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Georgetown carefully announces findings of preliminary resveratrol/Alzheimer’s study

WASHINGTON (Sept. 11, 2015) — 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 results, published online today in Neurology, “are very interesting,” says the study’s 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. “This is a single, small study with findings that call for further research to interpret properly.”

The resveratrol clinical trial was a randomized, phase II, placebo-controlled, double blind study in 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 study enrolled 119 participants. The highest dose of resveratrol tested was one gram by mouth twice daily — equivalent to the amount found in about 1,000 bottles of red wine.

John Bozza, 80, participated in the study. 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 says. “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 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 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 (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.

“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.

The study, funded by the National Institute on Aging and conducted with the Alzheimer’s 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.

“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,” 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 Center

Georgetown 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’s 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.

Resveratrol impacts Alzheimer's disease biomarker

Our Review Summary

Resveratrol is an antioxidant compound found in grapes and red wine.

Resveratrol is an antioxidant compound found in grapes and red wine.

This news release from Georgetown University Medical Center does a thorough job laying out the main points of a resveratrol phase II clinical trial. It reasonably talks about the study’s findings and design, while cautioning readers on how researchers must pursue further studies before recommending the drug.

Given this cautious overall framing, we view the release’s omissions as relatively minor. One concern is that the release could have put the potential benefits and the harms into better perspective. For example, readers aren’t told how much levels of the biomarker (Abeta40) would normally decrease in Alzheimer’s patients and how this compares to what was found in the study. Readers also don’t know how many patients suffered from side effects from the concentrated supplement. It would also be interesting to know what existing Alzheimer’s drugs already on the market can do and how resveratrol might compare.

But for the most part, this news release – including its use of language – was appropriately tempered and very informative, hitting home the message that these research findings are preliminary.

Note: We also looked at how this study was covered by Time magazine and CNN, and compared the framing of the results in this news release vs. the subsequent stories. 


Why This Matters

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills. It is a condition associated with aging, since most symptoms appear when people hit their mid-60s. Estimates vary, but experts suggest that more than 5 million Americans may have Alzheimer’s, according to the National Institute on Aging.

Many of these treatments concentrate not on reversing the disease, but on helping people maintain mental function, manage behavioral symptoms, and slow or delay disease progression. In addition, drugs on the market help only some patients and may be effective for only a limited amount of time.

Consequently, any research highlighting a new drug candidate that prevents Alzheimer’s or delays its onset would be newsworthy for both patients and clinicians. Since Alzheimer’s is also a complex disease, having a variety of treatment options would also prove to be beneficial.


Does the news release adequately discuss the costs of the intervention?

Not Applicable

Although resveratrol is found in some foods, it was tested here as an investigational new drug. This means that it is not available commercially in 1-gram pills. The news release points out this fact, which is why we rate this Not Applicable.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

The news release does a good job explaining how Abeta40 levels were stabilized in patients taking resveratrol in its purified form, pointing out that those “treated with increasing doses of resveratrol over 12 months showed little or no change” in the biomarker.

But we wish the news release could have quantified, or at least provided some indication as to the importance of, the decrease in Abeta40 seen in patients with worsening dementia. How big is the decline in levels? And is there a significant difference between that level and the baseline point?

It would also have been great to see the caveat noted later in the piece (“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.) mentioned sooner in the release. By talking about this biomarker in the lead sentence, the clear implication is that the finding suggests a benefit — only several paragraphs later do we learn that this isn’t necessarily the case.

Does the news release adequately explain/quantify the harms of the intervention?


The news release mentions resveratrol’s most common side effects, which include nausea, diarrhea and weight loss. It would have been helpful to know how commonly these effects occurred. It also lists loss of brain volume as an effect, but states it could interpreted as either a benefit (since it could have reduced inflammation) or harm.

Does the news release seem to grasp the quality of the evidence?


The news release does a thorough job describing the context, significance and design of the study. It mentions the resveratrol clinical trial was a “randomized, phase II, placebo-controlled, double blind study in patients with mild to moderate dementia due to Alzheimer’s disease.” It talks about why the researchers chose to study resveratrol (because it activates compounds known as sirtuins) and why the study is significant (the trial was the largest, longest and highest dose trial of resveratrol in humans to date).

But as noted above, we can almost always find suggestions for improvement. The study’s primary objective was to determine whether resveratrol was safe and tolerated at the 1-gram oral dose – not to see whether it was effective in the treatment of dementia in people with Alzheimer’s. The release might have briefly explained the purpose of a phase II trial, as we felt this was not clear enough in the news release.

In addition, the fact that resveratrol levels stabilize in these patients does not necessarily translate into better health, like prolonged life and better cognitive function. The use of the patient anecdote and of the word “cure” in one of the comments could give readers the wrong impression. The news release could have been a bit clearer when cautioning readers on extrapolating surrogate markers to primary outcomes, even though Turner is quoted as saying, “…still, we can’t conclude from this study that the effects of resvertrol treatment are beneficial.”

But again, we applaud the release’s overall careful characterization of the study, including that the findings “cannot be used to recommend resveratrol.” In a couple of instances, the release calls for further research.

Does the news release commit disease-mongering?


There is no disease mongering in the news release. And the news release did a nice job bringing in a patient/family story, though it might have been helpful to describe the symptoms associated with mild Alzheimer’s to place this story in context.

Does the news release identify funding sources & disclose conflicts of interest?


The news release discloses the funding source, which was the National Institute on Aging. The study’s principal investigator R. Scott Turner, according to the disclosure statement attached to the original journal article, states he has received research support from Ceregene, Eli Lilly, Merck, Biogen Idec, Toyama, Elan/Transition Therapeutics and Pfizer, as well as the NIH and the DOD. The news release doesn’t list these disclosures, and says only that that Dr. Turner “reports no personal financial interests related to the study.”

We’d argue that it would have been better to list those disclosures in the news release, since they were deemed important enough to include the journal manuscript. But since we couldn’t easily find any indication that these companies are developing resveratrol-based drugs — which would be a clear conflict of interest — we’ll give the benefit of the doubt and rule this Satisfactory.

Does the news release compare the new approach with existing alternatives?

Not Satisfactory

It would have been helpful to know what standard treatments for Alzheimer’s are and how resveratrol could compare with these drugs in the future. According to the National Institute on Aging, several other drugs on the market – like Donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®) – may help slow down cognitive decline, but do not change the underlying disease process. The release could have discussed the lack of great treatments, further supporting the importance of this work.

Does the news release establish the availability of the treatment/test/product/procedure?


The news release states resveratrol is not available commercially in the 1-gram oral form.

Does the news release establish the true novelty of the approach?


The news release sends a clear message in the first paragraph on what this clinical trial brings to the existing body of knowledge. “The study Turner led… is the largest, longest and highest dose trial of resveratrol in humans to date,” it states.

The release also does a nice job of mentioning other research applications of resveratrol.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?


The news release uses appropriate, neutral language and steers clear (for the most part) of sensational wording. The only potential deviation comes from the patient family quote, where the quoted individual talks about wanting to find a “cure.” The release in no way suggests that resveratrol might be such a cure, however we’re not sure that the quotation adds much in the way of value to the release.

Total Score: 7 of 9 Satisfactory


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