Review| Volume 27, ISSUE 3, P191-200, March 2017

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Impact of omega-3 polyunsaturated fatty acids on vascular function and blood pressure: Relevance for cardiovascular outcomes


      • The relevance of omega-3 polyunsaturated fatty acids (PUFA) for the cardiovascular system is under the spotlight.
      • We overviewed the effects of omega-3 PUFA on vascular function and blood pressure (BP).
      • Multiple mechanisms account for the anti-atherogenic properties of omega-3 PUFA.
      • Omega-3 PUFA decrease the BP in hypertensive subjects.
      • The current evidence supporting the role of omega-3 PUFA in cardiovascular prevention is weak.



      To overview the effects of omega-3 polyunsaturated fatty acids (PUFA) on blood vessels and blood pressure (BP) and their relevance for cardiovascular prevention.

      Data synthesis

      The importance of omega-3 PUFA for the cardiovascular system has come under the spotlight during the last decades. These fatty acids are present in variable amounts in cell membranes of mammal species, and their content affects a variety of cellular functions. Evidence obtained in animal and human studies suggests that omega-3 PUFA affect many steps of the atherosclerotic process. In blood vessels, omega-3 PUFA improve endothelial function; promote vasodilatation through relaxation of smooth muscle cells; exert antioxidant, anti-inflammatory, and antithrombotic actions; delay development of plaques and increase their stability; and decrease wall stiffening. Omega-3 PUFA might affect BP, and studies conducted with ambulatory monitoring suggest that supplementation with these fatty acids decreases the average 24-h BP levels. This effect on BP is related to the pretreatment membrane content of omega-3 PUFA, and this might explain some inconsistencies among intervention trials. Meta-analyses indicate that omega-3 PUFA have a mild but significant BP lowering effect. While encouraging results were initially obtained with the use of omega-3 PUFA supplements in secondary prevention trials, meta-analyses have not confirmed the ability of these fatty acids to decrease the risk of coronary heart and cerebrovascular disease.


      Omega-3 PUFA are associated with significant improvement in vascular function and lowering of BP. However, the evidence currently supporting the role of these fatty acids in cardiovascular prevention is weak and needs further investigation.


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        • Davis B.C.
        • Kris-Etherton P.M.
        Achieving optimal essential fatty acid status in vegetarians: current knowledge and practical implications.
        Am J Clin Nutr. 2003; 78: 640S-646S
        • Welch A.A.
        • Shakya-Shrestha S.
        • Lentjes M.A.H.
        • Wareham N.J.
        • Khaw K.-T.
        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.
        Am J Clin Nutr. 2010; 92: 1040-1051
        • Yano Y.
        • Hoshide S.
        • Tamaki N.
        • Inokuchi T.
        • Nagata M.
        • Yokota N.
        • et al.
        Regional differences in hypertensive cardiovascular remodeling between fishing and farming communities in Japan.
        Am J Hypertens. 2011; 24: 437-443
        • Colussi G.
        • Catena C.
        • Sechi L.A.
        ω-3 polyunsaturated fatty acids effects on the cardiometabolic syndrome and their role in cardiovascular disease prevention: an update from the recent literature.
        Recent Pat Cardiovasc Drug Discov. 2015; 9: 78-96
        • López D.
        • Orta X.
        • Casós K.
        • Sáiz M.P.
        • Puig-Parellada P.
        • Farriol M.
        • et al.
        Upregulation of endothelial nitric oxide synthase in rat aorta after ingestion of fish oil-rich diet.
        Am J Physiol Heart Circ Physiol. 2004; 287: H567-H572
        • Raimondi L.
        • Lodovici M.
        • Visioli F.
        • Sartiani L.
        • Cioni L.
        • Alfarano C.
        • et al.
        n-3 polyunsaturated fatty acids supplementation decreases asymmetric dimethyl arginine and arachidonate accumulation in aging spontaneously hypertensive rats.
        Eur J Nutr. 2005; 44: 327-333
        • Wang H.-H.
        • Hung T.-M.
        • Wei J.
        • Chiang A.-N.
