Background: Regular consumption of nϪ3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk. Objective: This study aimed to determine whether eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have differential effects on serum lipids and lipoproteins, glucose, and insulin in humans. Design: In a double-blind, placebo-controlled trial of parallel design, 59 overweight, nonsmoking, mildly hyperlipidemic men were randomly assigned to receive 4 g purified EPA, DHA, or olive oil (placebo) daily while continuing their usual diets for 6 wk. Results: Fifty-six men aged 48.8 ± 1.1 y completed the study. Relative to those in the olive oil group, triacylglycerols fell by 0.45 ± 0.15 mmol/L (Ϸ20%; P = 0.003) in the DHA group and by 0.37 ± 0.14 mmol/L (Ϸ18%; P = 0.012) in the EPA group. Neither EPA nor DHA had any effect on total cholesterol. LDL, HDL, and HDL 2 cholesterol were not affected significantly by EPA, but HDL 3 cholesterol decreased significantly (6.7%; P = 0.032). Although HDL cholesterol was not significantly increased by DHA (3.1%), HDL 2 cholesterol increased by Ϸ29% (P = 0.004). DHA increased LDL cholesterol by 8% (P = 0.019). Adjusted LDL particle size increased by 0.25 ± 0.08 nm (P = 0.002) with DHA but not with EPA. EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA. DHA supplementation increased DHA and EPA in plasma and platelet phospholipids. Both EPA and DHA increased fasting insulin significantly. EPA, but not DHA, tended to increase fasting glucose, but not significantly so. Conclusions: EPA and DHA had differential effects on lipids, fatty acids, and glucose metabolism in overweight men with mild hyperlipidemia.Am J Clin Nutr 2000;71:1085-94.
KEY WORDSEicosapentaenoic acid, docosahexaenoic acid, EPA, DHA, hyperlipidemia, fish oil, nϪ3 fatty acids, lipids, LDL particle size, glucose metabolism, insulin metabolism, men
INTRODUCTIONThere is considerable evidence to support a protective effect of dietary nϪ3 polyunsaturated fatty acids against atherosclerotic heart disease (1). The 2 principal nϪ3 fatty acids in marine oils, eicosapentaenoic acid (EPA; 20:5nϪ3) and docosahexaenoic acid (DHA; 22:6nϪ3), have a wide range of biological effects (1-3). Those relevant to heart disease include influences on lipoprotein metabolism (4, 5), platelet and endothelial function, vascular reactivity, neutrophil and monocyte cytokine production, coagulation, fibrinolysis, and blood pressure (1-3, 6, 7). In addition, the effect of nϪ3 fatty acids may be dependent, to some extent, on the presence of underlying disorders such as dyslipidemia, hypertension, diabetes mellitus, and vascular disease.nϪ3 Fatty acid supplementation in animals and humans results in substantial increases in plasma and tissue EPA and DHA as well as variable incorporation in different phospholipid classes in different tissues (8-10). These differences may be important to the subsequent utilization and metabolism of EPA and DHA. Although both fatty acids are considered to ...