Seafood-Derived Omega-3 Fatty Acids and Cardiovascular Disease Prevention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
DOI:
https://doi.org/10.83080/rejost.vol6no6.310Keywords:
Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), Cardiovascular Disease, Systematic Review, Meta-Analysis, Atrial Fibrillation, Primary PreventionAbstract
Cardiovascular disease (CVD) remains the leading cause of death globally, representing 32 % of all deaths and necessitating effective preventive strategies. Despite widespread interest in omega-3 fatty acids for cardiovascular protection, conflicting evidence from randomized trials has created uncertainty regarding optimal formulations (EPA vs. EPA+DHA), efficacy, and risk-benefit profiles. This systematic review addresses critical knowledge gaps by synthesizing randomized controlled trial (RCT) evidence through 2024, providing formulation-specific comparison between EPA monotherapy and EPA+DHA combinations, as well as integrating comprehensive atrial fibrillation risk assessment. We searched EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov through August 2024 using comprehensive Boolean search strategies, identifying 38 RCTs involving 149,051 participants. Two independent reviewers performed both study selection and data extraction work. The researchers used the Cochrane Risk of Bias 2 tool to determine the risk of bias assessment. The meta-analysis used random-effects models to measure statistical diversity through I² statistics. GRADE methodology evaluated certainty of evidence. Omega-3 supplementation significantly reduced cardiovascular mortality (RR 0.93, 95 % CI: 0.88-0.98; moderate certainty evidence), non-fatal myocardial infarction (RR 0.87, 95 % CI: 0.81-0.93; moderate certainty), coronary heart disease events (RR 0.91, 95 % CI: 0.87-0.96; moderate certainty), and major adverse cardiovascular events (RR 0.95, 95 % CI: 0.92-0.98; moderate certainty). EPA monotherapy demonstrated superior efficacy versus EPA+DHA (interaction p<0.01 for MACE). No benefit was observed for all-cause mortality (RR 0.97, 95 % CI: 0.93-1.02; low certainty) or stroke (RR 1.04, 95 % CI: 0.91-1.18; low certainty). Atrial fibrillation risk increased (RR 1.26, 95 % CI: 1.08-1.48; moderate certainty), particularly with high-dose EPA. This meta-analysis provides updated synthesis through 2024, first systematic formulation-specific comparison, and integrated benefit-harm assessment, addressing critical gaps in omega-3 therapy guidance. We recommend 2-3 weekly fish servings for primary prevention and purified EPA supplementation (4 g/day) for high-risk patients with established CVD, hypertriglyceridemia, and concurrent statin use, with atrial fibrillation monitoring. Future research should optimize patient selection criteria and clarify formulation-specific mechanisms.
References
Alfaddagh, A., Elajami, T. K., Ashfaque, H., Saleh, M., Bistrian, B. R., & Welty, F. K. (2017). Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial. J Am Heart Assoc, 6(12). https://doi.org/10.1161/-jaha.117.006981
Andrieu, S., Guyonnet, S., Coley, N., Cantet, C., Bonnefoy, M., Bordes, S., Bories, L., Cufi, M. N., Dantoine, T., Dartigues, J. F., Desclaux, F., Gabelle, A., Gasnier, Y., Pesce, A., Sudres, K., Touchon, J., Robert, P., Rouaud, O., Legrand, P.,…Vellas, B. (2017). Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol, 16(5), 377-389. https://doi.org/10.1016/s1474-4422(17)30040-6
Aung, T., Halsey, J., Kromhout, D., Gerstein, H. C., Marchioli, R., Tavazzi, L., Geleijnse, J. M., Rauch, B., Ness, A., Galan, P., Chew, E. Y., Bosch, J., Collins, R., Lewington, S., Armitage, J., & Clarke, R. (2018). Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals. JAMA Cardiol, 3(3), 225-234. https://doi.org/-10.1001/jamacardio.2017.5205
