Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects

To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62 +/- 9 years, BMI 26 +/- 3 kg/m(2), LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P < 0.0001), total cholesterol by 4.4% (P < 0.001), and LDL cholesterol by 5.7% (P = 0.003) compared to animal protein. The TGFA-FSR was reduced by 13.3% (P = 0.018) and FC-FSR was increased by 7.6% (P = 0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P = 0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms.