Systematic review of the effect of omega-3 fatty acids on improvement of blood flow while focused on evaluation of claims for health functional food

Journal of Nutrition and Health

Volumn 46, Issue 3, 2013, Pages 226-238

  Jeong, Sewon ^a   Kim, Ji Yeon ^a   Paek, Ju Eun ^a   Kim, Joohee ^a   Kwak, Jin Sook ^b   Kwon, Oran ^c  

^a Biofood CRO Co Ltd   (South Korea)

^b Seoul National University of Science and Technology   (South Korea)

^c Ewha Womans University   (South Korea)

Author keywords

Blood flow; DHA; EPA; Health functional food; Omega 3 fatty acids; Re evaluation; Systematic review

Indexed keywords

EID: 84885073039     PISSN: 22883886     EISSN: 22883959     Source Type: Journal    
DOI: 10.4163/jnh.2013.46.3.226     Document Type: Article

References (165)

1. Yamada M, Omata K, Abe F., Ito S, Abe K. Changes in prostacyclin, thromboxane A2 and F2-isoprostanes, and influence of eicosapentaenoic acid and antiplatelet agents in patients with hypertension and hyperlipidemia. Immunopharmacology 1999; 44 (1-2): 193-198
2. Holub BJ. Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. CMAJ 2002; 166(5): 608-615 (Pubitemid 34251494)
3. Kris-Etherton P.M., Harris WS, Appel LJ; Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003; 23(2): e20-e30
4. Connor WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr 2000; 71(1 Suppl): 171S-175S (Pubitemid 30046112)
5. U.S. Food and Drug Administration. Guidance, compliance, & regulatory information. Silver Spring (MD): U.S. Food and Drug Administration; 2009 [cited 2012 Dec 27]. Available from: http://www.fda.gov/Food/GuidanceRegulation/ GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ucm073332.htm
6. Joint FAO/WHO Codex Alimentarius Commission; World Health Organization; Food and Agriculture Organization of the United Nations. Guidelines for use of nutrition and health claims (C-AC/GL 23-1997, Rev. 1-2004). Rome: Food and Agriculture Organization of the United Nations; 2004 [cited]. Available from: http://std.gdciq.gov.cn/gssw/JiShuFaGui/CAC/CXG-023e.pdf
7. Ministry of Food and Drug Safety. Regulation for evaluation on efficacy of health functional food. Cheongwon: Ministry of Food and Drug Safety; 2012 [cited 2012 Dec 27]. Available from: http://www.foodnara.go.kr/hfoodi/industry/
8. Baldassarre D, Amato M, Eligini S., Barbieri SS, Mussoni L, Frigerio B, Kozàkovà M, Tremoli E, Sirtori CR, Colli S. Effect of n-3 fatty acids on carotid atherosclerosis and haemostasis in patients with combined hyperlipoproteinemia: a double-blind pilot study in primary prevention. Ann Med 2006; 38(5): 367-375
9. Blonk MC, Bilo HJ, Nauta J.J., Popp-Snijders C, Mulder C, Donker AJ Dose-response effects of fish-oil supplementation in healthy volunteers. Am J Clin Nutr 1990; 52(1): 120-127
10. Engler MM, Engler MB, Malloy M, Chiu E., Besio D, Paul S, Stuehlinger M., Morrow J, Ridker P, Rifai N., Mietus-Snyder M. Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study. Int J Clin Pharmacol Ther 2004; 42(12): 672-679 (Pubitemid 39625126)
11. Fahs CA, Yan H, Ranadive S., Rossow LM, Agiovlasitis S, Wilund KR, Fernhall B. The effect of acute fish-oil supplementation on endothelial function and arterial stiffness following a high-fat meal. Appl Physiol Nutr Metab 2010; 35(3): 294-302
12. Finnegan YE, Howarth D, Minihane A.M., Kew S., Miller GJ, Calder PC, Williams CM Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans. J Nutr 2003; 133(7): 2210-2213 (Pubitemid 36841541)
13. Green P, Fuchs J, Schoenfeld N., Leibovici L, Lurie Y, Beigel Y., Rotenberg Z, Mamet R, Budowski P. Effects of fish-oil ingestion on cardiovascular risk factors in hyperlipidemic subjects in Israel: a randomized, double-blind crossover study. Am J Clin Nutr 1990; 52(6): 1118-1124 (Pubitemid 120008222)