Baldassarre, D., Amato, M., Eligini, S., Barbieri, S. S., Mussoni, L., Frigerio, B., Kozàkovà, M., Tremoli, E., Sirtori, C. R., & Colli, S. (2006). Effect of n-3 fatty acids on carotid atherosclerosis and haemostasis in patients with combined hyperlipoproteinemia: a double-blind pilot study in primary prevention. Ann Med, 38(5), 367-375. https://doi.org/10.1080/07853890600852880
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Jr., Juliano, R. A., Jiao, L., Granowitz, C., Tardif, J. C., Ballantyne, C. M., & Investigators, R.-I. (2019). Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med, 380(1), 11-22. https://doi.org/10.1056/NEJMoa1812792
Blacher, J., Czernichow, S., Paillard, F., Ducimetiere, P., Hercberg, S., Galan, P., & Group, S. F. O. S. R. (2013). Cardiovascular effects of B-vitamins and/or N-3 fatty acids: the SU.FOL.OM3 trial. Int J Cardiol, 167(2), 508-513. https://doi.org/10.1016/j.ijcard.2012.01.060
Bosch, J., Gerstein, H. C., Dagenais, G. R., Diaz, R., Dyal, L., Jung, H., Maggiono, A. P., Probstfield, J., Ramachandran, A., Riddle, M. C., Ryden, L. E., & Yusuf, S. (2012). n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med, 367(4), 309-318. https://doi.org/10.1056/NEJMoa1203859
Bowman, L., Mafham, M., Wallendszus, K., Stevens, W., Buck, G., Barton, J., Murphy, K., Aung, T., Haynes, R., Cox, J., Murawska, A., Young, A., Lay, M., Chen, F., Sammons, E., Waters, E., Adler, A., Bodansky, J., Farmer, A.,…Armitage, J. (2018). Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med, 379(16), 1540-1550. https://doi.org/10.1056/NEJMoa1804989
Brouwer, I. A., Zock, P. L., Camm, A. J., Bocker, D., Hauer, R. N., Wever, E. F., Dullemeijer, C., Ronden, J. E., Katan, M. B., Lubinski, A., Buschler, H., Schouten, E. G., & Group, S. S. (2006). 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. Jama, 295(22), 2613-2619. https://-doi.org/10.1001/jama.295.22.2613
Brox, J., Olaussen, K., Osterud, B., Elvevoll, E. O., Bjørnstad, E., Brattebøg, G., & Iversen, H. (2001). A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. Lipids, 36(1), 7-13. https://doi.org/10.1007-/s11745-001-0661-4
Chen, G., Qian, Z. M., Zhang, J., Zhang, S., Zhang, Z., Vaughn, M. G., Aaron, H. E., Wang, C., Lip, G. Y., & Lin, H. (2024b). Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study. BMJ Med, 3(1), e000451. https://doi.org/10.1136/bmj-med-2022-000451
Chen, H. C., Tai, C. J., Huang, J. Y., Kuo, T. A., Huang, Y. D., Yen, C. H., & Lee, M. C. (2024a). Associations of fish oil with cardiovascular disease events: results from the Taiwan longitudinal study in aging. BMC Public Health, 24(1), 1979. https://doi.org/10.1186/s12889-024-19512-8
Chew, E. Y., Clemons, T. E., Agrón, E., Launer, L. J., Grodstein, F., & Bernstein, P. S. (2015). Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. Jama, 314(8), 791-801. https://doi.org/-10.1001/jama.2015.9677
Derosa, G., Cicero, A. F., D'Angelo, A., Borghi, C., & Maffioli, P. (2016). Effects of n-3 pufas on fasting plasma glucose and insulin resistance in patients with impaired fasting glucose or impaired glucose tolerance. Biofactors, 42(3), 316-322. https://doi.org/10.1002/biof.1277
Einvik, G., Klemsdal, T. O., Sandvik, L., & Hjerkinn, E. M. (2010). A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk. Eur J Cardiovasc Prev Rehabil, 17(5), 588-592. https://doi.org/10.1097/HJR.0b013e328339cc70
Eritsland, J., Arnesen, H., Gronseth, K., Fjeld, N. B., & Abdelnoor, M. (1996). Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol, 77(1), 31-36. https://doi.org/10.1016/s0002-9149(97)8-9130-8
Feagan, B. G., Sandborn, W. J., Mittmann, U., Bar-Meir, S., D'Haens, G., Bradette, M., Cohen, A., Dallaire, C., Ponich, T. P., McDonald, J. W., Hébuterne, X., Paré, P., Klvana, P., Niv, Y., Ardizzone, S., Alexeeva, O., Rostom, A., Kiudelis, G., Spleiss, J.,…Rutgeerts, P. (2008). Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. Jama, 299(14), 1690-1697. https://doi.org/-10.1001/jama.299.14.1690
GISSI-Prevenzione, t. (1999). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet, 354(9177), 447-455.
