Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review

Project Summary Title and Description

Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review
The effect and association of omega−3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes.
Authors of Report
Methodology description
We included randomized controlled trials (RCTs) of any n-3 FA intake compared to no, lower, or other n-3 FA intake with an outcome of interest conducted in healthy adults, those at risk for CVD, or those with CVD. We also included prospective observational studies of the association between baseline n-3 FA intake or biomarker level and followup outcomes. We required 1 year or more of followup for clinical outcomes and 4 weeks for intermediate outcomes (blood pressure [BP] and lipids).
Data entered retrospectively into the SRDR Extraction Form. Report available at:
Funding Source
AHRQ (Contract No. 290-2012-00012-I)

Key Questions

1. RCTs and other Comparative studies
2. Observational studies (longitudinal; quantile or continuous analysis)

Associated Extraction Forms

Associated Studies (each link opens a new tab)

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.2013
A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects.2001
Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study.
Interaction between a CSK gene variant and fish oil intake influences blood pressure in healthy adults.
Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.2007
A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial).2013
Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial.
Effect of n-3 fatty acids and statins on oxidative stress in statin-treated hypercholestorelemic and normocholesterolemic women.2011
Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial.2009
Baseline lipoprotein lipids and low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl ester added to Simvastatin therapy.2010
Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).2012
Effects of varying dietary fat, fish, and fish oils on blood lipids in a randomized controlled trial in men at risk of heart disease.
Effects of stable fish oil and simvastatin on plasma lipoproteins in patients with hyperlipidemia.2003
Efficacy of a unique omega-3 formulation on the correction of nutritional deficiency and its effects on cardiovascular disease risk factors in a randomized controlled VASCAZEN(registered trademark) REVEAL Trial2014
Effects of dietary saturated, monounsaturated, and n-3 fatty acids on blood pressure in healthy subjects.2006
APOE genotype influences triglyceride and C-reactive protein responses to altered dietary fat intake in UK adults.2012
Impact of atorvastatin plus n-3 PUFA on metabolic, inflammatory and coagulative parameters in metabolic syndrome without and with type 2 diabetes mellitus2009
Complementary effects of multivitamin and omega-3 fatty acid supplementation on indices of cardiovascular health in individuals with elevated homocysteine.2012
Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).1989
N-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia.2012
Potent antihypertensive action of dietary flaxseed in hypertensive patients.2013
Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial.2010
Comparison of the effects of simultaneous administration of vitamin C and omega-3 fatty acids on lipoproteins, apo A-I, apo B, and malondialdehyde in hyperlipidemic patients.2003
Absence of prophylactic effect of linolenic acid in patients with coronary heart-disease.1966
Supplementation with omega3 polyunsaturated fatty acids and all-rac alpha-tocopherol alone and in combination failed to exert an anti-inflammatory effect in human volunteers.2004
Lack of benefit of dietary advice to men with angina: results of a controlled trial.
Can foods with added soya-protein or fish-oil reduce risk factors for coronary disease? A factorial randomised controlled trial.
n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.2012
Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.2002
OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction.2010
Effects of a rapeseed oil-enriched hypoenergetic diet with a high content of α-linolenic acid on body weight and cardiovascular risk profile in patients with the metabolic syndrome.2012
Omega-3 fatty acid supplements improve the cardiovascular risk profile of subjects with metabolic syndrome, including markers of inflammation and auto-immunity.2009
Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.2008
Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) trial.2013
n-3 polyunsaturated fatty acids in the prevention of atrial fibrillation recurrences after electrical cardioversion: a prospective, randomized study.2011
Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial.2005
Fish oil and neurovascular control in humans.2012
Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives.1994
Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.2005
n-3 fatty acids and cardiovascular events after myocardial infarction.2010
Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study.2008
n-3 fatty acids in patients with multiple cardiovascular risk factors.2013
Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil.2010
DHA-enriched high-oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial.
The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial.1999
Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans.1998
Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency.1996
Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group.1995
Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.1994
Investigation of the effects of a high fish diet on inflammatory cytokines, blood pressure, and lipids in healthy older Australians.2014
Alimentary habits, physical activity, and Framingham global risk score in metabolic syndrome.2014
Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial.2006
Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial.2014
A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk.2010
N-3 fatty acids do not lead to an increased diabetic risk in patients with hyperlipidemia and abnormal glucose tolerance. Italian Fish Oil Multicenter Study.
