History and future of omega-3 fatty acids in cardiovascular disease

Sperling, Laurence S.; Nelson, John R.

doi:10.1185/03007995.2015.1120190

Cited by 34Fatty Acid Research and HealthLipoproteins and Cardiovascular HealthAquaculture Nutrition and Growth

History and future of omega-3 fatty acids in cardiovascular disease

Sperling, Laurence S., Nelson, John R.·2016·Current Medical Research and Opinion

DOI 10.1185/03007995.2015.1120190

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Abstract

BACKGROUND/OBJECTIVES: Epidemiological, diet-based, and some interventional outcomes studies suggest that polyunsaturated omega-3 fatty acids (OM3FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), confer cardiovascular protection in some patient populations. This review examines the historical context of OM3FAs in cardiovascular disease and future perspectives on the place of OM3FA products in reducing cardiovascular risk. METHODS: Relevant articles were identified via PubMed/Medline and Google Scholar searches through 2015 and through reference lists of selected publications. Articles determined by the authors to be relevant to the topic of this review were included. RESULTS: Review of the identified articles indicated that inconsistent results among interventional outcomes studies have been attributed to use of low doses of OM3FAs, patient cohorts with non-elevated triglyceride (TG) levels, differential use of concomitant statin therapy, and study designs with insufficient statistical power. Several prescription OM3FA products are now approved as an adjunct to diet to reduce TG levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. Most formulations contain both EPA and DHA; one formulation contains purified EPA. In randomized controlled trials, these products significantly reduced TG levels in patients with very high TG levels (≥500 mg/dL [≥13.0 mmol/L]) and in statin-treated patients with high TG levels (200-499 mg/dL [5.2-12.9 mmol/L]). The DHA-containing products raised LDL-C levels in these studies, whereas the EPA-only product had no effect on LDL-C, suggesting that all OM3FA prescription products are not therapeutically equivalent. Besides lowering TG levels, OM3FAs (particularly EPA) exert anti-inflammatory effects and may slow multiple atherogenic processes. Two well designed interventional outcomes studies (REDUCE-IT and STRENGTH) are evaluating prescription-strength, high-dose OM3FAs (4 g/day) in statin-treated patients with persistently high TG levels. CONCLUSIONS: The results of the ongoing prescription-strength, high-dose OM3FA interventional trials will help define the potential role of OM3FAs in addressing residual cardiovascular risk despite statin therapy.

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The lack of effects on ALT, HDL, and LDL may reflect the selective action of omega-3 fatty acids, whose lipid-lowering effects primarily target the triglyceride metabolic pathway while exerting weaker direct effects on cholesterol reverse transport and synthesis.
“The lack of effects on ALT, HDL, and LDL may reflect the selective action of omega-3 fatty acids. Their lipid-lowering effects primarily target the triglyceride metabolic pathway, including promoting fatty acid oxidation and reducing lipogenesis by activating PPAR-α and inhibiting SREBP-1c,42,43 while exerting weaker direct effects on cholesterol reverse transport and synthesis.44,45”
From The Impact of Omega-3 Fatty Acids on Triglyceride Levels in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-Analysis of Randomized Controlled Trials with Subgroup Analysis by Diabetes Status (2026) · cites this paper as [45]

