August 2012

The grape divide

You’ve probably heard the adage “an apple a day keeps the doctor away.” But what about a glass of wine a day? Better yet, what about 1,000 bottles of wine a day?! In a national phase II clinical trial, researchers will be testing the equivalent amount of resveratrol, a compound found in red wine, to determine its effects on individuals with Alzheimer’s disease. Over the past few years, researchers have begun to support the postulation that grapes and their fermentation products affect the symptoms of the disease.

According to the National Institute on Aging, Alzheimer’s disease, the most common form of dementia in the elderly, affects nearly 5.1 million Americans. It is a disease with a slow progression beginning with mild memory loss and ending with severe brain damage and death. The cause of Alzheimer’s is not fully understood, but a hallmark of the disease is the accumulation of amyloid beta (Aβ) protein in the brain. Insoluble Aβ protein clusters form “plaques” known as oligomers that in excess become toxic. This can disrupt normal brain function, causing the cognitive decline associated with the disease. The drugs that are available to treat Alzheimer’s are not very effective and produce only modest and temporary effects.

The aforementioned clinical trial, which involves 26 academic institutions, is the first of its kind and will take place over the next couple of months. Although the red wine compound has received a lot of attention for ameliorating the neurodegenerative processes involved in Alzheimer’s (here’s a quick search of Journal of Biological Chemistry articles about the compound), some say its practical relevance may be deceiving, as implied by the whopping 1,000-bottles-of-wine-a-day dose used in the clinical study.

Giulio Pasinetti, a professor of neuroscience at Mount Sinai School of Medicine who is not involved in the clinical study, emphasizes that “despite all the information and the discussion and broadcasting (about resveratrol) … it is found in grapes in very miniscule amounts. So it would be impossible to have a diet that would be perceived as a supplement for resveratrol.”

Pasinetti’s research instead focuses on the commercially available and naturally derived grape seed extract MegaNatural-AZ (MN). Grape seed extract is a polyphenolic compound that is also found in red wine. In their JBC article entitled “Effects of Grape Seed-derived Polyphenols on Amyloid β-Protein Self-assembly and Cytotoxicity,” his group expanded on a previous study that demonstrated that MN was able to attenuate the cognitive decline associated with Alzheimer’s disease, by elucidating the mechanism through which this occurs. Back in 2008, they demonstrate that not only is MN a highly effective inhibitor of Aβ protein assembly and oligomerization, but it also prevents the neurotoxic effects of the amyloid plaques that are typically associated with brain cell death.

So, you may be wondering: What’s the difference between resveratrol and grape seed extract? One of the biggest differences is the concentration at which the two compounds act in the human body. Grape-seed-derived polyphenolic compounds are able to reach the brain in nanomolar concentrations, much lower than that required for resveratrol, which, according to Pasinetti, “allows for the development of therapeutic applications.”

There is no question that there is a growing trend in research on the connection between diet and brain health. However, one can’t help but wonder: Are scientists focusing on the most therapeutically viable red wine compound? The answer, it seems, needs a bit more time to ripen.


Shannadora HollisShannadora Hollis ( received her B.S. in chemical engineering from North Carolina State University and is a Ph.D. student in the molecular medicine program at the University of Maryland, Baltimore. Her research focuses on the molecular mechanisms that control salt balance and blood pressure in health and disease. She is a native of Washington, D.C., and in her spare time enjoys cooking, thrift-store shopping and painting.


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