14. Grundt H, Nilsen DW, Hetland Ø, Mansoor MA. Clinical outcome and atherothrombogenic risk profile after prolonged washout following long-term treatment with high doses of n-3 PU-FAs in patients with an acute myocardial infarction. Clin Nutr 2004; 23(4): 491-500 (Pubitemid 39107027)
15. Herrmann W, Biermann J, Kostner GM Comparison of effects of N-3 to N-6 fatty acids on serum level of lipoprotein (a) in patients with coronary artery disease. Am J Cardiol 1995; 76(7): 459-462
16. Park Y, Harris W. EPA, but not DHA, decreases mean platelet volume in normal subjects. Lipids 2002; 37(10): 941-946 (Pubitemid 36026488)
17. Passfall J, Philipp T, Woermann F., Quass P, Thiede M, Haller H. Different effects of eicosapentaenoic acid and olive oil on blood pressure, intracellular free platelet calcium, and plasma lipids in patients with essential hypertension. Clin Investig 1993; 71(8): 628-633 (Pubitemid 23240609)
18. Prisco D, Filippini M, Francalanci I., Paniccia R, Gensini GF, Serneri GG Effect of n-3 fatty acid ethyl ester supplementation on fatty acid composition of the single platelet phospholipids and on platelet functions. Metabolism 1995; 44(5): 562-569
19. Møller JM, Svaneborg N, Lervang HH, Varming K, Madsen P, Dyerberg J, Schmidt EB. The acute effect of a single very high dose of N-3 fatty acids on coagulation and fibrinolysis. Thromb Res 1992; 67(5): 569-577
20. Freese R, Mutanen M. Alpha-linolenic acid and marine long-chain n-3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects. Am J Clin Nutr 1997; 66(3): 591-598 (Pubitemid 27366782)
21. Piolot A, Blache D, Boulet L., Fortin LJ, Dubreuil D, Marcoux C, Davignon J., Lussier-Cacan S. Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in health. J Lab Clin Med 2003; 141(1): 41-49 (Pubitemid 36065085)
22. Rillaerts EG, Engelmann GJ, Van Camp KM, De Leeuw I. Effect of omega-3 fatty acids in diet of type I diabetic subjects on lipid values and hemorheological parameters. Diabetes 1989; 38(11): 1412-1416 (Pubitemid 19271723)
23. Walser B, Giordano RM, Stebbins CL Supplementation with omega-3 polyunsaturated fatty acids augments brachial artery dilation and blood flow during forearm contraction. Eur J Appl Physiol 2006; 97(3): 347-354 (Pubitemid 43881230)
24. Haglund O, Wallin R, Luostarinen R., Saldeen T. Effects of a new fluid fish oil concentrate, ESKIMO-3, on triglycerides, cholesterol, fibrinogen and blood pressure. J Intern Med 1990; 227(5): 347-353 (Pubitemid 20137146)
25. Agren JJ, Hänninen O, Laitinen M., Seppänen K, Bernhardt I., Fogelholm L, Herranen J, Penttilä I. Boreal freshwater fish diet modifies the plasma lipids and prostanoids and membrane fatty acids in man. Lipids 1988; 23(10): 924-929
26. Andrioli G, Carletto A, Guarini P., Galvani S, Biasi D, Bellavite P., Corrocher R. Differential effects of dietary supplementation with fish oil or soy lecithin on human platelet adhesion. Thromb Haemost 1999; 82(5): 1522-1527 (Pubitemid 29527649)
27. Bach R, Schmidt U, Jung F., Kiesewetter H, Hennen B, Wenzel E., Schieffer H, Bette L, Heyden S. Effects of fish oil capsules in two dosages on blood pressure, platelet functions, haemorheological and clinical chemistry parameters in apparently healthy subjects. Ann Nutr Metab 1989; 33(6): 359-367 (Pubitemid 20016378)
28. Coates AM, Sioutis S, Buckley J.D., Howe PR Regular consumption of n-3 fatty acid-enriched pork modifies cardiovascular risk factors. Br J Nutr 2009; 101(4): 592-597
