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].
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
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 .