Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Omega-3 fatty acids and lipoprotein associated phospholipase A2 in healthy older adult males and females Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid. Cardiac autonomic changes associated with fish oil vs soy oil supplementation in the elderly. Usefulness of omega-3 fatty acids and the prevention of coronary heart disease. Does vegetable oil attenuate the beneficial effects of fish oil in reducing risk factors for cardiovascular disease? Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Stearidonic Acid-Enriched Soybean Oil Increased the Omega-3 Index, an Emerging Cardiovascular Risk Marker Effects of a fish-oil and vegetable-oil formula on aggregation and ethanolamine-containing lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils. Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: design and baseline characteristics of the Alpha Omega Trial. Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Reduced prostaglandin F2α release from blood mononuclear leukocytes after oral supplementation of ω3 fatty acids: the OmegAD study Oily fish reduces plasma triacylglycerols: a primary prevention study in overweight men and women. Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyceridemia. A randomized trial of the effects of ezetimibe on the absorption of omega-3 fatty acids in cardiac disease patients: A pilot study. Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients Omega-3 Fatty Acid Supplementation Augments Sympathetic Nerve Activity Responses to Physiological Stressors in Humans Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Alpha-Linolenic Acid: Is It Essential to Cardiovascular Health? Dietary omega-3 fatty acids and fish consumption and risk of type 2 diabetes. [The effect of omega-3 fatty acids on risk factors for cardiovascular diseases]. Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects. Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children. Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction. The influence of a formula supplemented with dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in healthy full-term infants: a double-blind randomized controlled trial Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the product-precursor ratio [corrected] of α-linolenic acid to long-chain n-3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort. Comparison of Seal Oil to Tuna Oil on Plasma Lipid Levels and Blood Pressure in Hypertriglyceridaemic Subjects Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil omega-3 fatty acids. Update on the Vitamin D and OmegA-3 trial (VITAL) The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Comparison of the absorption and effect on platelet function of a single dose of n-3 fatty acids given as fish or fish oil. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans Dietary supplementation with long chain omega-3 polyunsaturated fatty acids and weight loss in obese adults. Effect of sodium restriction and fish oil supplementation on BP and thrombotic risk factors in patients treated with ACE inhibitors. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Blood pressure lowering in elderly subjects: a double-blind crossover study of omega-3 and omega-6 fatty acids.
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 Purpose Lipoprotein associated phospholipase A2 ( Lp-PLA2 ) is a novel inflammatory factor that has been independently associated with stroke and cardiovascular disease ( CVD ) . Omega-3 fats have been implicated in reducing inflammation associated with CVD . The aim of this study was to determine if an 8-week isocaloric diet supplemented with eicosapentaenoic acid ( EPA ) and docosahexaenoic ( DHA ) in the form of fish oil or α-linolenic acid ( ALA ) in the form of flaxseed oil would alter Lp-PLA2 among healthy adults ages 50 years and older . Methods Fifty-nine healthy adults ( ~75 % female , average age 61 years ) were r and omized to one of three groups with equal amounts of total fat intake . All capsules contained ~1 g of fat . The control group ( n = 19 ) consumed olive oil capsules ( ~11 g/day ) ; the ALA group ( n = 20 ) consumed flaxseed oil capsules ( ~11 g/day ) and the EPA/DHA group ( n = 20 ) consumed fish oil capsules ( ~2 g/day + 9 g/day of olive oil ) . Fasting blood sample s were obtained before and after the 8-week intervention for determination of Lp-PLA2 mass and activity as well as lipid values . Results We did not find any significant changes in Lp-PLA2 mass or activity after the intervention in any of the groups ; however , change in oxidized LDL was associated with change in Lp-PLA2 mass ( r = 0.37 , p < 0.01 ) . ConclusionS upplementing the diet with omega-3 fatty acids for 8-weeks did not influence Lp-PLA2 activity or mass among older adults ; altering oxidized LDL may be necessary to see changes in Lp-PLA2 levels BACKGROUND An increase in plasma n-3 fatty acid content , particularly eicosapentaenoic acid ( 20:5n-3 ; EPA ) and docosahexaenoic acid ( 22:6n-3 ; DHA ) , is observed after consumption of fish oil-enriched supplements . Because alpha-linolenic acid ( 18:3n-3 ; ALA ) is the direct precursor of EPA and DHA , ALA-enriched supplements such as flax may have a similar effect , although this hypothesis has been challenged because of reported low conversion of ALA into DHA . OBJECTIVE To address this question , we design ed a clinical trial in which flax oil , fish-oil , and sunflower oil ( placebo group ) capsules were given to firefighters ( n = 62 ) , a group traditionally exposed to cardiovascular disease risk factors . DESIGN Firefighters were r and omly divided into 6 experimental groups receiving 1.2 , 2.4 , or 3.6 g flax oil/d ; 0.6 or 1.2 g fish oil/d ; or 1 g sunflower oil/d for 12 wk . Blood was drawn every 2 wk , and the total phospholipid fatty acid composition of red blood cells was determined . RESULTS As expected , fish oil produced a rapid increase in erythrocyte DHA and total n-3 fatty acids . The consumption of either 2.4 or 3.6 g flax oil/d ( in capsules ) was sufficient to significantly increase erythrocyte total phospholipid ALA , EPA , and docosapentaenoic acid ( 22:5n-3 ) fatty acid content . There were no differences among groups in plasma inflammatory markers or lipid profile . CONCLUSIONS The consumption of ALA-enriched supplements for 12 wk was sufficient to elevate erythrocyte EPA and docosapentaenoic acid content , which shows the effectiveness of ALA conversion and accretion into erythrocytes . The amounts of ALA required to obtain these effects are amounts that are easily achieved in the general population by dietary modification INTRODUCTION Omega-3 fatty acid levels are associated with decreased risk for sudden death ; however , the protective cardiovascular mechanisms of omega-3 are poorly understood . This study addresses the heart rate variability ( HRV ) changes in a cohort of elderly subjects r and omized to receive either a daily high dose of marine-derived omega-3 fatty acids ( fish oil ) or a lower daily dose of a plant-derived omega-3 fatty acid ( alpha-linolenic acid ) in soy oil . METHODS A total of 58 elderly nursing home residents were r and omized to receive 2 g/d of fish oil capsules vs 2 g/d of soy oil capsules , and were subsequently followed up every other day for a period of 6 months with 6-min measurements of HRV while resting supine . An initial control period of 2 months without supplementation was allowed to establish an HRV baseline for each participant . RESULTS The average time- and frequency-domain parameters of HRV increased significantly during the supplementation period in both the fish oil and soy oil groups . In the regression model after adjusting for age and mean heart rate , supplementation with fish oil was associated with a significant increase in the high- and low-frequency components , and SD of normal RR intervals ( SDNN ) , whereas only SDNN increased significantly in the soy oil group . CONCLUSIONS Supplementation with 2 g/d of fish oil was well tolerated and was associated with a significant increase in HRV . Supplementation with 2 g/d of soy oil was associated with a lesser but significant increase in HRV Clinical trial