Top

Current Atherosclerosis Reports

Published in:

01-03-2021 | Dyslipidemia | Statin Drugs (R. Ceska, Section Editor)

The Truth About Fish (Oil) in the Treatment of Dyslipidemia

Authors: Jan Pitha, Rudolf Poledne

Published in: Current Atherosclerosis Reports | Issue 3/2021

Abstract

Purpose of Review

To discuss the effect of fish oils on dyslipidemias and associated disorders.

Recent Findings

The most important lipid effect of fish oils is reducing plasma triglycerides and the main potential protection against cardiovascular events is very probably mediated also through other mechanisms including anti-inflammatory ones. The best results are available for omega-3 fatty acids, namely, eicosapentaenoic acid. Less evidence is available for the impact of ω-3 fatty acids on liver steatosis/steatohepatitis and acute pancreatitis. In addition, particular fish oils have variable content of saturated and unsaturated fatty acids with different anti- or pro-oxidative potential, and the suboptimal ratio of these compounds could attenuate or abolish their beneficial properties.

Summary

Fish products with optimal proportion of fatty acids, particularly high content of eicosapentaenoic acid, could be recommended to patients with dyslipidemias, especially to those at high risk for cardiovascular disease; less evidence is available for liver disease and acute pancreatitis.

Libby P, Hansson GK. From focal lipid storage to systemic inflammation: JACC review topic of the week. J Am Coll Cardiol. 2019;74(12):1594–607. https://doi.org/10.1016/j.jacc.2019.07.061.CrossRefPubMedPubMedCentral

Langlois MR, Chapman MJ, Cobbaert C, Mora S, Remaley AT, Ros E, et al. European atherosclerosis society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) joint consensus initiative. Quantifying Atherogenic lipoproteins: current and future challenges in the era of personalized medicine and very low concentrations of LDL cholesterol. A consensus Statement from EAS and EFLM. Clin Chem. 2018;64(7):1006–33. https://doi.org/10.1373/clinchem.2018.287037.CrossRefPubMed

Váncsa S, Németh D, Hegyi P, Szakács Z, Hegyi PJ, Pécsi D, et al. Fatty liver disease and non-alcoholic fatty liver disease worsen the outcome in acute pancreatitis: a systematic review and meta-analysis. J Clin Med. 2020;9(9):E2698. https://doi.org/10.3390/jcm9092698.CrossRefPubMed

Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis 2019: 290:140–205. https://doi.org/10.1016/j.atherosclerosis.2019.08.014. Erratum in: Atherosclerosis. 2020 Feb;294:80–82.

•• Preston Mason R. New insights into mechanisms of action for omega-3 fatty acids in atherothrombotic cardiovascular disease. Curr Atheroscler Rep. 2019;21(1):2. https://doi.org/10.1007/s11883-019-0762-1Comprehensive but wide range summary focused on several effects of omega-3 fatty acids beyond lipid effects and stressing specific effects of eicosapentaenoic acid literally on molecular/cell membrane level.CrossRefPubMedPubMedCentral

Jia X, Kohli P, Virani SS. Omega-3 fatty acid and cardiovascular outcomes: insights from recent clinical trials. Curr Atheroscler Rep. 2019;21(1):1. https://doi.org/10.1007/s11883-019-0763-0.CrossRefPubMed

Rimm EB, Appel LJ, Chiuve SE, Djoussé L, Engler MB, Kris-Etherton PM, et al. American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease: a science advisory from the American Heart Association. Circulation. 2018;138(1):e35–47. https://doi.org/10.1161/CIR.0000000000000574.CrossRefPubMedPubMedCentral

•• Sherratt, Samuel CR, Lero M, Mason RP. Are dietary fish oil supplements appropriate for dyslipidemia management? A review of the evidence. Curr Opin Lipidol. 2020;31(2):94–100. https://doi.org/10.1097/MOL.0000000000000665Correctly and critically written review focused on the drawbacks of fish oils regarding their content and ensuing differences in biological effets, which could be even harmful.

•• Shearer GC, Savinova OV, Harris WS. Fish oil - how does it reduce plasma triglycerides? Biochim Biophys Acta. 2012;1821(5):843–51. https://doi.org/10.1016/j.bbalip.2011.10.011.Olderbut still one of the most complete and comprehensive overviews of mechanisms of fish oils/omega-3 fatty acids effects on lipid metabolism.CrossRefPubMed

10.

Annuzzi G, Rivellese AA, Wang H, Patti L, Vaccaro O, Riccardi G, et al. Lipoprotein subfractions and dietary intake of n-3 fatty acid: the genetics of coronary artery disease in Alaska natives study. Am J Clin Nutr. 2012;95(6):1315–22. https://doi.org/10.3945/ajcn.111.023887.CrossRefPubMedPubMedCentral

11.

