Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to similarly lower plasma TG concentrations but differentially regulate plasma LDL-C and HDL-C concentrations. OBJECTIVE: The aim of this study was to evaluate the common and differential effects of these ω-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects. METHODS: In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA (both as ethyl ester, ≥97% purity) on plasma lipid and lipoprotein concentrations and activities of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 older (>50 y) men and postmenopausal women with some characteristics of metabolic syndrome and low-grade chronic inflammation. RESULTS: Both EPA and DHA lowered plasma TG concentrations and increased LDL-C/apoB and HDL-C/apoA-I ratios, but only DHA increased LDL-C concentrations. The reductions in plasma TG were inversely associated with the changes in LPL activity after both EPA and DHA supplementation. EPA lowered CETP, while DHA lowered LCAT activity. EPA and DHA worked differently in men and women, with DHA increasing LPL activity and LDL-C concentrations in women, but not in men. CONCLUSIONS: EPA and DHA exerted similar effects on plasma TG, but differences were observed in LDL-C concentrations and activities of some enzymes involved in lipoprotein metabolism. It was also noted that EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism.

Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary omega-3 fatty acids in fish oil, have been shown to reduce cardiovascular disease (CVD) risk. OBJECTIVE: This study aimed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels, as well as on inflammatory biomarkers of CVD risk, using doses often used in the general population. DESIGN: A blinded, randomized 6-week trial was performed in 121 healthy, normolipidemic subjects who received olive oil placebo 6g/d, EPA 600mg/d, EPA 1800mg/d, or DHA 600mg/d. The EPA was derived from genetically modified yeast. RESULTS: The subjects tolerated the supplements well with no safety issues; and the expected treatment-specific increases in plasma EPA and DHA levels were observed. Compared to placebo, the DHA group had significant decreases in postprandial triglyceride (TG) concentrations (-20%, -52.2mg/dL, P=0.03), significant increases in fasting and postprandial low-density lipoprotein cholesterol (LDL-C) (+18.4%, 17.1mg/dL, P=0.001), with no significant changes in inflammatory biomarkers. No significant effects were observed in the EPA 600mg/d group. The high-dose EPA group had significant decreases in lipoprotein-associated phospholipase A2 concentrations (Lp-PLA2) (-14.1%, -21.4ng/mL, P=0.003). CONCLUSIONS: The beneficial effects of EPA 1800mg/d on CVD risk reduction may relate in part to the lowering of Lp-PLA2 without adversely affecting LDL-C. In contrast, DHA decreased postprandial TG, but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers.

Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression.

OBJECTIVE: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (PBMC). METHODS: Subjects were sampled at baseline and six weeks after receiving either: olive oil 6.0 g/day (n = 16), EPA 1.8 g/day (n = 16), or DHA 1.8 g/day (n = 18). PBMC were subjected to gene expression analysis by microarray with key findings confirmed by quantitative real-time polymerase chain reaction (Q-PCR). RESULTS: Plasma phospholipid EPA increased 3 fold in the EPA group, and DHA increased 63% in the DHA group (both p < 0.01), while no effects were observed in the olive oil group. Microarray analysis indicated that EPA but not DHA or olive oil significantly affected the gene expression in the following pathways: 1) interferon signaling, 2) receptor recognition of bacteria and viruses, 3) G protein signaling, glycolysis and glycolytic shunting, 4) S-adenosyl-l-methionine biosynthesis, and 5) cAMP-mediated signaling including cAMP responsive element protein 1 (CREB1), as well as many other individual genes including hypoxia inducible factor 1, α subunit (HIF1A). The findings for CREB1 and HIF1A were confirmed by Q-PCR analysis. CONCLUSIONS: Our data indicate that EPA supplementation was associated with significant effects on gene expression involving the interferon pathway as well as down-regulation of CREB1 and HIF1A, which may relate to its beneficial effect on CVD risk reduction.

Short communication: effects of omega-3 fatty acids on triglycerides and high-density lipoprotein subprofiles in HIV-infected persons with hypertriglyceridemia.

Hypertriglyceridemia and low high-density lipoprotein (HDL)-cholesterol (HDL-C) may contribute to a presumed accelerated risk for cardiovascular disease in HIV-infected individuals. We evaluated the effect of omega-3 fatty acid treatment on triglycerides, low-density lipoprotein (LDL)-C, HDL-C, and HDL subpopulations. Forty-one HIV-seropositive subjects with hypertriglyceridemia (≥150 mg/dl) on active antiretroviral therapy were enrolled in this placebo-controlled, double-blind, randomized, crossover trial comparing the effects of omega-3 fatty acid treatment (1.9 g EPA and 1.5 g DHA) on triglycerides, LDL-C, HDL-C, and HDL subpopulations. An independent sample t-test was used to assess the study start to posttreatment change for all components. After omega-3 fatty acid treatment, triglyceride levels decreased 63.2±86.9 mg/dl (p<0.001). No significant changes in total cholesterol, LDL-C, or HDL-C were found. Within HDL subpopulations, significant changes were seen in the most atheroprotective HDL particles, α-1, which increased by 2.5±5.6 mg/dl (p<0.05), and preα-1, which increased by 0.6±1.0 mg/dl (p<0.001). Preα-3, a presumably atherogenic HDL particle, decreased by 0.5±0.9 mg/dl (p<0.01). Omega-3 fatty acid treatment significantly lowered triglyceride levels in HIV-positive patients with moderate hypertriglyceridemia. While no study-wide improvements in LDL-C or HDL-C were detected, the HDL subpopulation profile changed in a beneficial way suggesting more cardioprotection after treatment.