food and Drug Administration to test the synthetic pharmaceutical-grade resveratrol (produced by Aptuit Laurus, Inc) in the study – which is not available commercially in this form.

The study enrolled 119 participants with mild to moderate Alzheimer's disease. The highest dose of resveratrol tested was one gram by mouth twice daily – which is equivalent to the amount of resveratrol found in about 1,000 bottles of red wine.

Turner said the study found that resveratrol was safe and well tolerated. The most common side effects experienced by participants were gastrointestinal-related, including nausea and diarrhea.

They found that resveratrol and its major metabolites penetrated the blood–brain barrier, and had effects on the central nervous system (CNS).

In addition to finding that levels of Abeta40 were stabilised and remained high compared to those on placebo, Turner noted that one particular outcome seemed to be confounding; The researchers obtained brain MRI scans on participants before and after the study, and found that resveratrol-treated patients lost more brain volume than the placebo-treated group.

"We're not sure how to interpret this finding,” ​said Turner.

“A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials,"​ he commented – noting that a working hypothesis is that the treatments may reduce inflammation (or brain swelling) found with Alzheimer's.

The team noted that further studies, including analysis of frozen blood and cerebrospinal fluid taken from patients, are underway to test possible mechanisms.

Source: Neurology
Published online ahead of print, Open Access, doi: 10.1212/WNL.0000000000002035
“A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease”
Authors: R. Scott Turner, et al

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