        Fish oil increases antioxidant enzyme activities in macrophages and reduces atherosclerotic lesions in apoE-knockout mice.
        Cardiovasc Res. 2004; 61: 169-176
        • Chisaki K.
        • Okuda Y.
        • Suzuki S.
        • Miyauchi T.
        • Soma M.
        • Ohkoshi N.
        • et al.
        Eicosapentaenoic acid suppresses basal and insulin-stimulated endothelin-1 production in human endothelial cells.
        Hypertens Res. 2003; 26: 655-661
        • Christensen M.S.
        • Therkelsen K.
        • Møller J.M.
        • Dyerberg J.
        • Schmidt E.B.
        n-3 fatty acids do not decrease plasma endothelin levels in healthy individuals.
        Scand J Clin Lab Invest. 1997; 57: 495-499
        • Wu S.-Y.
        • Mayneris-Perxachs J.
        • Lovegrove J.A.
        • Todd S.
        • Yaqoob P.
        Fish-oil supplementation alters numbers of circulating endothelial progenitor cells and microparticles independently of eNOS genotype.
        Am J Clin Nutr. 2014; 100: 1232-1243
        • Hoshi T.
        • Wissuwa B.
        • Tian Y.
        • Tajima N.
        • Xu R.
        • Bauer M.
        • et al.
        Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels.
        Proc Natl Acad Sci U S A. 2013; 110: 4816-4821
        • Sukumar P.
        • Sedo A.
        • Li J.
        • Wilson L.A.
        • O'Regan D.
        • Lippiat J.D.
        • et al.
        Constitutively active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin.
        Circ Res. 2012; 111: 191-200
        • Wu J.H.Y.
        • Cahill L.E.
        • Mozaffarian D.
        Effect of fish oil on circulating adiponectin: a systematic review and meta-analysis of randomized controlled trials.
        J Clin Endocrinol Metab. 2013; 98: 2451-2459
        • Grenon S.M.
        • Owens C.D.
        • Nosova E.V.
        • Hughes-Fulford M.
        • Alley H.F.
        • Chong K.
        • et al.
        Short-term, high-dose fish oil supplementation increases the production of Omega-3 fatty acid-derived mediators in patients with peripheral artery disease (the OMEGA-PAD I trial).
        J Am Heart Assoc. 2015; 4: e002034
        • Din J.N.
        • Sarma J.
        • Harding S.A.
        • Lyall K.
        • Newby D.E.
        • Flapan A.D.
        Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in patients with a previous myocardial infarction: a randomised controlled trial.
        BMJ Open. 2013; 3: e003054
        • Din J.N.
        • Archer R.M.
        • Harding S.A.
        • Sarma J.
        • Lyall K.
        • Flapan A.D.
        • et al.
        Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in male cigarette smokers.
        Heart Br Card Soc. 2013; 99: 168-174
        • Siasos G.
        • Tousoulis D.
        • Oikonomou E.
        • Zaromitidou M.
        • Verveniotis A.
        • Plastiras A.
        • et al.
        Effects of Ω-3 fatty acids on endothelial function, arterial wall properties, inflammatory and fibrinolytic status in smokers: a cross over study.
        Int J Cardiol. 2013; 166: 340-346
        • Oh P.C.
        • Koh K.K.
        • Sakuma I.
        • Lim S.
        • Lee Y.
        • Lee S.
        • et al.
        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.
        Int J Cardiol. 2014; 176: 696-702
        • Singhal A.
        • Lanigan J.
        • Storry C.
        • Low S.
        • Birbara T.
        • Lucas A.
        • et al.
        Docosahexaenoic acid supplementation, vascular function and risk factors for cardiovascular disease: a randomized controlled trial in young adults.
        J Am Heart Assoc Cardiovasc Cerebrovasc Dis. 2013; : 2
        • Wang Q.
        • Liang X.
        • Wang L.
        • Lu X.
        • Huang J.
        • Cao J.
        • et al.
        Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials.
        Atherosclerosis. 2012; 221: 536-543
        • Xin W.
        • Wei W.
        • Li X.
