Dietary restriction of saturated fat and cholesterol decreases HDL apoA-I secretion

We examined the mechanisms responsible for the decrease in HDL cholesterol (HDL-C) levels after the consumption of a diet low in total fat, saturated fat, and cholesterol. Twenty-one subjects with a mean age of 58+/-12 years were placed on a baseline isocaloric diet (15% protein, 49% carbohydrate, 3 6% fat, and 150 mg/1000 kcals of cholesterol) and then switched to an NCEP Step 2 diet (15% protein, 60% carbohydrate, 25% fat, and 45 mg/1000 kcals o f cholesterol). After 6 or 24 weeks on each diet, subjects received a 15-ho ur primed-constant infusion of [5,5,5-H-2(3)]-L-leucine. HDL apoA-I and apo A-II tracer curves were determined by gas chromatography-mass spectrometry and fitted to a monoexponential equation. Compared with The baseline diet, consumption of the Step 2 diet lowered HDL-C mean levels by 15% (1.03+/-0.2 3 to 0.88+/-0.16 mmol/L, P<0.001), apoA-I by 12% (1.25+/-0.15 to 1.10+/-0.1 3 gn, P<0.001) and the TC/HDL-C ratio by 5% (0.145+/-0.04 to 0.137+/-0.03). No significant changes were observed in apoA-II. levels and HDL particle s ize with diet. HDL apoA-I fractional catabolic rate did not change (0.219+/ -0.052 to 0.220+/-0.043 pools/day, P=0.91) but HDL apoA-I secretion rate de creased by 8% (12.26+/-3.07 to 10.84+/-2.11 mg kg(-1) day(-1), P=0.03) duri ng consumption of the Step 2 diet. There was no effect of diet on apoA-II f ractional catabolic rate or secretion rate. Our results indicate that the d ecrease in HDL-C and apoA-I levels during the isocaloric consumption of a S tep 2 diet paralleled the reductions in apoA-I secretion rate.