Circulating triacylglycerol and apoE levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid A serum amyloid A and LDL complex as a new prognostic marker in stable coronary artery disease. Impact of foods enriched with n-3 long-chain polyunsaturated fatty acids on erythrocyte n-3 levels and cardiovascular risk factors. Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Cardiovascular effects of milk enriched with omega-3 polyunsaturated fatty acids, oleic acid, folic acid, and vitamins E and B6 in volunteers with mild hyperlipidemia. The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation - insights from the LIPGENE study. Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Lipoprotein profile, plasma Ischemia Modified Albumin and LDL density change in the course of postprandial lipemia. Insights from the LIPGENE study
High doses of n-3 PUFA found in fish oils can reduce the circulating concentration of triacylglycerol ( TG ) , which may contribute to the positive impact of these fatty acids on the risk of CVD . The present study aim ed to establish the differential impact of EPA and docosahexaenoic ( DHA ) on plasma lipids and apo in adults . Forty-two normolipidaemic adult subjects completed a double-blind placebo controlled parallel study , receiving an EPA-rich oil ( 4.8 g EPA/d ) , DHA-rich oil ( 4.9 g DHA/d ) or olive oil as control , for a period of 4 weeks . No effects of treatment on total cholesterol , LDL-cholesterol or HDL-cholesterol were evident . There was a significant 22 % reduction in TG level relative to the control value following the DHA treatment ( P=0.032 ) , with the 15 % decrease in the EPA group failing to reach significance ( P=0.258 ) . There were no significant inter-group differences in response to treatment for plasma apoA1 , -C3 or -E levels , although a significant 15 % within-group increase in apoE was evident in the EPA ( P=0.006 ) and DHA ( P=0.003 ) groups . In addition , a within-group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group , suggesting a positive impact of DHA on HDL particle size . The DHA intervention result ed in a significant increase in the proportion of EPA P=0.000 and DHA P=0.000 in plasma phospholipids , whilst significant increases in EPA P=0.000 and docosapentaenoic acid P=0.002 , but not DHA P=0.193 , were evident following EPA supplementation ( P<0.05 ) . Our present results indicate that DHA may be more efficacious than EPA in improving the plasma lipid profile BACKGROUND Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk . OBJECTIVE This study aim ed 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 r and omly 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 ( approximately 20 % ; P = 0.003 ) in the DHA group and by 0.37 + /- 0.14 mmol/L ( approximately 18 % ; 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 approximately 29 % ( 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 BACKGROUND n-3 Fatty acids lower blood pressure , improve lipids , and benefit other cardiovascular disease risk factors . Effects on glycemia in patients with type 2 diabetes are uncertain . OBJECTIVE We determined whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) have differential effects on glycemic control , including insulin sensitivity and stimulated insulin secretion ; 24-h ambulatory blood pressure ; and serum lipids in type 2 diabetic patients with treated hypertension . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 subjects were r and omly assigned to consume 4 g EPA , DHA , or olive oil/d for 6 wk while continuing to consume their usual diet . RESULTS Thirty-nine men and 12 postmenopausal women with a mean ( + /- SE ) age of 61.2 + /- 1.2 y completed the study . In comparison with the change from baseline in fasting glucose in the olive oil group , fasting glucose in the EPA and DHA groups increased 1.40 + /- 0.29 mmol/L ( P = 0.002 ) and 0.98 + /- 0.29 mmol/L ( P = 0.002 ) , respectively . Neither EPA nor DHA had significant effects on glycated hemoglobin , fasting insulin or C-peptide , insulin sensitivity or secretion , or blood pressure . Serum triacylglycerols in the EPA and DHA groups decreased 19 % ( P = 0.022 ) and 15 % ( P = 0.022 ) , respectively . There were no significant changes in serum total , LDL , or HDL cholesterol , although HDL(2 ) cholesterol in the EPA and DHA groups increased 16 % ( P = 0.026 ) and 12 % ( P = 0.05 ) , respectively . HDL(3 ) cholesterol decreased 11 % ( P = 0.026 ) with EPA supplementation . CONCLUSIONS EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients . The overall implication s for cardiovascular disease require long-term evaluation Objective —A large-scale , prospect i ve , r and omized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid ( EPA ) to low-dose statin therapy significantly reduces the incidence of major coronary events . Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules . Methods and Results —A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 ( VCAM-1 ) and nuclear translocation of nuclear factor-&kgr;B p65 in EPA-treated mice relative to vehicle-treated groups . In an in vitro adhesion assay system under physiological flow conditions , EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules . We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 ( sICAM-1 ) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA ( 1.8 g daily ) . Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1 . Conclusions —This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro BACKGROUND Although some reports have indicated that acute phase proteins such as C-reactive protein ( CRP ) and serum amyloid A ( SAA ) can predict the prognosis in patients with acute coronary syndrome , the value of these markers in patients with stable coronary artery disease ( CAD ) still remains obscure . Therefore , our aim was to determine the prognostic value of inflammatory markers in patients with stable coronary artery disease . METHODS AND RESULTS We conducted a prospect i ve cohort study in 140 consecutive patients with stable coronary artery disease who had at least one coronary stenosis more than 50 % in diameter seen on diagnostic coronary angiography ( CAG ) .  We determined serum levels of the SAA/LDL complex as a new marker in addition to CRP and SAA .  Serum levels of the SAA/LDL complex  were measured by a s and wich enzyme-linked immunosorbent assay ( ELISA ) . End-points were defined as cardiac death , myocardial infa rct ion , cerebral infa rct ion , and coronary revascularization . End-point events occurred in 21 patients ( 2 death from myocardial infa rct ion , 2 cerebral infa rct ion , and 17 revascularization ) . Age ( year ) ( OR = 1.14 , CI : 1.05 - 1.25 ) , diabetes mellitus ( OR = 3.50 , CI : 1.08 - 11.40 ) , triglyceride ( 10mg/dl ) ( OR = 1.12 , CI : 1.01 - 1.23 ) and SAA/LDL complex ( 10 microg/ml ) ( OR = 2.32 , CI : 1.05 - 4.70 ) were independently related to the events . A reconstitution experiment suggested that the SAA/LDL complex is derived by oxidative interaction between SAA and lipoproteins . CONCLUSIONS The SAA/LDL complex reflects intravascular inflammation directly and can be a new marker more sensitive than CRP or SAA for prediction of prognosis in patients with stable coronary artery disease Consumption of fish or fish oils rich in the n-3 long chain PUFA EPA and DHA may improve multiple risk factors for CVD . The objective of this study was to determine whether regular consumption of foods enriched with n-3 long-chain PUFA can improve n-3 long-chain PUFA status ( erythrocytes ) and cardiovascular health .  Overweight volunteers with high levels of triacylglycerols ( TG ; > 1.6 mmol/l ) were enrolled in a 6-month dietary intervention trial conducted in Adelaide ( n 47 ) and Perth ( n 39 ) , and r and omised to consume control foods or n-3-enriched foods  to achieve an EPA + DHA intake of 1 g/d . Test foods were substituted for equivalent foods in their regular diet .  Erythrocyte fatty acids , plasma TG and other CVD risk factors were monitored at 0 , 3 and 6 months . There were no significant differences between groups for blood pressure , arterial compliance , glucose , insulin , lipids , C-reactive protein ( CRP ) or urinary 11-dehydro-thromboxane B2 ( TXB2 ) over 6 months , even though regular consumption of n-3-enriched foods increased  EPA + DHA intake from 0.2 to 1.0 g/d . However , the n-3 long-chain PUFA content of erythrocytes increased by 35 and 53 % at 3 and 6 months , respectively , in subjects consuming the n-3-enriched foods . These increases were positively associated with measures of arterial compliance and negatively associated with serum CRP and urinary 11-dehydro-TXB2 excretion . Sustainable increases in dietary intakes and erythrocyte levels of n-3 long-chain PUFA can be achieved through regular consumption of suitably enriched processed foods . Such increases may be associated with reduced CV risk Subjects with the metabolic syndrome ( MetS ) have enhanced oxidative stress and inflammation . Dietary fat quality has been proposed to be implicated in these conditions . We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α ( a major F2-isoprostane and oxidative stress indicator ) , 15-keto-13,14-dihydro-PGF2α ( 15-keto-dihydro-PGF2α , a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation ) and C-reactive protein ( CRP ) . In a 12-week parallel multicentre dietary intervention study ( LIPGENE ) , 417 volunteers with the MetS were r and omly assigned to one of the four diets : two high-fat diets ( 38 % energy ( % E ) ) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets ( 28 % E ) with ( LFHCC n-3 ) or without ( LFHCC ) 1·24 g/d of very long chain n-3 fatty acid supplementation . Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels . Serum concentration of CRP was measured by ELISA . Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline ( P>0·07 ) or at the end of the study ( P>0·44 ) . Also , no differences in changes of the markers were observed between the diet groups ( 8-iso-PGF2α , P = 0·83 ; 15-keto-dihydro-PGF2α , P = 0·45 ; and CRP , P = 0·97 ) . In conclusion , a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study BACKGROUND Japan EPA Lipid Intervention Study ( JELIS ) was a large-scale clinical trial examining the effects of eicosapentaenoic acid ( EPA ) on coronary artery disease ( CAD ) in hypercholesterolemic patients . Herein , we focused on risk factors other than low-density lipoprotein cholesterol ( LDL-C ) to investigate the effects of EPA on CAD among JELIS primary prevention cases . METHODS Hypercholesterolemic patients on statin therapy but without evidence of CAD ( n=14,981 ) were r and omly assigned to an EPA group ( n=7503 ) or a control group ( n=7478 ) . The relationships between incident CAD , the number of CAD risk factors ( hypercholesterolemia ; obesity ; high triglyceride ( TG ) or low high-density lipoprotein cholesterol ( HDL-C ) ; diabetes ; and hypertension ) and EPA treatment were investigated . RESULTS For the control and EPA groups combined , a higher number of risk factors was directly associated with an increased incidence of CAD . Incidence was lower for the EPA group than for the control group regardless of the numbers of risk factors . Compared to patients with normal serum TG and HDL-C levels , those with abnormal levels ( TG > or=150 mg/dL ; HDL-C < 40 mg/dL ) had significantly higher CAD hazard ratio ( HR : 1.71 ; 95 % CI : 1.11 - 2.64 ; P=0.014 ) . In this higher risk group , EPA treatment suppressed the risk of CAD by 53 % ( HR : 0.47 ; 95 % CI : 0.23 - 0.98 ; P=0.043 ) . CONCLUSIONS Multiple risk factors besides cholesterol are associated with markedly increased incidence of CAD . High TG with low HDL-C represents a particularly potent risk factor . EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern , suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels OBJECTIVE Results from epidemiologic studies and clinical trials have indicated that consumption of omega-3 fatty acids , oleic acid , and folic acid have beneficial effects on health , including decreased risk of cardiovascular disease . We evaluated the combined effects of these nutrients through the consumption of milk enriched with omega-3 polyunsaturated fatty acids , oleic acid , vitamins E and B6 , and folic acid on risk factors for cardiovascular disease in volunteers with mild hyperlipidemia . METHODS Thirty subjects ages 45 to 65 y ( 51.3 + /- 5.3 y ) were given 500 mL/d of semi-skimmed milk for 4 wk and then 500 mL/d of the enriched milk for 8 wk .  Plasma and low-density lipoproteins were obtained at the beginning of the study and at 4 , 8 , and 12 wk . RESULTS Consumption of enriched milk for 8 wk increased plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid and significantly ( P < 0.05 ) decreased plasma concentrations of triacylglycerol ( 24 % ) , total cholesterol ( 9 % ) , and low-density lipoprotein cholesterol ( 13 % ) . Plasma and low-density lipoprotein oxidation and vitamin E concentration remained unchanged throughout the study . Significant decreases in plasma concentrations of vascular cell adhesion molecule-1 ( 9 % ) and homocysteine ( 17 % ) were found , accompanied by a 98 % increase in plasma concentration of folic acid . CONCLUSIONS Dairy supplementation strategies with omega-3 polyunsaturated fatty acids , oleic acid , and vitamins may be useful for decreasing risk factors for cardiovascular disease BACKGROUND & AIMS LDL phenotype B is associated with obesity , insulin resistance , hypertriglyceridemia and oxidative stress . The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated . METHODS Patients with metabolic syndrome ( n=99 ) received one of four isocaloric diets : ( A ) High-fat ( 38 % energy ) SFA-rich diet ( HSFA ) ; ( B ) High-fat ( 38 % energy ) , MUFA-rich diet ( HMUFA ) ; ( C ) , low-fat ( LF ) ( 28 % energy ) , high-complex carbohydrate diet with 1.24g/d oleic sunflower oil ( LFHCC ) and ( D ) : low-fat ( 28 % energy ) , high-complex carbohydrate diet , with 1.24g/d LC n-3 PUFA ( LFHCC n-3 ) for 12 weeks . Analysis of plasma lipid profile and LDL phenotype was done pre- and post- interventions . RESULTS Post-dietary change of LDL density was a main effect observed in all groups . LFHCC n-3 and HFMUFA diets result ed in favorable alteration of LDL phenotype from B to A and decreased LDL density . In contrast , increased LDL density was observed in HSFA and LFHCC groups . The plasma pre-n3/n6 PUFA , Apo E change and pre-Apo CIII/CII ratios explained in 65 % the post-dietary change of LDL density in diet LFHCC n-3 consumers . CONCLUSIONS Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome . Study identifier at Clinical Trials.gov was NCT00429195 Fatty acids ( FA ) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA . Here we tested for acute effects of marine n-3 FA on insulin sensitivity , insulin secretion , energy metabolism , and oxidative stress . This was a r and omized , double-blind , crossover study in 11 subjects with type 2 diabetes mellitus . A 4-hour lipid infusion ( Intralipid [ Fresenius Kabi , Halden , Norway ] , total of 384 mL ) was compared with a similar lipid infusion partly replaced by Omegaven ( Fresenius Kabi ) that contributed a median of 0.1 g fish oil per kilogram body weight , amounting to 0.04 g/kg of marine n-3 FA . Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps ; insulin secretion ( measured after the clamps ) , by C-peptide glucagon tests ; and energy metabolism , by indirect calorimetry . Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids ( NEFA ) compared with Intralipid alone ( 20:5n-3 : median , 1.5 % [ interquartile range , 0.6 % ] vs -0.2 % [ 0.2 % ] , P = .001 ; 22:6n-3 : 0.8 % [ 0.4 % ] vs -0.7 % [ 0.2 % ] , P = .001 ) . However , glucose utilization was not affected ; neither was insulin secretion or total energy production ( P = .966 , .210 , and .423 , respectively , for the differences between the lipid clamps ) . Omegaven tended to lower oxidation of fat ( P = .062 ) compared with Intralipid only , correlating with the rise in individual n-3 NEFA ( r = 0.627 , P = .039 ) . The effects of clamping on phospholipid FA composition , leptin , adiponectin , or F(2)-isoprostane concentrations were not affected by Omegaven . Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity , insulin secretion , or markers of oxidative stress in subjects with type 2 diabetes mellitus Since the first AHA Science Advisory “ Fish Consumption , Fish Oil , Lipids , and Coronary Heart Disease,”1 important new findings , including evidence from r and omized controlled trials ( RCTs ) , have been reported about the beneficial effects of omega-3 ( or n-3 ) fatty acids on cardiovascular disease ( CVD ) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function ( including antiarrhythmic effects ) , hemodynamics ( cardiac mechanics ) , and arterial endothelial function have helped clarify potential mechanisms of action . The present Statement will address distinctions between plant-derived ( α-linolenic acid , C18:3n-3 ) and marine-derived ( eicosapentaenoic acid , C20:5n-3 [ EPA ] and docosahexaenoic acid , C22:6n-3 [ DHA ] ) omega-3 fatty acids . ( Unless otherwise noted , the term omega-3 fatty acids will refer to the latter . ) Evidence from epidemiological studies and RCTs will be review ed , and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid ( plant- and marine-derived ) supplementation . This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration ( FDA ) about the presence of environmental contaminants in certain species of fish . # # # Coronary Heart Disease As review ed by Stone,1 three prospect i ve epidemiological studies within population s reported that men who ate at least some fish weekly had a lower coronary heart disease ( CHD ) mortality rate than that of men who ate none.3–6 ⇓ ⇓ ⇓ More recent evidence that fish consumption favorably affects CHD mortality , especially nonsudden death from myocardial infa rct ion ( MI ) , has been reported in a 30-year follow-up of the Chicago Western Electric Study .7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33 . In an Abstract Postpr and ial lipemia is associated with elevated risk of cardiovascular disease . Very little data exists regarding postpr and ial response in subjects with metabolic syndrome ( MetS ) . The current study was conducted within the LIPGENE EU Integrated Project . Patients were r and omized to one of the four isocaloric fatty meals ( Oral Fat Tolerance Tests , OFTT ) : ( A ) high-fat , saturated fatty acid (SFA)-rich ( HFSA ) , ( B ) high-fat , monounsaturated fatty acid (MUFA)-rich ( HFMUFA ) , ( C ) low-fat , high-complex carbohydrate with 1.24 g high oleic sunflower oil supplement ( LFHCC ) and ( D ) low-fat high-complex carbohydrate with 1.24 g long chain n-3 poly-unsaturated fatty acid ( LC n-3 PUFA ) supplement ( LFHCCn-3 ) . The total and incremental areas under the curve ( tAUC and iAUC ) of plasma lipid and lipoprotein , Ischemia Modified Albumin ( IMA ) and LDL density were examined in patients with MetS to define effect of OFTT . All types of OFTT transiently increased plasma triglyceride and LDL density ( LDLdens ) . It was paralleled by temporal decrease in total cholesterol ( TC ) , LDL cholesterol ( LDL-C ) , and HDL cholesterol ( HDL-C ) . This last effect was partly alleviated in LFHCCn-3 test . A reversible increase of IMA was statistically significant only in the course of HSFA and HMUFA tests . EPA and DHA supplement in combined high complex-carbohydrate meal may attenuate adverse effect of tested meal on LDL particle profile and plasma ischemia modified albumin . No expected associations between measures of central adiposity ( waist , WHR ) , adipose tissue insulin resistance ( Adipo-IR ) , and postpr and ial responses of TG , TC , LDL-C , HDL-C , LDLdens and IMA/Alb ratio were found in subgroup analysis . Trial registration : Clinical Trials.gov identifier : NCT00429195
Metabolic syndrome ( MS ) is characterised by accumulation of CVD risk factors .
The use of very long chain n-3 polyunsaturated fatty acids ( VLC n3 PUFA ) could potentially benefit MS by reducing risk factors .