29. Derosa G, Maffioli P, D'Angelo A., Salvadeo SA, Ferrari I, Fogari E, Gravina A., Mereu R, Randazzo S, Cicero AF Effects of long chain omega-3 fatty acids on metalloproteinases and their inhibitors in combined dyslipidemia patients. Expert Opin Pharmacother 2009; 10(8): 1239-1247
30. Mann NJ, O'Connell SL, Baldwin KM, Singh I, Meyer BJ Effects of seal oil and tuna-fish oil on platelet parameters and plasma lipid levels in healthy subjects. Lipids 2010; 45(8): 669-681
31. Mann N, Sinclair A, Pille M., Johnson L, Warrick G, Reder E., Lorenz R. The effect of short-term diets rich in fish, red meat, or white meat on thromboxane and prostacyclin synthesis in humans. Lipids 1997; 32(6): 635-644 (Pubitemid 27278575)
32. Mesa MD, Buckley R, Minihane A.M., Yaqoob P. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on the oxidizability and thrombogenicity of low-density lipoprotein. Atherosclerosis 2004; 175(2): 333-343 (Pubitemid 38942914)
33. Mori TA, Vandongen R, Mahanian F., Douglas A. Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation. Metabolism 1992; 41(10): 1059-1067
34. Myrup B, Rossing P, Jensen T., Parving HH, Hølmer G, Gram J, Kluft C, Jespersen J. Lack of effect of fish oil supplementation on coagulation and transcapillary escape rate of albumin in insulin-dependent diabetic patients with diabetic nephropathy. Scand J Clin Lab Invest 2001; 61(5): 349-356 (Pubitemid 32758450)
35. Schmidt EB, Kristensen SD, Dyerberg J. The effect of fish oil on lipids, coagulation and fibrinolysis in patients with angina pectoris. Artery 1988; 15(6): 316-329
36. Serebruany VL, Miller M, Pokov A.N., Lynch D., Jensen JK, Hallén J, Atar D. Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia. Cardiology 2011; 118(3): 187-194
37. Tremoli E, Maderna P, Marangoni F., Colli S, Eligini S, Catalano I., Angeli MT, Pazzucconi F, Gianfranceschi G, Davi G., Stragliotto E, Sirtori CR, Galli C. Prolonged inhibition of platelet aggregation after n-3 fatty acid ethyl ester ingestion by healthy volunteers. Am J Clin Nutr 1995; 61(3): 607-613
38. Tremoli E, Eligini S, Colli S., Maderna P, Risè P, Pazzucconi F, Marangoni F, Sirtori CR, Galli C. n-3 fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes. Arterioscler Thromb 1994; 14(10): 1600-1608
39. Véricel E., Calzada C, Chapuy P., Lagarde M. The influence of low intake of n-3 fatty acids on platelets in elderly people. Atherosclerosis 1999; 147(1): 187-192 (Pubitemid 29486788)
40. von Schacky C., Weber PC Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. J Clin Invest 1985; 76(6): 2446-2450 (Pubitemid 16155547)
41. Westerveld HT, de Graaf JC, van Breugel HH, Akkerman JW, Sixma JJ, Erkelens DW, Banga JD Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NI-DDM. Diabetes Care 1993; 16(5): 683-688 (Pubitemid 23127170)
42. Woodcock BE, Smith E, Lambert W.H., Jones WM, Galloway JH, Greaves M, Preston FE Beneficial effect of fish oil on blood viscosity in peripheral vascular disease. Br Med J (Clin Res Ed) 1984; 288(6417): 592-594 (Pubitemid 14081392)
43. Wright SA, O'Prey FM, McHenry MT, Leahey W.J., Devine AB, Duffy EM, Johnston DG, Finch M.B., Bell AL, McVeigh GE A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus. Ann Rheum Dis 2008; 67(6): 841-848 (Pubitemid 351829386)
44. Zucker ML, Bilyeu DS, Helmkamp G.M., Harris WS, Dujovne CA Effects of dietary fish oil on platelet function and plasma lipids in hyperlipoproteinemic and normal subjects. Atherosclerosis 1988; 73(1): 13-22
45. Toft I, Bønaa KH, Ingebretsen OC, Nordøy A, Jenssen T. Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids. Arterioscler Thromb Vasc Biol 1997; 17(5): 814-819 (Pubitemid 27209256)