evidence exists that supports a role for the omega-3 polyunsaturated fatty acids in coronary heart disease prevention . However , the results from these clinical trials have varied and were conducted in diverse population groups using several different types of omega-3 polyunsaturated fatty acids , including eicosapentaenoic acid , docosahexaenoic acid , and alpha-linolenic acid ( ALA ) . Thus , we systematic ally review ed previously published reports assessing the different types of omega-3 polyunsaturated fatty acid interventions and cardiovascular outcomes . Fourteen r and omized clinical trials were included in the review . Six trials were included with fish oil , with 1 large trial ( 10,000 patients ) dominating the analysis . In aggregate , the fish oil trials demonstrated a reduction in total mortality and sudden death without a clinical ly significant reduction in nonfatal myocardial infa rct ion . The 6 trials with ALA supplements or an ALA-enriched diet were of poorer design than the fish oil trials and had limited power . Many of the trials with ALA involved other changes in dietary components . In aggregate , the ALA trials demonstrated possible benefits in reducing sudden death and nonfatal myocardial infa rct ion , but with wider confidence intervals than in the fish oil trials . In conclusion , the evidence suggests a role for fish oil ( eicosapentaenoic acid , docosahexaenoic acid ) or fish in secondary prevention because recent clinical trial data have demonstrated a significant reduction in total mortality , coronary heart disease death , and sudden death . The data on ALA have been limited by studies of smaller sample size and limited quality Contradictory reports on the protective effect of fish consumption on cardiovascular disease ( CVD ) risk could be due to variations in the intake of n-3 and n-6 polyunsaturated fatty acids ( PUFAs ) . Metabolic competition between n-3 and n-6 PUFAs suggests that n-6 PUFAs in vegetable oils could attenuate the efficacy of n-3 PUFAs in fish oil to favorably alter endpoints relevant to CVD risk . We determined the effects of varying dietary amounts of fish oil on lipid and thrombotic endpoints relevant to risk factors for CVD and whether these effects were attenuated by vegetable oils . Two r and omized , double-blind , placebo-controlled , parallel studies were conducted in human subjects fed varying amounts of n-3 and n-6 PUFAs ; n-3 PUFA intake was varied by using fish or placebo oil capsules , and n-6 PUFA intake was modified by incorporating varying amounts of safflower oil into the diet . Endpoints included changes in membrane fatty acid composition , blood lipids , and thrombotic profile . The results indicated that absolute amounts of fish oil , and not the relative amounts of fish and vegetable oil ( ratios of n-3 to n-6 PUFAs ) , determined the magnitude of the reduction of arachidonic acid and increase in eicosapentaenoic acid in phospholipids of plasma and platelets . The suppression of plasma triacylglycerols by fish oil was not affected by varying amounts of dietary n-6 PUFAs . Fibrinogen concentrations decreased with 15 g but not with 9 g fish oil/d fed at the same ratio of n-3 to n-6 PUFAs . The efficacy of fish oil in favorably modifying certain risk factors for CVD was not attenuated by vegetable oil Recent studies have suggested that omega 3-fats of marine origin may have a protective role in heart disease . This study aim ed to compare the effects of fish or fish oil , in the setting of a high- or low-fat diet , on platelet aggregation and platelet thromboxane in men with increased risk of cardiovascular disease . One hundred twenty men who were nonsmokers , 30 to 60 years old , with mildly elevated blood pressure and cholesterol were r and omly allocated to one of five high-fat ( 40 % of daily energy ) or two low-fat ( 30 % ) groups for 12 weeks . The five high-fat groups took either 6 or 12 fish oil capsules daily ; fish ; a combination of fish and fish oil ; or placebo capsules . The two low-fat groups took either fish or placebo capsules . Fish meals provided 1.3 g of eicosapentaenoic acid daily , equivalent to 6 fish oil capsules , and contained an average of 3.65 g/d of omega 3-fatty acids . Multiple regression analysis of the combined groups showed that all groups taking omega 3-fatty acids reduced platelet aggregation to both collagen ( P < .0001 ) and platelet-activating factor ( PAF ) ( P < .05 ) and platelet thromboxane B2 responses ( P < .05 ) to collagen-induced aggregation . The low-fat diet alone had no effect on PAF-induced platelet aggregation and only a small effect on platelet responses to collagen ( P < .05 ) . Platelet aggregation responses to PAF were reduced more by fish oil than fish in a high-fat diet , whereas fish had a greater effect when part of a low-fat rather than a high-fat diet . There was no significant difference in collagen-induced platelet aggregation or platelet thromboxane between fish and fish oils on a high or low fat intake . In conjunction with our previous findings of improvements in lipoproteins , blood pressure , and heart rate in this population , these results on platelet function suggest that dietary omega 3-fatty acids incorporated into a low- rather than a high-fat diet have a wider spectrum of more favorable effects on cardiovascular risk factors A plant source of omega-3 fatty acid ( FA ) that can raise tissue eicosapentaenoic acid ( EPA ) and /or docosahexaenoic acid ( DHA ) is needed . A soybean oil ( SBO ) containing approximately 20 % stearidonic acid [ SDA ; the delta-6 desaturase product of alpha-linolenic acid ( ALA ) ] derived from genetically modified soybeans is under development . This study compared the effects of EPA to SDA-SBO on erythrocyte EPA + DHA levels ( the omega-3 index ) . Overweight healthy volunteers ( n = 45 ) were r and omized to SDA-SBO ( 24 ml/day providing ~3.7 g SDA ) or to regular SBO ( control group ) without or with EPA ethyl esters ( ~1 g/day ) for 16 weeks . Serum lipids , blood pressure , heart rate , platelet function and safety laboratory tests were measured along with the omega-3 index . A per- protocol analysis was conducted on 33 subjects ( 11 per group ) . Compared to baseline , average omega-3 index levels increased 19.5 % in the SDA group and 25.4 % in the EPA group ( p < 0.05 for both , vs. control ) . DHA did not change in any group . Relative to EPA , SDA increased RBC EPA with about 17 % efficiency . No other clinical endpoints were affected by SDA or EPA treatment ( vs. control ) . In conclusion , SDA-enriched SBO significantly raised the omega-3 index . Since EPA supplementation has been shown to raise the omega-3 index and to lower risk for cardiac events , SDA-SBO may be a viable plant-based alternative for providing meaningful intakes of cardioprotective omega-3 FAs The effects of consuming a liquid formula containing either fish oil enriched in omega-3 fatty acids or vegetable oil enriched in oleic acid was evaluated in 20 male subjects r and omly allocated into two groups over a 42-d period . A decrease in collagen-induced aggregation by using washed platelet suspensions was found in both groups after nutritional supplementation . A considerable rise in omega-3 and a decrease in omega-6 fatty acids occurred in the platelet phospholipid with fish-oil consumption . The degree of eicosapentaenoic acid ( EPA , 20:5n-3 ) enrichment ( fish-oil group ) was dramatically greater in the ether-containing plasmenylethanolamine ( 13.5 mol% of fatty acids ; mol% of fatty acids = moles per 100 moles of total fatty acids ) than in phosphatidylethanolamine ( 2.8 mol% ) or phosphatidylcholine ( 2.9 mol% ) . Neither treatment significantly influenced the agonist-induced accumulation of lysoplasmenylethanolamine as derived via phospholipase A2 hydrolysis of plasmenylethanolamine . HPLC measurements of eicosanoid production in A23187-stimulated neutrophils revealed a considerable decrease in the formation of arachidonic acid-derived leukotriene B4 ( LTB4 ) , by 41 % , and 5-HETE ( 5-hydroxyeicosatetraenoic acid ) , by 30 % , in the fish-oil group along with the appearance of the corresponding EPA-derived products [ LTB5 and 5-HEPE ( 5-hydroxyeicosapentaenoic acid ) ] . No such alterations in the formation of lipoxygenase products were found with the vegetable oil treatment BACKGROUND Weekly fish consumption has been related to a lower risk of fatal coronary heart disease ( CHD ) and incident stroke in population s with a low fish intake . This relation has mainly been attributed to n-3 fatty acids in fish , that is , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . It is at present unclear whether alpha-linolenic acid ( ALA ) , a n-3 fatty acid from vegetable origin , could also be protective against cardiovascular diseases ( CVDs ) . There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention . OBJECTIVES The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infa rct ion . DESIGN The multicenter Alpha Omega Trial is a r and omized , double-blind , placebo-controlled trial with a 2 x 2 factorial design . Between May 2002 and December 2006 , we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infa rct ion within 10 years before entering the study . Subjects were r and omized to 1 of 4 margarine spreads that were enriched with EPA + DHA and /or ALA , or placebo . Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma . Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD . RESULTS The cohort was on average 69 years old at the start of the study and comprised 22 % women . Subjects had their ( last ) myocardial infa rct ion approximately 4 years before enrollment . Mean body mass index was 27.7 kg/m(2 ) , and 17 % smoked . Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L , respectively , and 85 % used statins . Mean blood pressure was 142/80 mm Hg , and most subjects were on antihypertensive medication ( 88 % ) . Diabetes mellitus was reported by 17 % of the subjects , and 7 % reported a history of stroke . The overall mortality rate during the trial period was 23 per 1,000 person-years , with approximately 40 % due to CVD . CURRENT STATUS Follow-up of the patients was completed in November 2009 , and findings will be reported in the second part of 2010 BACKGROUND Dietary intake of fish rich in omega-3 fatty acids is associated with a reduction in cardiovascular events . The mechanisms for this are uncertain and previous studies investigating effects on platelet function have produced inconsistent results . Platelet-monocyte aggregation is a sensitive marker of platelet activation and may contribute to the initiation and progression of atherothrombosis . This study assessed the effect of dietary intervention with oily fish on platelet-monocyte aggregation in healthy subjects . METHODS Fourteen subjects had their diet supplemented with 500 g of oil-rich fish per week for 4 weeks . A control group of 14 subjects received no dietary intervention  over a 4-week period . Platelet-monocyte aggregates were assessed with flow cytometry . RESULTS Dietary intervention with fish led to an increase in omega-3 fatty acids in plasma phospholipids ( 14.2+/-3.4 % versus 5.8+/-1.3 % , P<0.001 ) . In contrast to the control group , platelet-monocyte aggregates were reduced by 35 % following dietary intervention with oily fish ( 16.0+/-9.0 % versus 24.8+/-10.9 % , P<0.01 ) , and returned to basal levels 4 weeks after discontinuation of supplementation . There was an inverse correlation between platelet-monocyte aggregation and plasma omega-3 fatty acid concentrations ( r=-0.421 , P=0.006 ) . There were no changes in the plasma markers of platelet activation , soluble P-selectin or soluble CD40 lig and . CONCLUSIONS We have demonstrated , for the first time , that dietary intervention with oil-rich fish reduces platelet-monocyte aggregation in man . Our results suggest that reduced platelet activation provides a potential mechanism through which fish oils confer their cardiovascular preventative benefits This study was conducted to compare the effects of omega 3 fatty acids , taken as fish or fish-oil supplements in the setting of a high- or low-fat dietary background , on blood pressure and heart rate in men with moderate cardiovascular risks . One hundred twenty men were r and omly allocated to five high-fat ( 40 % of daily energy ) and two low-fat ( 30 % of energy ) groups to undertaken a 12-week dietary intervention period involving fish , fish oil , or a combination of these . Sodium intake was restricted to less than 90 mmol/d . The five high-fat groups were assigned to take either 6 or 12 fish-oil capsules daily , fish or a combination of fish oil and fish , or placebo capsules . The two low-fat groups took either fish or placebo capsules . Fish meals were devised to provide 1.3 g of eicosapentaenoic acid daily , equivalent to that contained in 6 fish-oil capsules . Subjects were instructed to eat a selection of fish that provided an average of 3.65 g/d ( range , 3.2 to 4.1 g/d ) of total omega 3 fatty acids . Subjects were seen at regular intervals during the baseline and dietary intervention periods for measurement of weight , blood pressure , heart rate , dietary compliance , urinary electrolyte excretion , platelet phospholipid fatty acids , blood glucose , and insulin concentration . There was a greater fall in both systolic and diastolic blood pressures in subjects allocated fish or fish oil , particularly in the low-fat groups , compared with control subjects . However , there was no significant group effect . ( ABSTRACT TRUNCATED AT 250 WORDS Omega-3 fatty acids , e.g. , dokosahexaenoic acid ( DHA ) and eikosapentaenoic acid ( EPA ) , ameliorate inflammatory reactions by various mechanisms , but the role of prostagl and ins remains unclear . Our aim was to determine if dietary supplementation with a DHA-rich fish oil influenced the release of PGF2α from peripheral blood mononuclear cells ( P BMC ) . In the OmegAD study , 174 Alzheimer disease patients received either 1.7 g DHA plus 0.6 g EPA or a placebo daily for six months . P BMC s from the 21 ( 9 on fish oil and 12 on placebo ) first-r and omized patients were stimulated with either lipopolysaccharide ( LPS ) or phytohemagglutinin ( PHA ) before and after 6 months . Our results showed that plasma concentrations of DHA and EPA increased significantly at 6 months in the omega-3 group . PGF2α release from LPS- ( but not from PHA- ) stimulated P BMC was significantly diminished in this group ; no change was noted in the placebo group . PGF2α changes correlated inversely with changes in plasma DHA and EPA . Decreased IL-6 and IL-1β levels correlated with decreased PGF2α levels . The stimulus-specific PGF2α release from P BMC after 6 months of oral supplementation with the DHA-rich fish oil might be one event related to reduced inflammatory reactions associated with omega-3 fatty acid intake OBJECTIVE Previous studies have demonstrated benefits of high-dose long-chain omega-3 polyunsaturated fatty acid ( LC omega-3 PUFA ) supplements on  metabolic risk .  Effects of increased dietary omega-3 PUFA , via oily fish and /or plant-derived omega-3 PUFAs , are less clear and may be modulated by the omega-6:omega-3 PUFA of the habitual diet . This study examined the effect on  cardiovascular disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in linoleic acid : alpha-linolenic acid ( LA : LNA ) and /or increasing LC omega-3 PUFA . It tested whether decreases in LA : LNA modulate effects of LC omega-3 PUFA . METHODS One hundred forty-two subjects , recruited to a 24-wk r and omized study , were assigned to a control group or one of four interventions . Intervention groups received two portions of oily fish ( 4.5 g eicosapentaenoic acid + docosahexanoic acid ) or white fish ( 0.7 g eicosapentaenoic acid + docosahexanoic acid ) per week , and replaced habitual household fats with ones high in sunflower ( high LA : LNA ) or rapeseed ( low LA : LNA ) oil . RESULTS Modest dietary manipulations of omega-6 and omega-3 PUFAs result ed in significant group x time interactions for serum triacylglycerols ( TAGs ; P = 0.05 ) ; at 24 wk the control and two oily fish groups showed lower TAG than did the white fish/sunflower group ( P = 0.05 ) . Reductions in TAG , associated with increased oily fish intakes , were maximized when combined with lower dietary LA : LNA . There were no significant changes in several other cardiovascular disease risk markers . CONCLUSIONS Two portions of oily fish per week led to significant reductions in TAG relative to consumption of two portions of white fish per week . Changes in TAG were maximized when combined with lower LA : LNA Chronic consumption of fish and fish oil high in ( n-3 ) PUFA reduces triacylglycerols ( TG ) but may increase oxidative stress , whereas consumption of soy isoflavones may reduce oxidative stress . Elevated serum TG and oxidative stress are considered cardiovascular disease ( CVD ) risk factors , but the effects of acute ( n-3 ) PUFA and soy isoflavones on these CVD risk factors are unknown . The purpose of the study was to determine the effects of acutely supplementing a high-fat , high-fructose meal with fish oil and isoflavone placebo ( FO ) and fish oil placebo and soy isoflavones ( ISO ) . In a r and omized , double-blind , placebo-controlled , crossover study , 10 overweight or obese men consumed a high-fat , high-fructose meal with 4 dietary supplement combinations : fish oil placebo and isoflavone placebo ( placebo ) ; fish oil and isoflavone placebo ( FO ) ; fish oil placebo and isoflavones ( ISO ) ; and fish oil and isoflavones ( FO + ISO ) . Serum collected at baseline and at 2 , 4 , and 6 h postpr and ially was analyzed for fatty acids , isoflavones , TG , and oxidative stress biomarkers ( lipid hydroperoxides , oxidized-LDL , total antioxidant status ) . FO significantly increased serum ( n-3 ) PUFA and ISO increased serum isoflavones . The study meal significantly increased serum total fatty acids and TG without affecting oxidative stress biomarkers . Serum TG and oxidative stress biomarkers did not differ between treatments . The FO and ISO were bioavailable but did not attenuate the postpr and ial rise in serum TG . Neither the study meal nor the FO or ISO induced significant changes in oxidative stress biomarkers . The current study adds to a limited literature on the acute effects of FO and ISO interventions on postpr and ial biomarkers of CVD risk BACKGROUND Omega-3 fatty acids ( fish oils ) reduce fasting serum triglyceride levels and cardiovascular disease risk in individuals without HIV infection . Whether omega-3 fatty acid supplementation can reduce hypertriglyceridemia associated with antiretroviral therapy is not known . METHODS We conducted an open-label , r and omized trial that enrolled 52 patients receiving > or =3 active antiretrovirals who had fasting triglyceride levels of > 200 mg/dL and were r and omized to receive nutritionist-administered dietary and exercise counseling with or without fish oil supplementation for 16 weeks . RESULTS Patients assigned to receive fish oil experienced a 25 % mean decline in fasting triglyceride levels at week 4 ( 95 % CI , -34.6 % to -15.7 % change ) , compared with a 2.8 % mean increase among patients assigned to receive counseling alone ( 95 % CI , -17.5 % to + 23.1 % change ) ( P=.007 ) . By week 16 , the mean reduction in triglyceride levels in the fish oil arm remained significant , at 19.5 % ( 95 % CI , -34.9 % to -4.0 % change ) , whereas the mean decrease in the diet and exercise only arm was 5.7 % ( 95 % CI , -24.6 % to + 13.2 % change ) ; however , the difference between study arms was no longer statistically significant ( P=.12 ) . Low-density lipoprotein cholesterol levels had increased by 15.6 % ( 95 % CI , + 4.8 % to + 26.4 % change ) at week 4 and by 22.4 % ( 95 % CI , + 7.91 % to + 36.8 % change ) at week 16 in the fish oil arm but did not change in the diet and exercise only group . Fish oil was well tolerated ; only 1 patient experienced treatment-limiting toxicity . Patients assigned to receive fish oil experienced a 25 % mean decline in fasting triglyceride levels at week 4 ( 95 % CI , -34.6 % to -15.7 % change ) , compared with a 2.8 % mean increase in patients assigned to receive counseling alone ( 95 % CI , -17.5 % to 23.1 % change ) ( P=.007 ) . By week 16 , the mean reduction in triglyceride levels in the fish oil arm remained significant , at 19.5 % ( 95 % CI , -34.9 % to -4.0 % change ) , whereas the mean decrease in the diet and exercise only arm was 5.7 % ( 95 % CI , -24.6 % to 13.2 % change ) ; however , the difference between study arms was no longer statistically significant ( P=.12 ) . Low-density lipoprotein cholesterol levels had increased by 15.6 % ( 95 % CI , 4.8%-26.4 % change ) at week 4 and by 22.4 % ( 95 % CI , 7.91%-36.8 % change ) at week 16 in the fish oil arm but did not change in the diet and exercise only group . Fish oil was well tolerated ; only 1 patient experienced treatment-limiting toxicity . CONCLUSIONS Supplementation with omega-3 fatty acids in combination with dietary and exercise counseling was well tolerated and reduced fasting triglyceride levels in patients receiving antiretrovirals . To what extent the increase in low-density lipoprotein cholesterol levels observed in patients assigned this intervention is attributable to omega-3 fatty acid supplementation and whether this increase attenuates any benefit in lowering triglyceride levels is unclear . Given these results , further investigation of omega-3 fatty acid supplementation for the treatment of hypertriglyceridemia in HIV-infected patients is warranted BACKGROUND AND AIMS Elevated levels of circulating omega-3 polyunsaturated fatty acids like alpha linolenic acid ( ALA ) may be beneficial for cardiovascular health . Circulating ALA concentrations are elevated dramatically by a cholesterol supplemented diet which increases ALA bioavailability through enhanced micelle formation in the intestines . Conversely , it is possible that drugs which inhibit cholesterol metabolism in the intestine may also inhibit fatty acid absorption . The purpose of this study is to determine if a cholesterol absorption inhibitor , ezetimibe , will decrease circulating levels of ALA . METHODS AND RESULTS Cardiac patients ( n = 34 ) between 44 and 80 years old , requiring statin therapy to regulate blood cholesterol levels , were r and omly assigned to one of four groups for a 6 week trial : 1 ) placebo ; 2 ) ezetimibe therapy ; 3 ) a supplement of flaxseed oil ( containing 1.0 g ALA in 2.0 g of flaxseed oil ) ; or 4 ) ezetimibe and flaxseed oil supplementation . Ingestion of flaxseed oil result ed in a significant increase in circulating ALA levels ( 6 ug/dl ) in patients who were not given ezetimibe . However , in the presence of ezetimibe , circulating ALA levels did not increase significantly even in the presence of flax oil supplementation ( a decrease of 4 ug/dl ) . There were no significant differences amongst the groups in terms of circulating total cholesterol , LDL , HDL , triglyceride levels in the blood . CONCLUSION Ezetimibe therapy inhibited the absorption of omega-3 fatty acids . Patients receiving ezetimibe therapy may not receive the expected cardiovascular benefits from dietary supplementation with omega-3 fatty acids . CLINICAL TRIAL REGISTRATION NCT00955227 Objective : Alpha-linolenic acid ( ALA ) is the natural precursor of the cardioprotective long-chain n−3 fatty acids . Available data indicate a possible beneficial effect of ALA on cardiovascular disease ( CVD ) , but the response of various CVD risk factors to increased ALA intake is not well characterized . The purpose of the present study was to examine the effect of increased ALA intake on blood pressure in man . Design , setting , subjects and interventions : We used a prospect i ve , two-group , parallel-arm design to examine the effect of a 12-week dietary supplementation with flaxseed oil , rich in ALA ( 8 g/day ) , on blood pressure in middle-aged dyslipidaemic men ( n=59 ) . The diet of the control group was supplemented with safflower oil , containing the equivalent n−6 fatty acid ( 11 g/day linoleic acid ( LA ) ; n=28 ) . Arterial blood pressure was measured at the beginning and at the end of the dietary intervention period . Results : Supplementation with ALA result ed in significantly lower systolic and diastolic blood pressure levels compared with LA ( P=0.016 and P=0.011 , respectively , from analysis of variance ( ANOVA ) for repeated measures ) . Conclusions : We observed a hypotensive effect of ALA , which may constitute another mechanism accounting in part for the apparent cardioprotective effect of this n−3 fatty acid . Sponsorship : Greek Ministry of Development , General Secretariat for Research and Technology An inverse relation exists between omega-3 fatty acid intake and risk of cardiovascular disease development/mortality and sudden cardiac death in humans . Mechanisms underlying this cardioprotective effect are unknown , but could involve the autonomic nervous system . We tested the hypothesis that omega-3 fatty acid supplementation ( “ fish oil ” ) would reduce muscle sympathetic nerve activity ( MSNA ) at rest and attenuate increases during physiological stressors . MSNA ( peroneal microneurography ) was measured during rest , ischemic h and grip to fatigue ( IHG ) , and a cold pressor test ( CPT ) . Measurements were obtained before ( PRE ) and after ( POST ) 1 month of daily ingestion of either fish oil ( experimental group , n=9 ) or olive oil capsules ( control group , n=9 ) . MSNA at rest was comparable PRE and POST in control ( 3±1 versus 3±1 bursts/30 seconds ) and experimental ( 4±1 versus 5±1 bursts/30 seconds ) subjects . IHG and CPT increased MSNA in both groups PRE and POST . MSNA , arterial blood pressure , and heart rate responses to the stressors were similar PRE and POST in the control group . In contrast , MSNA responses to IHG ( & Dgr;4±2 and & Dgr;9±2 bursts/30 seconds ; P<0.05 for PRE and POST , respectively ) and CPT ( & Dgr;4±1 versus & Dgr;10±2 bursts/30 seconds ; P<0.05 ) were augmented after omega-3 fatty acid supplementation  whereas arterial blood pressure and heart rate responses were unchanged . These data indicate that 1 month of omega-3 fatty acid supplementation does not change MSNA at rest but augments sympathetic outflow to physiological stressors . The mechanism underlying augmented MSNA responses to physiological stressors after omega-3 fatty acid supplementation is unknown , but may involve impaired peripheral vasoconstriction BACKGROUND Greatly increasing dietary flaxseed oil [ rich in the n-3 polyunsaturated fatty acid ( PUFA ) alpha-linolenic acid ( ALA ) ] or fish oil [ rich in the long-chain n-3 PUFAs eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids ] can reduce markers of immune cell function . The effects of more modest doses are unclear , and it is not known whether ALA has the same effects as its long-chain derivatives . OBJECTIVE The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils , monocytes , and lymphocytes . DESIGN In a placebo-controlled , double-blind , parallel study , 150 healthy men and women aged 25 - 72 y were r and omly assigned to 1 of 5 interventions : placebo ( no additional n-3 PUFAs ) , 4.5 or 9.5 g ALA/d , and 0.77 or 1.7 g EPA+DHA/d for 6 mo . The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules . Blood sample s were taken at 0 , 3 , and 6 mo . RESULTS The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA . The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity , the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester , the proliferation of lymphocytes in response to a T cell mitogen , the production of numerous cytokines by monocytes and lymphocytes , or the in vivo delayed-type hypersensitivity response . CONCLUSION An intake of < or= 9.5 g ALA/d or < or= 1.7 g EPA+DHA/d does not alter the functional activity of neutrophils , monocytes , or lymphocytes , but it changes the fatty acid composition of mononuclear cells There is a large body of scientific evidence that has been confirmed in r and omized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish . For alpha-linolenic acid ( ALA ) , which is the omega-3 fatty acid from plants , the relation to cardiovascular health is less clear . We review ed the recent literature on dietary ALA intake , ALA tissue concentrations , and cardiovascular health in humans . Short-term trials ( 6–12 weeks ) in generally healthy participants mostly showed no or inconsistent effects of ALA intake ( 1.2–3.6 g/d ) on blood lipids , low-density lipoprotein oxidation , lipoprotein(a ) , and apolipoproteins A-I and B. Studies of ALA in relation to inflammatory markers and glucose metabolism yielded conflicting results . With regard to clinical cardiovascular outcomes , there is observational evidence for a protective effect against nonfatal myocardial infa rct ion . However , no protective associations were observed between  ALA status and risk of heart failure , atrial fibrillation , and sudden death . Findings from long-term trials of ALA supplementation are awaited to answer the question whether food-based or higher doses of ALA could be important for cardiovascular health in cardiac patients and the general population BACKGROUND Although dietary omega-3 ( n-3 ) fatty acids may confer some cardiovascular benefits , it is unclear whether these nutrients may also unfavorably affect risk of type 2 diabetes ( T2D ) . OBJECTIVE We evaluated whether dietary omega-3 fatty acids and fish consumption were associated with increased risk of T2D . DESIGN This was a prospect i ve study of 36,328 women ( mean age : 54.6 y ) who participated in the Women 's Health Study and who were followed from 1992 to 2008 .  Incident T2D was self-reported and vali date d primarily through the collection of supplementary information from participants . Information on omega-3 and fish intakes was obtained by using a vali date d food-frequency question naire . We used Cox proportional hazard models to estimate adjusted relative risks . RESULTS During an average follow-up of 12.4 y , 2370 women developed T2D .  Marine but not plant-based omega-3 fatty acids were positively associated with incident T2D . From the lowest to highest quintiles of marine omega-3 intake , the multivariable-adjusted hazard ratios ( 95 % CIs ) for T2D were 1.0 ( referent ) , 1.17 ( 1.03 , 1.33 ) , 1.20 ( 1.05 , 1.38 ) , 1.46 ( 1.28 , 1.66 ) , and 1.44 ( 1.25 , 1.65 ) , respectively ( P for trend < 0.0001 ) . A similar association was observed with fish intake , but additional adjustment for docosahexaenoic acid led to the elimination of the association . The relation between marine omega-3 fatty acids and T2D was observed in hypertensive and nonhypertensive subjects and in women who reported infrequent fish consumption . CONCLUSION Our data suggest an increased risk of T2D with the intake of long-chain omega-3 fatty acids , especially with higher intakes ( ≥ 0.20 g omega-3/d or ≥ 2 servings of fish/d ) . The Women 's Health Study was registered at clinical trials.gov as NCT00000479 UNLABELLED Cardiovascular disease ( CVD ) is associated with dyslipidemia and frequently with insulin resistance , both of which are in general no alleviated by antilipidemic drugs . Our objective was to examine whether a dietary supplement containing omega-3 fatty acids ( n-3 FA ) can reduce the levels of serum lipids , fasting insulin and glucose in documented CVD patients treated by statins or  bezafibrates .  