Toggle Health Problems and D

Omega-3 reduces many aspects of heart problems - Jan 2024

Omega-3 reduces heart problems in both observational and RCT studies - Dr. Manson June 2024

Who Benefits From Omega-3/Fish Oil Supplements? - Medscape

5 minute video

This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital. I'd like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).

This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.

Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.

For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.

The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.

What should be done in the meantime? It's important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.

What about patients who don't meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American. 

Someone who rarely or never eats fish and has multiple risk factors for CVD, but doesn't meet criteria for prescription omega-3 medication, may want to discuss with their clinician the use of over-the-counter fish oil supplements. But fish oil and other dietary supplements will never be a substitute for healthy diet and healthy lifestyle. There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it's important to use reputable sources of the supplement, and check the bottle for a quality control seal. It's also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding. 

Omega-3 supplementation and outcomes of heart failure - A systematic review of clinical trials

Mahin Nomali, PhDa, Mohammad Eghbal Heidari, PhDb, Aryan Ayati, MD, MPHc, Amirhossein Tayebi, MDd , Oksana Shevchuk, MD, PhDe, Ramin Mohammadrezaei, MDf, Hossein Navid, MDg,
Sayyed Saeid Khayyatzadeh, MDh,i, Svitlana Palii, PhD, MDj, Fahimeh Valizade Shiran, MDk,
Atie Sadat Khorasanian, MSc1, Zahra Veysi, PhDm, Atena Jamalzehi, PhDn, Azadeh Lesani, PhDo,
Golnoosh Assari, BSc, MScp, Shiva Khani, MScq, Kamyab Hassanpour, MDr, Hadis Gerami, PhDh,s*

Backgrounds: Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.
Methods: A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.

Results: The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.

Conclusion: Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.
 Download the PDF from VitaminDWiki