46. Cobiac L, Clifton PM, Abbey M, Belling G.B., Nestel PJ Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n-3 fatty acids in mildly hyperlipidemic males. Am J Clin Nutr 1991; 53 (5): 1210-1216
47. Croset M, Véricel E, Rigaud M., Hanss M, Courpron P, Dechavanne M., Lagarde M. Functions and tocopherol content of blood platelets from elderly people after low intake of purified eicosapentaenoic acid. Thromb Res 1990; 57(1): 1-12 (Pubitemid 20023895)
48. De Caterina R., Caprioli R, Giannessi D., Sicari R, Galli C, Lazzerini G., Bernini W, Carr L, Rindi P. n-3 fatty acids reduce proteinuria in patients with chronic glomerular disease. Kidney Int 1993; 44(4): 843-850 (Pubitemid 23290527)
49. Driss F, Vericel E, Lagarde M., Dechavanne M, Darcet P. Inhibition of platelet aggregation and thromboxane synthesis after intake of small amount of icosapentaenoic acid. Thromb Res 1984; 36(5): 389-396 (Pubitemid 15194127)
50. Grundt H, Nilsen DW, Hetland O, Mansoor M.A., Aarsland T., Woie L. Atherothrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia. Thromb Haemost 1999; 81(4): 561-565 (Pubitemid 29178941)
51. Landgraf-Leurs M.M., Drummer C, Fröschl H, Steinhuber R., Von Schacky C, Landgraf R. Pilot study on omega-3 fatty acids in type I diabetes mellitus. Diabetes 1990; 39(3): 369-375 (Pubitemid 20076221)
52. Okumura T, Fujioka Y, Morimoto S., Tsuboi S, Masai M, Tsujino T., Ohyanagi M, Iwasaki T. Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability. Am J Med Sci 2002; 324(5): 247-253 (Pubitemid 35278769)
53. von Schacky C., Fischer S, Weber PC Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J Clin Invest 1985; 76(4): 1626-1631 (Pubitemid 16193585)
54. Sanders TA, Roshanai F. The influence of different types of omega 3 polyunsaturated fatty acids on blood lipids and platelet function in healthy volunteers. Clin Sci (Lond) 1983; 64(1): 91-99 (Pubitemid 13207257)
55. Haglund O, Mehta JL, Saldeen T. Effects of fish oil on some parameters of fibrinolysis and lipoprotein(a) in healthy subjects. Am J Cardiol 1994; 74(2): 189-192 (Pubitemid 24219314)
56. Fumeron F, Brigant L, Ollivier V., de Prost D, Driss F, Darcet P., Bard JM, Parra HJ, Fruchart JC, Apfelbaum M. n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men. Am J Clin Nutr 1991; 54(1): 118-122 (Pubitemid 21898925)
57. Goyens PL, Mensink RP Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects. Eur J Clin Nutr 2006; 60(8): 978-984 (Pubitemid 44161019)
58. Green D, Barreres L, Borensztajn J., Kaplan P, Reddy MN, Rovner R, Simon H. A double-blind, placebo-controlled trial of fish oil concentrate (MaxEpa) in stroke patients. Stroke 1985; 16(4): 706-709 (Pubitemid 15007250)
59. Hansen JB, Olsen JO, Wilsgård L, Lyngmo V., Svensson B. Comparative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on lipids, haemostasis and platelet function in normolipaemic men. Eur J Clin Nutr 1993; 47(7): 497-507 (Pubitemid 23234364)
60. Hendra TJ, Britton ME, Roper D.R., Wagaine-Twabwe D, Jeremy JY, Dandona P, Haines A.P., Yudkin JS Effects of fish oil supplements in NIDDM subjects. Controlled study. Diabetes Care 1990; 13(8): 821-829 (Pubitemid 20331535)
61. Pirich C, Gaszo A, Granegger S., Sinzinger H. Effects of fish oil supplementation on platelet survival and ex vivo platelet function in hypercholesterolemic patients. Thromb Res 1999; 96(3): 219-227 (Pubitemid 29531570)
62. Rizza S, Tesauro M, Cardillo C., Galli A, Iantorno M, Gigli F., Sbraccia P, Federici M, Quon M.J., Lauro D. Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Atherosclerosis 2009; 206(2): 569-574
