Soy protein diets lower plasma cholesterol in hyperlipoproteinemic human subjects, as well as in animal models. We fed 7-wk-old male obese (fa/fa) and lean Zucker rats a modified AIN-76 diet (20 g protein/kg diet) containing casein (C), low isoflavone soy protein (38 mg isoflavones/kg diet; LI), or high isoflavone soy protein (578 mg isoflavones/kg diet; HI) for 70 d. In obese rats, plasma total cholesterol was 21 and 29% lower in the LI and HI groups, respectively, than in the C group (P less than or equal to 0.004). Liver weight and liver triglyceride and cholesteryl ester concentrations were 27, 33 and 46% lower, respectively, in the LI group than in the C group (P < 0.003). These liver measurements were 23, 24 and 57% lower, respectively, in the HI group than in the LI group (P < 0.05). In a complementary study, 5-wk-old male Sprague-Dawley rats were fed the same C, LI and HI diets for 42 d. Thrombin-mediated platelet serotonin release in vitro was 13% lower in the HI group than in the C group (P = 0.003). In a third study, 7-wk-old male Sprague-Dawley rats were fed either a modified AIN-76 control diet or a high fat casein-based atherogenic diet (140 g fat, 12 g cholesterol, and 2 g cholic acid/kg diet) with or without a soy isoflavones extract (983 mg isoflavones/kg diet) for 63 d. Addition of the isoflavones extract to the atherogenic diet lowered the liver triglyceride concentration by 33% relative to the atherogenic diet without isoflavones (P = 0.0001). Our studies suggest that the hypocholesterolemic mechanism of dietary soy protein involves a cooperative interaction between the protein and isoflavone-enriched fraction that lowers hepatic lipid concentrations. We speculate that modulation of liver and plasma lipid homeostasis can also lower blood platelet sensitivity.
