fatty acid, omega-3 (Epanova)

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Introduction

Unsaturation 3 carbons from the C terminus of the long-chain fatty acid.

Origin

Indications

* no significant reduction in cardiovascular disease & mortality[13][33][39][40]

* no cardiovascular benefit[21][25][33][36][39]

* no reduction in cardiovascular events in high-risk patients[50]

* reduces risk of sudden cardiac death[31]

* 19-45% reduction in cardiovascular events[14]

* no benefit for secondary prevention of heart disease[24]

* no benefit for secondary prevention after myocardial infarction[51]

* high plasma levels of long-chain omega-3 fatty acids are associated with reduced mortality, especially cardiovascular mortality[26]

* plasma levels of seafood-derived long-chain omega-3 fatty acids in elderly subjects is associated with healthy aging[44]

* may be of benefit in patients with recent MI[38]

* reduced mortality & hospitalization in patients with chronic heart failure (2% absolute risk reduction)[15]

* reduced risk of ischemic stroke WITHOUT increased risk of hemorrhagic stroke

* reduced cardiovascular mortality & improved cardiovascular outcomes[56]

* no effect on cancer[13]

Contraindications

Dosage

Adverse effects

Drug interactions

* not explained what the interactions are or what the clinical effects are[31]

Laboratory

Mechanism of action

More general terms

More specific terms

Additional terms

Component of

References

  1. ↑ Prescriber's Letter 9(5):30 2002
  2. ↑ 2.0 2.1 Prescriber's Letter 10(7):38 2003
  3. ↑ Laurin D, Verreault R, Lindsay J, Dewailly E, Holub BJ. Omega-3 fatty acids and risk of cognitive impairment and dementia. J Alzheimers Dis. 2003 Aug;5(4):315-22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14624027
  4. ↑ Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003 Jul;60(7):940-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12873849
  5. ↑ Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ. Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Br J Nutr. 2003 Apr;89(4):483-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12654166
  6. ↑ Hashimoto M, Hossain S, Shimada T, Sugioka K, Yamasaki H, Fujii Y, Ishibashi Y, Oka J, Shido O. Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats. J Neurochem. 2002 Jun;81(5):1084-91. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12065621
  7. ↑ Kyle DJ, Schaefer E, Patton G, Beiser A. Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. Lipids. 1999;34 Suppl:S245. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10419166
  8. ↑ Prescriber's Letter 12(7): 2005 Omega-3 Fatty Acids Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210709&pb=PRL (subscription needed) http://www.prescribersletter.com
  9. ↑ 9.0 9.1 Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 2003 Jul 15;108(2):155-60. Epub 2003 Jun 23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12821543
  10. ↑ 10.0 10.1 Parikh P, McDaniel MC, Ashen MD, Miller JI, Sorrentino M, Chan V, Blumenthal RS, Sperling LS. Diets and cardiovascular disease: an evidence-based assessment. J Am Coll Cardiol. 2005 May 3;45(9):1379-87. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15862406
  11. ↑ Morris MC et al, Fish consumption and cognitive decline with age in a large community study Arch Neurol 2005;62:1849 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16216930
  12. ↑ Solfrizzi V et al, Dietary fatty acids intake: possible role in cognitive decline and dementia. Exp Gerontol 2005; 40:257 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15820606
  13. ↑ 13.0 13.1 13.2 Hooper L et al, Risks and benefits of omega-3 fats for mortality, cardiovascular disease, and cancer. BMJ 2006; 332:752 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16565093
  14. ↑ 14.0 14.1 14.2 Lee JH et al, Omega-3 fatty acids for cardioprotection. Mayo Clin Proc 2008, 83:324 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18316000
  15. ↑ 15.0 15.1 Gissi-Hf Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Aug 29. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/18757090
  16. ↑ Prescriber's Letter 16(7): 2009 CHART: Omega Fatty Acids COMMENTARY: Flaxseed: Is It As Beneficial As Fish Oil? Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250708&pb=PRL (subscription needed) http://www.prescribersletter.com
  17. ↑ 17.0 17.1 Carney RM et al Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: A randomized controlled trial. JAMA 2009 Oct 21; 302:1651. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19843899
