Clinical effectiveness of fish oil on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials

Published:January 23, 2021DOI:



      The increase of arterial stiffness is an independent risk factor for cardiovascular diseases (CVD). Fish oil supplementation was shown to reduce the risk of CVD outcomes. However, the effects of fish oil on arterial stiffness remains controversial. This meta-analysis summarized existing randomized clinical trials (RCTs) to determine whether fish oil can affect arterial stiffness in adults.

      Data synthesis

      Systematic searches were performed using the PubMed/Medline, EMbase, Cochrane database, Clinical trials, and Web of Science. All RCTs assessed the effect of fish oil intervention on carotid to femoral-Pulse Wave Velocity (cf-PWV), brachial to ankle-PWV (ba-PWV), augmentation index (AIx) and AIx75 were considered. A fixed-effect model was used to calculate the pooled effect.
      A total of 14 RCTs were included. The pooled data analysis showed that fish oil significantly reduced PWV levels (SMD: −0.145, 95%CI: −0.265 to −0.033, P = 0.012) compared to the control group. In subgroup analyses, a significant decrease in PWV was found in trials that fish oil with low dosages (≤1.8 g/d), short time (<24 weeks), low DHA to EPA ratio (DHA/EPA<1) and among young participant (<50 years old). Besides, the effect of fish oil was more obvious in ba-PWV compared to cf-PWV. In contrast, the effect of fish oil supplementation on AIx (WMD: −0.588%, 95% CI: −2.745 to 1.568, P = 0.593) and AIx75 (WMD: 0.542%, 95% CI: −1.490 to 2.574, P = 0.601) was nonsignificant.


      The current study showed that fish oil supplementation had a beneficial effect on pulse wave velocity.



      cf-PWV (carotid to femoral-Pulse Wave Velocity), ba-PWV (brachial to ankle- Pulse Wave Velocity), AIx (augmentation index), AIx75 (AIx standardized with a heart rate 75 beats per minute), EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), n3 PUFA (n-3 polyunsaturated fatty acids), CVD (cardiovascular disease)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Nutrition, Metabolism and Cardiovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Antza C.
        • Doundoulakis I.
        • Akrivos E.
        • Stabouli S.
        • Chrysaidou K.
        • Gidaris D.
        • et al.
        Estimated arterial stiffness and prediction of vascular aging: the rising of a new era.
        Curr Pharmaceut Des. 2020;
        • Cecelja M.
        • Chowienczyk P.
        Role of arterial stiffness in cardiovascular disease.
        JRSM Cardiovasc Dis. 2012; 1
        • Nemcsik J.
        • Cseprekal O.
        • Tisler A.
        Measurement of arterial stiffness: a novel tool of risk stratification in hypertension.
        Adv Exp Med Biol. 2017; 956: 475-488
        • Vlachopoulos C.
        • Aznaouridis K.
        • Stefanadis C.
        Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis.
        J Am Coll Cardiol. 2010; 55: 1318-1327
        • Vlachopoulos C.
        • Aznaouridis K.
        • Terentes-Printzios D.
        • Ioakeimidis N.
        • Stefanadis C.
        Prediction of cardiovascular events and all-cause mortality with brachial-ankle elasticity index: a systematic review and meta-analysis.
        Hypertension. 2012; 60: 556-562
        • Laurent S.
        • Cockcroft J.
        • Van Bortel L.
        • Boutouyrie P.
        • Giannattasio C.
        • Hayoz D.
        • et al.
        Expert consensus document on arterial stiffness: methodological issues and clinical applications.
        Eur Heart J. 2006; 27: 2588-2605
        • Tomiyama H.
        • Koji Y.
        • Yambe M.
        • Shiina K.
        • Motobe K.
        • Yamada J.
        • et al.
        Brachial -- ankle pulse wave velocity is a simple and independent predictor of prognosis in patients with acute coronary syndrome.
        Circ J. 2005; 69: 815-822
        • Matsuoka O.
        • Otsuka K.
        • Murakami S.
        • Hotta N.
        • Yamanaka G.
        • Kubo Y.
        • et al.
        Arterial stiffness independently predicts cardiovascular events in an elderly community - longitudinal investigation for the longevity and aging in Hokkaido county (LILAC) study.
