Health-food activists have long touted the value of taking grape seed extract, but with little or no scientific proof of its actual 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 of the Journal of Agricultural and Food Chemistry.

"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, PhD, 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 nontoxic 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, which 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."

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 was initiated four years ago by the National Institutes of Health Office of Dietary Supplements and the National Center for Complementary and Alternative Medicine. It is 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," she said.

Identification of the brain proteins affected by GSE was based on two-dimensional protein electrophoretic separation followed by mass spectrometry (Deshane J, Chaves L, Sarikonda KV, et al., “Proteomics analysis of rat brain protein modulations by grape seed extract.” J Agric Food Chem, 2004;52(26):7872-7883).

In a separate study, published in Journal of Nutrition, 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 beneficial activities of GSE or genistein. "It could be that certain chemicals are better taken up with plant proteins, or that the plant protein preparations contain chemicals that act synergistically to enable the bioactivities of grape seed or soy genistein. 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; outcomes could depend significantly on the diet in which they are given to the animal, or to the patient." she said.