63. Vognild E, Elvevoll EO, Brox J, Olsen R.L., Barstad H., Aursand M, Osterud B. Effects of dietary marine oils and olive oil on fatty acid composition, platelet membrane fluidity, platelet responses, and serum lipids in healthy humans. Lipids 1998; 33(4): 427-436 (Pubitemid 28217389)
64. Phang M, Sinclair AJ, Lincz L.F., Garg ML Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation. Nutr Metab Cardiovasc Dis 2012; 22(2): 109-114
65. Phang M, Lincz L, Seldon M., Garg ML Acute supplementation with eicosapentaenoic acid reduces platelet microparticle activity in healthy subjects. J Nutr Biochem 2012; 23(9): 1128-1133
66. Axelrod L, Camuso J, Williams E., Kleinman K, Briones E, Schoenfeld D. Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. Diabetes Care 1994; 17(1): 37-44
67. Berrettini M, Parise P, Ricotta S., Iorio A, Peirone C, Nenci GG Increased plasma levels of tissue factor pathway inhibitor (TF-PI) after n-3 polyunsaturated fatty acids supplementation in patients with chronic atherosclerotic disease. Thromb Haemost 1996; 75(3): 395-400 (Pubitemid 26099701)
68. Flaten H, Høstmark AT, Kierulf P, Lystad E, Trygg K, Bjerkedal T, Osland A. Fish-oil concentrate: effects on variables related to cardiovascular disease. Am J Clin Nutr 1990; 52(2): 300-306
69. Haberka M, Mizia-Stec K, Mizia M., Janowska J, Gieszczyk K, Chmiel A., Zahorska-Markiewicz B, Ga̧sior Z. N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction. Clin Nutr 2011; 30(1): 79-85
70. Honstra G, van Houwelingen AC, Kivits GA, Fischer S, Uedelhoven W. Influence of dietary fish on eicosanoid metabolism in man. Prostaglandins 1990; 40(3): 311-329 (Pubitemid 20284195)
71. Lau CS, McLaren M, Belch JJ Effects of fish oil on plasma fibrinolysis in patients with mild rheumatoid arthritis. Clin Exp Rheumatol 1995; 13(1): 87-90
72. Lindman AS, Pedersen JI, Hjerkinn E.M., Arnesen H., Veierød MB, Ellingsen I., Seljeflot I. The effects of long-term diet and omega-3 fatty acid supplementation on coagulation factor VII and serum phospholipids with special emphasis on the R353Q polymorphism of the FVII gene. Thromb Haemost 2004; 91(6): 1097-1104 (Pubitemid 38821265)
73. McVeigh GE, Brennan GM, Cohn J.N., Finkelstein SM, Hayes RJ, Johnston GD Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb 1994; 14(9): 1425-1429
74. Mehta JL, Lopez LM, Lawson D, Wargovich T.J., Williams LL Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease. Effects on indices of platelet and neutrophil function and exercise performance. Am J Med 1988; 84(1): 45-52
75. Moertl D, Berger R, Hammer A., Hutuleac R, Koppensteiner R, Kopp C.W., Steiner S. 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(3): 457-465
76. Mori TA, Beilin LJ, Burke V, Morris J., Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997; 17(2): 279-286 (Pubitemid 27098185)
77. Solomon SA, Cartwright I, Pockley G., Greaves M, Preston FE, Ramsay L.E., Waller PC A placebo-controlled, double-blind study of eicosapentaenoic acid-rich fish oil in patients with stable angina pectoris. Curr Med Res Opin 1990; 12(1): 1-11 (Pubitemid 20144343)
78. Wensing AG, Mensink RP, Hornstra G. Effects of dietary n-3 polyunsaturated fatty acids from plant and marine origin on platelet aggregation in healthy elderly subjects. Br J Nutr 1999; 82 (3): 183-191 (Pubitemid 29438387)
79. Woodman RJ, Mori TA, Burke V, Puddey I.B., Barden A., Watts GF, Beilin LJ Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 2003; 166(1): 85-93 (Pubitemid 35449604)
80. Grundt H, Nilsen DW, Mansoor M.A., Hetland Ø, Nordøy A. Reduction in homocysteine by n-3 polyunsaturated fatty acids after 1 year in a randomised double-blind study following an acute myocardial infarction: no effect on endothelial adhesion properties. Pathophysiol Haemost Thromb 2003; 33(2): 88-95 (Pubitemid 37449283)