In a double-blind placebo-controlled trial of parallel design , 52 patients , age 69.2 years + /- 3.6 treated by antilipidemic drugs  , were r and omly assigned to receive daily 7 gr of a dietary concentrated supplement containing 67 % n-3 FA ( 185 mg EPA and 465 mg/g DHA ) in a form of spread ( Yamega Ltd , Israel ) or olive oil spread ( placebo ) and recommended to reduce the consumption of omega-6 fatty acids for 12 weeks . The average values + /- SD before and after dietary supplementations were compared . RESULTS 44 patients ( 23 in the n-3 FA group ) completed the study . In the n-3FA group we observed a significant decrease ( p < 0.05 ) of total cholesterol ( 12.2 % ) . LDL-cholesterol ( 16.8 % ) , triglycerides ( 36.1 % ) , insulin in hyperinsulinemic subjects ( > 20 microunits/ml ) ( 34.9 % ) , and no significant changes in HDL-cholesterol and glucose . No hyperglycemia was detected . In the olive oil group we observed a significant decrease ( p < 0.05 ) in the LDL-cholesterol values of 15.5 % and no significant changes in the other parameters . No side effects were reported during the study in any of the participants . Our findings demonstrate that the incorporation of the dietary supplement containing EPA and DHA omega-3 fatty acids reduces significantly the above risk factors for CVD There is convincing evidence that consumption of fish and fish oil rich in long-chain ( LC ) n-3 PUFA ( n-3 LCPUFA ) , EPA ( 20 : 5n-3 ) and DHA ( 22 : 6n-3 ) reduce the risk of CHD . The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers . A parallel 7-week intervention trial was performed where 159 healthy men and women were r and omised to consume either 34 g fish pâté ( n 44 ) , 500 ml fruit juice ( n 38 ) or three capsules of concentrated fish oil ( n 40 ) , all contributing to a daily intake of approximately 1 g EPA and DHA . A fourth group did not receive any supplementation or food product and served as controls ( n 37 ) . Plasma fatty acid composition , serum lipids , and markers of inflammation and oxidative stress were measured . Compared with the control group , plasma n-3 LCPUFA and EPA : arachidonic acid ratio increased equally in all intervention groups . However , no significant changes in blood lipids and markers of inflammation and oxidative stress were observed . In conclusion , enriched fish pâté and fruit juice represent suitable delivery systems for n-3 LCPUFA . However , although the dose given is known to reduce the risk of CVD , no significant changes were observed on cardiovascular risk markers in this healthy population We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids . Thirty nine asthmatic children aged 8 - 12 yrs participated in a double-blind , r and omized , controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine ( omega-3 group ) or safflower oil capsules plus sunflower oil and margarine ( omega-6 group ) . Plasma fatty acids , stimulated tumour necrosis factor alpha ( TNFalpha ) production , circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification . Day and night symptoms , peak flow rates and medication use were recorded for 1 week prior to laboratory visits . Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group ( p<0.001 ) . In the omega-3 group TNFalpha production fell significantly compared with baseline ( p=0.026 ) , but the magnitude of change between groups did not reach significance ( p=0.075 ) . There were no significant changes in clinical outcome measures . Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids , reduced stimulated tumour necrosis factor alpha production , but had no effect on the clinical severity of asthma in these children OBJECTIVE Dietary intervention studies suggest that a daily fish meal can improve blood pressure ( BP ) ; however , such a dietary regimen might be difficult to sustain . The objective of the present study was to investigate whether salmon consumption three times per week improves BP during energy restriction in young adults . METHODS In this 8-wk intervention , 324 subjects ( 20 - 40 y of age , body mass index 27.5 - 32.5kg/m(2 ) , from Icel and , Spain , and Irel and ) were r and omized to one of four energy-restricted diets ( -30 % relative to estimated requirements ) : salmon ( 150 g three times per week , result ing in a daily consumption of 2.1 g of omega-3 long-chain polyunsaturated fatty acids [ omega-3 LC-PUFAs ] ) , cod ( 150 g three times per week , 0.3 g of omega-3 LC-PUFAs per day ) , fish oil capsules ( 1.3 g of omega-3 LC-PUFAs per day ) , or control ( sunflower oil capsules , no seafood ) . Body weight , diastolic BP ( DBP ) , systolic BP ( SBP ) , and docosahexaenoic acid ( DHA ) in erythrocyte membrane were measured at baseline and endpoint . RESULTS Participants showed weight loss ( -5.2+/-3.2 kg , P<0.001 ) and decreases in SBP ( -4.4+/-8.6 mmHg , P<0.001 ) and DBP ( -4.1+/-7.4 mmHg , P<0.001 ) after the intervention . The salmon ( B=-2.71 , P=0.032 ) and fish oil ( B=-2.48 , P=0.044 ) groups had significantly lower endpoint DPB than the cod group , but not significantly different from control . Lower baseline DHA ( percentage ) in erythrocytes was associated with greater DBP reductions ( B=0.576 , P=0.017 ) . CONCLUSION Salmon consumption three times per week can decrease DBP similar to fish oil and significantly more than lean fish during an 8-wk energy restriction in young overweight individuals . A lower DHA content in erythrocyte membrane at baseline , which might indentify infrequent fish eaters , is associated with a greater DBP reduction in the course of an 8-wk dietary intervention providing fatty seafood Background Human milk is the optimal nutrition for infants . When breastfeeding is not possible , supplementation of infant formula with long chain polyunsaturated fatty acids appears to promote neurodevelopmental outcome and visual function .  Plant oils , that are the only source of fat in most of infant formulas , do not contain specific fatty acids that are present in human and cow milk and do not encounter milk fat triglyceride structure . Experimental data suggest that a mix of dairy lipids and plant oils can potentiate endogenous synthesis of n-3 long chain polyunsaturated fatty acids . This trial aims to determine the effect of an infant formula supplemented with a mixture of dairy lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in full-term infants ( primary outcome ) . Erythrocyte membrane long chain polyunsaturated fatty acids and fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level , the gastrointestinal tolerance , the changes throughout the study in blood fatty acids content , in growth and body composition are evaluated as secondary outcomes . Methods / Design In a double-blind controlled r and omized trial , 75 healthy full-term infants are r and omly allocated to receive for four months a formula supplemented with a mixture of dairy lipids and plant oils or a formula containing only plant oils or a formula containing plant oils supplemented with arachidonic acid and docosahexaenoic acid .  Twenty-five breast-fed infants constitute the reference group .  Erythrocyte membrane omega-3 fatty acid profile , long chain polyunsaturated fatty acids and the other fatty acids content , the plasma lipid profile and the insulin-growth factor 1 level are measured after four months of intervention . Gastrointestinal tolerance , the changes in blood fatty acids content , in growth and body composition , assessed by means of an air displacement plethysmography system , are also evaluated throughout the study . Discussion The achievement of an appropriate long chain polyunsaturated fatty acids status represents an important goal in neonatal nutrition . Gaining further insight in the effects of the supplementation of a formula with dairy lipids and plant oils in healthy full-term infants could help to produce a formula whose fat content , composition and structure is more similar to human milk . Trial registration Clinical Trials.gov Identifier BACKGROUND Intakes of n-3 ( omega-3 ) polyunsaturated fatty acids ( PUFAs ) are important for health . Because fish is the major source of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , non-fish-eaters may have suboptimal n-3 PUFA status , although the importance of the conversion of plant-derived α-linolenic acid ( ALA ) to EPA and DHA is debated . OBJECTIVE The objective was to determine intakes , food sources , and status of n-3 PUFAs  according to dietary habit ( fish-eaters and non-fish-eating meat-eaters , vegetarians , or vegans ) and estimated conversion between dietary ALA and circulating long-chain n-3 PUFAs . DESIGN This study included 14,422 men and women aged 39 - 78 y from the EPIC ( European Prospect i ve Investigation into Cancer and Nutrition)-Norfolk cohort with 7-d diary data and a sub study in 4902 individuals with plasma phospholipid fatty acid measures .  