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December 1, 2010: by ResveratrolNews
Human and Experimental Toxicology, 29(12) 1016–1017
Dipak K Das
Cardiovascular Research Center, University of Connecticut, Farmington, CT, USA
Resveratrol, a grape skin and red wine-derived polyphenolic phytoalexin, exhibits hormetic action delivering numerous health benefits at lower doses while being detrimental at higher doses. Epidemiologic and clinical trials need to be based on the clear understanding of hormetic health benefits of resveratrol.
Hormesis is defined as a dose-response relationship that is stimulatory at low doses but detrimental at higher doses, resulting in a J-shaped or an inverted U-shaped dose response curve. It has been known for quite some time that cardioprotective effects of alcohol or wine intake follow a J-shaped curve.1 Extensive literature search implicates that resveratrol present in red wine also demonstrates a similar health benefit, being highly effective at lower doses and detrimental at higher doses. Such hormesis has been known for more than hundred years, and is frequently observed among the toxins. Resveratrol is a phytoalexin, whose growth is stimulated by environmental stress such as fungal infection, UV radiation and water deprivation.2 Cardioprotective effects of resveratrol is exerted through its ability to precondition a heart, which causes the development of intracellular stress leading to the upregulation of intracellular defense system such as antioxidants and heat shock protein.3 Preconditioning is another example of hormesis, which is potentiated by subjecting an organ like heart to cyclic episodes of short durations of ischemia, each followed by another short durations of reperfusion.4 Such small but therapeutic amount of stress renders the heart resistant to subsequent lethal ischemic injury. Such an adaptive response is commonly observed with aging. Consistent with this idea, resveratrol has been found to stimulate longevity genes, and at least in prokaryotic species extend the life span.5,6 In this respect,resveratrol may fulfil the definition of a hormetins.7 There is no doubt that alcohol, wine and wine-derived resveratrol all display hormesis.The present review by Calabrese and his co-authors from an extensive literature search describes how resveratrol displays hormesis. The review should be very important for the basic scientists, clinicians as well as for the common people to understand the importance of using resveratrol only at lower doses as completely opposite effects can occur at higher doses, resulting in adverse effects on health. Epidemiologic and clinical trials need to be based on the clear understanding of hormetic beneficial effects of resveratrol.