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Icosapent Ethyl, a Pure Ethyl Ester of Eicosapentaenoic Acid: Effects on Circulating Markers of Inflammation from the MARINE and ANCHOR Studies
Bays, H. E., Ballantyne, C. M., Braeckman, R. A., Stirtan, W. G., & Soni, P. N. (2013) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-012-0002-3 · Cited by 141 · see citing works
DHA Supplementation Decreases Serum C-Reactive Protein and Other Markers of Inflammation in Hypertriglyceridemic Men
Kelley, D. S., Siegel, D., Fedor, D. M., Adkins, Y. C., & Mackey, B. E. (2009) · Journal of Nutrition · doi:10.3945/jn.108.100354 · Cited by 139 · see citing works
Fish Oil for the Treatment of Cardiovascular Disease
Weitz, D., Weintraub, H., Fisher, E., & Schwartzbard, A. Z. (2010) · Cardiology in Review · doi:10.1097/crd.0b013e3181ea0de0 · Cited by 138 · see citing works
Stabilizing effect of combined eicosapentaenoic acid and statin therapy on coronary thin-cap fibroatheroma
Nishio, R., Shinke, T., Otake, H., Nakagawa, M., Nagoshi, R., Inoue, T., Kozuki, A., Hariki, H., Osue, T., Taniguchi, Y., et al. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.02.025 · Cited by 133 · see citing works
Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS)
Oikawa, S., Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., Sasaki, J., Hishida, H., Itakura, H., et al. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.03.029 · Cited by 125 · see citing works
Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis
Eiselein, L., Wilson, D. W., Lamé, M. W., & Rutledge, J. C. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00686.2006 · Cited by 105 · see citing works
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)
Maki, K. C., Orloff, D. G., Nicholls, S. J., Dunbar, R. L., Roth, E. M., Curcio, D., Johnson, J., Kling, D., & Davidson, M. H. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.07.420 · Cited by 104 · see citing works
A comparison of actual versus stated label amounts of <scp>EPA</scp> and <scp>DHA</scp> in commercial omega‐3 dietary supplements in the United States
Kleiner, A. C., Cladis, D. P., & Santerre, C. R. (2015) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.6816 · Cited by 93 · see citing works
Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type II diabetes mellitus
Fukushima, H., Sugiyama, S., Honda, O., Koide, S., Nakamura, S., Sakamoto, T., Yoshimura, M., Ogawa, H., Fujioka, D., & Kugiyama, K. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.09.074 · Cited by 91 · see citing works
A randomized clinical trial onn-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk
Einvik, G., Klemsdal, T. O., Sandvik, L., & Hjerkinn, E. M. (2010) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1097/hjr.0b013e328339cc70 · Cited by 89 · see citing works
Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: An integrated backscatter intravascular ultrasound study
Amano, T., Matsubara, T., Uetani, T., Kato, M., Kato, B., Yoshida, T., Harada, K., Kumagai, S., Kunimura, A., Shinbo, Y., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.05.030 · Cited by 83 · see citing works
Orally Administered Eicosapentaenoic Acid Induces Rapid Regression of Atherosclerosis Via Modulating the Phenotype of Dendritic Cells in LDL Receptor-Deficient Mice
Nakajima, K., Yamashita, T., Kita, T., Takeda, M., Sasaki, N., Kasahara, K., Shinohara, M., Rikitake, Y., Ishida, T., Yokoyama, M., et al. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.229443 · Cited by 81 · see citing works
Serum Fatty Acids and Incidence of Ischemic Stroke Among Postmenopausal Women
Yaemsiri, S., Sen, S., Tinker, L. F., Robinson, W. R., Evans, R. G., Rosamond, W. D., Wasserthiel-Smoller, S., & He, K. (2013) · Stroke · doi:10.1161/strokeaha.111.000834 · Cited by 81 · see citing works
“Fishing” for the Origins of the “Eskimos and Heart Disease” Story: Facts or Wishful Thinking?
FODOR, J. G., Helis, E., Yazdekhasti, N., & Vohnout, B. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.04.007 · Cited by 78 · see citing works
Letters to the Editor
Burr, M. L., SWEETNAM, P. M., & FEHILEY, A. M. (1994) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a060645 · Cited by 74 · see citing works
