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. 1985 Oct;76(4):1626–1631. doi: 10.1172/JCI112147

Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans.

C von Schacky, S Fischer, P C Weber
PMCID: PMC424148  PMID: 2997286

Abstract

We studied the incorporation and metabolism of eicosapentanoic (EPA) and docosahexaenoic acid in six human volunteers who supplemented their normal Western diet for 5 mo daily with 10-40 ml of cod liver oil, rich in omega-3 polyunsaturated fatty acids. EPA and docosahexaenoic acid were incorporated into the total phospholipids of plasma, platelets, and erythrocytes in a dose- and time-dependent manner. During omega-3 fatty acid ingestion serum triacylglycerols were lowered and platelet aggregation upon low doses of collagen was reduced. Concomitantly, formation and excretion of prostanoids showed a characteristic change. As measured in serum from whole clotted blood, thromboxane A3 was formed in small amounts, whereas thromboxane A2 formation was reduced to 50% of control values. Excretion of the main urinary thromboxane A metabolites was unaltered in subjects with low basal excretion rates, but decreased markedly in two subjects with high control values. As determined from the main urinary metabolite, prostaglandin I3 was formed from EPA at rates up to 50% of unaltered prostaglandin I2 formation. The biochemical and functional changes observed lasted for the entire supplementation period of 5 mo and were reversible within 12 wk after cessation of cod liver oil intake. Favorable changes induced by long-chain omega-3 fatty acids include a dose-related and sustained shift of the prostaglandin I/thromboxane A balance to a more antiaggregatory and vasodilatory state.

