Plant-derived estrogen analogs (phytoestrogens) may confer significant health advantages including cholesterol reduction, antioxidant activity, and possibly a reduced cancer risk. However, the concern has also been raised that phytoestrogens may be endocrine disrupters and major health hazards. We therefore assessed the effects of soy foods as a rich source of isoflavonoid phytoestrogens on LDL oxidation and sex hormone receptor activity. Thirty-one hyperlipidemic subjects underwent two 1-month low-fat metabolic diets in a randomized crossover study. The major differences between the test and control diets were an increase in soy protein foods (33 g/d soy protein) providing 86 mg isoflavones/2,000 kcal/d and a doubling of the soluble fiber intake. Fasting blood samples were obtained at the start and at weeks 2 and 4, with 24-hour urine collections at the end of each phase. Soy foods increased urinary isoflavone excretion on the test diet versus the control (3.8+/-0.7 v 0.0+/-0.0 mg/d, P < .001). The test diet decreased both oxidized LDL measured as conjugated dienes in the LDL fraction (56+/-3 v 63+/-3 micromol/L, P < .001) and the ratio of conjugated dienes to LDL cholesterol (15.0+/-1.0 v 15.7+/-0.9, P = .032), even in subjects already using vitamin E supplements (400 to 800 mg/d). No significant difference was detected in ex vivo sex hormone activity between urine samples from the test and control periods. In conclusion, consumption of high-isoflavone foods was associated with reduced levels of circulating oxidized LDL even in subjects taking vitamin E, with no evidence of increased urinary estrogenic activity. Soy consumption may reduce cardiovascular disease risk without increasing the risk for hormone-dependent cancers.