87 References
  1. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143:e254-743.
  2. Chia N, Fulcher J, Keech A. Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2)): an evidence-based mnemonic for the treatment of sys­tolic heart failure. Intern Med J. 2016;46:653-62.
  3. Bertero E, Maack C. Calcium signaling and reactive oxygen species in mitochondria. Circ Res. 2018;122:1460-78.
  4. Bacmeister L, Schwarzl M, Warnke S, et al. Inflammation and fibrosis in murine models of heart failure. Basic Res Cardiol. 2019;114:19.
  5. Lázaro I, Lupón J, Cediel G, et al. Relationship of circulating vegetable omega-3 to prognosis in patients with heart failure. J Am Coll Cardiol. 2022;80:1751-8.
  6. Nodari S, Triggiani M, Campia U, et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2011;57:870-9.
  7. Tavazzi L, Maggioni AP, Marchioli R, 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 (London, England). 2008;372:1223-30.
  8. Tal S. Mortality predictors in the oldest-old in an acute geriatric ward. Isr Med Assoc J. 2022;24:638-42.
  9. Balta I, Stef L, Pet I, et al. Essential fatty acids as biomedicines in car­diac health. Biomedicines. 2021;9:1466.
  10. Thomas IC, Nishimura M, Ma J, et al. Clinical characteristics and out­comes of patients with heart failure and methamphetamine abuse. J Card Fail. 2020;26:202-9.
  11. Belin RJ, Greenland P, Martin L, et al. Fish intake and the risk of incident heart failure: the women’s health initiative. Circulation. 2011;4:404-13.
  12. Mozaffarian D, Bryson CL, Lemaitre RN, et al. Fish intake and risk of incident heart failure. J Am Coll Cardiol. 2005;45:2015-21.
  13. Bernasconi AA, Wiest MM, Lavie CJ, et al. Effect of omega-3 dosage on cardiovascular outcomes: an updated meta-analysis and meta­regression of interventional trials. Mayo Clin Proc. 2021;96:304-13.
  14. Barbarawi M, Lakshman H, Barbarawi O, et al. Omega-3 supplemen­tation and heart failure: a meta-analysis of 12 trials including 81,364 participants. Contemp Clin Trials. 2021;107:106458.
  15. Djoussé L, Cook NR, Kim E, et al. Diabetes mellitus, race, and effects of omega-3 fatty acids on incidence of heart failure hospitalization. Heart Failure. 2022;10:227-34.
  16. Mozaffarian D, Wu JHY. Omega-3 fatty acids and cardiovascular dis­ease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58:2047-67.
  17. Ruppar TM, Cooper PS, Mehr DR, et al. Medication adherence inter­ventions improve heart failure mortality and readmission rates: system­atic review and meta-analysis of controlled trials. J Am Heart Assoc. 2016;5:e002606.
  18. Sakamoto A, Saotome M, Iguchi K, et al. Marine-derived omega-3 polyunsaturated fatty acids and heart failure: current understanding for basic to clinical relevance. Int J Mol Sci. 2019;20:4025.
  19. Glück T, Alter P. Marine omega-3 highly unsaturated fatty acids: from mechanisms to clinical implications in heart failure and arrhythmias. Vascul Pharmacol. 2016;82:11-9.
  20. Wu C, Kato TS, Ji R, et al. Supplementation of l-alanyl-l-glutamine and fish oil improves body composition and quality of life in patients with chronic heart failure. Circulation. 2015;8:1077-87.
  21. Lennie TA, Moser DK, Biddle MJ, et al. Nutrition intervention to decrease symptoms in patients with advanced heart failure. Res Nurs Health. 2013;36:120-45.#Jiang W, Whellan DJ, Adams KF, et al. Long-chain omega-3 fatty acid supplements in depressed heart failure patients: results of the OCEAN trial. JACC Heart Failure. 2018;6:833-43.
  22. Jain AP, Aggarwal KK, Zhang PY. Omega-3 fatty acids and cardiovas­cular disease. Eur Rev Med Pharmacol Sci. 2015;19:441-5.
  23. Shen S, Gong C, Jin K, et al. Omega-3 fatty acid supplementation and coronary heart disease risks: a meta-analysis of randomized controlled clinical trials. Front Nutr. 2022;9:809311.
  24. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduc­tion with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.
  25. Oner T, Ozdemir R, Doksoz O, et al. Cardiac function in children with premature ventricular contractions: the effect of omega-3 polyunsatu­rated fatty acid supplementation. Cardiol Young. 2018;28:949-54.
  26. Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in athero­sclerosis. Atherosclerosis. 2015;242:357-66.
  27. Chow SL, Bozkurt B, Baker WL, et al. Complementary and alternative medicines in the management of heart failure: a scientific statement from the American Heart Association. Circulation. 2023;147:e4-e30.
  28. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12.
  29. Radaelli A, Cazzaniga M, Viola A, et al. Enhanced baroreceptor control of the cardiovascular system by polyunsaturated fatty acids in heart failure patients. J Am Coll Cardiol. 2006;48:1600-6.
  30. Mehra MR,Lavie CJ,Ventura HO,et al.Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant. 2006;25:834-8.
  31. O’Keefe JH Jr, Abuissa H, Sastre A, et al. Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions. Am J Cardiol. 2006;97:1127-30.
  32. Morgan DR, Dixon LJ, Hanratty CG, et al. Effects of dietary omega-3 fatty acid supplementation on endothelium-dependent vasodilation in patients with chronic heart failure. Am J Cardiol. 2006;97:547-51.