Plasma n-3 polyunsaturated fatty acids in chronic heart failure in the GISSI-Heart Failure Trial: Relation with fish intake, circulating biomarkers, and mortality
Masson, S., Marchioli, R., Mozaffarian, D., Bernasconi, R., Milani, V., Dragani, L. K., Tacconi, M. T., Marfisi, R. M., Borgese, L., Cirrincione, V., et al. (2013) · American Heart Journal · doi:10.1016/j.ahj.2012.10.021 · Cited by 74 · see citing works
Overview of Prescription Omega-3 Fatty Acid Products for Hypertriglyceridemia
WEINTRAUB, H. S. (2014) · Postgraduate Medicine · doi:10.3810/pgm.2014.11.2828 · Cited by 74 · see citing works
Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia
Davidson, M. H., Maki, K. C., Bays, H., Carter, R., & Ballantyne, C. M. (2009) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2009.08.001 · Cited by 71 · see citing works
Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil. Their incorporation into advanced human atherosclerotic plaques.
Rapp, J. H., CONNOR, W. E., Lin, D. S., & Porter, J. M. (1991) · Arteriosclerosis and Thrombosis A Journal of Vascular Biology · doi:10.1161/01.atv.11.4.903 · Cited by 70 · see citing works
Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study
Brinton, E. A., Ballantyne, C. M., Bays, H. E., Kastelein, J. J., Braeckman, R. A., & Soni, P. N. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-100 · Cited by 70 · see citing works
Preventive Effects of Eicosapentaenoic Acid on Coronary Artery Disease in Patients With Peripheral Artery Disease - Subanalysis of the JELIS Trial -
Ishikawa, Y., Yokoyama, M., Saitō, Y., Matsuzaki, M., Origasa, H., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., Kita, T., et al. (2010) · Circulation Journal · doi:10.1253/circj.cj-09-0520 · Cited by 63 · see citing works
Omega-6 Fatty Acids and Cardiovascular Disease
Harris, W. S., & Shearer, G. C. (2014) · Circulation · doi:10.1161/circulationaha.114.012534 · Cited by 63 · see citing works
Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects
Kelley, D. S., & Adkins, Y. C. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000080 · Cited by 62 · see citing works
Uptake of type III hypertriglyceridemic VLDL by macrophages is enhanced by oxidation, especially after remnant formation
Whitman, S. C., Miller, D. B., Wolfe, B. M., Hegele, R. A., & Huff, M. W. (1997) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.17.9.1707 · Cited by 59 · see citing works
Effects of Serum n-3 to n-6 Polyunsaturated Fatty Acids Ratios on Coronary Atherosclerosis in Statin-Treated Patients With Coronary Artery Disease
Nozue, T., Yamamoto, S., Tohyama, S., Fukui, K., Umezawa, S., Onishi, Y., Kunishima, T., Sato, A., Nozato, T., Miyake, S., et al. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.08.038 · Cited by 51 · see citing works
Early eicosapentaenoic acid treatment after percutaneous coronary intervention reduces acute inflammatory responses and ventricular arrhythmias in patients with acute myocardial infarction: A randomized, controlled study
Doi, M., Nosaka, K., Miyoshi, T., Iwamoto, M., Kajiya, M., Okawa, K., Nakayama, R., Takagi, W., Takeda, K., Hirohata, S., et al. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.08.055 · Cited by 51 · see citing works
Oxidized type IV hypertriglyceridemic VLDL-remnants cause greater macrophage cholesteryl ester accumulation than oxidized LDL
Whitman, S. C., Sawyez, C. G., Miller, D. B., Wolfe, B. M. J., & Huff, M. W. (1998) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33868-2 · Cited by 51 · see citing works
ω-3 Fatty acids, atherosclerosis progression and cardiovascular outcomes in recent trials: new pieces in a complex puzzle
Wu, J. H. Y., & Mozaffarian, D. (2014) · Heart · doi:10.1136/heartjnl-2013-305257 · Cited by 47 · see citing works
Cardiovascular effects of B-vitamins and/or N-3 fatty acids: The Su.Fol.Om3 trial
Blacher, J., Czernichow, S., Paillard, F., Ducimetière, P., Herçberg, S., & Galan, P. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.01.060 · Cited by 42 · see citing works
Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: The omega-3 fatty acids randomized double-blind (ORD) study
Tatsuno, I., Saito, Y., Kudou, K., & Ootake, J. (2013) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2013.01.006 · Cited by 42 · see citing works
