Circulating triacylglycerol and apoE levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil. Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on fatty acid absorption, incorporation into serum phospholipids and postprandial triglyceridemia EPA, but not DHA, decreases mean platelet volume in normal subjects Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Differential eicosapentaenoic acid elevations and altered cardiovascular disease risk factor responses after supplementation with docosahexaenoic acid in postmenopausal women receiving and not receiving hormone replacement therapy. 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. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Triacylglycerol-rich lipoprotein margination: a potential surrogate for whole-body lipoprotein lipase activity and effects of eicosapentaenoic and docosahexaenoic acids. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study. The effect of highly purified eicosapentaenoic and docosahexaenoic acids on monocyte phagocytosis in man Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Influence of three rapeseed oil-rich diets, fortified with α-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages. Comparison of the Effects of Eicosapentaenoic Acid With Docosahexaenoic Acid on the Level of Serum Lipoproteins in Helicobacter pylori: A Randomized Clinical Trial Docosahexaenoic and eicosapentaenoic acids in plasma phospholipids are divergently associated with high density lipoprotein in humans. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on the oxidizability and thrombogenicity of low-density lipoprotein. Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance Published, JLR Papers in Press, December 1, 2002. DOI 10.1194/jlr.M200282-JLR200 Omega-3 Fatty Acids in Cardiac Biopsies From Heart Transplantation Patients: Correlation With Erythrocytes and Response to Supplementation Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Vascular Reactivity of the Forearm Microcirculation in Hyperlipidemic, Overweight Men Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study. Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial. Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men. Differential effects of EPA versus DHA on postprandial vascular function and the plasma oxylipin profile in men[S] The Omega-3 Index: a new risk factor for death from coronary heart disease? Reduction of prothrombin and Factor V levels following supplementation with omega-3 fatty acids is sex dependent: a randomised controlled study. The omega-3 fatty acids EPA and DHA decrease plasma F2-isoprostanes: Results from two placebo-controlled interventions A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. The cumulative dose response effect of eicosapentaenoic and docosahexaenoic acid on blood pressure, plasma lipid profile and diet pattern in mild to moderate essential hypertensive black patients. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans.
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 Animal studies suggest that the 2 major omega3 fatty acids found in fish , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , may have differential effects on blood pressure ( BP ) and heart rate ( HR ) . The aim of this study was to determine whether there were significant differences in the effects of purified EPA or DHA on ambulatory BP and HR in humans . In a double-blind , placebo-controlled trial of parallel design , 59 overweight , mildly hyperlipidemic men were r and omized to 4 g/d of purified EPA , DHA , or olive oil ( placebo ) capsules and continued their usual diets for 6 weeks . Fifty-six subjects completed the study . Only DHA reduced 24-hour and daytime ( awake ) ambulatory BP ( P<0.05 ) . Relative to the placebo group , 24-hour BP fell 5.8/3.3 ( systolic/diastolic ) mm Hg and daytime BP fell 3.5/2.0 mm Hg with DHA . DHA also significantly reduced 24-hour , daytime , and nighttime ( asleep ) ambulatory HRs ( P=0 . 001 ) . Relative to the placebo group , DHA reduced 24-hour HR by 3 . 5+/-0.8 bpm , daytime HR by 3.7+/-1.2 bpm , and nighttime HR by 2 . 8+/-1.2 . EPA had no significant effect on ambulatory BP or HR . Supplementation with EPA increased plasma phospholipid EPA from 1 . 66+/-0.07 % to 9.83+/-0.06 % ( P<0.0001 ) but did not change DHA levels . Purified DHA capsules increased plasma phospholipid DHA levels from 4.00+/-0.27 % to 10.93+/-0.62 % ( P<0.0001 ) and led to a small , nonsignificant increase in EPA ( 1.52+/-0.12 % to 2.26+/-0.16 % ) . Purified DHA but not EPA reduced ambulatory BP and HR in mildly hyperlipidemic men . The results of this study suggest that DHA is the principal omega3 fatty acid in fish and fish oils that is responsible for their BP- and HR-lowering effects in humans . These results have important implication s for human nutrition and the food industry OBJECTIVES To investigate the impact of apolipoprotein E ( apoE ) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid ( EPA ) versus docosahexaenoic acid ( DHA ) intervention in humans . METHODS AND RESULTS 38 healthy normolipidaemic males , prospect ively recruited on the basis of apoE genotype ( n=20 E3/E3 and n=18 E3/E4 ) , completed a double-blind placebo-controlled cross-over trial , consisting of 3 x 4 week intervention arms of either control oil , EPA-rich oil ( ERO , 3.3 g EPA/day ) or DHA-rich oil ( DRO , 3.7 g DHA/day ) in r and om order , separated by 10 week wash-out periods . A significant genotype-independent 28 % and 19 % reduction in plasma triglycerides in response to ERO and DRO was observed . For total cholesterol ( TC ) , no significant treatment effects were evident ; however a significant genotype by treatment interaction emerged ( P=0.045 ) , with a differential response to ERO and DRO in E4 carriers . Although the genotype x treatment interaction for LDL-cholesterol ( P=0.089 ) did not reach significance , within DRO treatment analysis indicated a 10 % increase in LDL ( P=0.029 ) in E4 carriers with a non-significant 4 % reduction in E3/E3 individuals . A genotype-independent increase in LDL mass was observed following DRO intervention ( P=0.018 ) . Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins ( VLDL ) from the human trial , indicated that following DRO treatment , VLDL(2 ) fractions obtained from E3/E4 individuals result ed in a significant 32 % ( P=0.002 ) reduction in LDL uptake relative to the control . CONCLUSIONS High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers , which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup BACKGROUND Recent studies suggest that eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids have distinct effects on cardiometabolic risk factors . The Omega-3 Index ( O3I ) , which is calculated as the proportion of EPA and DHA in red blood cell ( RBC ) membranes , has been inversely associated with the risk of coronary heart diseases and coronary mortality . The objective of this study was to compare the effects of EPA and DHA supplementation on the O3I in men and women with abdominal obesity and sub clinical inflammation . METHODS In a double-blind controlled crossover study , 48 men and 106 women with abdominal obesity and sub clinical inflammation were r and omized to a sequence of three treatment phases : 1 - 2.7g/d of EPA , 2 - 2.7g/d of DHA , and 3 - 3g/d of corn oil ( 0 g of EPA+DHA ) . All supplements were provided as 3 × 1 g capsules for a total of 3g/d . The 10-week treatment phases were separated by nine-week washouts . RBC membrane fatty acid composition and O3I were assessed at baseline and the end of each phase . Differences in O3I between treatments were assessed using mixed models for repeated measures . RESULTS The increase in the O3I after supplementation with DHA ( + 5.6 % compared with control , P<0.0001 ) was significantly greater than after EPA ( + 3.3 % compared with control , P<0.0001 ; DHA vs. EPA , P<0.0001 ) . Compared to  control , DHA supplementation decreased ( -0.8 % , P<0.0001 ) while EPA increased ( + 2.5 % , P<0.0001 ) proportion of docosapentaenoic acid ( DPA ) in RBCs ( DHA vs. EPA , P<0.0001 ) . The baseline O3I was higher in women than in men ( 6.3 % vs. 5.8 % , P=0.011 ) . The difference between DHA and EPA in increasing the O3I tended to be higher in men than in women ( + 2.6 % vs. + 2.2 % respectively , P for the treatment by sex interaction=0.0537 ) . CONCLUSIONS The increase in the O3I is greater with high dose DHA supplementation than with high dose EPA , which is consistent with the greater potency of DHA to modulate cardiometabolic risk factors . The extent to which such differences between EPA and DHA in increasing the O3I relates to long-term cardiovascular risk needs to be investigated in the future Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects , but less is known about the independent effects of DHA . This study was design ed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss . In this r and omized , controlled , double-blind trial , 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo . Markers of cardiovascular risk were assessed before and after treatment . In the DHA-supplemented group , the decrease in mean VLDL particle size ( P ≤ 0.001 ) and increases in mean LDL ( P ≤ 0.001 ) and HDL ( P ≤ 0.001 ) particle sizes were significantly greater than changes in the placebo group . DHA supplementation also increased the concentrations of large LDL ( P ≤ 0.001 ) and large HDL particles ( P = 0.001 ) and decreased the concentrations of small LDL ( P = 0.009 ) and medium HDL particles ( P = 0.001 ) . As calculated using NMR-derived data , DHA supplementation reduced VLDL TG ( P = 0.009 ) and total TG concentrations ( P = 0.006 ) . Plasma IL-10 increased with DHA supplementation to a greater extent than placebo ( P = 0.021 ) , but no other significant changes were observed in glucose metabolism , insulin sensitivity , blood pressure , or markers of inflammation with DHA . In summary , DHA supplementation result ed in potentially beneficial changes in some markers of cardiometabolic risk , whereas other markers were unchanged The aim of this study was to determine whether eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , or both , were responsible for the triglyceride (TG)-lowering effects of fish oil . EPA ( 91 % pure ) and DHA ( 83 % pure ) , a fish oil concentrate ( FOC ; 41 % EPA and 23 % DHA ) and an olive oil ( OO ) placebo ( all ethyl esters ) were tested . A total of 49 normolipidemic subjects participated . Each subject was given placebo for 2–3 wk and one of the n-3 supplements for 3 wk in r and omized , blinded trials . The target n-3 fatty acid ( FA ) intake was 3 g/day in all studies . Blood sample s were drawn twice at the end of each supplementation phase and analyzed for lipids , lipoproteins , and phospholipid FA composition . In all groups , the phospholipid FA composition changed to reflect the n-3 FA given . On DHA supplementation , EPA levels increased to a small but significant extent , suggesting that some retroconversion may have occurred . EPA supplementation did not raise DHA levels , however , FOC and EPA produced significant decreases in both TG and very low density lipoprotein ( VLDL ) cholesterol ( C ) levels ( P<0.01 ) and increases in low density lipoprotein ( LDL ) cholesterol levels ( P<0.05 ) . DHA supplementation did not affect cholesterol , triglyceride , VLDL , LDL , or high density lipoprotein ( HDL ) levels , but it did cause a significant increase in the HDL2/HDL3 cholesterol ratio . We conclude that EPA appears to be primarily responsible for TG-lowering ( and LDL-C raising ) effects of fish oil Fourteen healthy volunteers were r and omly allocated to receive 4 g highly purified ethyl esters of eicosapentaenoic acid ( EPA ) ( 95 % pure , n=7 ) or docosahexaenoic acid ( DHA ) ( 90 % pure , n=7 ) daily for 5 wk in supplement to their ordinary diet . The n−3 fatty acids were given with a st and ard high-fat meal at the beginning and the end of the supplementation period . EPA and DHA induced a similar incorporation into chylomicrons which peaked 6 h after the meal . The relative uptake of EPA and DHA from the meal was > 90 % compared with the uptake of oleic acid . During absorption , there was no significant elongation or retroconversion of EPA or DHA in total chylomicron fatty acids . The concentration of EPA decreased by 13 % and DHA by 62 % ( P<0.001 ) between 6 and 8 h after the meal . During the 5-wk supplementation period , EPA showed a more rapid and comprehensive increase in serum phospholipids than did DHA . DHA was retroconverted to EPA , whereas EPA was elongated to docosapentaenoic acid ( DPA ) . The postpr and ial triglyceridemia was suppressed by 19 and 49 % after prolonged intake of EPA and DHA , respectively , indicating that prolonged intake of DHA is equivalent to or even more efficient than that of EPA in lowering postpr and ial triglyceridemia . This study indicates that there are metabolic differences between EPA and DHA which may have implication s for the use of n−3 fatty acids in preventive and clinical medicine The first indication of platelet activation is an increase in mean platelet volume ( MPV ) . n−3 FA are known to inhibit platelet function and to reduce the risk for coronary heart disease . The purpose of this study was to determine the effects of FPA and DHA on MPV . Healthy subjects received olive oil placebo for 4 wk and then were r and omly assigned to receive 4 g of ethyl esters of either safflower oil ( n=11 ) , EPA ( n=10 ) , or DHA ( n=12 ) for 4 wk . At the end of placebo run-in and treatment periods , MPV ( fL ; mean±SEM ) and platelet count ( PLT-CT ; 103/μL blood ) were measured in the basal state and after ex vivo stimulation with collagen ( 10 μg/mL ) , cold ( 4 ° C ) , and heat ( 37 ° C ) . Unlike DHA , EPA lowered MPV as compared with safflower oil ( 7.2±0.1 vs. 7.5±0.1 fL ; P<0.05 ) and raised PLT-CT ( 211±18 vs. 192±18 103/μL ; P<0.05 ) in the fasting state . Collagen and cold significantly increased MPV whereas heat lowered MPV regardless of treatment . All stimuli decreased PLT-CT . EPA significantly increased platelet EPA ( 0.2±0.1 vs. 3.3±0.4 % ) and docosapentaenoic acid ( DPA ; 2.2±0.3 vs. 2.9±0.3 % ) concentrations , but not DHA .  