  18. ↑ 18.0 18.1 Farzaneh-Far R et al. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA 2010 Jan 20; 303:250 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20085953
  19. ↑ Prescriber's Letter 17(4): 2010 Omega-3 Fatty Acid Supplementation in Pediatrics Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260406&pb=PRL (subscription needed) http://www.prescribersletter.com
  20. ↑ Dangour AD et al. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: A randomized, double-blind, controlled trial. Am J Clin Nutr 2010 Apr 21 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20410089 <Internet> http://dx.doi.org/10.3945/ajcn.2009.29121
  21. ↑ 21.0 21.1 Kromhout D et al for the Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010 Aug 29 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20929341 <Internet> http://dx.doi.org/10.1056/NEJMoa1003603
  22. ↑ 22.0 22.1 Kowey PR et al Efficacy and safety of prescription omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: A randomized controlled trial. JAMA 2010 Nov 15; 304:[e-pub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21078810 <Internet> http://jama.ama-assn.org/cgi/content/full/jama.2010.1735
  23. ↑ 23.0 23.1 Galan P et al. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: A randomised placebo controlled trial. BMJ 2010 Nov 29; 341:c6273 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21115589
  24. ↑ 24.0 24.1 24.2 Kwak SM et al. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: A meta-analysis of randomized, double-blind, placebo- controlled trials. Arch Intern Med 2012 May 14; 172:686 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22493407
    Hu FB and Manson JE. Omega-3 fatty acids and secondary prevention of cardiovascular disease - Is it just a fish tale? Arch Intern Med 2012 May 14; 172:694 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22493410
  25. ↑ 25.0 25.1 Rizos EC 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(10):1024-1033 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22968891 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1357266
  26. ↑ 26.0 26.1 Mozaffarian D et al Plasma Phospholipid Long-Chain omega-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. Ann Intern Med. 2 April 2013;158(7):515-525 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23546563 <Internet> http://annals.org/article.aspx?articleid=1671714
  27. ↑ The Risk and Prevention Study Collaborative Group. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013 May 9; 368:1800 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23656645 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1205409
  28. ↑ 28.0 28.1 Zheng J-S et al Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ 2013;346:f3706 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23814120 <Internet> http://www.bmj.com/content/346/bmj.f3706
  29. ↑ 29.0 29.1 Brasky TM, Darke AK, Song X et al Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. JNCI J Natl Cancer Inst. July 10, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23843441 <Internet> http://jnci.oxfordjournals.org/content/early/2013/07/09/jnci.djt174.abstract
  30. ↑ 30.0 30.1 30.2 Deprecated Reference
  31. ↑ 31.0 31.1 31.2 31.3 31.4 31.5 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
    Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  32. ↑ 32.0 32.1 Chowdhury R et al Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. Ann Intern Med. 2014;160(6):398-406 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24723079 <Internet> http://annals.org/article.aspx?articleid=1846638
    Writing Group for the AREDS2 Research Group Effect of Long-Chain omega-3 Fatty Acids and Lutein + Zeaxanthin Supplements on Cardiovascular Outcomes. Results of the Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. JAMA Intern Med. Published online March 17, 2014. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24638908 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1835351
    Rizos EC and Ntzani EE omega-3 Fatty Acids and Lutein + Zeaxanthin Supplementation for the Prevention of Cardiovascular Disease. JAMA Intern Med. Published online March 17, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24638082 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1835344
  33. ↑ 33.0 33.1 33.2 Rizos EC1, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012 Sep 12;308(10):1024-33 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22968891
  34. ↑ AstraZeneca Press Release. May 6, 2014 FDA approves EPANOVA for the treatment of adults with severe hypertriglyceridemia. http://www.astrazeneca-us.com/media/press-releases/Article/20140506-epanova-press-release