Distinct regulation of plasma LDL cholesterol by eicosapentaenoic acid and docosahexaenoic acid in high fat diet-fed hamsters: Participation of cholesterol ester transfer protein and LDL receptor
Ishida, T., Ohta, M., Nakakuki, M., Kami, H., Uchiyama, R., Kawano, H., Notsu, T., Imada, K., & Shimano, H. (2013) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2013.01.001 · Cited by 41 · see citing works
Differential Association of Docosahexaenoic and Eicosapentaenoic Acids With Carotid Intima-Media Thickness
Sekikawa, A. M., Kadowaki, T., El‐Saed, A., Okamura, T., Sutton‐Tyrrell, K., Nakamura, Y., Evans, R. G., Mitsunami, K., Edmundowicz, D., Nishio, Y., et al. (2011) · Stroke · doi:10.1161/strokeaha.110.613042 · Cited by 39 · see citing works
Long Chain Omega-3 Dietary Supplements: A Review of the National Library of Medicine Herbal Supplement Database
Zargar, A., & Ito, M. K. (2011) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2011.0004 · Cited by 39 · see citing works
Eicosapentaenoic Acid Combined with Optimal Statin Therapy Improves Endothelial Dysfunction in Patients with Coronary Artery Disease
Toyama, K., Nishioka, T., Isshiki, A., Ando, T., Inoue, Y., Kirimura, M., Kamiyama, T., Sasaki, O., Ito, H., Maruyama, Y., et al. (2013) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-013-6496-3 · Cited by 38 · see citing works
Omega‐3 fatty acid therapy reduces triglycerides and interleukin‐6 in hypertriglyeridemic <scp>HIV</scp> patients
Metkus, T., Timpone, J., Leaf, D., Goetz, M. B., Harris, W., & Brown, T. (2013) · HIV Medicine · doi:10.1111/hiv.12046 · Cited by 34 · see citing works
Administration of highly purified eicosapentaenoic acid to statin-treated diabetic patients further improves vascular function
Sasaki, J., Miwa, T., & Odawara, M. (2012) · Endocrine Journal · doi:10.1507/endocrj.ej11-0394 · Cited by 31 · see citing works
Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men
Dawson, K., Zhao, L., Adkins, Y., Vemuri, M., Rodriguez, R. L., Gregg, J. P., Kelley, D. S., & Hwang, D. H. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.03.004 · Cited by 24 · see citing works
Eicosapentaenoic Acid Supplementation Changes Fatty Acid Composition and Corrects Endothelial Dysfunction in Hyperlipidemic Patients
Yamakawa, K., Shimabukuro, M., Higa, N., Asahi, T., Ohba, K., Arasaki, O., Higa, M., Oshiro, Y., Yoshida, H., Higa, T., et al. (2012) · Cardiology Research and Practice · doi:10.1155/2012/754181 · Cited by 20 · see citing works
Abstract 12007: Combination Therapy of Eicosapentaenoic Acid and Pitavastatin for Coronary Plaque Regression Evaluated by Integrated Backscatter Intravascular Ultrasonography: A Randomized Controlled Trial
Ando, K., Watanabe, T., Daidoji, H., Otaki, Y., Hashimoto, N., Kumagai, Y., Hashimoto, N., Narumi, T., Kadowaki, S., Yamaura, G., et al. (2015) · Circulation · doi:10.1161/circ.132.suppl_3.12007 · Cited by 16 · see citing works
Ezetimibe
McPherson, R., & Hegele, R. A. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.305012 · Cited by 15 · see citing works
Abstract 16803: Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester): Effects on Remnant-Like Particle Cholesterol From the MARINE and ANCHOR Studies
Ballantyne, C. M., Bays, H. E., Braeckman, R. A., Philip, S., Stirtan, W. G., Doyle, R. T., Soni, P. N., & Juliano, R. A. (2014) · Circulation · doi:10.1161/circ.130.suppl_2.16803 · Cited by 7 · see citing works
Perspectives on a new prescription omega-3 fatty acid, icosapent ethyl, for hypertriglyceridemia
Jacobson, T. A. (2014) · Clinical Lipidology · doi:10.2217/clp.14.10 · Cited by 6 · see citing works
Relationship between baseline triglyceride concentration and triglyceride reduction with 4 g/d long‐chain omega‐3 acid ethyl esters (1035.6)
Nieman, K. M., Dicklin, M. R., Bell, M., Rains, T. M., & Maki, K. C. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.1035.6 · Cited by 5 · see citing works
Abstract WP413: High Purity Eicosapentaenoic Acid In Addition To A Strong Statin Makes Regression Of Intima-media Thickness In Patients With Asymptomatic Cerebral Infarction.
Wakita, Y., Wakida, Y., Itou, T., & Mizuno, R. (2013) · Stroke · doi:10.1161/str.44.suppl_1.awp413 · Cited by 4 · see citing works