        Effect of fish oil supplementation on fasting vascular endothelial function in humans: a meta-analysis of randomized controlled trials.
        PLoS ONE. 2012; 7: e46028
        • Jump D.B.
        The biochemistry of n-3 polyunsaturated fatty acids.
        J Biol Chem. 2002; 277: 8755-8758
        • Serhan C.N.
        Pro-resolving lipid mediators are leads for resolution physiology.
        Nature. 2014; 510: 92-101
        • Meydani S.N.
        • Endres S.
        • Woods M.M.
        • Goldin B.R.
        • Soo C.
        • Morrill-Labrode A.
        • et al.
        Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women.
        J Nutr. 1991; 121: 547-555
        • Oh D.Y.
        • Talukdar S.
        • Bae E.J.
        • Imamura T.
        • Morinaga H.
        • Fan W.
        • et al.
        GPR120 is an Omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects.
        Cell. 2010; 142: 687-698
        • Williams-Bey Y.
        • Boularan C.
        • Vural A.
        • Huang N.-N.
        • Hwang I.-Y.
        • Shan-Shi C.
        • et al.
        Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhancing autophagy.
        PloS One. 2014; 9: e97957
        • Colussi G.
        • Catena C.
        • Dialti V.
        • Mos L.
        • Sechi L.A.
        Effects of the consumption of fish meals on the carotid Intima Media thickness in patients with hypertension: a prospective study.
        J Atheroscler Thromb. 2014; 21: 941-956
        • Skilton M.R.
        • Ayer J.G.
        • Harmer J.A.
        • Webb K.
        • Leeder S.R.
        • Marks G.B.
        • et al.
        Impaired fetal growth and arterial wall thickening: a randomized trial of Omega-3 supplementation.
        Pediatrics. 2012; 129: e698-703
        • Thies F.
        • Garry J.M.C.
        • Yaqoob P.
        • Rerkasem K.
        • Williams J.
        • Shearman C.P.
        • et al.
        Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial.
        Lancet. 2003; 361: 477-485
        • Yamano T.
        • Kubo T.
        • Shiono Y.
        • Shimamura K.
        • Orii M.
        • Tanimoto T.
        • et al.
        Impact of eicosapentaenoic acid treatment on the fibrous cap thickness in patients with coronary atherosclerotic plaque: an optical coherence tomography study.
        J Atheroscler Thromb. 2015; 22: 52-61
        • Wang J.H.
        • Eguchi K.
        • Matsumoto S.
        • Fujiu K.
        • Komuro I.
        • Nagai R.
        • et al.
        The ω-3 polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling.
        PloS One. 2014; 9: e96286
        • Colussi G.
        • Catena C.
        • Mos L.
        • Sechi L.A.
        The metabolic syndrome and the membrane content of polyunsaturated fatty acids in hypertensive patients.
        Metab Syndr Relat Disord. 2015; 13: 343-351
        • Colussi G.L.
        • Baroselli S.
        • Sechi L.
        Omega-3 polyunsaturated fatty acids decrease plasma lipoprotein(a) levels in hypertensive subjects.
        Clin Nutr. 2004; 23: 1246-1247
        • Pase M.P.
        • Grima N.A.
        • Sarris J.
        Do long-chain n-3 fatty acids reduce arterial stiffness? A meta-analysis of randomised controlled trials.
        Br J Nutr. 2011; 106: 974-980
        • Tousoulis D.
        • Plastiras A.
        • Siasos G.
        • Oikonomou E.
        • Verveniotis A.
        • Kokkou E.
        • et al.
        Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome.
        Atherosclerosis. 2014; 232: 10-16
        • Bryant J.
        • Hanson M.
        • Peebles C.
        • Davies L.
        • Inskip H.
        • Robinson S.
        • et al.
        Higher oily fish consumption in late pregnancy is associated with reduced aortic stiffness in the child at Age 9 years.
        Circ Res. 2015; 116: 1202-1205
        • Colussi G.
        • Catena C.
        • Dialti V.
        • Mos L.
        • Sechi L.A.
