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How does Fish Oil Prevent Heart Disease

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How does Fish Oil Prevent Heart Disease
5 months ago 1511 Views

There is evidence that omega-3 fatty acids can reduce adhesion molecules and the buildup of plaque they cause. Fish oil has been extensively studied to determine how it may prevent cardiovascular diseases. That beneficial effect is often attributed to the ability of omega-3s to reduce inflammation, which drives the formation of artery-clogging plaque. Other cardioprotective effects of fish oil include lowering of triglycerides and reduced platelet aggregation that can otherwise block a coronary or cerebral artery.

Heart disease and strokes, however, have another major underlying cause: adhesion molecules. These are tiny Velcro-like barbs present on endothelial cells and on the surface of circulating white blood cells. They are a critical initiator of atherosclerosis.1,2 A recent review reports on clinical studies showing that omega-3s (EPA and DHA) in fish oil can reduce adhesion molecules by up to 28%. This is another way that fish oil functions to curtail atherosclerosis and lower heart disease and stroke risk.2

How Adhesion Molecules Form Plaque

Endothelial cells line the inside of all blood vessels, including the arteries. Adhesion molecules on endothelial cells and on white blood cells promote atherosclerosis.1,3 Adhesion molecules are like tiny barbs on the surface of those cells, making white blood cells stick to the blood vessel lining.1,2,4 This adhering of white blood cells to a blood vessel sets in motion the process of arterial plaque formation. The consequences are blood flow blockage and acute rupture of unstable arterial plaques.2 Efforts to reduce adhesion molecule production have become a topic in cardiovascular disease prevention research.

Fish Oil Reduces Adhesion Molecules

There is evidence that omega-3 fatty acids can reduce adhesion molecules and the buildup of plaque they cause. 2,3 A meta-analysis of 18 randomized, controlled, human trials found significant reductions in adhesion molecules in subjects who supplemented with omega-3s.5 And a recent review found reductions in adhesion molecules of up to 28% in people taking fish oil or its omega-3 constituents, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid).2 Doses in this report ranged as high as 4,000 mg EPA and 3,500 mg DHA per day.

Multiple Effects of Omega-3s

Lab studies of human endothelial cells in culture show the impact of omega-3 fatty acids on adhesion molecules:

  • Omega-3s , particularly EPA, lower the production of inflammatory cytokines and adhesion molecules. This can stop white blood cells from sticking to artery walls.6,7
  • DHA, an omega-3 also found in fish, significantly reduces cell adhesion in response to the inflammation-promoting cytokine tumor necrosis factor-alpha (TNF-alpha).8
  • Maresin 1 is formed from DHA and has anti-inflammatory properties. It reduces the secretion of inflammatory cytokines and adhesion molecules.

It also reduces stress on the cell that can lead to premature cell death.9 Maresins have such robust cell-protective, anti-inflammatory, and pro-healing properties that they’re being explored as drugs.10-12 Animal studies confirm the importance of these findings:

  • Hamsters given EPA and DHA-rich fish oil had up to a six-fold reduction in white blood cells “sticking” to small artery walls.13,14
  • In mouse aortas treated with fish oil, reductions in atherosclerosis were accompanied by significant decreases in adhesion molecules that lead to the progression of plaque.15
  • Hamsters taking fish oil had significantly less vessel damage during ischemia and reperfusion. These terms (ischemia and reperfusion) refer to the loss of blood flow that occurs during a heart attack or stroke and the impact of sudden restoration of circulation that occurs when a stent is inserted or a blood clot dissolved or mechanically removed from an occluded artery. Fish oil’s ability to suppress the release of adhesion molecules was an important contributor to this beneficial effect.14
  • Mice given fish oil had significantly reduced early atherosclerotic plaque, as a result of sharp reductions in molecules that promote the release of inflammatory cytokines and adhesion molecules.16

Summary

Adhesion molecules are produced on white blood cells and the cells lining our arteries when they are stressed. They act like tiny barbs of Velcro that attach to each other and initiate atherosclerotic plaque formation and create further inflammation-driven dysfunction. Reducing amounts and function of adhesion molecules is a major goal of modern cardiovascular medicine. Studies reveal that daily intake of omega-3 fatty acids from fish oil reduces adhesion molecules, preventing the sticky, white blood cell/blood vessel interaction, and permitting smoother flow of blood. This reduced adhesion molecule production is associated with reductions in early atherosclerotic plaque and lower risk of cardiovascular disease.


Editor: Matea Kuzmanic

References

  1. Blankenberg S, Barbaux S, Tiret L. Adhesion molecules and atherosclerosis. Atherosclerosis. 2003 Oct;170(2):191-203.
  2. Baker EJ, Yusof MH, Yaqoob P, et al. Omega-3 fatty acids and leukocyte-endothelium adhesion: Novel anti-atherosclerotic actions. Mol Aspects Med. 2018 Dec;64: 169-81.
  3. Del Gobbo LC, Imamura F, Aslibekyan S, et al. omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies. JAMA Intern Med. 2016 Aug 1;176(8): 1155-66.
  4. Galkina E, Ley K. Vascular Adhesion Molecules in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27(11):2292-301.
  5. Yang Y, Lu N, Chen D, et al. Effects of n-3 PUFA supplementation on plasma soluble adhesion molecules: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012 Apr;95(4):972-80.
  6. Sethi S, Ziouzenkova O, Ni H, et al. Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR alpha. Blood. 2002 Aug 15;100(4):1340-6.
  7. De Caterina R, Madonna R, Massaro M. Effects of omega-3 fatty acids on cytokines and adhesion molecules. Curr Atheroscler Rep. 2004 Nov;6(6):485-91.
  8. Schaefer MB, Schaefer CA, Schifferings S, et al. N-3 vs. n-6 fatty acids differentially influence calcium signalling and adhesion of inflammatory activated monocytes: impact of lipid rafts. Inflamm Res. 2016 Nov;65(11):881-94.
  9. Jung TW, Park HS, Choi GH, et al. Maresin 1 attenuates pro-inflammatory reactions and ER stress in HUVECs via PPARalpha-mediated pathway. Mol Cell Biochem. 2018 Nov;448(1-2):335-47.
  10. Drouin G, Rioux V, Legrand P. The n-3 docosapentaenoic acid (DPA): A new player in the n-3 long chain polyunsaturated fatty acid family. Biochimie. 2019 Apr;159:36-48.
  11. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014 Jun 5;510(7503):92-101.
  12. Serhan CN. Discovery of specialized pro-resolving mediators marks the dawn of resolution physiology and pharmacology. Mol Aspects Med. 2017 Dec;58:1-11.
  13. Lehr HA, Hubner C, Finckh B, et al. Dietary fish oil reduces leukocyte/endothelium interaction following systemic administration of oxidatively modified low density lipoprotein. Circulation. 1991 Oct;84(4):1725-31.
  14. de Souza M, Conde CM, Laflor CM, et al. n-3 PUFA induce microvascular protective changes during ischemia/reperfusion. Lipids. 2015 Jan;50(1):23-37.
  15. Casos K, Saiz MP, Ruiz-Sanz JI, et al. Atherosclerosis prevention by a fish oil-rich diet in apoE(-/-) mice is associated with a reduction of endothelial adhesion molecules. Atherosclerosis. 2008 Dec;201(2):306-17.
  16. Speck N, Brandsch C, Schmidt N, et al. The Antiatherogenic Effect of Fish Oil in Male Mice Is Associated with a Diminished Release of Endothelial ADAM17 and ADAM10 Substrates. J Nutr. 2015 Jun;145(6):1218-26.
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