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The role of non-resolving inflammation in atherosclerosis
Kasikara, C., Doran, A. C., Cai, B., & Tabas, I. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97950 · Cited by 266 · see citing works
PPAR Agonists and Metabolic Syndrome: An Established Role?
Botta, M., Audano, M., Sahebkar, A., Sirtori, C. R., Mitro, N., & Ruscica, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041197 · Cited by 253 · see citing works
Macrophage Trafficking, Inflammatory Resolution, and Genomics in Atherosclerosis
Moore, K. J., Koplev, S., Fisher, E. A. A., Tabas, I. A., Björkegren, J., Doran, A. C., & Kovacic, J. C. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.08.2147 · Cited by 221 · see citing works
Effects of dietary fats on blood lipids: a review of direct comparison trials
DiNicolantonio, J. J., & O’Keefe, J. H. (2018) · Open Heart · doi:10.1136/openhrt-2018-000871 · Cited by 136 · see citing works
Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids
Husson, M.-O., Ley, D., Portal, C., Aumar, M., Hueso, T., Desseyn, J., & Gottrand, F. (2016) · Journal of Infection · doi:10.1016/j.jinf.2016.10.001 · Cited by 103 · see citing works
Omega-3 Fatty Acids in Atherosclerosis and Coronary Artery Disease
Bäck, M. (2017) · Future Science OA · doi:10.4155/fsoa-2017-0067 · Cited by 69 · see citing works
High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine
Reijnders, E., van der Laarse, A., Jukema, J. W., & Cobbaert, C. M. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1264319 · Cited by 55 · see citing works
Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids
Burke, M. F., Burke, F. M., & Soffer, D. E. (2017) · Current Atherosclerosis Reports · doi:10.1007/s11883-017-0700-z · Cited by 39 · see citing works
Inflammation Resolution in the Cardiovascular System: Arterial Hypertension, Atherosclerosis, and Ischemic Heart Disease
Gonzalez, A. L., Dungan, M. M., Smart, C. D., Madhur, M. S., & Doran, A. C. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0284 · Cited by 41 · see citing works
Enhancement of docosahexaenoic acid production by low-energy ion implantation coupled with screening method based on Sudan black B staining in Schizochytrium sp.
Fu, J., Chen, T., Lu, H., Lin, Y., Xie, X., Tian, H., Zheng, C., & He, D. (2016) · Bioresource Technology · doi:10.1016/j.biortech.2016.09.058 · Cited by 33 · see citing works
Controversies in omega-3 efficacy and novel concepts for application
Radcliffe, J., Thomas, J., Bramley, A. L., Kouris‐Blazos, A., Radford, B. E., Scholey, A. B., Pipingas, A., Thomas, C., & Itsiopoulos, C. (2016) · Journal of Nutrition & Intermediary Metabolism · doi:10.1016/j.jnim.2016.05.002 · Cited by 27 · see citing works
Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions
Jiao, Y., Hannafon, B. N., Zhang, R. R., Fung, K.-M. A., & Ding, W. (2017) · Oncotarget · doi:10.18632/oncotarget.14702 · Cited by 26 · see citing works
Protective activities of distinct omega-3 enriched oils are linked to their ability to upregulate specialized pro-resolving mediators
Sobrino, A., Walker, M. E., Colas, R. A., & Dalli, J. (2020) · PLoS ONE · doi:10.1371/journal.pone.0242543 · Cited by 25 · see citing works
Microbial Production of Fatty Acids
Ratledge, C., & Lippmeier, J. C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809521-8.00006-4 · Cited by 21 · see citing works
The case for adding eicosapentaenoic acid (icosapent ethyl) to the ABCs of cardiovascular disease prevention
Trivedi, K., Le, V. T., & Nelson, J. R. (2020) · Postgraduate Medicine · doi:10.1080/00325481.2020.1783937 · Cited by 20 · see citing works
Self-citation
Soutenir la sécurité alimentaire dans le Grand Nord : projets communautaires d’agriculture sous serre au Nunavik et au Nunavut
Lamalice, A., Avard, E., Coxam, V., Herrmann, T. M., Desbiens, C., Wittrant, Y., & Blangy, S. (2017) · Études/Inuit/Studies · doi:10.7202/1040149ar · Cited by 17 · see citing works
Dietary Calanus oil recovers metabolic flexibility and rescues postischemic cardiac function in obese female mice
Jansen, K. M., Moreno, S., García-Rovés, P. M., & Larsen, T. S. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00191.2019 · Cited by 17 · see citing works
A porous cervical mucus plug leads to preterm birth induced by experimental vaginal infection in mice
