Red Clover Phytoestrogens Effects on Atherosclerosis

Goodrich, James

Abstract

The majority of current epidemiologic and experimental evidence demonstrates the cardiovascular benefits of estrogen replacement therapy (ERT) for postmenopausal women. In spite of the great potential health benefits, compliance among the population that could benefit is low. Alternatives to conventional ERT, primarily conjugated equine estrogens, are needed because of legitimate concerns of increased risk of uterine cancer, possibly breast cancer and the need for accompanying progestin therapy. Plant estrogens, also termed isoflavones or phytoestrogens found in legumes such as soybeans and red clover are a natural alternative which may have greater acceptance from the public. Soy protein containing phytoestogens has been shown to provide beneficial decreases in plasma cholesterol in people and coronary atherosclerosis in animal models. Phytoestrogens are hypothesized to produce this cholesterol lowering effect by increasing activity of LDL receptors which in turn removes cholesterol from the circulation to make bile acids that are excreted in the feces. Additionally a bile acid sequestrant such as the undigested fraction of soy protein is essential to prevent reabsorption of the bile acids.
The specific aims of this proposal are to obtain pilot data to show that a bile acid sequestrant (i.e.,cholestyramine) is essential to produce a cholesterol lowering and antiatherogenic effect from red clover phytoestrogens (i.e. Promensil) without hyperplasia of breast and uterine tissue. Specifically, it will compare plasma cholesterol, size of coronary atherosclerosis lesions and effects on uterus and breast among placebo, Promensil, cholestyramine, and Promensil plus cholestyramine treated groups of ovariectomized Yucatan Micropigs. The overall objective is to advance knowledge of how to optimize the cardioprotective effects of phytoestogens and to determine if there are any associated risks to reproductive tissues.