Resveratrol shows benefit in Alzheimer`s phase 2 trial

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - A biomarker that declines as Alzheimer's disease progresses was stabilized in patients who took resveratrol in a phase II trial.

In people with mild to moderate AD who took purified synthetic resveratrol for one year, the cerebrospinal fluid and plasma biomarker amyloid beta40 (Abeta40) declined significantly less than in the placebo group, the study authors reported online September 11 in Neurology.

"Abeta40 was stabilized in blood and CSF in those who took resveratrol. We proved that resveratrol penetrated the blood-brain barrier to affect the brain and that high doses were safe and well tolerated in older patients with Alzheimer's disease," Dr. R. Scott Turner, director of the Memory Disorders Program at Georgetown University Medical Center in Washington, DC, told Reuters Health by email.

"This opens the door to a new Alzheimer's disease treatment strategy because amyloid proteins are depleted in CSF as dementia commences and worsens," he said.

"These findings will have no impact on patient care," Dr. Turner cautioned. "This phase 2 study was conducted in preparation for a Phase 3 trial to test effectiveness. We are not recommending resveratrol supplements on the market, which are unregulated, and have unknown and variable quantities of resveratrol. Nor are we recommending more than one glass of red wine daily, although several studies have shown that a Mediterranean diet may delay the onset of dementia."

The double-blind 52-week Alzheimer's Disease Cooperative Study of resveratrol involved patients older than 49 with mild to moderate AD. The researchers examined resveratrol's safety and tolerability and its effects on the biomarkers plasma Abeta40 and Abeta42, CSF Abeta40, Abeta42, tau, and phospho-tau 181.

At 26 U.S. medical centers, 64 participants took daily oral resveratrol capsules, starting at 500 mg and increasing their doses every 13 weeks until they reached 2,000 mg daily, which Dr. Turner stated in a press release is "equivalent to about a thousand bottles of red wine per day." Fifty-five participants received placebo.

The patients underwent volumetric brain MRI and CSF collection at baseline and at 52 weeks. In addition, the researchers performed detailed pharmacokinetic studies on 15 participants at baseline and at weeks 13, 26, 39, and 52.

At week 52, CSF Abeta40 had declined from 6574 to 6513 ng/mL in the treated group and from 6560 to 5622 ng/mL in the placebo group (p=0.002).

This difference persisted in secondary analyses of study completers (p=0.002), in the mild dementia subgroup (p=0.01), and in APOE4 carriers (p=0.05) and noncarriers (p=0.01).

Plasma Abeta40 dropped from 163 to 153 ng/mL in the treated group and from 165 to 132 ng/mL with placebo (p=0.024).

Surprisingly, brain volume (excluding CSF, brainstem, and cerebellum) decreased more in the treatment group (p=0.025), with an increase in ventricular volume (p=0.05) at week 52.

Specifically, in the treatment group, mean brain volume fell from 866 to 839 mL, and mean ventricular volume increased from 55 to 81 mL. Mean brain volume in the placebo group decreased from 850 to 840 mL, and mean ventricular volume rose from 56 to 76 mL.

"The brain volume results were surprising. We did not expect more atrophy with resveratrol treatment, but this is being found with immunotherapy trials of AD as well," Dr. Turner said.

He added that the major side effect in the resveratrol group was about two pounds of weight loss. Other common adverse events were nausea and diarrhea.

Dr. Neelum T. Aggarwal, associate professor in the Rush Alzheimer's Disease Center and Department of Neurological Sciences of Rush University Medical Center in Chicago and site principal investigator for the study, told Reuters Health by email, "This study is important for clinicians as it demonstrates that the scientific community is seriously looking at how nutrients found in food may alter disease states and/or cognitive functioning."

"As biomarkers for Alzheimer's disease become more sensitive, it is critical that we start to look at nutrition, at individual nutrients, and how they are linked to cognitive function and possibly to dementia," she advised.

"We are seeing high rates of cognitive decline in racially and ethnically diverse populations and we need to investigate potential treatments that are accessible to all," Dr. Aggarwal said. "That resveratrol is a natural compound found in various foods including grapes, berries, chocolate, peanuts, and red wine makes it a potential treatment accessible to many persons through food and diet and thus does not discriminate based on who can afford the treatment."

Dr. Aggarwal suggested that future studies include more diverse participants to identify any ethnic, racial, and sex differences in biomarkers and their responses to resveratrol.

The National Institute on Aging supported the study.

SOURCE: https://bit.ly/1KU3nTf

Neurology 2015.

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