Hill, C. L., March, L. M., Aitken, D., Lester, S. E., Battersby, R., Hynes, K., Fedorova, T., Proudman, S. M., James, M., Cleland, L. G., & Jones, G. (2016). Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose. Ann Rheum Dis, 75(1), 23-29. https://doi.org-/10.1136/annrheumdis-2014-207169
Hjerkinn, E. M., Abdelnoor, M., Breivik, L., Bergengen, L., Ellingsen, I., Seljeflot, I., Aase, O., Ole Klemsdal, T., Hjermann, I., & Arnesen, H. (2006). Effect of diet or very long chain omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil, 13(3), 325-333. https://doi.org/10.1097/01.hjr.0000209817.28444.fb
Jialal, I., Devaraj, S., Huet, B. A., & Traber, M. (1999). GISSI-Prevenzione trial. The Lancet, 354(9189), 1554. https://-doi.org/10.1016/S0140-6736(99)-90191-5
Kalstad, A. A., Myhre, P. L., Laake, K., Tveit, S. H., Schmidt, E. B., Smith, P., Nilsen, D. W. T., Tveit, A., Fagerland, M. W., Solheim, S., Seljeflot, I., Arnesen, H., & Investigators, O. (2021). Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction: A Randomized, Controlled Trial. Circulation, 143(6), 528-539. https://doi.org/10.1161/-CIRCULATIONAHA.120.052209
Khan, S. U., Lone, A. N., Khan, M. S., Virani, S. S., Blumenthal, R. S., Nasir, K., Miller, M., Michos, E. D., Ballantyne, C. M., Boden, W. E., & Bhatt, D. L. (2021). Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis. EClinicalMedicine, 38, 100997. https://doi.org/10.1016/j.eclinm.2021.100997
Kris-Etherton, P. M., Richter, C. K., Bowen, K. J., Skulas-Ray, A. C., Jackson, K. H., Petersen, K. S., & Harris, W. S. (2019). Recent Clinical Trials Shed New Light on the Cardiovascular Benefits of Omega-3 Fatty Acids. Methodist Debakey Cardiovasc J, 15(3), 171-178. https://doi.org/10.14797/mdcj-15-3-171
Kromhout, D., Giltay, E. J., & Geleijnse, J. M. (2010). n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med, 363(21), 2015-2026. https://doi.org/10.1056/NEJMoa1003603
Kumar, S., Sutherland, F., Morton, J. B., Lee, G., Morgan, J., Wong, J., Eccleston, D. E., Voukelatos, J., Garg, M. L., & Sparks, P. B. (2012). Long-term omega-3 polyunsaturated fatty acid supplementation reduces the recurrence of persistent atrial fibrillation after electrical cardioversion. Heart Rhythm, 9(4), 483-491. https://doi.org/10.1016/j.hrthm.20-11.11.034
Kwong, R. Y., Heydari, B., Ge, Y., Abdullah, S., Fujikura, K., Kaneko, K., Harris, W. S., Jerosch-Herold, M., Antman, E. M., Seidman, J. G., & Pfeffer, M. A. (2019). Genetic profiling of fatty acid desaturase polymorphisms identifies patients who may benefit from high-dose omega-3 fatty acids in cardiac remodeling after acute myocardial infarction-Post-hoc analysis from the OMEGA-REMODEL randomized controlled trial. PLoS One, 14(9), e0222061. https://doi.org/10.1371/journal.-pone.0222061
Leaf, A., Albert, C. M., Josephson, M., Steinhaus, D., Kluger, J., Kang, J. X., Cox, B., Zhang, H., & Schoenfeld, D. (2005). Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation, 112(18), 2762-2768. https://doi.org/10.1161/circu-lationaha.105.549527
Macchia, A., Grancelli, H., Varini, S., Nul, D., Laffaye, N., Mariani, J., Ferrante, D., Badra, R., Figal, J., Ramos, S., Tognoni, G., & Doval, H. C. (2013). 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. J Am Coll Cardiol, 61(4), 463-468. https://doi.org/10.1016/j.jacc.2012.11.021