Lacroix, G., Gouyer, V., Rocher, M., Gottrand, F., & Desseyn, J. (2022) · iScience · doi:10.1016/j.isci.2022.104526 · Cited by 15 · see citing works
Omega‑3 polyunsaturated fatty acids prevent murine dilated cardiomyopathy by reducing oxidative stress and cardiomyocyte apoptosis
Li, Q., Yu, Q., Na, R., & Liu, B. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5338 · Cited by 15 · see citing works
Recent developments in pharmacotherapy for hypertriglyceridemia: what’s the current state of the art?
Florentin, M., Kostapanos, M. S., Anagnostis, P. G., & Liamis, G. L. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1691523 · Cited by 14 · see citing works
Cardiovascular and lipid-lowering effects of a marine lipoprotein extract in a high-fat diet-induced obesity mouse model
Carrera, I., Corzo, L., Naidoo, V., Martínez-Iglesias, O. A., & Cacabelos, R. (2023) · International Journal of Medical Sciences · doi:10.7150/ijms.80727 · Cited by 12 · see citing works
Isolation of Non‐methylene Interrupted or Acetylenic Fatty Acids from Seed Oils Using Semi‐preparative Supercritical Chromatography
Montañés, F., Tallon, S. J., & Catchpole, O. J. (2017) · Journal of the American Oil Chemists Society · doi:10.1007/s11746-017-2999-6 · Cited by 8 · see citing works
Partitioning of Rumen‐Protected n‐3 and n‐6 Fatty Acids is Organ‐Specific in Growing Angus Heifers
Wolf, C., Gredig, N., Ulbrich, S. E., Kreuzer, M., Bérard, J., & Giller, K. (2019) · Lipids · doi:10.1002/lipd.12183 · Cited by 7 · see citing works
28-Day oral (gavage) and 13-week (dietary) toxicity studies of DHA canola oil and DHA canola meal in rats
Murillo, G., Horn, T. L., Johnson, W. D., & Macintosh, S. C. (2021) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2021.105050 · Cited by 5 · see citing works
Associations of dietary linoleic acid and alpha linolenic acid intake with cardiovascular, cancer and all-cause mortalities in patients with diabetes: NHANES 1999-2008
Jiang, M., Zhu, H., Zhou, X., Zhai, X., Li, S., Ma, W., Liu, K., Cao, J., & Eshak, E. S. (2024) · Frontiers in Clinical Diabetes and Healthcare · doi:10.3389/fcdhc.2024.1318578 · Cited by 5 · see citing works
Unperturbed hydrocarbon chains and liquid phase bilayer lipid chains: a computer simulation study
Rabinovich, A. L., Lyubartsev, A. P., & Викторович, Ж. Д. (2017) · European Biophysics Journal · doi:10.1007/s00249-017-1231-9 · Cited by 4 · see citing works
Achieving coronary plaque regression: a decades-long battle against coronary artery disease
Manubolu, V. S., & Budoff, M. J. (2022) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2022.2069559 · Cited by 4 · see citing works
Multimodality Imaging Trials Evaluating the Impact of Omega-3 Fatty Acids on Coronary Artery Plaque Characteristics and Burden
Manubolu, V. S., Budoff, M. J., & Lakshmanan, S. (2022) · Heart International · doi:10.17925/hi.2022.16.1.2 · Cited by 3 · see citing works
Omega-3 supplements and cardiovascular disease. Re: Sperling LS, Nelson JR. History and future of omega-3 fatty acids in cardiovascular disease. Curr Med Res Opin 2015: 32(2);301–311
Rizos, E. C., & Elisaf, M. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1134462 · Cited by 3 · see citing works
Revisiting Bill Lands’ Hypotheses: HUFA Balance, Immuno-Metabolic Regulation, and Conflicting Clinical Evidence
Suchner, U. (2026) · Nutrients · doi:10.3390/nu18040626 · Cited by 1 · see citing works
Icosabutate, a More Potent Form of Omega 3 Fatty Acids, Shows Promise in Lowering Triglycerides
Riesen, W. F. (2016) · Cardiology · doi:10.1159/000445286 · Cited by 1 · see citing works
The Impact of Omega-3 Fatty Acids on Triglyceride Levels in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-Analysis of Randomized Controlled Trials with Subgroup Analysis by Diabetes Status
Li, L., Cong, C., Zhang, X., & Zhang, X. (2026) · Diabetes, Metabolic Syndrome and Obesity · doi:10.2147/dmso.s573711
“44,45 ALT levels exhibit spontaneous fluctuations and may not respond significantly to short-term intervention.”
Associations of 26 Dietary Habits with Infection of Intervertebral Disc: A Comprehensive Two-Sample Mendelian Randomization StudyPreprint
Qi, B., Wang, W., Meng, C.-Y., Wang, H., & li, Q. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4934379
Géographie du système alimentaire des Inuit du Nunavik : du territoire nourricier au supermarché
Lamalice, A. (2019) · theses.fr (ABES) · doi:10.70675/0d86da06zb16bz47a5z9e4fze872e352b4a7