        The vascular response to vasodilators is related to the membrane content of polyunsaturated fatty acids in hypertensive patients.
        J Hypertens. 2015; 33: 993-1000
        • Bønaa K.H.
        • Bjerve K.S.
        • Straume B.
        • Gram I.T.
        • Thelle D.
        Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromsø study.
        N Engl J Med. 1990; 322: 795-801
        • Liu J.C.
        • Conklin S.M.
        • Manuck S.B.
        • Yao J.K.
        • Muldoon M.F.
        Long-chain omega-3 fatty acids and blood pressure.
        Am J Hypertens. 2011; 24: 1121-1126
        • Park Y.
        • Oh S.-H.
        • Rhee M.-Y.
        Association between 24-hour ambulatory blood pressure and erythrocyte n-3 polyunsaturated fatty acids in Korean subjects with hypertension.
        Nutr Res. 2010; 30: 807-814
        • Prisco D.
        • Paniccia R.
        • Bandinelli B.
        • Filippini M.
        • Francalanci I.
        • Giusti B.
        • et al.
        Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients.
        Thromb Res. 1998; 91: 105-112
        • Mori T.A.
        • Bao D.Q.
        • Burke V.
        • Puddey I.B.
        • Beilin L.J.
        Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans.
        Hypertension. 1999; 34: 253-260
        • Russo C.
        • Olivieri O.
        • Girelli D.
        • Azzini M.
        • Stanzial A.M.
        • Guarini P.
        • et al.
        Omega-3 polyunsaturated fatty acid supplements and ambulatory blood pressure monitoring parameters in patients with mild essential hypertension.
        J Hypertens. 1995; 13: 1823-1826
        • Colussi G.
        • Catena C.
        • Dialti V.
        • Pezzutto F.
        • Mos L.
        • Sechi L.A.
        Fish meal supplementation and ambulatory blood pressure in patients with hypertension: relevance of baseline membrane fatty acid composition.
        Am J Hypertens. 2014; 27: 471-481
        • Appel L.J.
        • Miller E.R.
        • Seidler A.J.
        • Whelton P.K.
        Does supplementation of diet with “fish oil” reduce blood pressure? A meta-analysis of controlled clinical trials.
        Arch Intern Med. 1993; 153: 1429-1438
        • Morris M.C.
        • Sacks F.
        • Rosner B.
        Does fish oil lower blood pressure? A meta-analysis of controlled trials.
        Circulation. 1993; 88: 523-533
        • Geleijnse J.M.
        • Giltay E.J.
        • Grobbee D.E.
        • Donders A.R.T.
        • Kok F.J.
        Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials.
        J Hypertens. 2002; 20: 1493-1499
        • Campbell F.
        • Dickinson H.O.
        • Critchley J.A.
        • Ford G.A.
        • Bradburn M.
        A systematic review of fish-oil supplements for the prevention and treatment of hypertension.
        Eur J Prev Cardiol. 2013; 20: 107-120
        • Miller P.E.
        • Van Elswyk M.
        • Alexander D.D.
        Long-chain Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.
        Am J Hypertens. 2014; 27: 885-896
        • Yang B.
        • Shi M.-Q.
        • Li Z.-H.
        • Yang J.-J.
        • Li D.
        Fish, long-chain n-3 PUFA and incidence of elevated blood pressure: a meta-analysis of prospective cohort studies.
        Nutrients. 2016; 8: 58
        • Danaei G.
        • Ding E.L.
        • Mozaffarian D.
        • Taylor B.
        • Rehm J.
        • Murray C.J.
        • et al.
        The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.
        PLoS Med. 2009 Apr 28; 6: e1000058
        • Bang H.O.
        • Dyerberg J.
        • Sinclair H.M.
        The composition of the Eskimo food in north western Greenland.
        Am J Clin Nutr. 1980; 33: 2657-2661
        • Burr M.L.
        • Fehily A.M.
        • Gilbert J.F.
        • Rogers S.
        • Holliday R.M.
        • Sweetnam P.M.
        • et al.
        Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).
        Lancet. 1989; 2: 757-761
        • Dietary supplementation with n-3 polyunsaturated fatty acids
        Vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico.
