Resveratrol stabilises Alzheimer’s disease biomarker

A clinical trial studying high-dose resveratrol long-term in people with mild to moderate Alzheimer’s disease found that a biomarker that declines when the disease progresses was stabilised in people who took the purified form of resveratrol.

Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate and some red wines.

The results “are very interesting” says the study’s principal investigator, R. Scott Turner, MD, PhD, director of the Memory Disorders Programme at Georgetown University Medical Centre. Turner cautions that the findings cannot be used to recommend resveratrol. “This is a single, small study with findings that call for further research to interpret properly.”

The resveratrol clinical trial was a randomised, Phase II, placebo-controlled, double blind study in patients with mild to moderate dementia due to Alzheimer’s disease. The study enrolled 119 participants. The highest dose of resveratrol tested was one gram by mouth twice daily – equivalent to the amount found in about 1,000 bottles of red wine.

Patients treated with resveratrol showed little change in amyloid-beta40

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 explains. “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.”

The researchers studied resveratrol because it activates proteins called sirtuins, the same proteins activated by caloric restriction. The biggest risk factor for developing Alzheimer’s is aging, and studies with animals found that most age-related diseases can be prevented or delayed by long-term caloric restriction.

Resveratrol-treated patients lost brain volume

One outcome in particular was confounding, Turner notes. 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. A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials,” Turner adds. A working hypothesis is that the treatments may reduce inflammation (or brain swelling) found with Alzheimer’s.

Further studies, including analysis of frozen blood and cerebrospinal fluid taken from patients, are underway to test possible drug mechanisms.

“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,” Turner said.