A nationwide clinical trial has found that high doses of resveratrol stabilizes a biomarker that declines as Alzheimer’s disease progresses.
Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate, and some red wines.
The results are “very interesting,” according to the study’s principal investigator, R. Scott Turner, M.D., Ph.D., director of the Memory Disorders Program at Georgetown University Medical Center.
But Turner cautions that the findings cannot be used to recommend resveratrol — at least not yet.
“This is a single, small study with findings that call for further research to interpret properly,” he noted.
The clinical trial was a randomized, placebo-controlled, double blind study with 119 patients with mild to moderate dementia due to Alzheimer’s disease.
An “investigational new drug” 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 researchers noted.
The highest dose of resveratrol tested was one gram by mouth twice daily, which is equivalent to the amount found in about 1,000 bottles of red wine.
One of the participants in the study was John Bozza, 80. Five years ago, his wife, Diana, began noticing “something wasn’t quite right.” He was diagnosed with mild cognitive impairment, but only a year later, his condition progressed to mild Alzheimer’s.
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.
“I definitely want the medical community to find a cure,” she said. “And of course I thought there’s always a chance that John could have been helped, and who knows, maybe he was.”
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 their blood and cerebrospinal fluid, according to the study’s findings.
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,” Turner said. “Still, we can’t conclude from this study that the effects of resveratrol treatment are beneficial. 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.”
According to Turner, the researchers studied resveratrol because it activates proteins called 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. That means consuming two-thirds the normal caloric intake, the researchers explained.
According to Turner, the study also found that resveratrol was safe and well-tolerated. The most common side effects experienced were gastrointestinal-related, including nausea and diarrhea. Patients taking resveratrol also experienced weight loss while those on the placebo gained weight, he reported.
However, there was one outcome that was particularly confounding, according to Turner. 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.
“We’re not sure how to interpret this finding,” he said. “A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials.”
A working hypothesis is that the treatments may reduce inflammation (or brain swelling) found with Alzheimer’s, he said.
Further studies, including analysis of frozen blood and cerebrospinal fluid taken from patients, are underway to test possible drug mechanisms.
“Given safety and positive trends toward effectiveness in this phase two study, a larger phase three study is warranted to test whether resveratrol is effective for individuals with Alzheimer’s or at risk for Alzheimer’s,” Turner said.
The study, supported by a grant from the National Institute on Aging, was published in Neurology.