        Lancet. 1999; 354: 447-455
        • Burr M.L.
        • Ashfield-Watt P. a. L.
        • Dunstan F.D.J.
        • Fehily A.M.
        • Breay P.
        • Ashton T.
        • et al.
        Lack of benefit of dietary advice to men with angina: results of a controlled trial.
        Eur J Clin Nutr. 2003; 57: 193-200
        • Ness A.R.
        • Hughes J.
        • Elwood P.C.
        • Whitley E.
        • Smith G.D.
        • Burr M.L.
        The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART).
        Eur J Clin Nutr. 2002; 56: 512-518
        • Yokoyama M.
        • Origasa H.
        • Matsuzaki M.
        • Matsuzawa Y.
        • Saito Y.
        • Ishikawa Y.
        • et al.
        Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
        Lancet. 2007; 369: 1090-1098
        • Greene S.J.
        • Temporelli P.L.
        • Campia U.
        • Vaduganathan M.
        • Degli Esposti L.
        • Buda S.
        • et al.
        Effects of polyunsaturated fatty acid treatment on postdischarge outcomes after acute myocardial infarction.
        Am J Med. 2016; 117: 340-346
        • Investigators Gissi-HF.
        • Tavazzi L.
        • Maggioni A.P.
        • Marchioli R.
        • Barlera S.
        • Franzosi M.G.
        • et al.
        Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.
        Lancet. 2008; 372: 1223-1230
        • Kromhout D.
        • Giltay E.J.
        • Geleijnse J.M.
        n-3 fatty acids and cardiovascular events after myocardial infarction.
        N Engl J Med. 2010; 363: 2015-2026
        • Rauch B.
        • Schiele R.
        • Schneider S.
        • Diller F.
        • Victor N.
        • Gohlke H.
        • et al.
        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.
        Circulation. 2010; 122: 2152-2159
        • Galan P.
        • Kesse-Guyot E.
        • Czernichow S.
        • Briancon S.
        • Blacher J.
        • Hercberg S.
        • et al.
        Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial.
        BMJ. 2010; 341: c6273
        • Trial Investigators O.R.I.G.I.N.
        • Bosch J.
        • Gerstein H.C.
        • Dagenais G.R.
        • Díaz R.
        • Dyal L.
        • et al.
        n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.
        N Engl J Med. 2012; 367: 309-318
        • Risk and Prevention Study Collaborative Group
        • Roncaglioni M.C.
        • Tombesi M.
        • Avanzini F.
        • Barlera S.
        • Caimi V.
        • et al.
        n-3 fatty acids in patients with multiple cardiovascular risk factors.
        N Engl J Med. 2013; 368: 1800-1808
        • Writing Group for the AREDS2 Research Group
        • Bonds D.E.
        • Harrington M.
        • Worrall B.B.
        • Bertoni A.G.
        • Eaton C.B.
        • et al.
        Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial.
        JAMA Intern Med. 2014; 174: 763-771
        • Wen Y.T.
        • Dai J.H.
        • Gao Q.
        Effects of Omega-3 fatty acid on major cardiovascular events and mortality in patients with coronary heart disease: a meta-analysis of randomized controlled trials.
        Nutr Metab Cardiovasc Dis. 2014; 24: 470-475
        • Zheng T.
        • Zhao J.
        • Wang Y.
        • Liu W.
        • Wang Z.
        • Shang Y.
        • et al.
        The limited effect of omega-3 polyunsaturated fatty acids on cardiovascular risk in patients with impaired glucose metabolism: a meta-analysis.
        Clin Biochem. 2014; 47: 369-377
        • Chowdhury R.
        • Warnakula S.
        • Kunutsor S.
        • Crowe F.
        • Ward H.A.
        • Johnson L.
        • et al.
        Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis.
        Ann Intern Med. 2014; 160: 398-406
        • Chowdhury R.
        • Stevens S.
        • Gorman D.
        • Pan A.
        • Warnakula S.
        • Chowdhury S.
        • et al.
        Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis.
        BMJ. 2012; 345: e6698