Intakes and status of n-3 PUFAs were measured , and the product-precursor ratio [ corrected ] of ALA to circulating n-3 PUFAs was calculated . RESULTS Most of the dietary intake of  EPA and DHA was supplied by fish ; however , meat was the major source in meat-eaters , and spreading fats , soups , and sauces were the major sources in vegetarians . Total n-3 PUFA intakes in non-fish-eaters were 57 - 80 % of those in fish-eaters , but status differences were considerably smaller [ corrected ] . The estimated product-precursor ratio [ corrected ] was greater in women than in men and greater in non-fish-eaters than in fish-eaters . CONCLUSIONS Substantial differences in intakes and in sources of n-3 PUFAs existed between the dietary-habit groups , but the differences in status were smaller than expected , possibly because the product-precursor ratio [ corrected ] was greater in non-fish-eaters than in fish-eaters , potentially indicating increased estimated conversion of ALA . If intervention studies were to confirm these findings , it could have implication s for fish requirements As meat is a rich source of the omega-3 fatty acid docosapentaenoic acid ( DPA ) and Australians consume six times more meat than fish , investigation of the potential health benefit of DPA is warranted . The aims were to compare the effects of seal oil supplementation with fish oil , on measures of plasma lipids and blood pressure in hypertriglyceridaemic subjects . Forty-eight volunteers were recruited from the Wollongong community and were r and omly allocated to one of three groups either receiving 1 g/day of long-chain omega-3 polyunsaturated fatty acids ( LC n-3 PUFA ) using one of three oils : seal oil capsules ( 340 mg eicosapentaenoic acid ( EPA ) , 230 mg DPA , 450 mg DHA ) , fish oil capsules ( 210 mg EPA , 30 mg DPA , 810 mg DHA ) or placebo capsules ( containing sunola oil ) for 6 weeks . Plasma triglycerides remained unchanged in the placebo group , whilst reductions of 7 and 14 % ( P < 0.05 ) were seen in the fish oil and seal oil groups respectively . Systolic blood pressure improved by 8 and 5 mmHg with seal oil and fish oil respectively ( P < 0.05 ) . The mean arterial pressure was significantly lower after seal oil supplementation ( P < 0.005 ) compared with the placebo group . These results indicate that seal oil is as effective as fish oil in lowering plasma triglycerides and blood pressure OBJECTIVE The potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis . Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis ( UC ) , but the precise mechanism of the action of fish oil on oxidative stress is still controversial . The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress . METHODS Nine patients ( seven female and two male ; mean age = 40 + /- 11 y ) with mild or moderate active UC were studied in a r and omized crossover design . In addition to their usual medication ( 2 g/d of sulfasalazine ) , they received fish oil omega-3 fatty acids ( 4.5 g/d ) or placebo for 2-mo treatment periods that were separated by 2 mo , when they only received sulfasalazine .  Nine healthy individuals served as control subjects to study the oxidative stress status . Disease activity was assessed by laboratory indicators ( C-reactive protein , alpha1-acid glycoprotein , alpha1-antitrypsin , erythrocyte sedimentation rate , albumin , hemoglobin , and platelet count ) , sigmoidoscopy , and histology scores . Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation , both induced by tert butyl hydroperoxide ( t-BuOOH ) and by plasma malondialdehyde . Antioxidant status was assayed by total plasma antioxidant capacity ( TRAP ) and microsomal lipid peroxidation inhibition ( LPI ) . Superoxide dismutase ( SOD ) and catalase erythrocyte enzymatic activities were also determined . RESULTS No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores , with the exception of erythrocyte sedimentation rate , which decreased with both treatments . Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels , increased chemiluminescence induced by t-BuOOH , and higher SOD activity in patients with UC . Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine .  Levels of plasma malondialdehyde , erythrocyte lipid peroxidation , and catalase were not different from those in the control group . CONCLUSIONS The results indicated that plasma oxidative stress occurs in patients with UC , and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids . However , there was no improvement in most laboratory indicators , sigmoidoscopy , and histology scores . The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease ( CVD ) , there remain no completed large-scale , r and omized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk . The VITamin D and OmegA-3 TriaL ( VITAL ) is a 2 × 2 factorial r and omized , double-blind , placebo-controlled trial of the benefits and risks of vitamin D ( vitamin D3 [ cholecalciferol ] , 2000 IU/d ) and marine omega-3 fatty acids ( Omacor ( ® ) fish oil , a 1 g/d ) in the primary prevention of cancer and CVD among 25,875 men and women , aged ≥50 and ≥55 years , respectively . R and omization began in November 2011 and was completed in March 2014 . This report will describe the rationale for the trial and currently available r and omized trial data , summarize related ongoing large-scale trials , and provide a brief overview of study design , and an up date on r and omization milestones , racial/ethnic diversity , biorepository activities , in-depth phenotyping of a subcohort , and ancillary studies Data from laboratory studies , observational research , and /or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease ( CVD ) , but primary prevention trials with adequate dosing in general population s ( i.e. , unselected for disease risk ) are lacking . The ongoing VITamin D and OmegA-3 TriaL ( VITAL ) is a large r and omized , double-blind , placebo-controlled , 2 x 2 factorial trial of vitamin D ( in the form of vitamin D(3 ) [ cholecalciferol ] , 2000 IU/day ) and marine omega-3 fatty acid ( Omacor fish oil , eicosapentaenoic acid [EPA]+docosahexaenoic acid [ DHA ] , 1g/day ) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥ 50 and women aged ≥ 55 . The mean treatment period will be 5 years . Baseline blood sample s will be collected in at least 16,000 participants , with follow-up blood collection in about 6000 participants . Yearly follow-up question naires will assess treatment compliance ( plasma biomarker measures will also assess compliance in a r and om sample of participants ) , use of non- study drugs or supplements , occurrence of endpoints , and cancer and vascular risk factors . Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment , and deaths will be ascertained through national registries and other sources . Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance ; hypertension ; cognitive decline ; depression ; osteoporosis and fracture ; physical disability and falls ; asthma and other respiratory diseases ; infections ; and rheumatoid arthritis , systemic lupus erythematosus , thyroid diseases , and other autoimmune disorders To compare their relative absorption and effect on platelet function , concentrated fish oil and tuna were given to 10 subjects in a r and omized crossover study . Although plasma enrichment of eicosapentaenoic acid ( EPA ) from either preparation was similar , relative absorption of EPA from tuna was significantly greater than that from fish oil ( 46.6 + /- 3.0 mg . L-1.g EPA-1 from tuna compared with 16 + /- 1.0 mg . L-1.g EPA-1 from fish oil , P less than 0.001 ) . Relative absorption of docosahexaenoic acid ( DHA ) was equivalent ( 54.0 + /- 9.0 mg . L-1.g DHA-1 from tuna , 56 + /- 9.0 mg . L-1.g DHA-1 from fish oil , NS ) . Platelet aggregation in response to the endoperoxide analog U46619 was significantly diminished after either preparation but aggregation in response to other agonists , bleeding time , and membrane n-3 ( omega-3 ) fatty acid content were not changed . Thus , n-3 fatty acids are well absorbed after one dose of either tuna or fish oil but EPA absorption appears to be more efficient from tuna . Additionally , a single dose of n-3 fatty acids decreases platelet aggregation by a mechanism not requiring incorporation into platelet membranes Human , animal , and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 ( n-3 ) polyunsaturated fatty acids ( PUFA ) on bone health . This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover , assessed by serum concentrations of N-telopeptides ( NTx ) and bone-specific alkaline phosphatase ( BSAP ) .  