• Amigó N, Akinkuolie AO, Chiuve SE, Correig X, Cook NR, Mora S. Habitual fish consumption, ω-3 fatty acids, and nuclear magnetic resonance lipoprotein subfractions in women. J Am Heart Assoc. 2020;9(5):e014963. https://doi.org/10.1161/JAHA.119.014963.Studyof the association between consumption of fish and ω-3 fatty acids with complex lipoproteins measurements including nuclear magnetic resonance spectroscopy in 26 000 women. Differences observed for high intake of eicosapentaenoic acid versus docosahexaenoic acid and alfa-linolenic acid.CrossRefPubMedPubMedCentral

12.

Oelrich B, Dewell A, Gardner CD. Effect of fish oil supplementation on serum triglycerides, LDL cholesterol and LDL subfractions in hypertriglyceridemic adults. Nutr Metab Cardiovasc Dis. 2013;23(4):350–7. https://doi.org/10.1016/j.numecd.2011.06.003.CrossRefPubMed

13.

Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006;189(1):19–30. https://doi.org/10.1016/j.atherosclerosis.2006.02.012.CrossRefPubMed

14.

Harris WS, Connor WE, Alam N, Illingworth DR. Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res. 1988;29(11):1451–60.CrossRef

15.

Kasbi Chadli F, Nazih H, Krempf M, Nguyen P, Ouguerram K. Omega 3 fatty acids promote macrophage reverse cholesterol transport in hamster fed high fat diet. PLoS One. 2013;8(4):e61109. https://doi.org/10.1371/journal.pone.0061109.CrossRefPubMedPubMedCentral

16.

Langsted A, Freiberg JJ, Tybjaerg-Hansen A, Schnohr P, Jensen GB, Nordestgaard BG. Nonfasting cholesterol and triglycerides and association with risk of myocardial infarction and total mortality: the Copenhagen City heart study with 31 years of follow-up. J Intern Med. 2011;270:65–75. https://doi.org/10.1111/j.1365-2796.2010.02333.CrossRefPubMed

17.

Innes JK, Calder PC. The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiometabolic risk factors: a systematic review. Int J Mol Sci. 2018;19(2):532. https://doi.org/10.3390/ijms19020532.CrossRefPubMedCentral

18.

Poledne R, Malinska H, Kubatova H, Fronek J, Thieme F, Kauerova S, et al. Polarization of macrophages in human adipose tissue is related to the fatty acid spectrum in membrane phospholipids. Nutrients. 2019;12(1):8. https://doi.org/10.3390/nu12010008.CrossRefPubMedCentral

19.

Mason RP, Jacob RF, Shrivastava S, Sherratt SCR, Chattopadhyay A. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic- like model membranes. Biochim Biophys Acta. 1858;2016:3131–40. https://doi.org/10.1016/j.bbamem.2016.10.002.CrossRef

20.

• Mason RP, Sherratt SC, Jacob RF. Eicosapentaenoic acid inhibits oxidation of ApoB-containing lipoprotein particles of different size in vitro when administered alone or in combination with atorvastatin active metabolite compared with other triglyceride-lowering agents. J Cardiovasc Pharmacol 2016: 68:33–40. https://doi.org/10.1097/FJC.0000000000000379 95. Inhibition of oxidative processes by EPA was described only with metabolite of atorvastatin but not with fibrates, niacin and vitamin E.

21.

Mason RP, Jacob RF. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism. Biochim Biophys Acta. 1848;2015:502–9. https://doi.org/10.1016/j.bbamem.2014.10.016.CrossRef

22.

•• Mason RP, Libby P, Bhatt DL. Emerging mechanisms of cardiovascular protection for the omega-3 fatty acid eicosapentaenoic acid. Arterioscler Thromb Vasc Biol. 2020;40(5):1135–47. https://doi.org/10.1161/ATVBAHA.119.313286Review focused on proved but mainly newly discussed mechanisms of the effects of omega-3 fatty acids including cell membrane composition. In addition, it is also proposing potential future directions of research.CrossRefPubMedPubMedCentral

23.

Stansby ME. Nutritional properties of fish oils. World Rev Nutr Diet. 1969;11:46–105.CrossRef

24.

Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic west-coast Eskimos. Lancet. 1971;1(7710):1143–5. https://doi.org/10.1016/s0140-6736(71)91658-8.CrossRefPubMed

25.

