A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins.

CONTEXT Isolated soy protein reduces plasma concentrations of total and low-density lipoprotein (LDL) cholesterol. OBJECTIVE To identify the agent(s) responsible for the cholesterol-lowering effect of soy in mildly hypercholesterolemic volunteers: isoflavones isolated together with soy protein or soy protein itself. DESIGN Double-blind randomized parallel trial. SETTING Single-center study. PARTICIPANTS A total of 156 healthy men and women with LDL cholesterol levels between 3.62 mmol/L (140 mg/dL) and 5.17 mmol/L (200 mg/dL) after instruction in a National Cholesterol Education Program Step I diet and recruited by advertisement from the community. INTERVENTION One of 5 daily diets (25 g of casein [for isoflavone-free comparison] or 25 g of isolated soy protein containing 3, 27, 37, or 62 mg of isoflavones). MAIN OUTCOME MEASURES Change and percent change from baseline in plasma concentrations of triglycerides and total, LDL, and high-density lipoprotein cholesterol after 9 weeks. RESULTS Compared with casein, isolated soy protein with 62 mg of isoflavones lowered total and LDL cholesterol levels by 4% (P = .04) and 6% (P = .01), respectively. In patients with LDL cholesterol levels in the top half of the population studied (>4.24 mmol/L [>164 mg/dL]), comparable reductions were 9% (P<.001) and 10% (P = 001), respectively; in this group, isolated soy protein with 37 mg of isoflavones reduced total (P = .007) and LDL (P = .02) cholesterol levels by 8%, and there was a dose-response effect of increasing amounts of isoflavones on total and LDL cholesterol levels. Plasma concentrations of triglycerides and high-density lipoprotein cholesterol were unaffected. Ethanol-extracted isolated soy protein containing 3 mg of isoflavones did not significantly reduce plasma concentrations of total or LDL cholesterol. CONCLUSIONS Naturally occurring isoflavones isolated with soy protein reduce the plasma concentrations of total and LDL cholesterol without affecting concentrations of triglycerides or high-density lipoprotein cholesterol in mildly hypercholesterolemic volunteers consuming a National Cholesterol Education Program Step I diet. Ethanol-extracted isolated soy protein did not significantly reduce plasma concentrations of total or LDL cholesterol.