DHA treatment significantly increased DHA ( 1.4±0.2 vs. 4.1±0.5 % ) and DPA ( 2.0±0.4 vs. 3.0±0.4 % ) concentrations , but not EPA . In conclusion , EPA , but not DHA , reduces platelet activation , an early step in platelet aggregation To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on serum lipids , apolipoproteins , and serum phospholipid fatty acids in humans , we conducted a double-blind , placebo-controlled , parallel design intervention study . Healthy nonsmoking men ( n = 234 ) aged 36 - 56 y were r and omly assigned to dietary supplementation with 3.8 g EPA/d , 3.6 g DHA/d , or 4.0 g corn oil/d ( placebo ) for 7 wk . Serum triacylglycerols decreased 26 % ( P < 0.0001 ) in the DHA group and 21 % ( P = 0.0001 ) in the EPA group compared with the corn oil group . Although not significant , net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations . Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L ( P = 0.0002 ) in the DHA group . In the EPA group , serum total cholesterol decreased 0.15 mmol/L ( P = 0.02 ) and apolipoprotein A-I decreased 0.04 g/L ( P = 0.0003 ) . In the DHA group , serum phospholipid DHA increased by 69 % and EPA increased by 29 % , indicating retroconversion of DHA to EPA . In the EPA group , serum phospholipid EPA increased by 297 % whereas DHA decreased by 15 % , suggesting that EPA is not elongated to DHA in humans . The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups , whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group . We conclude that both DHA and EPA decrease serum triacylglycerols , but have differential effects on lipoprotein and fatty acid metabolism in humans The hemodynamic effects of highly purified eicosapentaenoic acid ( EPA , 20:5n-3 ) and docosahexaenoic acid ( DHA , 22:6n-3 ) have not been evaluated in humans . We therefore conducted a r and omized , double-blind , parallel- design intervention study to assess possible separate effects of EPA and DHA on blood pressure , heart rate , and cardiac mechanics .  Healthy , nonsmoking men aged 36 - 56 y ( n = 224 ) were r and omly assigned to dietary supplementation with 4 g/d of ethyl ester concentrates of DHA or EPA or 4 g corn oil/d ( control ) .  Mean blood pressure at baseline was 122/77 mm Hg and was positively associated with concentrations of serum phospholipid saturated fatty acids . Blood pressure did not change during the intervention . Mean heart rate at baseline was 63.4 beats/min ; it decreased 2.2 beats/min in the DHA group ( P = 0.006 compared with control ) , increased 1.9 beats/min in the EPA group ( P = 0.04 compared with control ) , and remained practically unchanged in the control group . In a pooled analysis , changes in heart rate were independent of baseline heart rate and were associated with changes in concentrations of serum phospholipid DHA and docosapentaenoic acid ( 22:5n-3 ) . Echocardiography in a sub sample of 52 men showed improved left ventricular diastolic filling in the marine oil groups compared with the corn oil group ( P = 0.02 ) . In contrast , an increase in plasma concentrations of saturated fatty acids was associated with delayed diastolic filling . We conclude that dietary DHA and EPA influence heart rate and that the fatty acid composition of plasma phospholipids may affect cardiac mechanics in humans BACKGROUND Dietary docosahexaenoic acid ( DHA ) has triacylglycerol-lowering potential and undergoes in vivo retroconversion to eicosapentaenoic acid ( EPA ) in humans . Hormone replacement therapy ( HRT ) influences circulating lipid concentrations and fatty acid metabolism . DHA supplementation has not been studied in postmenopausal women . OBJECTIVE We studied the effects of supplementation with DHA ( free of EPA ) on the result ing elevation in EPA and on selected cardiovascular disease risk factors in postmenopausal women . DESIGN Women receiving ( n = 18 ) and not receiving ( n = 14 ) HRT completed a r and omized , double-blind , placebo-controlled crossover trial with a DHA supplement ( 2.8 g DHA/d ) . A washout period of > or = 6 wk divided the two 28-d intervention periods . Fasting blood sample s were collected for analysis . RESULTS In all women , DHA supplementation was associated with significant changes ( P < 0.05 ) , including 20 % lower serum triacylglycerol concentrations , 8 % higher HDL-cholesterol concentrations , a 28 % lower overall ratio of serum triacylglycerol to HDL cholesterol , and a 7 % decrease in resting heart rate .  DHA supplementation result ed in a 45 % lower net increase ( P = 0.02 ) in EPA and a 42 % lower ( P = 0.0028 ) estimated percentage retroconversion of DHA to EPA [ DeltaEPA/(DeltaEPA + DeltaDHA ) x 100 ] in women receiving than in those not receiving HRT . CONCLUSION With DHA supplementation , the accumulation of EPA in serum phospholipids is significantly attenuated in postmenopausal women receiving HRT compared with that in women not receiving HRT . DHA supplementation can also favorably influence selected cardiovascular disease risk factors in postmenopausal women 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 BACKGROUND n-3 Fatty acids influence vascular function , but the effect of individual fatty acids on systemic arterial compliance ( SAC ) has not been reported . SAC , which reflects arterial elasticity , is emerging as a new cardiovascular risk factor and appears to predict future cardiovascular events . OBJECTIVE We tested whether the n-3 fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) improve SAC in dyslipidemic subjects . DESIGN Thirty-eight dyslipidemic subjects were r and omly assigned to receive 3 g EPA/d ( n = 12 ) , 3 g DHA/d ( n = 12 ) , or a placebo ( n = 14 ) in a 7-wk parallel , double-blind trial . Arterial functions were measured at the beginning and end of the interventions . Plasma lipids and plasma fatty acids were also measured . RESULTS Consumption of the n-3 fatty acids significantly increased SAC , whereas consumption of the placebo did not ( P = 0.043 ; repeated- measures analysis of variance across the 3 groups ) ; the increase was 36 % with EPA and 27 % with DHA . The major components contributing to the increase in SAC ( systolic and pulse pressures and total vascular resistance ) tended to decrease but not significantly . Plasma total and VLDL triacylglycerol were significantly lower in the n-3 fatty acid groups ( P = 0.026 and 0.006 , respectively ; repeated- measures analysis of variance ) than in the placebo group . CONCLUSION EPA and DHA increase SAC and tend to reduce pulse pressure and total vascular resistance , effects that may reduce the risk of adverse cardiovascular events BACKGROUND Margination occurs when blood borne particles attach to the vessel wall . Triacylglycerol-rich lipoprotein ( TRL ) particles marginate when they bind to endothelial lipoprotein lipase ( LpL ) . OBJECTIVE This study was undertaken to determine whether TRL margination reflects in vivo LpL activity and whether n-3 fatty acids affect fasting and fed TRL margination . DESIGN Healthy subjects ( n = 33 ) began with a 4-wk , placebo ( olive oil ; 4 g/d ) run-in period and were then r and omly assigned to 4 wk of treatment with 4 g/d of ethyl esters of either safflower oil ( SAF ; control ) , eicosapentaenoic acid ( EPA ) , or docosahexaenoic acid ( DHA ) .  