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 micromol/liter) and placebo regimens (+47.9 +/- 198 micromol/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.