  33. Del Turco S, Basta G, Lazzerini G, et al. Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparti­cles in patients with a previous myocardial infarction. Haematologica. 2008;93:892-9.
  34. Zhao Y, Shao L, Teng L, et al. Effects of n-3 polyunsaturated fatty acid therapy on plasma inflammatory markers and N-terminal pro-brain natriuretic peptide in elderly patients with chronic heart failure. J Int Med Res. 2009;37:1831-41.
  35. Nodari S, Metra M, Milesi G, et al. The role of n-3 PUFAs in preventing the arrhythmic risk in patients with idiopathic dilated cardiomyopathy. Cardiovasc Drugs Ther. 2009;23:5-15.
  36. Ghio S, Scelsi L, Latini R, et al. Effects of n-3 polyunsaturated fatty acids and of rosuvastatin on left ventricular function in chronic heart failure: a substudy of GISSI-HF trial. Eur J Heart Fail. 2010;12:1345-53.
  37. Eschen O, Christensen JH, Romano P, et al. Effects of marine n-3 fatty acids on circulating levels of soluble adhesion molecules in patients with chronic heart failure. Cell Mol Biol. 2010;56:45-51.
  38. Moertl D, Berger R, Hammer A, et al. Dose-dependent decrease of platelet activation and tissue factor by omega-3 polyunsaturated fatty acids in patients with advanced chronic heart failure. Thromb Haemost. 2011;106:457-65.
  39. Moertl D, Hammer A, Steiner S, et al. Dose-dependent effects of omega-3- polyunsaturated fatty acids on systolic left ventricular function, endo­thelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study. Am Heart J. 2011;161:915.e1-9.
  40. Kojuri J, Ostovan MA, Rezaian GR, et al. Effect of omega-3 on brain natriuretic peptide and echocardiographic findings in heart failure: double-blind placebo-controlled randomized trial. J Cardiovasc Dis Res. 2013;4:20-4.
  41. Kohashi K, Nakagomi A, Saiki Y, et al. Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long­term prognosis in chronic heart failure patients with dyslipidemia. J Atheroscler Thromb. 2014;21:712-29.
  42. Chrysohoou C, Metallinos G, Georgiopoulos G, et al. Short term omega-3 polyunsaturated fatty acid supplementation induces favor­able changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; a randomized clinical trial. Vascul Pharmacol. 2016;79:43-50.
  43. Wurm R, Schrutka L, Hammer A, et al. Polyunsaturated fatty acids sup­plementation impairs anti-oxidant high-density lipoprotein function in heart failure. Eur J Clin Invest. 2018;48:e12998.
  44. Selvaraj S, Bhatt DL, Steg PG, et al. Impact of icosapent ethyl on cardio­vascular risk reduction in patients with heart failure in REDUCE-IT. J Am Heart Assoc. 2022;11:e024999.
  45. Calder PC. n-3 Polyunsaturated fatty acids, inflammation, and inflam­matory diseases. Am J Clin Nutr. 2006;83:1505S-19S.
  46. Campos-Staffico AM, Costa APR, Carvalho LSF, et al. Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction. Nutr J. 2019;18:1-8.
  47. Calder PC. Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie. 2009;91:791-5.
  48. Castiglione V, Aimo A, Vergaro G, et al. Biomarkers for the diagnosis and management of heart failure. Heart Fail Rev. 2021;27:625-43.
  49. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 Suppl):1645S-54S.
  50. Thierer J, Acosta A, Vainstein N, et al. Relation of left ventricular ejec­tion fraction and functional capacity with metabolism and inflamma­tion in chronic heart failure with reduced ejection fraction (from the MIMICA Study). Am J Cardiol. 2010;105:977-83.
  51. Lan T, Liao Y-H, Zhang J, et al. Mortality and readmission rates after heart failure: a systematic review and meta-analysis. Ther Clin Risk Manag. 2021;17:1307-20.
  52. Emmons-Bell S, Johnson C, Roth G. Prevalence, incidence and survival of heart failure: a systematic review. Heart. 2022;108:1351-1360.
  53. Feltner C, Jones CD, Cené CW, et al. Transitional care interventions to prevent readmissions for persons with heart failure: a systematic review and meta-analysis. Ann Intern Med. 2014;160:774-84.
  54. Wleklik M, Uchmanowicz I, Jankowska-Polañska B, et al. The role of nutritional status in elderly patients with heart failure. J Nutr Health Aging. 2018;22:581-8.
  55. Angkananard T, Anothaisintawee T, Eursiriwan S, et al. The associ­ation of serum magnesium and mortality outcomes in heart failure patients: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95:e5406.
  56. Abu-Sawwa R, Dunbar SB, Quyyumi AA, et al. Nutrition inter­vention in heart failure: should consumption of the DASH eating pattern be recommended to improve outcomes? Heart Fail Rev. 2019;24:565-73.
  57. Djoussé L, Akinkuolie AO, Wu JH, et al. Fish consumption, omega-3 fatty acids and risk of heart failure: a meta-analysis. Clin Nutr (Edinburgh, Scotland). 2012;31:846-53.
  58. Jiang H, Wang L, Wang D, et al. Omega-3 polyunsaturated fatty acid biomarkers and risk of type 2 diabetes, cardiovascular disease, cancer, and mortality. Clin Nutr (Edinburgh, Scotland). 2022;41:1798-807.
  59. Harris WS, Tintle NL, Imamura F, et al. Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nat Commun. 2021;12:1-9.