  35. ↑ 35.0 35.1 35.2 Bonds DE et al. Effect of long-chain omega-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: Results of the Age- Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med 2014 May; 174:763 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24638908 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1835351
  36. ↑ 36.0 36.1 Agency for Healthcare Research and Quality, Rockville, MD Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review. Content last reviewed August 2016. http://www.ahrq.gov/research/findings/evidence-based-reports/er223-abstract.html
  37. ↑ 37.0 37.1 Sala-Vila A, Diaz-Lopez A, Valls-Pedret C et al Dietary Marine omega-3 Fatty Acids and Incident Sight- Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes. Prospective Investigation From the PREDIMED Trial. JAMA Ophthalmol. Published online August 18, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27541690 <Internet> http://archopht.jamanetwork.com/article.aspx?articleid=2543478
    Larsen M Eat Your Fish or Go for Nuts. JAMA Ophthalmol. Published online August 18, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27541163 <Internet> http://archopht.jamanetwork.com/article.aspx?articleid=2543475
  38. ↑ 38.0 38.1 38.2 38.3 Siscovick DS, Barringer TA, Fretts AM et al Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. March 13, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28289069 <Internet> http://circ.ahajournals.org/content/early/2017/03/13/CIR.0000000000000482
  39. ↑ 39.0 39.1 39.2 Wendling P. No CVD Benefit With Omega-3 Fatty Acids Medscape - Feb 02, 2018. https://www.medscape.com/viewarticle/892201
    Aung T, Halsey J, Kromhout D, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77,917 individuals. JAMA Cardiol. January 31, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29387889 https://jamanetwork.com/journals/jamacardiology/fullarticle/2670752
  40. ↑ 40.0 40.1 40.2 Young K, Fairchild DG, Di Francesco L Higher Omega-3 Intake May Not Provide CV Benefit Physician's First Watch, July 18, 2018 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
    Abdelhamid AS, Martin N, Bridges C et al Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018 Jul 18;7:CD012345 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30019767
  41. ↑ 41.0 41.1 The ASCEND Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus N Engl J Med 2018 Aug 26; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30146932 Free Article https://www.nejm.org/doi/10.1056/NEJMoa1804989
  42. ↑ 42.0 42.1 Su K-P, Tseng P-T, Lin P-Y et al. Association of use of omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms: A systematic review and meta-analysis. JAMA Netw Open 2018 Sep 14; 1:e182327 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30646157 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2702216
  43. ↑ 43.0 43.1 43.2 Manson JE, Cook NR, Lee IM et al Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. Nov 10, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30415637 https://www.nejm.org/doi/full/10.1056/NEJMoa1811403
  44. ↑ 44.0 44.1 Lai HT, de Oliveira Otto MC, Lemaitre RN et al Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: Prospective cohort study. BMJ 2018 Oct 17; 363:k4067. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30333104 Free PMC Article
    Zhu Y, Ferrara A, Forman MR. Omega 3 polyunsaturated fatty acids and healthy ageing: Fresh evidence provides clues to healthier, not just longer lives. BMJ 2018 Oct 17; 363:k4263 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30333101 Free PMC Article
  45. ↑ 45.0 45.1 Skulas-Ray AC, Wilson PWF, Harris WS et al Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation, Aug 19, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31422671 https://www.ahajournals.org/doi/10.1161/CIR.0000000000000709
  46. ↑ 46.0 46.1 Brown TJ, Brainard J, Song F et al Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials. BMJ 2019;366:l4697 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31434641 https://www.bmj.com/content/366/bmj.l4697
  47. ↑ 47.0 47.1 Song M et al Effect of Supplementation With Marine omega-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population. A Prespecified Ancillary Study of a Randomized Clinical Trial. JAMA Oncol. Published online November 21, 2019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31750855 https://jamanetwork.com/journals/jamaoncology/fullarticle/2755431