Manson, J. E., Bassuk, S. S., Lee, I. M., Cook, N. R., Albert, M. A., Gordon, D., Zaharris, E., Macfadyen, J. G., Danielson, E., Lin, J., Zhang, S. M., & Buring, J. E. (2012). The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials, 33(1), 159-171. https://doi.org/10.1016/j.cct.2011.09.009
Manson, J. E., Cook, N. R., Lee, I. M., Christen, W., Bassuk, S. S., Mora, S., Gibson, H., Albert, C. M., Gordon, D., Copeland, T., D'Agostino, D., Friedenberg, G., Ridge, C., Bubes, V., Giovannucci, E. L., Willett, W. C., Buring, J. E., & Group, V. R. (2019). Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med, 380(1), 23-32. https://doi.org/10.1056/NEJMoa1811403
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2010). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. International Journal of Surgery, 8(5), 336-341. https://doi.org/https:-doi.org/10.1016/j.ijsu.2010.02.007
Nicholls, S. J., Lincoff, A. M., Garcia, M., Bash, D., Ballantyne, C. M., Barter, P. J., Davidson, M. H., Kastelein, J. J. P., Koenig, W., McGuire, D. K., Mozaffarian, D., Ridker, P. M., Ray, K. K., Katona, B. G., Himmelmann, A., Loss, L. E., Rensfeldt, M., Lundström, T., Agrawal, R.,…Nissen, S. E. (2020). Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. Jama, 324(22), 2268-2280. https://doi.org/10.1001-/jama.2020.22258
Nigam, A., Talajic, M., Roy, D., Nattel, S., Lambert, J., Nozza, A., Jones, P., Ramprasath, V. R., O'Hara, G., Kopecky, S., Brophy, J. M., & Tardif, J. C. (2014). Fish oil for the reduction of atrial fibrillation recurrence, inflammation, and oxidative stress. J Am Coll Cardiol, 64(14), 1441-1448. https://doi.org/10.1016/-j.jacc.2014.07.956
Nilsen, D. W., Albrektsen, G., Landmark, K., Moen, S., Aarsland, T., & Woie, L. (2001). 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. Am J Clin Nutr, 74(1), 50-56. https://doi.org/10.1093/ajcn/74.1.50
Nosaka, K., Miyoshi, T., Iwamoto, M., Kajiya, M., Okawa, K., Tsukuda, S., Yokohama, F., Sogo, M., Nishibe, T., Matsuo, N., Hirohata, S., Ito, H., & Doi, M. (2017). Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomes than statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study. Int J Cardiol, 228, 173-179. https://doi.org/10.1016/j.ijcard.2016.11.105
Nye, E. R., Ablett, M. B., Robertson, M. C., Ilsley, C. D., & Sutherland, W. H. (1990). Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. Aust N Z J Med, 20(4), 549-552. https://doi.org/10.1111/j.1445-5994.1990.tb-01311.x
Olamide, O., Adebayo, O., Emmanuel, A., Eyitayo, L., Beatrice, O., & Tomisin, M. (2023). Prevalence and Risk Factors of Cardiovascular Diseases among the Nigerian Population: A New Trend among Adolescents and Youths. In D. C. Gaze (Ed.), Novel Pathogenesis and Treatments for Cardiovascular Disease. IntechOpen. https://doi.org/10.5772/-intechopen.108180
Pahor, M., Anton, S. D., Beavers, D. P., Cauley, J. A., Fielding, R. A., Kritchevsky, S. B., Leeuwenburgh, C., Lewis, K. H., Liu, C. K., Lovato, L. C., Lu, J., Manini, T. M., McDermott, M. M., Miller, M. E., Newman, A. B., Radziszewska, B., Stowe, C. L., Tracy, R. P., Walkup, M. P.,…Ambrosius, W. T. (2019). Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci, 74(10), 1612-1619. https://doi.org/10.1093/gerona/gly277
Proudman, S. M., Cleland, L. G., Metcalf, R. G., Sullivan, T. R., Spargo, L. D., & James, M. J. (2015). Plasma n-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis. Br J Nutr, 114(6), 885-890. https://doi.org/10.1017/S0007114515002718
