The largest nationwide clinical trial to study 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 stabilized 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 resveratrol clinical trial was a randomized, phase II, placebo-controlled, double blind study in 119 patients with mild to moderate dementia due to Alzheimer’s disease. An “investigational new drug” application was required by FDA to test the pure synthetic (pharmaceutical-grade) resveratrol in the study. It is not available commercially in this form.The highest dose of resveratrol tested was 1g by mouth twice daily = to amount in 1,000 bottles of red wine.
Patients, like John, 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 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 -including Alzheimer’s -can be prevented or delayed by long-term caloric restriction (consuming 2/3 the normal caloric intake).
The resveratrol was safe and well tolerated. The most common side effects experienced by participants were gastrointestinal-related, including nausea and diarrhea. Patients on resveratrol also had weight loss while those on placebo gained weight. Brain MRI scans on participants before and after the study, 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. http://gumc.georgetown.edu/news/resveratrol-impacts-alzheimers-disease-biomarker
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