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Selected References

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  1. AHRENS E. H., Jr, INSULL W., Jr, HIRSCH J., STOFFEL W., PETERSON M. L., FARQUHAR J. W., MILLER T., THOMASSON H. J. The effect on human serum-lipids of a dietary fat, highly unsaturated, but poor in essential fatty acids. Lancet. 1959 Jan 17;1(7064):115–119. doi: 10.1016/s0140-6736(59)90002-9. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Bang H. O., Dyerberg J., Nielsen A. B. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet. 1971 Jun 5;1(7710):1143–1145. doi: 10.1016/s0140-6736(71)91658-8. [DOI] [PubMed] [Google Scholar]
  4. Bills T. K., Smith J. B., Silver M. J. Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin. J Clin Invest. 1977 Jul;60(1):1–6. doi: 10.1172/JCI108745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black K. L., Culp B., Madison D., Randall O. S., Lands W. E. The protective effects of dietary fish oil on focal cerebral infarction. Prostaglandins Med. 1979 Nov;3(5):257–268. doi: 10.1016/0161-4630(79)90067-3. [DOI] [PubMed] [Google Scholar]
  6. Brox J. H., Killie J. E., Gunnes S., Nordøy A. The effect of cod liver oil and corn oil on platelets and vessel wall in man. Thromb Haemost. 1981 Oct;46(3):604–611. [PubMed] [Google Scholar]
  7. Crawford M. A., Hassam A. G., Williams G. Essential fatty acids and fetal brain growth. Lancet. 1976 Feb 28;1(7957):452–453. doi: 10.1016/s0140-6736(76)91476-8. [DOI] [PubMed] [Google Scholar]
  8. Culp B. R., Lands W. E., Lucches B. R., Pitt B., Romson J. The effect of dietary supplementation of fish oil on experimental myocardial infarction. Prostaglandins. 1980 Dec;20(6):1021–1031. doi: 10.1016/0090-6980(80)90056-8. [DOI] [PubMed] [Google Scholar]
  9. Dyerberg J., Bang H. O., Stoffersen E., Moncada S., Vane J. R. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet. 1978 Jul 15;2(8081):117–119. doi: 10.1016/s0140-6736(78)91505-2. [DOI] [PubMed] [Google Scholar]
  10. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  11. Falardeau P., Oates J. A., Brash A. R. Quantitative analysis of two dinor urinary metabolites of prostaglandin I2. Anal Biochem. 1981 Aug;115(2):359–367. doi: 10.1016/0003-2697(81)90018-x. [DOI] [PubMed] [Google Scholar]
  12. Fischer S., Struppler M., Böhlig B., Bernutz C., Wober W., Weber P. C. The influence of selective thromboxane synthetase inhibition with a novel imidazole derivative, UK-38,485, on prostanoid formation in man. Circulation. 1983 Oct;68(4):821–826. doi: 10.1161/01.cir.68.4.821. [DOI] [PubMed] [Google Scholar]
  13. Fischer S., Weber P. C. Prostaglandin I3 is formed in vivo in man after dietary eicosapentaenoic acid. Nature. 1984 Jan 12;307(5947):165–168. doi: 10.1038/307165a0. [DOI] [PubMed] [Google Scholar]
  14. Fischer S., Weber P. C. Thromboxane A3 (TXA3) is formed in human platelets after dietary eicosapentaenoic acid (C20:5 omega 3). Biochem Biophys Res Commun. 1983 Nov 15;116(3):1091–1099. doi: 10.1016/s0006-291x(83)80254-x. [DOI] [PubMed] [Google Scholar]
  15. Fischer S., von Schacky C., Siess W., Strasser T., Weber P. C. Uptake, release and metabolism of docosahexaenoic acid (DHA, c22:6 omega 3) in human platelets and neutrophils. Biochem Biophys Res Commun. 1984 May 16;120(3):907–918. doi: 10.1016/s0006-291x(84)80193-x. [DOI] [PubMed] [Google Scholar]
  16. Gerber J. G., Barnes J. S., Nies A. S. Measurement of arachidonic acid in the plasma by gas-liquid chromatography-flame ionization using dihomo-gamma-linolenic acid as an internal standard. J Lipid Res. 1979 Sep;20(7):912–914. [PubMed] [Google Scholar]
  17. Goodnight S. H., Jr, Harris W. S., Connor W. E., Illingworth D. R. Polyunsaturated fatty acids, hyperlipidemia, and thrombosis. Arteriosclerosis. 1982 Mar-Apr;2(2):87–113. doi: 10.1161/01.atv.2.2.87. [DOI] [PubMed] [Google Scholar]
  18. Gryglewski R. J., Salmon J. A., Ubatuba F. B., Weatherly B. C., Moncada S., Vane J. R. Effects of all cis-5,8,11,14,17 eicosapentaenoic acid and PGH3 on platelet aggregation. Prostaglandins. 1979 Sep;18(3):453–478. doi: 10.1016/s0090-6980(79)80063-5. [DOI] [PubMed] [Google Scholar]
  19. Hornstra G., Christ-Hazelhof E., Haddeman E., ten Hoor F., Nugteren D. H. Fish oil feeding lowers thromboxane- and prostacyclin production by rat platelets and aorta and does not result in the formation of prostaglandin I3. Prostaglandins. 1981 May;21(5):727–738. doi: 10.1016/0090-6980(81)90230-6. [DOI] [PubMed] [Google Scholar]
  20. Illingworth D. R., Harris W. S., Connor W. E. Inhibition of low density lipoprotein synthesis by dietary omega-3 fatty acids in humans. Arteriosclerosis. 1984 May-Jun;4(3):270–275. doi: 10.1161/01.atv.4.3.270. [DOI] [PubMed] [Google Scholar]
  21. Karmali R. A., Marsh J., Fuchs C. Effect of omega-3 fatty acids on growth of a rat mammary tumor. J Natl Cancer Inst. 1984 Aug;73(2):457–461. doi: 10.1093/jnci/73.2.457. [DOI] [PubMed] [Google Scholar]
  22. Kromann N., Green A. Epidemiological studies in the Upernavik district, Greenland. Incidence of some chronic diseases 1950-1974. Acta Med Scand. 1980;208(5):401–406. [PubMed] [Google Scholar]
