Dietary soy-derived isoflavone phytoestrogens - Could they have a role in coronary heart disease prevention?

Soy protein-containing foods are a rich source of isoflavone phytoestrogens , such as genistein and daidzein. There is great interest in these substanc es, as lower rates of chronic diseases, including coronary heart disease, h ave been associated with high dietary intake of soy-containing foods. Soy p hytoestrogens bind weakly to estrogen receptors, and some bind more strongl y to estrogen receptor-beta compared with estrogen receptor-alpha. A meta-a nalysis has indicated that isoflavone phytoestrogens lowered plasma cholest erol concentrations in subjects with initially elevated levels, but had lit tle effect in subjects with normal cholesterol concentrations. These substa nces reportedly may also have beneficial effects on arterial endothelial fu nction. In addition to these potentially antiatherogenic effects, many labo ratories are investigating other possible mechanisms, including antioxidati ve and antiproliferative properties of these substances. We have shown that dietary supplementation with soy-derived isoflavones reduced the in vitro oxidation susceptibility of low-density lipoprotein (LDL). To further explo re this phenomenon, we incorporated genistein and daidzein into LDL molecul es in vitro with the aid of an artificial transfer system. However, it was necessary to convert the isoflavone molecules to fat-soluble derivatives, f atty acid esters (analogous to esterified endogenous estrogens, which are k nown to occur in vivo), to achieve significant incorporation. The LDLs cont aining esterified isoflavones were shown to be less susceptible to oxidatio n in vitro than native LDL. We also employed U937 cell cultures for investi gating the effects of isoflavone-containing LDLs on cell proliferation. Som e of these LDLs exhibited antiproliferative effects in cultured U937 cells. In summary, lipophilic phytoestrogen derivatives could be incorporated int o LDLs, increasing their oxidation resistance and antiproliferative efficac y ex vivo, both of which are, in theory, antiatherogenic effects. Further s tudies are needed to assess to what extent analogous effects could be produ ced in vivo and whether such substances have a role in hormone replacement and coronary heart disease prevention in postmenopausal women. BIOCHEM PHAR MACOL 60;1:1-5, 2000. (C) 2000 Elsevier Science Inc.