No abstract

Coronary artery disease is the leading overall cause of mortality for women and increases dramatically after menopause. Estrogen has many beneficial cardiovascular actions although concerns have been raised about its effects on the progression of breast and uterine neoplasms and its tendency to increase coagulability. Selective estrogen agonists may be superior to conventional estrogens. A dietary source of a partial estrogen agonist is the plant-based group of phytoestrogens, which include isoflavones, lignans and coumestans. Phytoestrogens have a similar structure to estradiol and have weak affinity for the estrogen receptor. Epidemiologic data indicate that women ingesting high amounts of phytoestrogens, particularly as isoflavones in soy products, have less cardiovascular disease, breast and uterine cancer and menopausal symptoms than those eating Western diets. Preclinical and clinical studies have found that isoflavones have lipid-lowering effects as well as the ability to inhibit low-density lipoprotein oxidation. They have been shown to normalize vascular reactivity in estrogen-deprived primates. Furthermore, phytoestrogens have antineoplastic effects with inhibition of cellular proliferation as well as angiogenesis, properties that could be protective against cancer development. Finally, menopausal symptoms and bone density may be favorably influenced by phytoestrogens. In summary, phytoestrogens, in the form of dietary isoflavones, represent a new area to explore in pursuit of nutritional approaches to cardiovascular protection.

This randomized clinical trial was designed to assess the effects of dietary isoflavones on vascular reactivity, lipid levels, and markers of inflammation in post-menopausal women. Epidemiological studies have revealed that populations consuming large amounts of soy protein have lower cardiovascular morbidity and mortality. The benefits of soy protein may be due to its hypolipidemic effects; its anti-oxidant properties; its high content of L-arginine; and/or or its phytoestrogen content. Two putative mediators of the effects of soy protein are the isoflavones genistein and daidzein. Forty post-menopausal, hypercholesterolemic women who did not take estrogen replacement therapy were recruited for this study of isoflavone supplementation. Baseline flow-mediated vasodilation and response to nitroglycerin were measured, along with urinary isoflavone and nitrite/nitrate levels and serum lipids. After 6 weeks of 90 mg of isoflavones daily versus placebo, women receiving isoflavones demonstrated improved responsiveness to nitroglycerin, an assessment of endothelium-independent vasodilation, with an effect size (percentage points change from baseline) of 7.2 +/- 1.9 versus 1.2 +/- 1.3; p = 0.01. There was a trend towards improvement of flow-mediated vasodilation, which is an endothelium-dependent response (effect size: 3.4 +/- 2.0% versus -0.6 +/- 1.7%; p = 0.12). Lipid levels were unchanged after isoflavone treatment. In conclusion, dietary isoflavones may have cardiovascular benefit in the form of improved vascular reactivity, but not by lowering cholesterol, for women who do not take estrogen replacement therapy.