Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men

Abstract

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 ...

The Pro12Ala polymorphism of the PPAR-γ2 gene affects associations of fish intake and marine n−3 fatty acids with glucose metabolism

“…Although the controversy in earlier data concerning marine fatty acids and glucose metabolism (Salomaa et al, 1990;Feskens et al, 1991Feskens et al, , 1995Borkman et al, 1993;Adler et al, 1994;Vessby et al, 1994aVessby et al, , b, 2001Pan et al, 1995;Marshall et al, 1997;Baur et al, 1998;Gustafsson et al, 1998;Bjerregaard et al, 2000;Ekblond et al, 2000;Mori et al, 2000;Hu et al, 2001;Salmeró n et al, 2001;Dewailly et al, 2001a, b;van Dam et al, 2002;Wang et al, 2003;Harding et al, 2004;Thorsdottir et al, 2004) may be partly explained by different doses and durations of supplementation in intervention studies, and by different background diets between the study populations, inclusion of subjects with different PPARG Pro12Ala genotypes could also influence the outcome of the study. That PPARG genotype may affect the associations of dietary fat composition with insulin concentrations (Luan et al, 2001) and serum triacylglycerol response to fish oil supplementation (Lindi et al, 2003) was suggested previously.…”

“…Especially, long-chain nÀ3 polyunsaturated fatty acids have been found to be associated with enhanced glucose metabolism (Feskens et al, 1991;Adler et al, 1994;Feskens et al, 1995;Baur et al, 1998;Ekblond et al, 2000;Hu et al, 2001;Salmeró n et al, 2001;Thorsdottir et al, 2004) and to lower serum free fatty acid (FFA) concentrations (Gustafsson et al, 1998), although there are also contradictory results (Salomaa et al, 1990;Borkman et al, 1993;Vessby et al, 1994aVessby et al, , b, 2001Pan et al, 1995;Marshall et al, 1997;Bjerregaard et al, 2000;Mori et al, 2000;Dewailly et al, 2001a, b;van Dam et al, 2002;Wang et al, 2003;Harding et al, 2004). It is not known whether some of the discrepancies in previous results could be attributed to differences in the genetic background of the subjects.…”

Dietary n-3 PUFA and CVD: a review of the evidence

“…In overweight, treated hypertensive patients (52) and in dyslipidaemic men (53) , n-3 fatty acids increased HDL cholesterol due primarily to an increase in HDL 2 -cholesterol subfraction. A reduction in hepatic very-low density lipoprotein cholesterol synthesis probably contributes to the fall in plasma TAG.…”

A valid semiquantitative food frequency questionnaire to measure fish consumption

“…The erythrocyte fraction was washed and packed. Processed plasma and erythrocyte samples were stored at À80 1C until transferred to a separate laboratory for PUFA analysis by gas liquid chromatography using a Hewlett-Packard model 5980A gas chromatograph (Mori et al, 2000). Individual fatty acids were calculated as a relative percentage with the evaluated fatty acids set at 100%.…”