Resveratrol is a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi. Resveratrol has also been produced by chemical synthesis, and is sold as a nutritional supplement derived primarily from Japanese knotweed. Resveratrol extends the life span of several short-living species of animals; however, this effect have not yet been demonstrated in mammals. In mouse and rat experiments, anti-cancer, anti-inflammatory, blood-sugar-lowering and other beneficial cardiovascular effects of resveratrol have been reported. As of July 2008, most of these results are yet to be confirmed in humans. In the only positive human trial, extremely high doses (3–5g) of resveratrol in a special proprietary formulation have been necessary to significantly lower blood sugar. Resveratrol is found in the skin of red grapes and is a constituent of red wine but apparently not in sufficient amounts to explain the "French paradox" that the incidence of coronary heart disease is relatively low in southern France despite high dietary intake of saturated fats.