Raitt, M. H., Connor, W. E., Morris, C., Kron, J., Halperin, B., Chugh, S. S., McClelland, J., Cook, J., MacMurdy, K., Swenson, R., Connor, S. L., Gerhard, G., Kraemer, D. F., Oseran, D., Marchant, C., Calhoun, D., Shnider, R., & McAnulty, J. (2005). Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. Jama, 293(23), 2884-2891. https://doi.org/10.1001/jama.293.23.2884
Roncaglioni, M. C., Tombesi, M., Avanzini, F., Barlera, S., Caimi, V., Longoni, P., Marzona, I., Milani, V., Silletta, M. G., Tognoni, G., & Marchioli, R. (2013). n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med, 368(19), 1800-1808. https://doi.org/10.1056/NEJMoa1205409
Sacks, F. M., Stone, P. H., Gibson, C. M., Silverman, D. I., Rosner, B., & Pasternak, R. C. (1995). Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol, 25(7), 1492-1498. https://doi.org/10.1016/0735-1097(95)00095-l
Sanyal, A. J., Abdelmalek, M. F., Suzuki, A., Cummings, O. W., & Chojkier, M. (2014). No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology, 147(2), 377-384.e371. https://doi.org/10.1053/j.gastro.2014.04.046
Sherratt, S. C. R., Libby, P., Budoff, M. J., Bhatt, D. L., & Mason, R. P. (2023). Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues. Curr Atheroscler Rep, 25(1), 1-17. https://doi.org/10.1007/s11883-022-01075-x
Shinto, L., Quinn, J., Montine, T., Dodge, H. H., Woodward, W., Baldauf-Wagner, S., Waichunas, D., Bumgarner, L., Bourdette, D., Silbert, L., & Kaye, J. (2014). A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer's disease. J Alzheimers Dis, 38(1), 111-120. https://doi.org/10.3233/JAD-130722
Tavazzi, L., Maggioni, A. P., Marchioli, R., Barlera, S., Franzosi, M. G., Latini, R., Lucci, D., Nicolosi, G. L., Porcu, M., & Tognoni, G. (2008). 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, 372(9645), 1223-1230. https://doi.org/10.1016/s0140-6736(08)61239-8
Toth, P. P., Chapman, M. J., Parhofer, K. G., & Nelson, J. R. (2022). Differentiating EPA from EPA/DHA in cardiovascular risk reduction. American Heart Journal Plus: Cardiology Research and Practice, 17, 100148. https://doi.org/https://doi.org/10.1016/j.ahjo.2022.100148
von Schacky, C., Baumann, K., & Angerer, P. (2001). The effect of n-3 fatty acids on coronary atherosclerosis: results from SCIMO, an angiographic study, background and implications. Lipids, 36 Suppl, S99-102. https://doi.org/10.1007/s11745-001-0689-5
Yokoyama, M. (2009). [Japan EPA Lipid Intervention Study (JELIS). Randomized clinical trial involving primary and secondary prevention of cardiovascular events with EPA in hypercholesterolemia]. Nihon Ronen Igakkai Zasshi, 46(1), 22-25. https://doi.org/-10.3143/geriatrics.46.22
Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., & Shirato, K. (2007). Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet, 369(9567), 1090-1098. https://doi.org/10.1016/s0140-6736(07)60527-3
Zimmer, R., Riemer, T., Rauch, B., Schneider, S., Schiele, R., Gohlke, H., Diller, F., Steinbeck, G., Katus, H., Senges, J., & Group, O. M.-S. (2013). Effects of 1-year treatment with highly purified omega-3 fatty acids on depression after myocardial infarction: results from the OMEGA trial. J Clin Psychiatry, 74(11), e1037-1045. https://doi.org/10.4088/JCP.13m08453
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Researchers Journal of Science and Technology
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
