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

The results, published online today in Neurology, 鈥渁re very interesting,鈥� says the study鈥檚 principal investigator, R. Scott Turner, MD, PhD, director of the Memory Disorders Program at Georgetown University Medical Center. Turner, who treats patients at MedStar Georgetown University Hospital, cautions that the findings cannot be used to recommend resveratrol. 鈥淭his is a single, small study with findings that call for further research to interpret properly.鈥�

The resveratrol clinical trial was a randomized, phase II, placebo-controlled, double blind study in patients with mild to moderate dementia due to Alzheimer鈥檚 disease. An 鈥渋nvestigational new drug鈥� application was required by the U.S. Food and Drug Administration to test the pure synthetic (pharmaceutical-grade) resveratrol in the study. It is not available commercially in this form.

The investigators enrolled 119 participants for the one-year study. The highest dose of resveratrol tested was one gram by mouth twice daily 鈥� equivalent to the amount found in about 1,000 bottles of red wine.

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.

鈥淎 decrease in Abeta40 is seen as dementia worsens and Alzheimer鈥檚 disease progresses; still, we can鈥檛 conclude from this study that the effects of resveratrol treatment are beneficial,鈥� Turner explains. 鈥淚t 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.鈥�

John Bozza, 80, participated in the study. Five years ago, his wife, Diana, began noticing 鈥渟omething wasn鈥檛 quite right.鈥� He was diagnosed with mild cognitive impairment, but only a year later, his condition progressed to mild Alzheimer鈥檚. Diana, whose twin sister died from the same disease, says there are multiple reasons she and John decided to participate in the resveratrol study, and they now know he was assigned to take the active drug.

鈥淚 definitely want the medical community to find a cure,鈥� she says. 鈥淎nd of course I thought there鈥檚 always a chance that John could have been helped, and who knows, maybe he was.鈥�

The researchers studied resveratrol because it activates proteins called sirtuins, the same proteins activated by caloric restriction. The biggest risk factor for developing Alzheimer鈥檚 is aging, and studies with animals found that most age-related diseases鈥攊ncluding Alzheimer鈥檚鈥攃an be prevented or delayed by long-term caloric restriction (consuming two-thirds the normal caloric intake).

Turner says the study 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.

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. 鈥淲e鈥檙e not sure how to interpret this finding. A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials,鈥� Turner adds. A working hypothesis is that the treatments may reduce inflammation (or brain swelling) found with Alzheimer鈥檚.

The study, funded by the National Institute on Aging and conducted with the Alzheimer鈥檚 Disease Cooperative Study, began in 2012 and ended in 2014. GUMC was one of 21 participating medical centers across the U.S.

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

鈥淕iven 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鈥檚 鈥� or at risk for Alzheimer鈥檚,鈥� Turner says.

Resveratrol and similar compounds are being tested in many age-related disorders including cancer, diabetes and neurodegenerative disorders. The study Turner led, however, is the largest, longest and highest dose trial of resveratrol in humans to date.

The research was supported by a grant from the National Institute on Aging (U01 AG010483). Turner reports no personal financial interests related to the study.

About Georgetown University Medical CenterGeorgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC鈥檚 mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.###