Margination volume ( MV ) was calculated by subtracting true from apparent plasma volume . RESULTS MVs were 3 times as great during the fasting state as during the fed state ( P < 0.0001 ) . In both the fasting and the fed states , MV was significantly correlated with plasma triacylglycerol and TRL half-lives . In the fed state , MV was also correlated with preheparin LpL , whereas in the fasting state it was not . There was no significant correlation between preheparin LpL and postheparin LpL in the fasting state . Relative to SAF , EPA and DHA supplementation result ed in higher MVs by 64 % and 53 % ( both P < 0.001 ) , respectively , in the fasting state , without significantly reducing fasting triacylglycerol concentrations . In the fed state , DHA doubled the MV ( P < 0.05 ) , whereas EPA had no significant effect . CONCLUSIONS The correlations between MV and TRL half-lives and preheparin LpL suggest that MV could be a reflection of whole-body LpL binding capacity . The increases in MVs with EPA and DHA supplementation suggest that these fatty acids may increase the amount of endothelial-bound LpL or its affinity for TRL BACKGROUND Supplementation of the diet with fish oil , which is rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , is reported to decrease several markers of immune function . However , whether EPA , DHA , or a combination of the 2 exerts these immunomodulatory effects is unclear . OBJECTIVE The objective of the study was to determine the effects of supplementation with an EPA-rich or DHA-rich oil on a range of immune outcomes representing key functions of human neutrophils , monocytes , and lymphocytes in healthy humans . DESIGN In a placebo-controlled , double-blind , parallel study , 42 healthy subjects were r and omly allocated to receive supplementation with either placebo ( olive oil ) , EPA ( 4.7 g/d ) , or DHA ( 4.9 g/d ) for 4 wk . Blood sample s were taken before and after supplementation . RESULTS The fatty acid composition of plasma phospholipids and neutrophils was dramatically altered by supplementation with EPA or DHA , and the effects of EPA differed notably from those of DHA . DHA supplementation decreased T lymphocyte activation , as assessed by expression of CD69 , whereas EPA supplementation had no significant effect . Neither the EPA-rich oil nor the DHA-rich oil had any significant effect on monocyte or neutrophil phagocytosis or on cytokine production or adhesion molecule expression by peripheral blood mononuclear cells . CONCLUSIONS Supplementation with DHA , but not with EPA , suppresses T lymphocyte activation , as assessed by expression of CD69 . EPA alone does not , therefore , influence CD69 expression . No other marker of immune function assessed in this study was significantly affected by either EPA or DHA BACKGROUND To date , most studies on the anti-inflammatory effects of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) in humans have used a mixture of the 2 fatty acids in various forms and proportions . OBJECTIVES We compared the effects of EPA supplementation with those of DHA supplementation ( re-esterified triacylglycerol ; 90 % pure ) on inflammation markers ( primary outcome ) and blood lipids ( secondary outcome ) in men and women at risk of cardiovascular disease . DESIGN In a double-blind , r and omized , crossover , controlled study , healthy men ( n = 48 ) and women ( n = 106 ) with abdominal obesity and low- grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk : 1 ) EPA ( 2.7 g/d ) , 2 ) DHA ( 2.7 g/d ) , and 3 ) corn oil as a control with each supplementation separated by a 9-wk washout period . Primary analyses assessed the difference in cardiometabolic outcomes  between EPA and DHA . RESULTS Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 ( IL-18 ) ( -7.0 % ± 2.8 % compared with -0.5 % ± 3.0 % , respectively ; P = 0.01 ) and a greater increase in adiponectin ( 3.1 % ± 1.6 % compared with -1.2 % ± 1.7 % , respectively ; P < 0.001 ) . Between DHA and EPA , changes in CRP ( -7.9 % ± 5.0 % compared with -1.8 % ± 6.5 % , respectively ; P = 0.25 ) , IL-6 ( -12.0 % ± 7.0 % compared with -13.4 % ± 7.0 % , respectively ; P = 0.86 ) , and tumor necrosis factor-α ( -14.8 % ± 5.1 % compared with -7.6 % ± 10.2 % , respectively ; P = 0.63  ) were NS . DHA compared with EPA led to more pronounced reductions in triglycerides ( -13.3 % ± 2.3 % compared with -11.9 % ± 2.2 % , respectively ; P = 0.005 ) and the cholesterol : HDL-cholesterol ratio ( -2.5 % ± 1.3 % compared with 0.3 % ± 1.1 % , respectively ; P = 0.006 ) and greater increases in HDL cholesterol ( 7.6 % ± 1.4 % compared with -0.7 % ± 1.1 % , respectively ; P < 0.0001 ) and LDL cholesterol ( 6.9 % ± 1.8 % compared with 2.2 % ± 1.6 % , respectively ; P = 0.04 ) . The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women ( P-treatment × sex interaction = 0.046 ) . CONCLUSIONS DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids . Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk . This trial was registered at clinical trials.gov as NCT01810003 The n-3 fatty acids ( FA ) from marine sources are known to exert antiinflammatory effects on monocyte function . There is still controversy whether n-3 FA may increase the susceptibility to infections . The present study was design ed to assess the effect of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHa ) on monocyte phagocytosis and respiratory burst activity .  Fifty-eight healthy men were r and omized to take a daily supplement of 3.8 g highly purified EPA ( n=20 ) , 3.6 g DHA ( n=19 ) , or corn oil ( n=19 ) for 7 wk . Mononuclear leukocytes were collected , isolated , and cryopreserved prior to and after dietary supplementation . Paired sample s were analyzed in the presence of autologous serum in a crossover design . Monocyte phagocytosis and respiratory burst activity were measured by flow cytometry after ingestion of Escherichia coli . Monocytes retained their phagocytic ability and respiratory burst activity after supplementation . No reduction in internalization of bacteria was registered . Dietary n-3 FA and particularly EPA improved bacterial adherence to the monocyte surface . In the crossover experiments , there was an adverse effect of serum enriched with n-3 FA on bacterial adherence . We conclude that monocytes retain their phagocytic potential after supplementation with purified EPA and DHA BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Objective : To compare the individual effects of dietary α-linolenic acid ( ALA ) , eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) on low-density lipoprotein ( LDL ) fatty acid composition , ex vivo LDL oxidizability and tocopherol requirement . Design , setting and subjects : A r and omized strictly controlled dietary study with three dietary groups and a parallel design , consisting of two