81. Johansen O, Seljeflot I, Høstmark AT, Arnesen H. The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease. Arterioscler Thromb Vasc Biol 1999; 19(7): 1681-1686 (Pubitemid 29323826)
82. Krishnan PV, Anuradha S, Bhattacharjee J., Gaiha M. Effects of low dose omega-3 fatty acids on platelet functions and coagulation profile in Indian patients with type 2 diabetes mellitus with vascular complications: a prospective, preliminary study. J Indian Acad Clin Med 2007; 8(1): 45-52 (Pubitemid 46353886)
83. Brox JH, Killie JE, Gunnes S, Nordøy A. The effect of cod liver oil and corn oil on platelets and vessel wall in man. Thromb Haemost 1981; 46(3): 604-611 (Pubitemid 11026289)
84. Mehta J, Lawson D, Saldeen TJ Reduction in plasminogen activator inhibitor-1 (PAI-1) with omega-3 polyunsaturated fatty acid (PUFA) intake. Am Heart J 1988; 116(5 Pt 1): 1201-1206 (Pubitemid 18265638)
85. Nordøy A., Hatcher L, Goodnight S., Fitzgerald GA, Conner WE Effects of dietary fat content, saturated fatty acids, and fish oil on eicosanoid production and hemostatic parameters in normal men. J Lab Clin Med 1994; 123(6): 914-920
86. Wojenski CM, Silver MJ, Walker J. Eicosapentaenoic acid ethyl ester as an antithrombotic agent: comparison to an extract of fish oil. Biochim Biophys Acta 1991; 1081(1): 33-38
87. Agren JJ, Väisänen S, Hänninen O, Muller AD, Hornstra G. Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. Prostaglandins Leukot Essent Fatty Acids 1997; 57(4-5): 419-421 (Pubitemid 27504736)
88. Almdahl SM, Nilsen DW, Osterud B, Sørlie DG, Vaage J. Thromboplastin activities and monocytes in the coronary circulation of reperfused human myocardium. No effect of preoperative treatment with n-3 fatty acids. Scand J Thorac Cardiovasc Surg 1993; 27(2): 81-86 (Pubitemid 23218300)
89. Conquer JA, Holub BJ Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr 1996; 126(12): 3032-3039 (Pubitemid 27023877)
90. Conquer JA, Cheryk LA, Chan E, Gentry P.A., Holub BJ Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects. Thromb Res 1999; 96(3): 239-250 (Pubitemid 29531572)
91. Demke DM, Peters GR, Linet O.I., Metzler CM, Klott KA Effects of a fish oil concentrate in patients with hypercholesterolemia. Atherosclerosis 1988; 70(1-2): 73-80 (Pubitemid 18091704)
92. Donnelly SM, Ali MA, Churchill DN Effect of n-3 fatty acids from fish oil on hemostasis, blood pressure, and lipid profile of dialysis patients. J Am Soc Nephrol 1992; 2(11): 1634-1639
93. Gajos G, Zalewski J, Rostoff P., Nessler J, Piwowarska W, Undas A. Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI clot). Arterioscler Thromb Vasc Biol 2011; 31(7): 1696-1702
94. Goodfellow J, Bellamy MF, Ramsey M.W., Jones CJ, Lewis MJ Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 2000; 35(2): 265-270 (Pubitemid 30125512)
95. Grundt H, Hetland Ø, Nilsen DW. Changes in tissue factor and activated factor XII following an acute myocardial infarction were uninfluenced by high doses of n-3 polyunsaturated fatty acids. Thromb Haemost 2003; 89(4): 752-759 (Pubitemid 36456974)
96. Hagve TA, Lie O, Grønn M. The effect of dietary N-3 fatty acids on osmotic fragility and membrane fluidity of human erythrocytes. Scand J Clin Lab Invest Suppl 1993; 215: 75-84 (Pubitemid 23204331)
97. Haines AP, Sanders TA, Imeson J.D., Mahler RF, Martin J, Mistry M, Vickers M., Wallace PG Effects of a fish oil supplement on platelet function, haemostatic variables and albuminuria in insulin-dependent diabetics. Thromb Res 1986; 43(6): 643-655 (Pubitemid 16049219)
