Wine and Health: A Paradigm for Alcohol and AntioxidantsModerate alcohol consumption has been shown in many epidemiological investigations to prolong overall life expectancy by reducing the risk of certain diseases. Those that account most for this reduction are coronary heart disease and ischemic stroke, both of which are caused by atherosclerotic vascular disease. It has been claimed that these effects are beverage-specific, with red wine being the most potent. This review examines the relative contributions of ethanol and the polyphenolic antioxidants of red wine by considering their potential to inhibit atherogenesis and the mechanisms involved. There is good evidence, bothin vitroandin vivo, that ethanol increases production and circulating levels of HDL-Cholesterol, and reduces clot formation by blocking thrombin activity as well as by inhibition of fibrinolysis. It also prevents migration of smooth-muscle cells to the intimal layer of arteries and reduces the incidence of Type II Diabetes Mellitus, a major risk factor for atherosclerotic disease. Red wine, in addition to ethanol, contains many polyphenolic antioxidants that are also present in fruit and vegetables (such as catechin and quercetin), as well as resveratrol that is almost restricted to grapes and red wine. These polyphenols, especially the last-named, have been shown byin vitroexperiments to exhibit many potent properties conducive to preventing atherosclerosis. In addition to lowering clot formation, they diminish inflammatory reactions by down-regulating production of eicosanoids and cytokines, they prevent oxidation of LDL, reduce expression of cell-adhesion molecules, and increase NO production. However, investigations in whole animals and human subjects have yielded conflicting results. The above paradox can be explained by studies demonstrating that these polyphenols, when taken orally, are rapidly conjugated with glucuronide and sulfate by the small-intestinal mucosa prior to absorption, following which the deactivated water-soluble conjugates are quickly excreted by the kidney. The free biologically-active parent compounds appear in the circulation in very low concentrations and with a very rapid halflife. Uptake by relevant tissues could not be demonstrated. In line with this evidence, red and white wines have comparable effects when administered to humans that are essentially attributable to their alcohol content alone. These findings suggest that dietary antioxidants may be less effective than previously thought.
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