consecutive periods . Sixty-one healthy young volunteers , students at a nearby college , were included . Forty-eight subjects ( 13 males , 35 females ) completed the study . Interventions : Subjects received a 2-week wash-in diet rich in monounsaturated fatty acids ( 21 % energy ) followed by experimental diets enriched with about 1 % of energy of ALA , EPA or DHA for 3 weeks . The omega-3 ( n-3 ) fatty acids were provided with special rapeseed oils and margarines . The wash-in diet and the experimental diets were identical , apart from the n-3 fatty acid composition and the tocopherol content , which was adjusted to the content of dienoic acid equivalents . Results : Ex vivo oxidative susceptibility of LDL was highest after the DHA diet , indicated by a decrease in lag time ( −16 % , P<0.001 ) and an increase in the maximum amount of conjugated dienes ( + 7 % , P<0.001 ) . The EPA diet decreased the lag time ( −16 % , P<0.001 ) and the propagation rate ( −12 % , P<0.01 ) . Tocopherol concentrations in LDL decreased in the ALA group ( −13.5 % , P<0.05 ) and DHA group ( −7.3 % , P<0.05 ) . Plasma contents of tocopherol equivalents significantly decreased in all three experimental groups ( ALA group : −5.0 % , EPA group : −5.7 % , DHA group : −12.8 % ) . The content of the three n-3 polyunsaturated fatty acid differently increased in the LDL : on the ALA diet , the ALA content increased by 89 % ( P<0.001 ) , on the EPA diet the EPA content increased by 809 % ( P<0.001 ) and on the DHA diet , the DHA content increased by 200 % ( P<0.001 ) . In addition , the EPA content also enhanced ( without dietary intake ) in the ALA group ( + 35 % , P<0.01 ) and in the DHA group ( + 284 % , P<0.001 ) . Conclusions : Dietary intake of ALA , EPA or DHA led to a significant enrichment of the respective fatty acid in the LDL particles , with dietary EPA preferentially incorporated . In the context of a monounsaturated fatty acid-rich diet , ALA enrichment did not enhance LDL oxidizability , whereas the effects of EPA and DHA on ex vivo LDL oxidation were inconsistent , possibly in part due to further changes in LDL fatty acid composition . Sponsorship : This research was financially supported by the German Federal Ministry of Education and Research ( BMBF ) within the project ‘ NAPUS 2000 – healthy foodstuffs from transgenic rapeseed ’ The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein ( LDL ) oxidation was examined in 20 treated hypertensive subjects . The r and omized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil . Fish oil significantly ( -24 % , P < 0.01 ) reduced plasma triglyceride , and increased LDL-cholesterol ( + 6 % , P < 0.01 compared to corn oil ) . LDL particles were larger ( P < 0.01 ) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride ( P < 0.001 ) both before and after fish oil supplementation , and positively correlated with high density lipoprotein cholesterol ( P < 0.01 ) . Fish oil reduced lag time before onset of copper-induced LDL oxidation ( -25 % , P < 0.001 ) and significantly increased production of thiobarbituric acid-reactive substances ( TBARS ) during oxidation , compared with corn oil . Corn oil had no significant effect on lag time and oxidation rate .  Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL .  Corn oil was without effect . Additionally , macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly ( P < 0.001 ) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids . We conclude that from the st and point of atherosclerosis , fish oil fatty acids adversely raise the susceptibility of LDL to copper-induced and macrophage-mediated oxidation but that the increase in plasma LDL cholesterol concentration reflects an increase in size that may be favorable Background : Helicobacter pylori infection is the most common chronic bacterial infection around the world and an important cause of gastrointestinal disorders , which might be involved in the pathogenesis of some extragastrointestinal disturbances as well as changes in serum lipid profile . Hypolipemic properties of omega-3 fatty acids have been studied in several studies . Objectives : The present study aim ed to compare the effects of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) supplementation on the level of serum lipoproteins in H. pylori . Patients and Methods : In a r and omized , double-blinded , placebo-controlled clinical trial in Iran , 105 Helicobacter pylori were r and omly allocated to receive 2 g of daily EPA ( 35 patients ) , DHA ( 35 patients ) , or medium-chain triglyceride ( MCT ) oil as placebo ( 33 patients ) along with conventional tetra-drug H. pylori eradication regimen for 12 weeks . Results : From 105 included patients , 97 ( 31 in EPA , 33 in DHA , and 33 in control groups ) completed the study and were included in final analysis . The levels of total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) and the ratios of TG/HDL-C , TC/HDL-C , and LDL-C/HDL-C were not significantly different among the three groups , while the level of triglyceride ( TG ) was statistically different . DHA ( -16.6 ± 30.34 ) and control ( + 15.32 ± 56.47 ) groups were statistically different with regard to changes in TG levels ( P = 0.000 ) . Conclusions : There was no difference between the effects of 2 g of EPA or DHA supplementation for 12 weeks on the levels of total cholesterol , LDL-C , HDL-C , TC/HDL-C , TG/HDL-C , and LDL-C/HDL-C ; however , it had a desirable effect on the level of TG in a way that the effect of DHA was clearer The effect of fish oil rich in eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids on serum lipoprotein concentrations is not clear , and it is not known whether EPA and DHA are similarly related to serum lipid or lipoprotein levels . We conducted a r and omized , 10-week , dietary supplementation trial in which the effects of 6 g per day of 85 % EPA and DHA were compared with 6 g per day of corn oil in 156 men and women . Multivariate analyses were used to assess independent relations between plasma phospholipid EPA and DHA and serum lipoprotein levels . In the fish oil group triglycerides fell 21 % ( p less than 0.001 ) and high density lipoprotein cholesterol ( HDL-C ) rose 3.8 % ( p less than 0.05 ) . In the corn oil group triglycerides did not change , but HDL-C rose 6.1 % ( p less than 0.01 ) . Compared with fish oil , apolipoprotein A-I ( apo A-I ) rose 5.1 % after corn oil intake ( p less than 0.05 ) . Plasma EPA and DHA levels rose after fish oil intake and fell after corn oil intake ( all p less than 0.001 ) . The change ( delta ) in EPA was inversely correlated with delta triglycerides ( p = 0.035 ) and positively correlated with delta HDL-C and delta apo A-I ( both p less than 0.001 ) in the multivariate analyses . In contrast , delta DHA was not correlated with delta triglycerides but was inversely correlated with delta HDL-C and delta apo A-I ( both p less than 0.001 ) . St and ardizing for DHA removed the difference in apo A-I levels between groups . This study suggests that EPA and DHA are divergently associated with HDL , possibly