        Biomed Pharmacother. 2005; 59: S40-S44
        • Kaess B.M.
        • Rong J.
        • Larson M.G.
        • Hamburg N.M.
        • Vita J.A.
        • Levy D.
        • et al.
        Aortic stiffness, blood pressure progression, and incident hypertension.
        J Am Med Assoc. 2012; 308: 875-881
        • Wang K.L.
        • Cheng H.M.
        • Sung S.H.
        • Chuang S.Y.
        • Li C.H.
        • Spurgeon H.A.
        • et al.
        Wave reflection and arterial stiffness in the prediction of 15-year all-cause and cardiovascular mortalities: a community-based study.
        Hypertension. 2010; 55: 799-805
        • Mori T.A.
        Marine OMEGA-3 fatty acids in the prevention of cardiovascular disease.
        Fitoterapia. 2017; 123: 51-58
        • Abdelhamid A.S.
        • Brown T.J.
        • Brainard J.S.
        • Biswas P.
        • Thorpe G.C.
        • Moore H.J.
        • et al.
        Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.
        Cochrane Database Syst Rev. 2020; 3: D3177
        • Root M.
        • Collier S.R.
        • Zwetsloot K.A.
        • West K.L.
        • McGinn M.C.
        A randomized trial of fish oil omega-3 fatty acids on arterial health, inflammation, and metabolic syndrome in a young healthy population.
        Nutr J. 2013; 12
        • Sanders T.A.B.
        • Hall W.L.
        • Maniou Z.
        • Lewis F.
        • Seed P.T.
        • Chowienczyk P.J.
        Effect of low doses of long-chain N-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial.
        Am J Clin Nutr. 2011; 94: 973-980
        • 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
        • Mita T.
        • Watada H.
        • Ogihara T.
        • Nomiyama T.
        • Ogawa O.
        • Kinoshita J.
        • et al.
        Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes.
        Atherosclerosis. 2007; 191: 162-167
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        Ann Intern Med. 2009; 151 (W64): 264-269
        • Shearer G.C.
        • Pottala J.V.
        • Hansen S.N.
        • Brandenburg V.
        • Harris W.S.
        Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial.
        J Lipid Res. 2012; 53: 2429-2435
        • DerSimonian R.
        • Laird N.
        Meta-analysis in clinical trials.
        Contr Clin Trials. 1986; 7: 177-188
        • Hedges L.V.
        • Borenstein J.M.
        Introduction to metaanalysis.
        John Wiley & Sons, 2011
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Peters J.L.
        • Sutton A.J.
        • Jones D.R.
        • Abrams K.R.
        • Rushton L.
        Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry.
        J Clin Epidemiol. 2008; 61: 991-996
        • Gijbels I.
        • Fan J.
        Local polynomial modelling and its applications: monographs on statistics and applied probability 66.
        CRC Press, 1996
        • Casanova M.A.
        • Medeiros F.
        • Trindade M.
        • Cohen C.
        • Oigman W.
        • Neves M.F.
        Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk.
        J Am Soc Hypertens. 2017; 11: 10-19
        • Siasos G.
        • Tousoulis D.
        • Oikonomou E.
        • Zaromitidou M.
        • Verveniotis A.
        • Plastiras A.
        • et al.
        Effects of omega-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
        • Soare A.
        • Weiss E.P.
        • Holloszy J.O.
        • Fontana L.
        Multiple dietary supplements do not affect metabolic and cardiovascular health.
        Aging. 2014; 6: 149-157
        • Cottin S.C.
        • Alsaleh A.
        • Sanders T.A.B.
        • Hall W.L.
        Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men.
        Nutr Metabol Cardiovasc Dis. 2016; 26: 743-751
        • Satoh N.
        • Shimatsu A.
        • Kotani K.
        • Himeno A.
        • Majima T.
        • Yamada K.
        • et al.
        Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in association with decreased serum amyloid A-LDL in metabolic syndrome.
        Hypertens Res. 2009; 32: 1004-1008
        • Takaki A.
        • Umemoto S.
        • Ono K.
        • Seki K.
        • Ryoke T.
        • Fujii A.
        • et al.
