Inhibition of low density lipoprotein synthesis by dietary omega-3 fatty acids in humans

Diets rich in omega-3 fatty acids derived from fish oils lower the plasma concentrations of low density lipoproteins (LDL) and very low density lipoproteins in humans. The present study was designed to examine the mechanism(s) by which diets enriched in omega-3 fatty acids reduce plasma LDL cholesterol levels in normal subjects. Seven healthy volunteers with normal plasma lipid levels consumed two metabolically controlled diets for a period of 4 weeks each. The control diet contained predominantly saturated and monounsaturated fatty acids, whereas the fish-oil diet contained 24 gm of omega-3 fatty acids per day. The total fat and cholesterol content of the two diets were similar for each subject. Total and LDL cholesterol levels decreased from 162 ± 26 mg/dl and 103 ± 27 mg/dl on the control diet to 124 ± 26 mg/dl and 82 ± 27 mg/dl on the omega-3-rich diet. Triglyceride levels fell from 91 ± 34 mg/dl to 52 ± 19 mg/dl. Kinetic studies of ¹²⁵I-LDL metabolism disclosed a significantly lower rate of synthesis of LDL apoprotein B on the omega-3-rich diet (9.5 ± 1.3 mg/kg/day) as compared to the control diet (13.6 ± 3.7 mg/kg/day; p < 0.05). In contrast, the fractional catabolic rate was similar on both diets. We conclude that dietary omega-3 fatty acids lower plasma LDL levels in normal human subjects by reducing the rate of synthesis of apoprotein B.