through different mechanisms Consumption of oily fish and fish oils is associated with protection against cardiovascular disease . Paradoxically , long-chain polyunsaturated fatty acids present in low-density lipoprotein ( LDL ) are suggested to be susceptible to oxidation . It is not clear whether eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) have similar effects on the susceptibility of LDL to oxidation or whether they affect the thrombogenicity of oxidized LDL . This study examined the influence of highly purified preparations of EPA and DHA on LDL oxidizability and LDL-supported thrombin generation in healthy human volunteers . Forty-two healthy volunteers were r and omly assigned to receive olive oil ( placebo ) , an EPA-rich oil or a DHA-rich oil for 4 weeks at a dose of 9 g oil/day . EPA and DHA were incorporated into LDL phospholipids and cholesteryl esters during the supplementation period , but were progressively lost during ex vivo copper-mediated oxidation . Following supplementation , the EPA treatment significantly increased the formation of conjugated dienes during LDL oxidation compared with baseline , whereas the DHA treatment had no effect . Neither treatment significantly affected the lag time for oxidation , oxidation rate during the propagation phase or maximum diene production . Neither EPA nor DHA significantly affected the thrombotic tendency of oxidized LDL compared with the placebo , although DHA tended to decrease it . In conclusion , there are subtle differences in the effects of EPA and DHA on the oxidizability and thrombogenicity of LDL . DHA does not appear to increase the susceptibility of LDL to oxidation to the same degree as EPA and has a tendency to decrease LDL-supported thrombin generation Omega-3 fatty acids ( FAs ) reduce postpr and ial triacylglycerol ( TG ) concentrations . This study was undertaken to determine whether this effect was due to reduced production or increased clearance of chylomicrons . Healthy subjects ( n = 33 ) began with a 4-week , olive oil placebo ( 4 g/d ) run-in period . After a 4-week wash-out period , subjects were r and omized to supplementation with 4 g/d of ethyl esters of either safflower oil ( SAF ) , eicosapentaenoic acid ( EPA ) , or docosahexaenoic acid ( DHA ) for 4 weeks . Results for  EPA and DHA  were similar , and therefore the data were combined into one ω-3 FA group . Omega-3 FA supplementation  reduced the postpr and ial TG and apolipoprotein B ( apo B)-48 and apoB-100 concentrations by 16 % ( P = 0.08 ) , 28 % ( P < 0.001 ) , and 24 % ( P < 0.01 ) , respectively . Chylomicron TG half-lives in the fed state were reduced after ω-3 FA treatment ( 6.0 ± 0.5 vs. 5.1 ± 0.4 min ; P < 0.05 ) , but not after SAF ( 6.9 ± 0.7 vs. 7.1 ± 0.7 min ) . Omega-3 FA supplementation  decreased chylomicron particle sizes ( mean diameter ; 293 ± 44 vs. 175 ± 25 nm ; P < 0.01 ) and increased preheparin lipoprotein lipase ( LPL ; 0.6 ± 0.1 vs. 0.9 ± 0.1 μmol/h/ml ; P < 0.05 ) activity during the fed state , but had no effect on postheparin LPL or hepatic lipase activities . The results suggest that ω-3 FA  supplementation accelerates chylomicron TG clearance by increasing LPL activity , and that EPA and DHA are equally effective Background —Omega-3 fatty acids ( FAs ) appear to reduce the risk of sudden death from myocardial infa rct ion . This reduction is believed to occur via the incorporation of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) into the myocardium itself , altering the dynamics of sodium and calcium channel function . The extent of incorporation has not been determined in humans . Methods and Results —We first determined the correlation between red blood cell ( RBC ) and cardiac omega-3 FA levels in 20 heart transplant recipients . We then examined the effects of 6 months of omega-3 FA supplementation ( 1 g/d ) on the FA composition of human cardiac and buccal tissue , RBCs , and plasma lipids in 25 other patients .  Cardiac and RBC EPA+DHA levels were highly correlated ( r=0.82 , P<0.001 ) . Supplementation increased EPA+DHA levels in cardiac tissue by 110 % , in RBCs by 101 % , in plasma by 139 % , and in cheek cells by 73 % ( P<0.005 versus baseline for all ; responses among tissues were not significantly different ) . Conclusions —Although any of the tissues examined could serve as a surrogate for cardiac omega-3 FA content , RBC EPA+DHA was highly correlated with cardiac EPA+DHA ; the RBC omega-3 response to supplementation was similar to that of the heart ; RBCs are easily collected and analyzed ; and they have a less variable FA composition than plasma . Therefore , RBC EPA+DHA ( also called the Omega-3 Index ) may be the preferred surrogate for cardiac omega-3 FA status Background Recent evidence supports differential effects of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , the 2 major & ohgr;3 fatty acids of marine origin , on blood pressure in humans and vascular reactivity in adult spontaneously hypertensive rats . We investigated possible differences in the effects of purified EPA or DHA on forearm vascular reactivity in overweight hyperlipidemic men that might contribute to the blood pressure – lowering effects of fish oils . Methods and Results With a double-blind , placebo-controlled trial of parallel design , 59 overweight , mildly hyperlipidemic men were r and omized to receive 4 g/d purified EPA , DHA , or olive oil ( placebo ) capsules while continuing their usual diets for 6 weeks . Forearm blood flow ( FBF ) was measured with venous occlusion , strain-gauge plethysmography during the sequential intra-arterial administration of acetylcholine ( 7.5 , 15 , and 30 & mgr;g/min ) , sodium nitroprusside ( 1.5 , 3 , and 10 & mgr;g/min ) , norepinephrine ( 10 , 20 , and 40 ng/min ) , a single-dose infusion of NG-monomethyl-l-arginine ( L-NMMA ) ( 1 mg/min ) , and coinfusion of acetylcholine ( 7.5 , 15 , and 30 & mgr;g/min ) and L-NMMA . Forty of the 56 subjects who completed the study underwent FBF measurements . Plasma phospholipid EPA levels increased significantly ( P < 0.0001 ) after supplementation with EPA , and DHA composition increased with DHA supplementation ( P < 0.0001 ) . Relative to placebo , DHA , but not EPA , supplementation significantly improved FBF in response to acetylcholine infusion ( P = 0.040 ) and coinfusion of acetylcholine with L-NMMA ( P = 0.040 ) . Infusion of L-NMMA alone showed no group differences . DHA significantly enhanced dilatory responses to sodium nitroprusside ( P < 0.0001 ) and attenuated constrictor responses to norepinephrine ( P = 0.017 ) . Conclusions Relative to placebo , DHA , but not EPA , enhances vasodilator mechanisms and attenuates constrictor responses in the forearm microcirculation . Improvements in endothelium-independent mechanisms appear to be predominant and may contribute to the selective blood pressure – lowering effect observed with DHA compared with EPA in humans BACKGROUND AND AIMS Whether EPA and DHA exert similar anti-inflammatory effects through modulation of gene expression in immune cells remains unclear . The aim of the study was to compare the impact of EPA and DHA supplementation on inflammatory gene expression in subjects at risk for cardiometabolic diseases . METHODS In this r and omized double-blind crossover trial , 154 men and women with abdominal obesity and low- grade inflammation were subjected to three 10-wk supplementation phases : 1 ) EPA ( 2.7 g/d ) ; 2 ) DHA ( 2.7 g/d ) ; 3 ) corn oil ( 3 g/d ) , separated by a 9-wk washout .  