        Add-on therapy of EPA reduces oxidative stress and inhibits the progression of aortic stiffness in patients with coronary artery disease and statin therapy: a randomized controlled study.
        J Atherosclerosis Thromb. 2011; 18: 857-866
        • Hallund J.
        • Overgaard Madsen B.
        • Bügel S.H.
        • Jacobsen C.
        • Jakobsen J.
        • Krarup H.
        • et al.
        The effect of farmed trout on cardiovascular risk markers in healthy men.
        Br J Nutr. 2010; 104: 1528-1536
        • Krantz M.J.
        • Havranek E.P.
        • Pereira R.I.
        • Beaty B.
        • Mehler P.S.
        • Long C.S.
        Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study.
        J Negat Results Biomed. 2015; 14
        • Kristensen S.
        • Schmidt E.B.
        • Schlemmer A.
        • Rasmussen C.
        • Lindgreen E.
        • Johansen M.B.
        • et al.
        The effect of marine N-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis: a randomised, double-blind, placebo-controlled trial.
        Lipids Health Dis. 2016; 15: 1-10
        • Brutto O.H. Del
        • Mera R.M.
        • Penaherrera E.
        • Penaherrera R.
        • Costa A.F.
        The relationship between oily fish intake and arterial stiffness in older adults living in rural coastal Ecuador.
        Nutr Metabol Cardiovasc Dis. 2018; 28: 1173-1174
        • Hamazaki K.
        • Terashima Y.
        • Itomura M.
        • Sawazaki S.
        • Inagaki H.
        • Kuroda M.
        • et al.
        The relationship between N-3 long-chain polyunsaturated fatty acids and pulse wave velocity in diabetic and non-diabetic patients under long-term hemodialysis. A horizontal study.
        Clin Nephrol. 2009; 71: 508-513
        • 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
        • 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
        • Tanaka H.
        • Munakata M.
        • Kawano Y.
        • Ohishi M.
        • Shoji T.
        • Sugawara J.
        • et al.
        Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness.
        J Hypertens. 2009; 27: 2022-2027
        • Sugawara J.
        • Hayashi K.
        • Yokoi T.
        • Cortez-Cooper M.Y.
        • DeVan A.E.
        • Anton M.A.
        • et al.
        Brachial-ankle pulse wave velocity: an index of central arterial stiffness?.
        J Hum Hypertens. 2005; 19: 401-406
        • Trumbo P.
        • Schlicker S.
        • Yates A.A.
        • Poos M.
        Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids.
        J Am Diet Assoc. 2002; 102: 1621-1630
        • Members Of The Working S.
        Capra, nutrient reference values for Australia nutrient reference values for Australia and New Zealand: including recommended dietary intakes Canberra.
        Commonwealth of Australia, Australia2006
        • Minister Of National Health Canada
        Nutrition recommendations: the report of the scientific review Committee.
        1990 (Ottawa, Ontario)
        • Arterburn L.M.
        • Hall E.B.
        • Oken H.
        Distribution, interconversion, and dose response of N-3 fatty acids in humans.
        Am J Clin Nutr. 2006; 83: 1467S-1476S
        • Zgheel F.
        • Alhosin M.
        • Rashid S.
        • Burban M.
        • Auger C.
        • Schini-Kerth V.B.
        Redox-sensitive induction of src/PI3-kinase/Akt and MAPKs pathways activate eNOS in response to EPA:DHA 6:1.
        PloS One. 2014; 9e105102
        • Liu L.
        • Hu Q.
        • Wu H.
        • Wang X.
        • Gao C.
        • Chen G.
        • et al.
        Dietary DHA/EPA ratio changes fatty acid composition and attenuates diet-induced accumulation of lipid in the liver of ApoE(-/-) mice.
        Oxid Med Cell Longev. 2018; 2018: 6256802
        • Allaire J.
        • Vors C.
        • Tremblay A.J.
        • Marin J.
        • Charest A.
        • Tchernof A.
        • et al.
        High-dose DHA has more profound effects on LDL-related features than high-dose EPA: the ComparED study.
        J Clin Endocrinol Metab. 2018; 103: 2909-2917
        • Itakura H.
        • Yokoyama M.
        • Matsuzaki M.