Subjects ( n = 23 ) consumed each diet for 6 weeks in a r and omized , 3-period crossover design : 1 ) Average American Diet ( AAD ; [ 34 % total fat , 13 % saturated fatty acids ( SFA ) , 13 % monounsaturated fatty acids ( MUFA ) , 9 % PUFA ( 7.7 % LA , 0.8 % ALA ) ] ) , 2 ) Linoleic Acid Diet ( LA ; [ 37 % total fat , 9 % SFA , 12 % MUFA , 16 % PUFA ( 12.6 % LA , 3.6 % ALA ) ] ) , and 3 ) α-Linolenic Acid Diet ( ALA ; [ 38 % total fat , 8 % SFA , 12 % MUFA , 17 % PUFA ( 10.5 % LA , 6.5 % ALA ) ] ) . Walnuts and flaxseed oil were the predominant sources of ALA . NTx levels were significantly lower following the ALA diet ( 13.20 ± 1.21 nM BCE ) , relative to the AAD ( 15.59 ± 1.21 nM BCE ) ( p < 0.05 ) . Mean NTx level following the LA diet was 13.80 ± 1.21 nM BCE . There was no change in levels of BSAP across the three diets . Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFα for all three diets . The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation BACKGROUND Obesity is associated with elevated levels of inflammation and metabolic abnormalities , with increased risk of developing insulin resistance , type 2 diabetes , stroke and CVD . Nutrients that can assist in weight loss may also reduce the risk of obesity related co-morbidities . AIM The aim of this study was to investigate whether LCn-3PUFA , combined with a reduced energy diet , facilitated weight loss and improvements in blood lipids and inflammatory mediators . DESIGN A double blind r and omised controlled trial with two parallel groups . Both groups followed a low energy diet for 12 weeks , one group consumed 6 × 1 g capsules/d monounsaturated oil ( Placebo ) ( n = 18 ) , the other 6 × 1 g capsules/d LCn-3PUFA ( fish oil ) ( n = 17 ) . Fasting blood sample s , anthropometric measurements and 3-day food diaries were collected at baseline and post intervention . RESULTS There was a two-fold increase in plasma levels of EPA and DHA in the fish oil group ( p < 0.001 ) . There were no significant difference within and between the placebo and the fish oil groups for weight reduction ( 3.37 % and 4.35 % respectively ) , fat mass reduction ( 8.95 % and 9.76 % respectively ) , or changes in inflammatory biomarkers and blood lipids apart from triglycerides , reduced by 27 % in fish oil group ( p < 0.05 ) . For fish oil group there were significant correlations between leptin and weight loss ( p = 0.01 ) and leptin and EPA and DHA ( p < 0.05 for both ) . CONCLUSION Dietary LCn-3PUFA supplementation during a weight loss program does not appear to assist weight loss . Poor dietary compliance may be a contributing factor in accurate assessment of the role of these fatty acids in weight loss Effects of dietary sodium restriction combined with fish oil supplementation on BP and related risk factors were assessed in hypertensives treated with angiotensin converting enzyme ( ACE ) inhibitors .  After a four week run-in phase , a six week intervention trial was conducted in which four matched groups of 14 patients , taking either captopril or enalapril  , were assigned to one of four dietary treatments : low sodium ( 80 mmol/day ) with fish oil ( 5 g of omega-3 fatty acids per day ) ; normal sodium ( 150 mmol/day ) with fish oil ; low sodium with olive oil ; normal sodium with olive oil . All subjects adopted a low sodium diet and adjustments of nutrient intake were made by double-blind administration of sodium and oils in supplementary tablets and capsules . BP fell in all treatment groups during intervention . However , the reduction of SBP was 4.2 mmHg greater in subjects on a low sodium intake than in those taking normal sodium . There were no differences in BP between those taking olive oil and those taking fish oil but plasma triglycerides and serum thromboxane production were reduced by 27 % and 51 % , respectively in the latter . Thus the antihypertensive effect of ACE inhibitors can be augmented by sodium restriction alone but supplementing the diet with fish oil may yield additional cardiovascular benefits Arachidonic acid metabolites formed by both the cyclooxygenase and lipoxygenase pathways may contribute to the clinical diarrhea and colitis of inflammatory bowel disease . Patients with active ulcerative colitis have increased levels of leukotriene B4 in their rectal mucosa , and these levels tend to correlate with severity of the disease . In this study , we evaluated the efficacy of ingestion of fish oil n-3-omega-fatty acids , inhibitors of leukotriene synthesis , in the treatment of ulcerative colitis . Eleven patients with ulcerative colitis of mild to moderate severity were studied in a 8-month , double-blind , placebo-controlled , crossover trial of dietary supplementation with fish oil , which provided about 4.2 g of omega-3- fatty acids per day . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mucosal leukotriene B4 production was measured by radioimmunoassay . Mean disease activity index declined 56 % for patients receiving fish oil and 4 % for patients on placebo ( p less than 0.05 ) . There were no statistically significant differences in histopathologic scores or colonic mucosal leukotriene B4 levels . All patients tolerated fish oil ingestion and showed no alteration in routine blood studies . No patient worsened ; anti-inflammatory drugs could be reduced or eliminated in eight patients ( 72 % ) while receiving fish oil . We conclude that fish oil dietary supplementation results in clinical improvement of active mild to moderate ulcerative colitis but is not associated with significant reduction in mucosal leukotriene B4 production , compared with placebo therapy . Further studies are needed to eluci date the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis In 46 elderly ( aged greater than or equal to 60 y ) hypertensive subjects with entry systolic blood pressure ( SBP ) greater than or equal to 160 or diastolic blood pressure ( DBP ) greater than or equal to 90 mm Hg , our specific aim in a r and omized , double-blind , crossover study ( two 8-wk treatment periods separated by a 3-wk washout ) was to compare blood pressure-lowering effects of 9 g fish oil/d [ omega-3 ( n-3 ) fatty acid ] vs 9 g corn oil/d [ omega-6 ( n-6 ) fatty acid ] . After a 4-wk baseline period , 22 subjects were r and omly assigned to receive fish oil and 24 to receive corn oil . For both 8-wk treatments there were no between-group differences in the change in blood pressure . There was a treatment difference for st and ing DBP when baseline values were compared with those after treatment 2 ; DBP decreased by 5.1 mm Hg in the fish-oil group vs 0.72 mm Hg in the corn-oil group ( P = 0.024 ) . Within groups during the first treatment , both fish oil and corn oil lowered all four blood pressure measures ( P less than 0.05 ) ; blood pressures were not further lowered during the second treatment compared with the washout period . There were no significant between-group differences in laboratory safety tests or categorical side effects .  Fish oil lowered triglycerides by 0.47 mmol/L ( P less than 0.001 ) . In elderly subjects , diet plus both omega-3 and omega-6 supplements ( 9 g/d ) safely and effectively lower SBP and DBP
Combining 21 trials evaluating lipid outcomes , fish oil consumption result ed in a summary net change in triglycerides of -27 ( 95 % CI -33 , -20)mg/dL , in HDL cholesterol of + 1.6 ( 95 % CI + 0.8 , + 2.3)mg/dL , and in LDL cholesterol of + 6 ( 95 % CI + 3 , + 8)mg/dL. There was no effect of fish oil on total cholesterol .
Across studies , higher fish oil dose and higher baseline levels were associated with greater reductions in serum triglycerides .
The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides , particularly among people with more elevated levels .
Fish oil consumption also modestly improves HDL cholesterol , increases LDL cholesterol levels , but does not appear to adversely affect glucose homeostasis .
The evidence regarding the effects of omega-3 fatty acids on hs-CRP is inconclusive , as are data on ALA
Greater fish oil consumption has been associated with reduced CVD risk , although the mechanisms are unclear .
Plant- source oil omega-3 fatty acids ( ALA ) have also been studied regarding their cardiovascular effect .