Pro- and anti-inflammatory gene expression was assessed in whole blood cells by RT-qPCR after each treatment in a representative sample of 44 participants . RESULTS No significant difference was observed between EPA and DHA in the expression of any of the genes investigated . Compared with control , EPA  enhanced TRAF3 and PPARA expression and lowered CD14 expression ( p < 0.01 ) whereas DHA  increased expression of PPARA and TNFA and decreased CD14 expression ( p < 0.05 ) . Variations in gene expression after EPA and after DHA were strongly correlated for PPARA ( r = 0.73 , p < 0.0001 ) and TRAF3 ( r = 0.66 , p < 0.0001 ) and less for TNFA ( r = 0.46 , p < 0.005 ) and CD14 ( r = 0.16 , p = 0.30 ) . CONCLUSIONS High-dose supplementation with either EPA or DHA has similar effects on the expression of many inflammation-related genes in immune cells of men and women at risk for cardiometabolic diseases . The effects of EPA and of DHA on anti-inflammatory gene expression may be more consistent than their effects on expression of pro-inflammatory genes in whole blood cells 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 aim ed 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 , r and omized 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 postpr and ial triglyceride ( TG ) concentrations ( -20 % , -52.2mg/dL , P=0.03 ) , significant increases in fasting and postpr and ial 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 postpr and ial TG , but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers BACKGROUND AND AIMS Eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) found in fish oil are postulated to have favourable effects on platelet , endothelial and vascular function . We investigated whether EPA has differential effects on in vivo platelet aggregation and other markers of cardiovascular risk compared to DHA . METHODS AND RESULTS Following a 2 wk run-in taking encapsulated refined olive oil , 48 healthy young men were r and omly allocated using a parallel design to receive EPA-rich ( 3.1 g EPA/d ) or DHA-rich ( 2.9 g DHA/d ) triglyceride concentrates or refined olive oil ( placebo ) , for a total supplementary lipid intake of 5 g/d . The specified primary outcome was change in platelet monocyte aggregates ( PMA ) ; secondary outcomes were capillary density , augmentation index , digital pulse volume measurements , 24 h ambulatory BP , plasma 8-isoprostanes-F2α . Changes in the proportions of DHA and EPA  in erythrocytes and non-esterified fatty acid composition indicated compliance to the intervention . There was no significant treatment effect on PMA ( P = 0.382 ) ; mean changes ( % ) ( 95 % CI ) were placebo -0.5 ( -2.0 , 1.04 ) , EPA 0.4 ( -0.8 , 1.6 ) , DHA 0.3 ( -1.5 , 2.0 ) . R-QUICKI , an index of insulin sensitivity , was greater following EPA compared to placebo ( P < 0.05 ) . No other significant differences were noted . CONCLUSION Neither EPA- nor DHA-rich fish oil supplementation influence platelet-monocyte aggregation or several markers of vascular function after 6 wk in healthy young males . This trial was registered at clinical trials.gov as NCT01735357 Our objective was to investigate the impact of EPA versus DHA on arterial stiffness and reactivity and underlying mechanisms ( with a focus on plasma oxylipins ) in the postpr and ial state . In a three-arm crossover acute test meal trial , men ( n = 26 , 35–55 years ) at increased CVD risk received a high-fat ( 42.4 g ) test meal providing 4.16 g of EPA or DHA or control oil in r and om order . At 0 h and 4 h , blood sample s were collected to quantify plasma fatty acids , long chain n-3 PUFA-derived oxylipins , nitrite and hydrogen sulfide , and serum lipids and glucose . Vascular function was assessed using blood pressure , reactive hyperemia index , pulse wave velocity , and augmentation index ( AIx ) . The DHA-rich oil significantly reduced AIx by 13 % ( P = 0.047 ) with the decrease following EPA-rich oil intervention not reaching statistical significance . Both interventions increased EPA- and DHA-derived oxylipins in the acute postpr and ial state , with an ( 1.3-fold ) increase in 19,20-dihydroxydocosapentaenoic acid evident after DHA intervention ( P < 0.001 ) . In conclusion , a single dose of DHA  significantly improved postpr and ial arterial stiffness as assessed by AIx , which if sustained would be associated with a significant decrease in CVD risk . The observed increases in oxylipins provide a mechanistic insight into the AIx effect BACKGROUND Low intakes or blood levels of eicosapentaenoic and docosahexaenoic acids ( EPA + DHA ) are independently associated with increased risk of death from coronary heart disease ( CHD ) . In r and omized secondary prevention trials , fish or fish oil have been demonstrated to reduce total and CHD mortality at intakes of about 1 g/day . Red blood cell ( RBC ) fatty acid ( FA ) composition reflects long-term intake of EPA + DHA . We propose that the RBC EPA + DHA ( hereafter called the Omega-3 Index ) be considered a new risk factor for death from CHD . METHODS We conducted clinical and laboratory experiments to generate data necessary for the validation of the Omega-3 Index as a CHD risk predictor . The relationship between this putative marker and risk for CHD death , especially sudden cardiac death ( SCD ) , was then evaluated in several published primary and secondary prevention studies . RESULTS The Omega-3 Index was inversely associated with risk for CHD mortality . An Omega-3 Index of > or = 8 % was associated with the greatest cardioprotection , whereas an index of < or = 4 % was associated with the least . CONCLUSION The Omega-3 Index may represent a novel , physiologically relevant , easily modified , independent , and grade d risk factor for death from CHD that could have significant clinical utility BACKGROUND LCn-3PUFA comprised of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) offer cardioprotection involving a decrease in coagulant activity ; however , the evidence is equivocal . We have previously demonstrated that the acute ( 24 h ) effects and chronic ( 4 weeks ) effects of LCn-3PUFA supplementation on platelet aggregation in human subjects are sex specific . This study investigated the mechanisms of the sex-dependent effects of LCn-3PUFA with 4 weeks supplementation of EPA-rich vs. DHA-rich oils on procoagulant and platelet activity in healthy subjects . DESIGN A double-blinded , placebo-controlled r and omised trial was conducted in 94 healthy adults : male ( n=41 ) and female ( n=53 ) .  