In the Journals

Phase 2 study shows resveratrol safe, effective for Alzheimer's disease

Study findings in Neurology show that resveratrol penetrated the blood-brain barrier in individuals with Alzheimer’s disease to have central nervous system effects, providing class II evidence that resveratrol is safe, well-tolerated and affects some Alzheimer’s disease biomarkers.

Resveratrol is a stilbenoid found in the skin of grapes, blueberries, raspberries and mulberries, with highest levels detected in in red grapes, red grape juice, red wine, chocolate, tomatoes and peanuts, according to study researcher R. Scott Turner, MD, PhD, of Georgetown University.

R. Scott Turner, MD, PhD

R. Scott Turner

Turner and colleagues conducted a randomized, placebo-controlled, double-blind trial to assess the effect of resveratrol on plasma and cerebrospinal fluid levels of the biomarkers amyloid-beta (Aβ) 42 and Aβ40, and cerebrospinal fluid tau and phospho-tau 181, and on volumetric MRI outcomes. They also evaluated safety and tolerability of resveratrol.

Study participants (n = 119) were randomly assigned placebo or 500 mg of resveratrol once daily, with a dose escalation of 500 mg every 13 weeks, ending with 1,000 mg twice daily. Brain MRI and cerebrospinal fluid collection were conducted at baseline and after treatment completion. A subset of 15 participants underwent detailed pharmacokinetics at baseline and weeks 13, 26, 39 and 52.

Researchers were able to measure resveratrol and its major metabolites in plasma and cerebrospinal fluid. There were greater declines in levels of Aβ40 in the cerebrospinal fluid and plasma among individuals in the placebo group compared with those who received resveratrol, which resulted in a significant difference at week 52.

Interestingly, researchers found that individuals who received resveratrol had greater declines in brain volume than individuals who received placebo, according to pre- and post-treatment brain scans.

“We’re not sure how to interpret this finding,” Turner said in a press release. “A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials.”

The most common adverse events were nausea, diarrhea and weight loss.

“We proved that high doses of resveratrol were safe and well-tolerated in older individuals with Alzheimer’s disease. The major side effect was weight loss (about 2 pounds over 12 months in the resveratrol-treated group),” Turner told Healio.com/Psychiatry. “We are not recommending resveratrol supplements or consuming more than one glass of red wine daily. However, several studies have shown that a Mediterranean diet may delay the onset of dementia.”

“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 said in the press release. –by Amanda Oldt

Disclosure: Turner reports receiving research support from Ceregene, Eli Lilly, Merck, Biogen Idec, Toyama, Elan/Transition Therapeutics and Pfizer, as well as the NIH (NIA U01 AG10483) and the U.S. Department of Defense. Please see the full study for a list of all authors’ relevant financial disclosures.

Study findings in Neurology show that resveratrol penetrated the blood-brain barrier in individuals with Alzheimer’s disease to have central nervous system effects, providing class II evidence that resveratrol is safe, well-tolerated and affects some Alzheimer’s disease biomarkers.

Resveratrol is a stilbenoid found in the skin of grapes, blueberries, raspberries and mulberries, with highest levels detected in in red grapes, red grape juice, red wine, chocolate, tomatoes and peanuts, according to study researcher R. Scott Turner, MD, PhD, of Georgetown University.

R. Scott Turner, MD, PhD

R. Scott Turner

Turner and colleagues conducted a randomized, placebo-controlled, double-blind trial to assess the effect of resveratrol on plasma and cerebrospinal fluid levels of the biomarkers amyloid-beta (Aβ) 42 and Aβ40, and cerebrospinal fluid tau and phospho-tau 181, and on volumetric MRI outcomes. They also evaluated safety and tolerability of resveratrol.

Study participants (n = 119) were randomly assigned placebo or 500 mg of resveratrol once daily, with a dose escalation of 500 mg every 13 weeks, ending with 1,000 mg twice daily. Brain MRI and cerebrospinal fluid collection were conducted at baseline and after treatment completion. A subset of 15 participants underwent detailed pharmacokinetics at baseline and weeks 13, 26, 39 and 52.

Researchers were able to measure resveratrol and its major metabolites in plasma and cerebrospinal fluid. There were greater declines in levels of Aβ40 in the cerebrospinal fluid and plasma among individuals in the placebo group compared with those who received resveratrol, which resulted in a significant difference at week 52.

Interestingly, researchers found that individuals who received resveratrol had greater declines in brain volume than individuals who received placebo, according to pre- and post-treatment brain scans.

“We’re not sure how to interpret this finding,” Turner said in a press release. “A similar decrease in brain volume was found with some anti-amyloid immunotherapy trials.”

The most common adverse events were nausea, diarrhea and weight loss.

“We proved that high doses of resveratrol were safe and well-tolerated in older individuals with Alzheimer’s disease. The major side effect was weight loss (about 2 pounds over 12 months in the resveratrol-treated group),” Turner told Healio.com/Psychiatry. “We are not recommending resveratrol supplements or consuming more than one glass of red wine daily. However, several studies have shown that a Mediterranean diet may delay the onset of dementia.”

“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 said in the press release. –by Amanda Oldt

Disclosure: Turner reports receiving research support from Ceregene, Eli Lilly, Merck, Biogen Idec, Toyama, Elan/Transition Therapeutics and Pfizer, as well as the NIH (NIA U01 AG10483) and the U.S. Department of Defense. Please see the full study for a list of all authors’ relevant financial disclosures.