Resveratrol is a compound that occurs naturally in certain foods, including the skin of grapes and red wine. It is also found in grape juice, peanuts, cocoa, and berries such as blueberries and cranberries.

Researchers’ interest in resveratrol was sparked when studies in the 1990s found health benefits to drinking moderate amounts of red wine, including the possibility of a lower risk of dementia. Ongoing clinical studies into its possible benefits in Alzheimer’s patients, however, are limited.

How resveratrol works

Scientists are still trying to understand how resveratrol works in the body, and whether it might help prevent or treat Alzheimer’s disease.

In some preclinical studies, resveratrol decreased the amount of beta-amyloid protein in cells grown in laboratories and in the brains of mice by promoting the breakdown of the protein. Beta-amyloid forms the plaques that are characteristic of Alzheimer’s disease.

Another theory is that resveratrol mimics the effect of restricting calorie intake. A low-calorie diet has been found in animal studies to prevent or delay the onset of age-related diseases, including Alzheimer’s. A low-calorie diet appears to activate a class of enzymes known as sirtuins, and resveratrol seems to have the same effect.

Resveratrol in clinical trials

A Phase 2 clinical trial (NCT01504854), completed in 2014, included 119 patients with mild to moderate Alzheimer’s disease. Participants took capsules containing placebo or resveratrol, starting with a dose of 500 mg a day and increasing to 1 gram twice a day.

Researchers measured participants’ blood levels of beta-amyloid-40, a protein that typically decreases in the blood as Alzheimer’s disease progresses. Patients treated with resveratrol showed little to no change in beta-amyloid-40 blood levels, while a decrease was observed in the placebo group. Results of the study were published in the journal Neurology in 2015 and discussed further in an article published in the Annuals of the New York Academy of Sciences in 2017.

An analysis of 19 participants from each of the resveratrol and placebo groups also showed evidence that resveratrol restores the integrity of the blood-brain barrier, whose role is to restrict the movement of molecules and cells between the blood system and the brain. The blood-brain barrier can start to break down when high levels of a protein called matrix metalloproteinase-9 (MMP-9) are present.

Patients treated with resveratrol had a fifty percent reduction in MMP-9 levels in their cerebrospinal fluid (the fluid that surrounds the brain and spinal cord). These findings were published in the Journal of Neuroinflammation in 2017.

Another clinical trial (NCT01716637), sponsored by the Life Extension Foundation, tested the effect of a multi-ingredient dietary supplement that included resveratrol in about 12 participants with mild to moderate Alzheimer’s disease. The supplement was administered alone or in addition to Enbrel (etanercept), a medicine used to treat autoimmune disorders, which was injected into tissues close to the spinal column (peri-spinally). The participants’ scores on cognitive tests were tracked. The Phase 1 pilot study was completed in May 2016 but results have not been reported.

Another Phase 1 study (NCT02502253) is testing a combination of resveratrol and grape seed polyphenolic extract in patients with prediabetes or type 2 diabetes and Mild Cognitive Impairment, who are also at risk for prodromal (early-onset) Alzheimer’s disease.   The study is co-sponsored by Johns Hopkins University and the Icahn School of Medicine at Mount Sinai.  The trial will compare three different dosages of the drug combination in an estimated 48 patients

 

Last updated: Aug. 17, 2019

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