Platelet coagulation parameters including factors I , II , V , VII , VIII , IX , X , vWF : Ag and endogenous thrombin potential were measured at baseline and 4 weeks postsupplementation with EPA-rich or DHA-rich oil capsules . RESULTS We have previously reported that platelet aggregation is specifically reduced by supplementation with EPA in males and DHA in females . This sex-specific effect was also observed for decreases in plasma levels of Factor II ( -7.9 ± 3.8 % , P=.026 ) , Factor V ( -6.5 ± 4.5 % , P=.022 ) and vWF : Ag ( -7.3 ± 2.1 % , P=.034 ) and was most pronounced in males supplemented with EPA . In contrast , DHA-mediated  reduction in platelet aggregation in females was not accompanied by any significant changes in the coagulation parameters tested . CONCLUSION Significant interactions between sex and specific LCn-3PUFA exist to reduce procoagulant activity differentially in males vs. females and could have profound effects on managing risk of thrombotic disease Abstract Omega-3 ( ω3 ) fatty acids , particularly eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , protect against cardiovascular disease . Despite these benefits , concern remains that ω3 fatty acids may increase lipid peroxidation . It has previously been shown that urinary F2-isoprostanes ( F2-IsoPs ) were reduced following ω3 fatty acid supplementation in humans . It is now determined whether EPA or DHA supplementation affects plasma F2-IsoPs . In two 6-week placebo-controlled interventions , Study A : overweight , dyslipidaemic men ; and Study B : treated-hypertensive Type 2 diabetic , patients were r and omized to 4 g daily EPA , DHA . Post-intervention plasma F2-IsoPs were significantly reduced by EPA ( 24 % in Study A , 19 % in Study B ) and by DHA ( 14 % in Study A , 23 % in Study B ) relative to the olive oil group . The fall in plasma F2-IsoPs was not altered in analyses that corrected for changes in plasma arachidonic acid , which was reduced with EPA and DHA supplementation . Neither F3- nor F4-IsoPs were observed in plasma in both studies . These results show that in  humans , EPA and DHA  reduce in vivo oxidant stress as measured in human plasma and urine Long-chain n-3 PUFA can lower blood pressure ( BP ) but their acute effects on cardiac output , BP and systemic vascular resistance ( SVR ) in response to dynamic exercise are uncertain . We compared the effects of high-fat meals rich in EPA ( 20 : 5n-3 ) , DHA ( 22 : 6n-3 ) or oleic acid ( control ) on cardiac output , BP and SVR in response to exercise stress testing . High-fat meals ( 50 g fat ) containing high-oleic sunflower oil enriched with 4·7 g of either EPA or DHA v. control ( high-oleic sunflower oil only ) were fed to twenty-two healthy males using a r and omised cross-over design . Resting measurements of cardiac output , heart rate and BP were made before and hourly over 5 h following the meal . A st and ardised 12 min exercise test was then conducted with further measurements made during and post-exercise . Blood sample s were collected at fasting , 5 h postpr and ially and immediately post-exercise for the analysis of lipid , glucose and 8-isoprostane-F2α ( 8-iso-PGF2α ) . Plasma concentrations of EPA and DHA increased by 0·22 mmol/l 5 h following the EPA and DHA meals , respectively , compared with the control ( P < 0·001 ) . Resting cardiac output and 8-iso-PGF2α increased similarly following all meals and there were no significant differences in cardiac output during exercise between the meals . SVR was lower at 5 h and during exercise following the DHA but not EPA meal , compared with the control meal , by 4·9 % ( 95 % CI 1·3 , 8·4 ; P < 0·01 ) . Meals containing DHA appear to differ from EPA with regard to their effects on cardiovascular haemodynamics during exercise In this study eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were given in a cumulative manner , every 6 weeks , starting with 10 mg , then 100 mg , 1000 mg and 10,000 mg EPA daily to mild to moderate essential hypertensive black patients . The corresponding DHA doses were 3 , 33 , 333 and 3333 mg . A control group was given olive oil as placebo for the entire 24 weeks . The placebo group had lower diastolic and systolic blood pressures after 24 weeks than the EPA and DHA group . No effect was seen on plasma triglycerides , cholesterol , HDL-cholesterol and gamma-glutamyltranspeptidase at any stage of the trial . In the EPA group plasma free-EPA increased significantly from 1000 mg onwards and plasma free-arachidonic acid ( AA ) decreased after 1000 mg EPA . No other plasma free essential fatty acid changed during the trial , although the HDL : cholesterol increased slightly but non-significantly with an increase in EPA and DHA . No significant changes in diet pattern or body mass was observed . It is therefore concluded that EPA and DHA supplementation had no beneficial effects in mild to moderate essential hypertensive black patients except for a lowering of plasma AA n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention .  Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects Our aim was to study the effects of increased dietary intake of alpha-linolenic acid ( ALA ) , eicosapentaenoic acid ( EPA ) , or docosahexaenoic acid ( DHA ) on serum lipids and LDL fatty acid compositions . To this end , a controlled parallel study was conducted in 74 healthy normolipidemic men and women aged 19 - 43 y. Participants were r and omly assigned to 1 of 3 interventions and consumed a total intake of 4.4 g/d ALA ( ALA group ) , 2.2 g/d EPA ( EPA group ) , and 2.3 g/d DHA ( DHA group ) for 6 wk . Fatty acid ethyl esters were incorporated into margarines , which replaced the participant 's normal spread . The ALA , EPA , or DHA intake led to a significant enrichment of the LDL with the respective ( n-3 ) fatty acid . In addition , LDL EPA contents in the ALA group increased by 36 % ( P < 0.05 ) with no changes in LDL DHA . The EPA intervention led to an additional enrichment with DHA ( 24 % ; P < 0.001 ) , whereas the DHA intervention further increased the amount of EPA ( 249 % ; P < 0.001 ) . ALA , EPA , or DHA intake did not affect fasting serum concentrations of total and LDL cholesterol , but fasting serum triacylglycerol concentrations significantly decreased in the EPA ( -0.14 mmol/L ) and DHA ( -0.30 mmol/L ) interventions and also in the ALA intervention ( -0.17 mmol/L ) . DHA intake significantly increased serum HDL cholesterol , whereas no changes were found with ALA or EPA intake . In conclusion , the present data support the hypothesis that isolated dietary ALA , EPA , and DHA intakes lead to differential enrichment in LDL due to interconversion . Moderate amounts of ALA , EPA , and DHA are effective in improving lipid profiles of normolipidemic humans
A large body of evidence supports the cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids ( PUFAs ) , eicosapentaenoic acid ( EPA ) , and docosahexaenoic acid ( DHA ) .
There is increasing interest in the independent effects of EPA and DHA in the modulation of cardiometabolic risk factors .
This systematic review aims to appraise the latest available evidence of the differential effects of EPA and DHA on such risk factors .