Updated on December 22, 2004 at 4:30 p.m.
Posted on December 20, 2004 at 10:10 a.m.

BIRMINGHAM, AL — Health-food activists have long touted the value of taking grape seed extract. However, there has been little or no scientific evidence of the molecular basis for its benefits. Now, researchers at the University of Alabama at Birmingham (UAB) report the first direct evidence that the popular dietary supplement affects specific proteins in healthy brains in ways that may protect against future age-related dementia.

The finding, including the identities of the specific proteins, is published in the December 2004 issue of the Journal of Agricultural and Food Chemistry, which is found on the Web at pubs.acs.org/journals/jafcau/index.html.

“This is the first identification of specific molecules in mammalian tissues that are changed in response to oral intake of complex dietary supplements like grape seed extract,” said senior author Helen Kim, Ph.D., UAB research associate professor of pharmacology and toxicology, and senior scientist at the federally-funded Purdue-UAB Botanicals Center for Dietary Supplements Research.

Using new-era proteomics technology, Kim’s team analyzed global protein changes in the brains of rats fed a high, but non-toxic level, of grape seed extract (GSE) in their normal diet.

“The directions of the changes we measured were opposite to those measured by others for several of the same proteins in diseased brain tissue. This suggests that, in normal brains, this dietary supplement could protect against potentially pathologic changes that eventually lead to dementias,” Kim said.

“Our studies were carried out in relatively young adult rats — not aged or diseased — suggesting that taking grape seed extract and similar supplements could have effects before onset of disease later in life,” she added.

She cautioned that the results of the study do not prove that GSE protects against age-related development of dementias — “that would be too good to be true; a conservative interpretation would be that the results are consistent with our hypothesis, that taking GSE may be neuroprotective.”

Kim’s group has long been interested in the molecular basis for the purported health benefits of dietary supplements that are marketed for their anti-oxidant benefits.

The Purdue-UAB Botanicals Center for Dietary Supplements Research is one of several that were initiated by the National Institutes of Health Office of Dietary Supplements and the National Center for Complementary and Alternative Medicine four years ago. They were charged with investigating the properties and effects of dietary supplements.

Kim said that Americans currently spend billions of dollars on over-the-counter dietary supplements; several, including GSE, are thought to have health benefits due to their high content of polyphenolic compounds, which have been shown to have high antioxidant activity in laboratory experiments. “The molecular basis of the anti-oxidant activities in target tissues has only begun to be examined, however. We are looking forward to many more experiments suggested by these findings,” she said.

She cautioned that the results of the study do not prove that GSE protects against age-related development of dementias — “that would be too good to be true; a conservative interpretation would be that the results are consistent with our hypothesis, that taking GSE may be neuroprotective.”

Lead author Jessy Deshane, now in graduate school at UAB, was instrumental in carrying out the experiments in Kim’s lab. Identification of the brain proteins affected by GSE was based on two-dimensional protein electrophoretic separation followed by mass spectrometry. It was carried out in conjunction with the UAB Proteomics and Mass Spectrometry Shared Facility. which Kim co-directs with Stephen Barnes, Ph.D., associate director of the Botanicals Center and a co-author on both articles.

Kim noted that the statistical analysis of the protein separation data, enabled by Dr. Sreelatha Meleth, part of the UAB Comprehensive Cancer Center Biostatistics Shared Facility, was an important part of the overall analysis. “Too often, the statistical issues in a biological experiment are not given enough attention, with the consequence that the results don’t have as much significance as they could have had. We were fortunate to have had all the right people involved in this study,” Kim said.

In a separate study in the Journal of Nutrition, also published this month, Kim and some of the same colleagues found that GSE was protective in an animal model of breast cancer — but that the benefit did not show up when the dietary supplement was fed to rats in a diet based on milk-casein protein. It only showed up when GSE was given in a more crude, plant protein-based rodent diet.

Another dietary supplement, the soy fraction genistein, also was protective in the mammary cancer model when included in the plant-protein-based diet, but not in the milk protein-based diet.

Kim cautioned that the lack of results with the milk protein-based diet does not mean that the milk protein necessarily inhibits any beneficial activities of GSE or the genistein. “It could be that certain chemicals are better taken up taken with plant proteins, or that the plant protein preparations contain chemicals that act synergistically to enable the bioactivities of grape seed or soy genistein,” she said.

“More research clearly needs to be done to address this issue. What it does suggest, however, is that perhaps we all need to be more mindful of results we get or don’t get when we test any chemicals for bioactivities; it could depend significantly on the diet in which they are given to the animal, or to the patient.” she said.

The article is on the Web at www.nutrition.org.