Nutritional regulation of cholesterol synthesis and apolipoprotein B kinetics: studies in patients with familial hypercholesterolemia and normal subjects treated with a high carbohydrate, low fat diet.

Nutritional regulation of cholesterol synthesis and apolipoprotein B kinetics: studies in patients with familial hypercholesterolemia and normal subjects treated with a high carbohydrate, low fat diet.

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High carbohydrate, low fat diets decrease plasma low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) mass in normal subjects and in patients with familial hypercholesterolemia (FH).To investigate the mechanisms for these effects, four normal, four FH heterozygous, and one FH homozygous subjects were studied on a basal (45% carbohydrate, 40% fat) diet and during continuous nasogastric infusion of Vivonex (90% carbohydrate, 1% fat).For the entire group, the mean changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides were -90, -95, -14 (all P less than 0.01) and +114 (P less than 0.02) mg/dl, respectively.

Fecal sterol balance measurements demonstrated a 24% decrease in whole body C Vitamins cholesterol synthesis in normals, from 8.4 +/- 4.4 (mean +/- SD) to 6.4 +/- 1.3 mg/kg per day and in FH subjects, a 58% decrease, from 11.

4 +/- 5.6 to 4.8 +/- 1.7 mg/kg per day (both P less than 0.05).

ApoB kinetic studies were performed using a [3H]leucine tracer Metal Desk Lamp (1/CN) in two normals and three FH heterozygotes on both basal and Vivonex regimens, and the results were analyzed by compartmental modeling using the SAAM program.Total apoB production was not altered in a consistent manner by carbohydrate feeding.ApoB secretion, however, was shifted from the production of small VLDL/IDL-like particles to large VLDL by Vivonex, with an accompanying increase in intrahepatic assemblage time before secretion.In the two normal subjects, Vivonex induced an increase in apoB loss as VLDL/IDL; however, in the FH patients no such loss occurred.A decrease (P less than 0.

05) in the residence time of LDL-apoB occurred for all subjects and was the primary determinant of the fall in plasma LDL concentration, since LDL-apoB transport did not change consistently.Thus, in FH patients, a high carbohydrate, low fat diet results in suppression of cholesterol synthesis and a fall in plasma LDL concentration due to an increased plasma clearance rate for LDL.