  48. ↑ 48.0 48.1 George J Omega-3s May Protect Brain From Air Pollution - Women in polluted areas with highest omega-3 levels had less brain shrinkage. MedPage Today July 16, 2020 https://www.medpagetoday.com/neurology/generalneurology/87598
    Chen C, Xun P, Kaufman JD et al Erythrocyte omega-3 index, ambient fine particle exposure and brain aging. Neurology 2020 July 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32669395 https://n.neurology.org/content/early/2020/07/15/WNL.0000000000010074
  49. ↑ 49.0 49.1 49.2 Bischoff-Ferrari HA, Vellas B, Rizzoli R et al Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults. The DO-HEALTH Randomized Clinical Trial. JAMA. 2020;324(18):1855-1868 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33170239 PMCID: PMC7656284 https://jamanetwork.com/journals/jama/article-abstract/2772758
  50. ↑ 50.0 50.1 Nicholls SJ et al. 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 2020 Nov 15; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33190147 https://jamanetwork.com/journals/jama/fullarticle/2773120
    Sharma G et al. Effects of omega-3 fatty acids on major adverse cardiovascular events: What matters most: The drug, the dose, or the placebo? JAMA 2020 Nov 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33190148 https://jamanetwork.com/journals/jama/fullarticle/2773118
  51. ↑ 51.0 51.1 Kalstad AA et al. on behalf of the OMEMI Investigators. Effects of n-3 fatty acid supplements in elderly patients after myocardial infarction: A randomized controlled trial. Circulation 2020 Nov 15; PMID: https://www.ncbi.nlm.nih.gov/pubmed/33191772 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052209
  52. ↑ 52.0 52.1 52.2 52.3 Stiles S EPA, DHA, and Inflammatory Markers: A Piece of the PUFA Puzzle? Medscape - Dec 16, 2020.MansonMansonManson https://www.medscape.com/viewarticle/942767
    So J, Wu D, Lichetenstein AH et al EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study. Atherosclerosis 2020. Dec 7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33303222 https://www.atherosclerosis-journal.com/article/S0021-9150(20)31527-6/fulltext
  53. ↑ 53.0 53.1 53.2 Gencer BAlbert CM et al. Effect of marine omega-3 fatty acid and vitamin D supplementation on incident atrial fibrillation: A randomized clinical trial. JAMA 2021 Mar 16; 325:1061 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33724323 https://jamanetwork.com/journals/jama/article-abstract/2777469
    Curfman G. Omega-3 fatty acids and atrial fibrillation. JAMA 2021 Mar 16; 325:1063 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33724309 https://jamanetwork.com/journals/jama/fullarticle/2777450
  54. ↑ 54.0 54.1 Manson JE High-Dose Marine Omega-3s Raise Risk for Atrial Fibrillation. Medscape. November 17, 2021 https://www.medscape.com/viewarticle/961473
    Gencer B, Djousse L, Al-Ramady OT et al Effect of Long-Term Marine omega-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Circulation. 2021 Dec 21;144(25):1981-1990 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34612056
  55. ↑ 55.0 55.1 Okereke OI et al. Effect of long-term supplementation with marine omega-3 fatty acids vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: A randomized clinical trial. JAMA 2021 Dec 21; 326:2385-2394. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34932079 https://jamanetwork.com/journals/jama/fullarticle/2787320
  56. ↑ 56.0 56.1 56.2 Khan SU, Lone AN, Khan MS, Virani SS et al Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis. EClinicalMedicine. 2021 Jul 8;38:100997 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34505026 PMCID: PMC8413259 Free PMC article
  57. ↑ 57.0 57.1 Christen WG et al. Efficacy of marine omega-3 fatty acid supplementation vs placebo in reducing incidence of dry eye disease in healthy US adults: A randomized clinical trial. JAMA Ophthalmol 2022 Jul; 140:707 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35679030 PMCID: PMC9185512 (available on 2023-06-09) https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2793162
  58. ↑ 58.0 58.1 Windle ML Rapid Rx Quiz: Omega-3 Fatty Acids. Medscape. August 25, 2022 https://reference.medscape.com/viewarticle/979228
  59. ↑ 59.0 59.1 Zhang X, Ritonja JA, Zhou N et al Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35647665 PMCID: PMC9238708 Free PMC article
  60. ↑ 60.0 60.1 Ong KL et al. Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: Pooled analysis of 19 cohorts. BMJ 2023 Jan 18; 380:e072909 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36653033 PMCID: PMC9846698 Free PMC article https://www.bmj.com/content/380/bmj-2022-072909
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