In response to the many media reports about resveratrol, it seems like every supplement company is offering some form of grape complex for sale that claims to contain some resveratrol.
Recent attention has focused on a publication in the journal Nature that demonstrated improved health and survival in mice fed a high-fat diet supplemented with resveratrol, the same flavonoid that has been shown to increase the life span of a variety of organisms, including yeast, worms, flies, fish, and mice.This research tied the beneficial effects of resveratrol to mechanisms that underlie caloric restriction, and showed that such approaches could be used to treat certain chronic disorders and diseases of aging.
However, some popular press reports that accompanied this scientific article generated a fair amount of controversy, especially related to the dose used in the experimental mice and the estimated human-equivalent dose that may be required to exert the same biological effects. The Life Extension Foundation, however, is the only organization that has taken a grape-seed/resveratrol product already being used by health-conscious individuals and shown that the favorable biological effects of resveratrol can be achieved at a dose that is more than 10-fold lower than that used in the most-referenced study (referred to as the Harvard study).
Just recently, Life Extension reported that experimental animal studies conducted by BioMarker Pharmaceuticals were under way using the same grape extract fortified with resveratrol that is currently used by Foundation members.6These studies were designed to evaluate the gene-expression response in mice fed resveratrol from the whole-grape extract found in the Grapeseed Extract with Resveratrol encapsulated product. The gene-expression data obtained from the grape extract group were compared to data from a group of animals subjected to caloric restriction. The preliminary data suggested a significant overlap in the favorable pattern of gene expression between the grape extract-fed mice and the calorie-restricted mice. In addition, experimental fruit flies (Drosophila) fed grape extract showed improvement in a model of Parkinson’s disease, as well as an extended life span. These findings paved the way for further analysis identifying the specific molecular pathways involved in these effects. Here we provide an update to these earlier findings.
Resveratrol and Other Health-Promoting Grape Constituents
The Life Extension Foundation constantly surveys the scientific literature in order to utilize the most important findings in promoting health and extending life. Mounting evidence demonstrates the broad-spectrum effects of biologically active molecules such as resveratrol, which is derived from natural plant extracts. In nature, molecular compounds like resveratrol are found in complex mixtures containing a diverse array of physiologically relevant molecules. Many of these constituents may be required in order to provide phytomedicinal agents with optimal bioavailability and synergistic action. Scientists must consider these points when conducting studies using either a single phytochemical (such as resveratrol alone) versus resveratrol combined with grape skin and grape seed extracts.
Classes of molecules found in natural whole grape, grape skin, and grape seed extracts include potent effectors like proanthocyanidins (in grape seed), anthocyanins (which give purple and red grapes their color), and single molecular entities such as resveratrol and quercetin. Scientific studies document the multiple health effects of these components, which can be characterized as antibiotic, anti-tumor, anti-diabetic, anti-ulcer, cardioprotective, anti-inflammatory, and anti-brain aging.
The cardiovascular health benefits of grape seed extract include favorable effects on blood pressure, enhanced endothelial function, and decreased oxidative stress.The potent antioxidant activity of grape seed extract may be responsible for its reported neuroprotective effects, as observed in animal models of Alzheimer’s disease.Recently, grape seed extract combined with calcium was found to be more effective than calcium alone in building healthy bone mass. Grape seed extract has effectively inhibited the growth of human colorectal tumor cells in the laboratory and in animals.
Recent findings on resveratrol’s effects in experimental animal models are attracting a great deal of interest from the scientific community, while raising many questions about resveratrol’s applications in humans. One of the most intriguing questions is what dose of resveratrol may help humans achieve the beneficial health effects that have been observed in animals. While extrapolating animal dosage to human dosage is difficult at best, scientists are using several approaches to address this question. The accumulating data from gene-expression studies in mice provide some clues. These findings are also helping to illuminate the molecular basis of the biological effects of resveratrol and grape extracts.
The Harvard Study generated a great deal of enthusiasm by showing that mice fed high-fat diets (60% of calories from fat) avoided numerous diet-related health problems when supplemented with res-veratrol. Compared to mice that were not given resveratrol, the supplemented mice exhibited increased survival, increased insulin sensitivity, decreased organ pathology, and in-creased numbers of mitochondria.1 Resveratrol was also responsible for shifting the gene-expression patterns of mice on the high-fat diet towards those of mice on a standard (moderate-fat) diet. These results were achieved by feeding the mice a daily resveratrol supplement equivalent to 22.4 milligrams per kilogram of body weight.* In preliminary studies of this type, scientists often choose relatively high individual doses that are likely to generate an observable effect. Typically, more formal dose-ranging studies would be conducted later to identify optimal doses to attain specific effects. This is partly responsible for the controversy in the popular press regarding the relatively high dose of resveratrol used in this study.
While the Harvard study was under way, BioMarker Pharmaceuticals had already completed an eight-week controlled feeding study in which mice received either resveratrol (a synthetic version) or grape extract (containing resveratrol and other constituents), along with a “normal” diet. Gene-expression profiles were completed on these animals and compared to those of a group of calorie-restricted mice. Genes affected by either resveratrol formulation (synthetic or natural grape extract) or by caloric restriction were then compared. Importantly, the resveratrol dosage used in this study was much lower—approximately 12-fold lower—than that used in the Harvard study .
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