  23. Lee T. H., Hoover R. L., Williams J. D., Sperling R. I., Ravalese J., 3rd, Spur B. W., Robinson D. R., Corey E. J., Lewis R. A., Austen K. F. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med. 1985 May 9;312(19):1217–1224. doi: 10.1056/NEJM198505093121903. [DOI] [PubMed] [Google Scholar]
  24. Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lorenz R., Spengler U., Fischer S., Duhm J., Weber P. C. Platelet function, thromboxane formation and blood pressure control during supplementation of the Western diet with cod liver oil. Circulation. 1983 Mar;67(3):504–511. doi: 10.1161/01.cir.67.3.504. [DOI] [PubMed] [Google Scholar]
  26. Majerus P. W. Arachidonate metabolism in vascular disorders. J Clin Invest. 1983 Nov;72(5):1521–1525. doi: 10.1172/JCI111110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mest H. J., Beitz J., Heinroth I., Block H. U., Förster W. The influence of linseed oil diet on fatty acid pattern in phospholipids and thromboxane formation in platelets in man. Klin Wochenschr. 1983 Feb 15;61(4):187–191. doi: 10.1007/BF01488973. [DOI] [PubMed] [Google Scholar]
  28. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  29. Needleman P., Raz A., Minkes M. S., Ferrendelli J. A., Sprecher H. Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Proc Natl Acad Sci U S A. 1979 Feb;76(2):944–948. doi: 10.1073/pnas.76.2.944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Neufeld E. J., Wilson D. B., Sprecher H., Majerus P. W. High affinity esterification of eicosanoid precursor fatty acids by platelets. J Clin Invest. 1983 Jul;72(1):214–220. doi: 10.1172/JCI110959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Neuringer M., Connor W. E., Van Petten C., Barstad L. Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest. 1984 Jan;73(1):272–276. doi: 10.1172/JCI111202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Prickett J. D., Robinson D. R., Steinberg A. D. Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB x NZW F1 mice. J Clin Invest. 1981 Aug;68(2):556–559. doi: 10.1172/JCI110288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sanders T. A., Vickers M., Haines A. P. Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men. Clin Sci (Lond) 1981 Sep;61(3):317–324. doi: 10.1042/cs0610317. [DOI] [PubMed] [Google Scholar]
  34. Saynor R., Verel D., Gillott T. The long-term effect of dietary supplementation with fish lipid concentrate on serum lipids, bleeding time, platelets and angina. Atherosclerosis. 1984 Jan;50(1):3–10. doi: 10.1016/0021-9150(84)90003-0. [DOI] [PubMed] [Google Scholar]
  35. Siess W., Cuatrecasas P., Lapetina E. G. A role for cyclooxygenase products in the formation of phosphatidic acid in stimulated human platelets. Differential mechanisms of action of thrombin and collagen. J Biol Chem. 1983 Apr 25;258(8):4683–4686. [PubMed] [Google Scholar]
  36. Siess W., Roth P., Scherer B., Kurzmann I., Böhlig B., Weber P. C. Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during a mackerel diet. Lancet. 1980 Mar 1;1(8166):441–444. doi: 10.1016/s0140-6736(80)90995-2. [DOI] [PubMed] [Google Scholar]
  37. Siess W., Roth P., Weber P. C. Stimulated platelet aggregation, thromboxane B2 formation and platelet sensitivity to prostacyclin - a critical evaluation. Thromb Haemost. 1981 Jun 30;45(3):204–207. [PubMed] [Google Scholar]
  38. Spector A. A., Kaduce T. L., Figard P. H., Norton K. C., Hoak J. C., Czervionke R. L. Eicosapentaenoic acid and prostacyclin production by cultured human endothelial cells. J Lipid Res. 1983 Dec;24(12):1595–1604. [PubMed] [Google Scholar]
  39. Strasser T., Fischer S., Weber P. C. Leukotriene B5 is formed in human neutrophils after dietary supplementation with icosapentaenoic acid. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1540–1543. doi: 10.1073/pnas.82.5.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stubbs C. D., Smith A. D. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta. 1984 Jan 27;779(1):89–137. doi: 10.1016/0304-4157(84)90005-4. [DOI] [PubMed] [Google Scholar]
  41. Terano T., Hirai A., Hamazaki T., Kobayashi S., Fujita T., Tamura Y., Kumagai A. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis. 1983 Mar;46(3):321–331. doi: 10.1016/0021-9150(83)90181-8. [DOI] [PubMed] [Google Scholar]
  42. Thorngren M., Gustafson A. Effects of 11-week increases in dietary eicosapentaenoic acid on bleeding time, lipids, and platelet aggregation. Lancet. 1981 Nov 28;2(8257):1190–1193. doi: 10.1016/s0140-6736(81)91436-7. [DOI] [PubMed] [Google Scholar]
  43. Vane J. R. Prostacyclin: a hormone with a therapeutic potential. The Sir Henry Dale Lecture for 1981. J Endocrinol. 1982 Nov;95(2):3P–43P. [PubMed] [Google Scholar]
  44. Velardo B., Lagarde M., Guichardant M., Dechavanne M., Beylot M., Sautot G., Berthezene F. Decrease of platelet activity after intake of small amounts of eicosapentaenoic acid in diabetics. Thromb Haemost. 1982 Dec 27;48(3):344–344. [PubMed] [Google Scholar]
  45. von Schacky C., Siess W., Fischer S., Weber P. C. A comparative study of eicosapentaenoic acid metabolism by human platelets in vivo and in vitro. J Lipid Res. 1985 Apr;26(4):457–464. [PubMed] [Google Scholar]

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