98. Hellsten G, Boman K, Saarem K., Hallmans G, Nilsson TK Effects on fibrinolytic activity of corn oil and a fish oil preparation enriched with omega-3-polyunsaturated fatty acids in a long-term study. Curr Med Res Opin 1993; 13(3): 133-139 (Pubitemid 23256075)
99. Montegaard C, Tulk HM, Lauritzen L, Tholstrup T., Robinson LE Acute ingestion of long-chain (n-3) polyunsaturated fatty acids decreases fibrinolysis in men with metabolic syndrome. J Nutr 2010; 140(1): 38-43
100. Neff LM, Culiner J, Cunningham-Rundles S, Seidman C., Meehan D, Maturi J, Wittkowski K.M., Levine B., Breslow JL Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. J Nutr 2011; 141(2): 207-213
101. Nilsen DW, Dalaker K, Nordøy A, Osterud B., Ingebretsen OC, Lyngmo V, Almdahl S, Vaage J., Rasmussen K. Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery. Thromb Haemost 1991; 66(2): 195-201
102. Poppitt SD, Howe CA, Lithander F.E., Silvers KM, Lin RB, Croft J, Ratnasabapathy Y., Gibson RA, Anderson CS Effects of moderate-dose omega-3 fish oil on cardiovascular risk factors and mood after ischemic stroke: a randomized, controlled trial. Stroke 2009; 40(11): 3485-3492
103. Prisco D, Paniccia R, Filippini M., Francalanci I, Bandinelli B, Comeglio P., Rostagno C, Abbate R, Neri Serneri GG. No changes in PAI-1 levels after four-month n-3 PUFA ethyl ester supplementation in healthy subjects. Thromb Res 1994; 76(3): 237-244 (Pubitemid 24327491)
104. Saifullah A, Watkins BA, Saha C, Li Y., Moe SM, Friedman AN Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in haemodialysis patients - a pilot study. Nephrol Dial Transplant 2007; 22(12): 3561-3567 (Pubitemid 350212489)
105. Sanders TA, Hall WL, Maniou Z, Lewis F., Seed PT, Chowienczyk PJ Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial. Am J Clin Nutr 2011; 94(4): 973-980
106. Sirtori CR, Gatti E, Tremoli E., Galli C, Gianfranceschi G, Franceschini G., Colli S, Maderna P, Marangoni F., Perego P, Stragliotto E. Olive oil, corn oil, and n-3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia. Am J Clin Nutr 1992; 56(1): 113-122
107. DeCaterina R, Giannessi D, Mazzone A., Bernini W, Lazzerini G, Maffei S., Cerri M, Salvatore L, Weksler B. Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery. Circulation 1990; 82(2): 428-438 (Pubitemid 20257821)
108. Din JN, Harding SA, Valerio C.J., Sarma J., Lyall K, Riemersma RA, Newby D.E., Flapan AD Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. Atherosclerosis 2008; 197(1): 290-296 (Pubitemid 351284475)
109. Nelson GJ, Schmidt PS, Bartolini G.L., Kelley DS, Kyle D. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 1997; 32(11): 1129-1136 (Pubitemid 27508104)
110. Boberg M, Pollare T, Siegbahn A., Vessby B. Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1992; 22(10): 645-650
111. Park Y, Harris WS Dose-dependent effects of n-3 polyunsaturated fatty acids on platelet activation in mildly hypertriglyceridemic subjects. J Med Food 2009; 12(4): 809-813
112. Brox J, Olaussen K, Osterud B., Elvevoll EO, Bjørnstad E, Brattebøg G, Iversen H. A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. Lipids 2001; 36 (1): 7-13 (Pubitemid 32163616)
113. Brox JH, Killie JE, Osterud B, Holme S., Nordøy A. Effects of cod liver oil on platelets and coagulation in familial hypercholesterolemia (type IIa). Acta Med Scand 1983; 213(2): 137-144 (Pubitemid 13144395)
114. Hwang DH, Chanmugam PS, Ryan D.H., Boudreau MD, Windhauser MM, Tulley RT, Brooks ER, Bray GA. Does vegetable oil attenuate the beneficial effects of fish oil in reducing risk factors for cardiovascular disease? Am J Clin Nutr 1997; 66(1): 89-96 (Pubitemid 27278904)
