The low cardiovascular risk in Asian women has been thought to result from high isoflavonoid intake. In a double-blind, randomized, placebo-controlled trial, we studied the effects of isolated isoflavonoids ( 114 mg/d) on lipids, lipoproteins, insulin sensitivity, and ghrelin in 56 nondiabetic postmenopausal women with a history of breast cancer. Isoflavonoid or placebo tablets were given for 3 months, and the treatment regimens crossed over after a 2-month washout period. The concentrations of total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, apolipoproteins B and A1, and lipoprotein ( a) were not affected by isoflavonoids. However, during the isoflavonoid regimen, women with low-density lipoprotein cholesterol level above the median 4.20 mmol/liter) showed a rise [0.65 +/- 0.60 (SD) mmol/ liter], which was statistically different from the fall during the placebo regimen ( - 0.45 +/- 0.67 mmol/ liter, P = 0.009). Isoflavonoids did not affect insulin sensitivity as assessed by an oral 2-h glucose tolerance test ( 75 g). Changes in ghrelin levels differed ( P = 0.048) during the isoflavonoid ( - 7.1 +/- 151 mumol/liter) and placebo regimens ( + 47.9 +/- 198 mumol/liter). In conclusion, we found no effects of isolated isoflavonoids on lipids, lipoproteins, or insulin sensitivity in postmenopausal women, implying no vascular benefit. Isoflavonoids may reduce ghrelin levels and thus hunger and weight.