One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations.1998
Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men.
Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention.1994
Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy.2011
Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.2014
The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial.1966
Fish, n-3 fatty acids, and cardiovascular diseases in women of reproductive age: a prospective study in a large national cohort.2012
Fish intake and risks of total and cause-specific mortality in 2 population-based cohort studies of 134,296 men and women.2013
A controlled trial of the effect of linolenic acid on incidence of coronary heart disease. The Norwegian vegetable oil experiment of 1965-66.1968
Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study.2010
Effects of long chain omega-3 fatty acids on metalloproteinases and their inhibitors in combined dyslipidemia patients.2009
Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I.2006
Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study.2008
Fish consumption, marine omega-3 fatty acids, and incidence of heart failure: a population-based prospective study of middle-aged and elderly men.2009
Marine (n-3) fatty acids, fish consumption, and the 10-year risk of fatal and nonfatal coronary heart disease in a large population of Dutch adults with low fish intake.2010
Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.1997
Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: a 24-year follow-up of NIPPON DATA80.2014
Relationships between plasma fatty acid composition and coronary artery disease.2011
Dietary fats and dietary cholesterol and risk of stroke in women.2012
Intake of total omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study.
Association between the intake of α-linolenic acid and the risk of CHD.2014
Soy and fish oil intake and mortality in a Japanese community.2002
Fish consumption and cardiovascular disease in the physicians' health study: a prospective study.1995
Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.2001
Fish and shellfish consumption in relation to death from myocardial infarction among men in Shanghai, China.2001
Dietary fatty acids and the risk of hypertension in middle-aged and older women.2010
Intake of very long-chain n-3 fatty acids from fish and incidence of atrial fibrillation. The Rotterdam Study.2006
Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study.2012
Fish oil, selenium and mercury in relation to incidence of hypertension: a 20-year follow-up study.2011
Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.2008
Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study.
Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.2013
Fish and omega-3 fatty acid intake and risk of coronary heart disease in women.2002
Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects.
Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men.1995
The prognostic value of adipose tissue fatty acids for incident cardiovascular disease: results from 3944 subjects in the Scottish Heart Health Extended Cohort Study.2011
N-6 and n-3 fatty acid cholesteryl esters in relation to incident stroke in a Dutch adult population: a nested case-control study.2013
Erythrocyte stearidonic acid and other n-3 fatty acids and CHD in the Physicians' Health Study.2013
Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men.2009
Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study.
Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction.2013
Genetic variation in FADS1 has little effect on the association between dietary PUFA intake and cardiovascular disease.2014
Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial.1992
Erythrocyte fatty acid composition is associated with the risk of hypertension in middle-aged and older women.2011
Oily fish reduces plasma triacylglycerols: a primary prevention study in overweight men and women.2006
Dietary α-linolenic acid, linoleic acid, and n-3 long-chain PUFA and risk of ischemic heart disease.2011
Fish intake and the risk of incident heart failure: the Women's Health Initiative.2011
The association between dietary omega-3 fatty acids and cardiovascular death: the Singapore Chinese Health Study.2013
Effects of stearidonic acid on serum triacylglycerol concentrations in overweight and obese subjects: a randomized controlled trial.2015
Efficacy of a unique omega-3 formulation on the correction of nutritional deficiency and its effects on cardiovascular disease risk factors in a randomized controlled VASCAZEN(®) REVEAL Trial.2014
White fish reduces cardiovascular risk factors in patients with metabolic syndrome: the WISH-CARE study, a multicenter randomized clinical trial.2014
Intake of long-chain ω-3 fatty acids from diet and supplements in relation to mortality.2014
Higher erythrocyte n-3 PUFAs are associated with decreased blood pressure in middle-aged and elderly Chinese adults.2014
Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose-dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women.2014
Dietary echium oil increases long-chain n-3 PUFAs, including docosapentaenoic acid, in blood fractions and alters biochemical markers for cardiovascular disease independently of age, sex, and metabolic syndrome.2014
Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: the Hisayama Study.2013
Effects of omega-3 on metabolic markers in postmenopausal women with metabolic syndrome.2015
The effects of long-chain omega-3 fish oils and multivitamins on cognitive and cardiovascular function: a randomized, controlled clinical trial.2015
Fish, omega-3 long-chain fatty acids, and all-cause mortality in a low-income US population: Results from the Southern Community Cohort Study.2015
Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women.2015
Plasma eicosapentaenoic acid is negatively associated with all-cause mortality among men and women in a population-based prospective study.2016

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