Overview of omega-3 Fatty Acid therapies.
Bradberry, J. C., & Hilleman, D. E. (2013) · PubMed Central · Cited by 109 · see citing works
Omega-3 Fatty Acids in the Management of Cardiovascular Disease Prevention
Finocchiaro, S., Cutore, L., Bordonaro, C., Cusmano, C., Nastasi, D., Nasisi, F., & Capodanno, D. (2026) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-026-07974-4
Overview of Prescription Omega-3 Fatty Acid Products for Hypertriglyceridemia
WEINTRAUB, H. S. (2014) · Postgraduate Medicine · doi:10.3810/pgm.2014.11.2828 · Cited by 74 · see citing works
Omega-3 Fatty Acids and Cardiovascular Disease: New Developments and Applications
Harris, W. S., Dayspring, T. D., & Moran, T. J. (2013) · Postgraduate Medicine · doi:10.3810/pgm.2013.11.2717 · Cited by 80 · see citing works
Omega-3 polyunsaturated fatty acids focusing on eicosapentaenoic acid and docosahexaenoic acid in the prevention of cardiovascular diseases: a review of the state-of-the-art
Watanabe, Y., & Tatsuno, I. (2020) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2021.1863784 · Cited by 42 · see citing works

Authors: Sperling, L. S., & Nelson, J. R.
Affiliations: Emory University (US)
University of California, San Francisco (US)
Corresponding author: Sperling, Laurence S.
ORCID: Sperling, Laurence S.
Nelson, John R.
Venue: Current Medical Research and Opinion
Publisher: Informa UK Limited
Published: 2015-12-03
Volume: 32
Issue: 2
Pages: 301-311
ISSN: 0300-7995 (ISSN-L)
1473-4877
DOI: 10.1185/03007995.2015.1120190
OpenAlex: W2180392647
Cited by: 34
References: 112
Citations by year: 2026: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 1
FWCI: 0.72
Type: journal article
Language: en
Open access: closed
Locations: Current Medical Research and Opinion (publishedVersion)
PubMed (publishedVersion)
Funders: Amgen
Pfizer
AstraZeneca
Danone
Regeneron Pharmaceuticals
Kowa Company
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Aquaculture Nutrition and Growth
Keywords: omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, cardiovascular disease, hypertriglyceridemia, triglyceride-lowering therapy, statin therapy, LDL cholesterol, anti-inflammatory activity, residual cardiovascular risk, REDUCE-IT trial
MeSH terms: Adult, Cardiovascular Diseases, Diet, Docosahexaenoic Acids, Humans, Risk Factors, Eicosapentaenoic Acid, Hypertriglyceridemia, Fatty Acids, Omega-3, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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