Childhood consumption of dietary polyunsaturated fat lowers risk for coronary artery atherosclerosis in African green monkeys.

Abstract

This study was designed to test the hypothesis that consumption of diets enriched in polyunsaturated fatty acids beginning at birth and continuing into young adulthood would lower the risk for atherosclerotic coronary heart disease early in life through their effects on plasma lipid and apolipoprotein concentrations while supporting good health and normal development Accordingly, African green monkeys (n=140) were raised on atherogenic diets (0.8 mg cholesterol per kcal) enriched with either saturated or n-6 polyunsaturated fatty acids. Breast milk from mothers fed the polyunsaturated fat diet became enriched in polyunsaturated fatty acids relative to the saturated group; thus, the period of nursing also reflected the dietary fatty acid shift. Age, gender, and dietary fat type independently affected plasma lipid and apolipoprotein concentrations. Age effects were similar for all lipid and lipoprotein variables; the concentrations were low immediately after birth, increased dramatically during the first 4-6 months of life, and then attained levels similar to those of adult animals by 2 years of age. Significant differences by gender were found such that females maintained lower total plasma cholesterol concentrations and higher high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations. Dietary fat effects were age dependent Before weaning at 5 months of age, total plasma cholesterol and apoB concentrations were lower in animals consuming polyunsaturated fat and this pattern was maintained into young adulthood. Lower concentrations of plasma triglycerides, HDL cholesterol, and apoA-I for polyunsaturated fat-fed animals were found only in the postweaning period (6-60 months of age). Since this pattern of response to dietary polyunsaturated fat in the juvenile animals was similar to that for adult animals fed these same diets in which there was less atherosclerosis and because subsequent studies have documented less coronary artery atherosclerosis in the polyunsaturated fat-fed juveniles, we conclude that early dietary intervention was beneficial in this group for lowering the risk of coronary artery atherosclerosis. The results in this primate model support the concept that intervention to modify coronary heart disease risk that is initiated early in childhood will have beneficial effects. (Arteriosclerosis and Thrombosis 1993;13:863-875) KEY WORDS • age • gender • polyunsaturated fat • nonhuman primates • risk factors • coronary artery atherosclerosis R esults from autopsy studies have provided evidence that atherosclerosis, both aortic and coronary, begins in childhood,'-4 although clinically significant childhood atherosclerosis has been reported primarily in children with familial hypercholesterolemia. 5 Although the factors initiating atherosclerosis are not fully understood, prospective studies in adult humans have identified associations between From the

Primates Highly Responsive to Dietary Cholesterol Up-regulate Hepatic ACAT2, and Less Responsive Primates Do Not

“…Cholesteryl ester was separated from other lipid classes by TLC for analysis of individual cholesteryl ester fatty acids by gas-liquid chromatography (20).…”

Hepatic origin of cholesteryl oleate in coronary artery atherosclerosis in African green monkeys. Enrichment by dietary monounsaturated fat.

“…The caudate lobe of the liver was removed after the liver had been flushed of blood but before recirculating perfusion was started, and was snap frozen in liquid nitrogen, and stored at Ϫ 80 Њ C. At the time of analysis, a portion of the frozen tissue was taken, weighed, and liver lipid concentrations were determined as above after lipid extraction (23). For measurement of cholesteryl ester fatty acid percentage composition, lipids were extracted in chloroform-methanol, 2:1, major classes were separated by thin layer chromatography using Empore TLC sheets (Analytichem International, Harbor City, CA), the cholesteryl ester band was scraped from the plate, and the fatty acids were isolated, methylated, and quantified by gas liquid chromatography (25).…”

Omega-6 Fatty Acids and Risk for Cardiovascular Disease

“…69 On the other hand, evidence from trials in nonhuman primates has demonstrated cardiovascular benefits and no evidence of harm with LA intakes of 25% of energy for up to 5 years, 70,71 and randomized trials in humans have shown reduced CHD risk with omega-6 PUFA intakes of 11% to 21% of energy for up to 11 years with no evidence of harm.…”