Fodor JG, Helis E, Yazdekhasti N, Vohnout B. "fishing" for the origins of the “Eskimos and heart disease” story: facts or wishful thinking? Can J Cardiol. 2014;30(8):864–8. https://doi.org/10.1016/j.cjca.2014.04.007.CrossRefPubMed

26.

Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. Omega-3 treatment trialists’ collaboration. Associations of Omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol. 2018;3(3):225–34. https://doi.org/10.1001/jamacardio.2017.5205.CrossRefPubMed

27.

Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020. https://doi.org/10.1002/14651858.CD003177.pub5.

28.

• Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019:380(1):11–22. https://doi.org/10.1056/NEJMoa1812792. Already well known study proving significant effect of eicosapentaenoic acid on clinical events - randomized, placebo control trial - the best recently available evidence.

29.

•• Budoff MJ, Bhatt DL, Kinninger A, Lakshmanan S, Muhlestein JB, Le VT, et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. Eur Heart J. 2020:ehaa652. https://doi.org/10.1093/eurheartj/ehaa652Randomized placebo controlled trial focused on regression of atherosclerosis which was observed at treatment identical to REDUCE-IT trial - supportive and mechanistic parallel study.

30.

Lakshmanan S, Shekar C, Kinninger A, Dahal S, Onuegbu A, Cai AN, et al. Comparison of mineral oil and non-mineral oil placebo on coronary plaque progression by coronary computed tomography angiography. Cardiovasc Res. 2020;116(3):479–82. https://doi.org/10.1093/cvr/cvz329.CrossRefPubMed

31.

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8. https://doi.org/10.1016/S0140-6736(07)60527-3 Erratum in: Lancet 2007: 370(9583):220.CrossRefPubMed

32.

• ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, et al. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379(16):1540–50. https://doi.org/10.1056/NEJMoa1804989Clinical trial using lower dose of omega-3 fatty acids (1 g/day) with negative results.CrossRef

33.

• Nicholls SJ, Lincoff AM, Bash D, Ballantyne CM, Barter PJ, Davidson MH, et al. Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: rationale and design of the STRENGTH trial. Clin Cardiol. 2018;41:1281–8. https://doi.org/10.1002/clc.23055Clinical trial using mixutre of omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acid) terminated for futility.CrossRefPubMedPubMedCentral

34.

URL: https://www.clinicaltrials. gov. Unique identifier: NCT02104817.

35.

Jump DB, Lytle KA, Depner CM, Tripathy S. Omega-3 polyunsaturated fatty acids as a treatment strategy for nonalcoholic fatty liver disease. Pharmacol Ther. 2018;181:108–25. https://doi.org/10.1016/j.pharmthera.2017.07.007.CrossRefPubMed

36.

Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, et al. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis. 2008;40(3):194–9. https://doi.org/10.1016/j.dld.2007.10.003.CrossRefPubMed

37.

Havel RJ. Pathogenesis, differentiation and management of hypertriglyceridemia. Adv Intern Med. 1969;15:117–54.PubMed

38.

Zhang Y, He W, He C, Wan J, Lin X, Zheng X, et al. Large triglyceride-rich lipoproteins in hypertriglyceridemia are associated with the severity of acute pancreatitis in experimental mice. Cell Death Dis. 2019;10(10):728. https://doi.org/10.1038/s41419-019-1969-3.CrossRefPubMedPubMedCentral

39.

Chang YT, Chang MC, Tung CC, Wei SC, Wong JM. Distinctive roles of unsaturated and saturated fatty acids in hyperlipidemic pancreatitis. World J Gastroenterol. 2015;21(32):9534–43. https://doi.org/10.3748/wjg.v21.i32.9534.CrossRefPubMedPubMedCentral

40.

Lei QC, Wang XY, Xia XF, Zheng HZ, Bi JC, Tian F, et al. The role of omega-3 fatty acids in acute pancreatitis: a meta-analysis of randomized controlled trials. Nutrients. 2015;7(4):2261–73. https://doi.org/10.3390/nu7042261.CrossRefPubMedPubMedCentral

41.

Langsted A, Madsen CM, Nordestgaard BG. Contribution of remnant cholesterol to cardiovascular risk. J Intern Med. 2020;288(1):116–27. https://doi.org/10.1111/joim.13059.CrossRefPubMed

Title: The Truth About Fish (Oil) in the Treatment of Dyslipidemia
Authors: Jan Pitha
Rudolf Poledne
Publication date: 01-03-2021
Publisher: Springer US
Keywords: Dyslipidemia
Acute Pancreatitis
Published in: Current Atherosclerosis Reports / Issue 3/2021
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-021-00904-9

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The Truth About Fish (Oil) in the Treatment of Dyslipidemia

Abstract

Purpose of Review

Recent Findings

Summary

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page