Largest ever human trial shows resveratrol impacts Alzheimer’s biomarker.

Alzheimer’s is the most common form of dementia, causing problems with memory, thinking and behaviour.  Symptoms usually develop slowly and get worse over time as it is a progressive disease; becoming severe enough to interfere with daily tasks.  As Alzheimer’s progresses, problems with memory loss, communication, reasoning and orientation become more severe. The person will need more day-to-day support from those who care for them.

There is currently no cure for Alzheimer’s disease, but there is a lot that can be done to enable someone to live well with the condition. This will involve pharmaceutical, psychiatric support and activities.  However, this will alleviate the condition not avoid it, therefore multiple research programmes around the world are working towards a cure for this disease.  Now, a study from researchers at Georgetown University shows that long-term resveratrol usage in people with mild to moderate Alzheimer’s disease causes a biomarker to stabilise which would normally decline as the disease progresses.  The opensource study is published in the journal Neurology.

Resveratrol is a member of a group of plant compounds called polyphenols. These naturally compounds are thought to have antioxidant properties, protecting the body against the kind of damage linked to increased risk for conditions such as cancer and heart disease. Resveratrol is found in foods such as red grapes, peanuts, raspberries, dark chocolate and some red wines.  The researchers studied resveratrol because earlier studies have shown that it activates proteins called sirtuins, the same proteins activated by caloric restriction. The biggest risk factor for developing Alzheimer’s is aging.  Previous studies in animals have found that most age-related diseases, including Alzheimer’s, can be prevented or delayed by long-term caloric restriction such as consuming two-thirds the normal caloric intake.

The current study was a randomized, phase II, placebo-controlled, double blind study in patients with mild to moderate dementia due to Alzheimer’s disease.  The study enrolled 119 participants with resveratrol administered orally on a twice daily basis.  Results showed that 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, data findings showed that those taking a placebo had a decrease in the levels of Abeta40 compared with their levels at the beginning of the study.

The team explain that a decrease in Abeta40 is seen as dementia worsens and Alzheimer’s disease progresses; they note that it can’t be concluded from this study that the effects of resveratrol treatment are beneficial.  However, they go to add that it does appear that resveratrol was able to penetrate the blood brain barrier, as resveratrol was measured in both blood and cerebrospinal fluid.

Results also found that resveratrol was safe and well tolerated. The most common side effects experienced by participants were gastrointestinal-related, including nausea and diarrhea. Also, patients taking resveratrol experienced weight loss while those on placebo gained weight.  The researchers also 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.  Data findings show that a similar decrease in brain volume was found with some anti-amyloid immunotherapy trials. A working hypothesis from the lab is that the treatments may reduce inflammation (or brain swelling) found with Alzheimer’s which would also insinuate that microglia is heavily involved in the disorder.

The team surmise that the study is the largest, longest and highest dose trial of resveratrol in humans to date with promising results, however; at this stage the findings cannot be used to recommend resveratrol.  They go on to conclude that 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.  For the future, further studies, including analysis of frozen blood and cerebrospinal fluid taken from patients, are underway to test possible drug mechanisms.

Source:  Georgetown University Medical Center