        • Saito Y.
        • Origasa H.
        • Ishikawa Y.
        • et al.
        The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid.
        J Atherosclerosis Thromb. 2012; 19: 673-679
        • Hidayat K.
        • Yang J.
        • Zhang Z.
        • Chen G.C.
        • Qin L.Q.
        • Eggersdorfer M.
        • et al.
        Effect of omega-3 long-chain polyunsaturated fatty acid supplementation on heart rate: a meta-analysis of randomized controlled trials.
        Eur J Clin Nutr. 2018; 72: 805-817
        • Innes J.K.
        • Calder P.C.
        The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiometabolic risk factors: a systematic review.
        Int J Mol Sci. 2018; 19
        • Guclu A.
        • Nar G.
        • Icli A.
        • Ozhan N.
        • Sezer S.
        Blood pressure and age are the main determinants of aortic stiffness.
        Med Princ Pract. 2017; 26: 496
        • Lee H.Y.
        • Oh B.H.
        Aging and Arterial Stiffness, Circ J. 2010; 74: 2257-2262
        • McEniery C.M.
        • Yasmin
        • Hall I.R.
        • Qasem A.
        • Wilkinson I.B.
        • Cockcroft J.R.
        Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the anglo-cardiff collaborative trial (ACCT).
        J Am Coll Cardiol. 2005; 46: 1753-1760
        • Kelly R.P.
        • Millasseau S.C.
        • Ritter J.M.
        • Chowienczyk P.J.
        Vasoactive drugs influence aortic augmentation index independently of pulse-wave velocity in healthy men.
        Hypertension. 2001; 37: 1429-1433
        • Nichols W.W.
        Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms.
        Am J Hypertens. 2005; 18: 3S-10S
        • Mozos I.
        • Luca C.T.
        Crosstalk between oxidative and nitrosative stress and arterial stiffness.
        Curr Vasc Pharmacol. 2017; 15: 446-456
        • Yasmin C.M.
        • McEniery S.
        • Wallace I.S.
        • Mackenzie
        • Cockcroft J.R.
        • Wilkinson I.B.
        C-reactive protein is associated with arterial stiffness in apparently healthy individuals.
        Arterioscler Thromb Vasc Biol. 2004; 24: 969-974
        • Cione E.
        • Plastina P.
        • Pingitore A.
        • Perri M.
        • Caroleo M.C.
        • Fazio A.
        • et al.
        Capsaicin analogues derived from n-3 polyunsaturated fatty acids (PUFAs) reduce inflammatory activity of macrophages and stimulate insulin secretion by beta-cells in vitro.
        Nutrients. 2019; 11
        • Heshmati J.
        • Morvaridzadeh M.
        • Maroufizadeh S.
        • Akbari A.
        • Yavari M.
        • Amirinejad A.
        • et al.
        Omega-3 fatty acids supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials.
        Pharmacol Res. 2019; 149: 104462
        • Zhan B.
        • Huang X.
        • Wang J.
        • Qin X.
        • Zhang J.
        • Cao J.
        • et al.
        Association between lipid profiles and arterial stiffness in Chinese patients with hypertension: insights from the CSPPT.
        Angiology. 2019; 70: 515-522
        • Wang L.
        • Zhi F.
        • Gao B.
        • Ni J.
        • Liu Y.
        • Mo X.
        • et al.
        Association between lipid profiles and arterial stiffness: a secondary analysis based on a cross-sectional study.
        J Int Med Res. 2020; 48 (1220737740)
        • Kobyliak N.
        • Abenavoli L.
        • Falalyeyeva T.
        • Mykhalchyshyn G.
        • Boccuto L.
        • Kononenko L.
        • et al.
        Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study.
        Minerva Med. 2018; 109: 418-428
        • de Leiris J.
        • de Lorgeril M.
        • Boucher F.
        Fish oil and heart health.
        J Cardiovasc Pharmacol. 2009; 54: 378-384
        • Gao C.
        • Liu Y.
        • Gan Y.
        • Bao W.
        • Peng X.
        • Xing Q.
        • et al.
        Effects of fish oil supplementation on glucose control and lipid levels among patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.
        Lipids Health Dis. 2020; 19: 87