  60. Rizos EC, Ntzani EE, Bika E, et al. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024-33.
  61. Salah HM, Minhas AMK, Khan MS, et al. Causes of hospitalization in the USA between 2005 and 2018. Eur Heart J Open. 2021;1:oeab001.
  62. Ditewig JB, Blok H, Havers J, et al. Effectiveness of self­management interventions on mortality, hospital readmissions, chronic heart failure hospitalization rate and quality of life in patients with chronic heart failure: a systematic review. Patient Educ Couns. 2010;78:297-315.
  63. Goldgrab D, Balakumaran K, Kim MJ, et al. Updates in heart failure 30-day readmission prevention. Heart Fail Rev. 2019;24:177-87.
  64. Rattarasarn I, Yingchoncharoen T, Assavapokee T. Prediction of rehos­pitalization in patients with acute heart failure using point-of-care lung ultrasound. BMC Cardiovasc Disord. 2022;22:1-7.
  65. 66 Aronow WS, Shamliyan TA. Exercise for preventing hospitalization and readmission in adults with congestive heart failure. Cardiol Rev. 2019;27:41-8.
  66. Siddiqui WJ, Kohut AR, Hasni SF, et al. Readmission rate after ultrafil­tration in acute decompensated heart failure: a systematic review and meta-analysis. Heart Fail Rev. 2017;22:685-98.
  67. Dalal J, Katekhaye V, Jain R. Effect of ferric carboxymaltose on hos­pitalization and mortality outcomes in chronic heart failure: a meta­analysis. Indian Heart J. 2017;69:736M1.
  68. Abshire M, Xu J, Baptiste D, et al. Nutritional interventions in heart fail­ure: a systematic review of the literature. J Card Fail. 2015;21:989-99.
  69. Djoussé L, Cook NR, Kim E, et al. Supplementation with vitamin D and omega-3 fatty acids and incidence of heart failure hospitalization: VITAL-heart failure. Circulation. 2020;141:784-6.
  70. Braunwald E. The Denolin lecture congestive heart failure: a half cen­tury perspective. Eur Heart J. 2001;22:825-36.
  71. GIS SI-Prevenzione Investigators. 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. 1999;354:447-55.
  72. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarc­tion trial (DART). Lancet. 1989;2:757-61.
  73. Oikonomou E, Vogiatzi G, Karlis D, et al. Effects of omega-3 polyun­saturated fatty acids on fibrosis, endothelial function and myocardial performance, in ischemic heart failure patients. Clin Nutr (Edinburgh, Scotland). 2019;38:1188-97.
  74. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med. 1988;318:549-57.
  75. Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004;6:461-7.
  76. Ruxton CH, Reed SC, Simpson MJ, et al. The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Diet. 2004;17:449-59.
  77. Ferrari R, Bachetti T, Confortini R, et al. Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure. Circulation. 1995;92:1479-86.
  78. Mann DL. Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res. 2002;91:988-98.
  79. Deswal A, Petersen NJ, Feldman AM, et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine data­base from the vesnarinone trial (VEST). Circulation. 2001;103:2055-9.
  80. Parish S, Mafham M, Offer A, et al. Effects of omega-3 fatty acid sup­plements on arrhythmias. Circulation. 2020;141:331-3.
  81. Myhre PL, Kalstad AA, Tveit SH, et al. Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: a secondary analysis of the OMEMI trial. J Intern Med. 2022;291:637-47.
  82. Murphy SP, Kakkar R, McCarthy CP, et al. Inflammation in heart failure: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75:1324-40.
  83. Calder PC. Dietary fatty acids and the immune system. Lipids. 1999;34(Suppl):S137-40.
  84. Moeinzadeh F, Shahidi S, Mortazavi M, et al. Effects of omega-3 fatty acid supplementation on serum biomarkers, inflammatory agents, and quality of life of patients on hemodialysis. Iran J Kidney Dis. 2016;10:381.
  85. Behboudi-Gandevani S, Hariri F-Z, Moghaddam-Banaem L. The effect of omega 3 fatty acid supplementation on premenstrual syndrome and health-related quality of life: a randomized clinical trial. J Psychosom Obstet Gynaecol. 2018;39:266-72.
  86. 87 Olenik A, Mahillo-Fernandez I, Alejandre-Alba N, et al. Benefits of omega-3 fatty acid dietary supplementation on health-related quality of life in patients with meibomian gland dysfunction. Clin Ophthalmol (Auckland, NZ). 2014;8:831-6.
  87. Collins N, Tighe AP, Brunton SA, et al. Differences between dietary supplement and prescription drug omega-3 fatty acid formula­tions: a legislative and regulatory perspective. J Am Coll Nutr. 2008;27:659-66.
  88. Hilleman DE, Wiggins BS, Bottorff MB. Critical differences between dietary supplement and prescription omega-3 fatty acids: a narrative review. Adv Ther. 2020;37:656-70.

VitaminDWiki - 34 studies in both categories Omega-3 and Cardiovascular

This list is automatically updated

See also Cardiovascular Disease is treated by Vitamin D - many studies

Omega-3 reduces many aspects of heart problems - Jan 2024        
3846 visitors, last modified 08 Jun, 2024,
(Cached) Printer Friendly Follow this page for updates

Attached files

ID Name Comment Uploaded Size Downloads
20745 Omega=3 benefits HF.png admin 03 Feb, 2024 230.49 Kb 99
20744 Omeg-3 heart failure Meta-analysis_CompressPdf.pdf admin 03 Feb, 2024 338.87 Kb 36