115. Gajos G, Rostoff P, Undas A., Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol 2010; 55(16): 1671-1678
116. Ahmed AA, Holub BJ Alteration and recovery of bleeding times, platelet aggregation and fatty acid composition of individual phospholipids in platelets of human subjects receiving a supplement of cod-liver oil. Lipids 1984; 19(8): 617-624 (Pubitemid 14034537)
117. Atkinson PM, Wheeler MC, Mendelsohn D, Pienaar N., Chetty N. Effects of a 4-week freshwater fish (trout) diet on platelet aggregation, platelet fatty acids, serum lipids, and coagulation factors. Am J Hematol 1987; 24(2): 143-149 (Pubitemid 17020781)
118. Bakken AM, Farstad M, Holmsen H. Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles. J Appl Physiol 1991; 70(6): 2669-2672
119. Bakken AM, Hervig T, Thorsen T., Holmsen H. Fatty acids in human platelets and plasma. Dietary seal oil decreases sensitivity toward microbubbles. Platelets 1995; 6(5): 259-264
120. Beitz J, Schimke E, Liebaug U., Block HU, Beitz A, Honigmann G, Sziegoleit W., Müller G, Mest HJ. Influence of a cod liver oil diet in healthy and insulin-dependent diabetic volunteers on fatty acid pattern, inhibition of prostacyclin formation by low density lipoprotein (LDL) and platelet thromboxane. Klin Wochenschr 1986; 64(17): 793-799 (Pubitemid 16044199)
121. Bradlow BA, Chetty N, van der Westhuyzen J, Mendelsohn D, Gibson JE. The effects of a mixed fish diet on platelet function, fatty acids and serum lipids. Thromb Res 1983; 29(6): 561-568 (Pubitemid 13080948)
122. Brister SJ, Buchanan MR Effects of linoleic acid and/or marine fish oil supplements on vessel wall thromboresistance in patients undergoing cardiac surgery. Adv Exp Med Biol 1997; 433: 275-278 (Pubitemid 28231830)
123. Brown AJ, Roberts DC Fish and fish oil intake: effect on haematological variables related to cardiovascular disease. Thromb Res 1991; 64(2): 169-178
124. Eritsland J, Arnesen H, Smith P., Seljeflot I, Dahl K. Effects of highly concentrated omega-3 polyunsaturated fatty acids and acetylsalicylic acid, alone and combined, on bleeding time and serum lipid profile. J Oslo City Hosp 1989; 39(8-9): 97-101
125. Fischer S, Weber PC Thromboxane A3 (TXA3) is formed in human platelets after dietary eicosapentaenoic acid (C20:5 omega 3). Biochem Biophys Res Commun 1983; 116(3): 1091-1099 (Pubitemid 14202690)
126. Gibney MJ, Bolton-Smith C. The effect of a dietary supplement of n-3 polyunsaturated fat on platelet lipid composition, platelet function and platelet plasma membrane fluidity in healthy volunteers. Br J Nutr 1988; 60(1): 5-12
127. Harris WS, Rothrock DW, Fanning A, Inkeles S.B., Goodnight SH Jr, Illingworth DR, Connor WE Fish oils in hypertriglyceridemia: a dose-response study. Am J Clin Nutr 1990; 51(3): 399-406
128. Hawthorne AB, Filipowicz BL, Edwards T.J., Hawkey CJ High dose eicosapentaenoic acid ethyl ester: effects on lipids and neutrophil leukotriene production in normal volunteers. Br J Clin Pharmacol 1990; 30(2): 187-194 (Pubitemid 20237890)
129. Hirai A, Terano T, Hamazaki T., Sajiki J, Kondo S, Ozawa A., Fujita T, Miyamoto T, Tamura Y., Kumagai A. The effects of the oral administration of fish oil concentrate on the release and the metabolism of [14C]arachidonic acid and [14C]eicosapentaenoic acid by human platelets. Thromb Res 1982; 28(3): 285-298 (Pubitemid 13254963)
130. Hirai A, Terano T, Takenaga M., Kobayashi S, Makuta H, Ozawa A., Fujita T, Tamura Y, Kitagawa H., Kumagai A, Yoshida S. Effect of supplementation of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemostatic function in healthy subjects. Adv Prostaglandin Thromboxane Leukot Res 1987; 17B: 838-845
131. Hirai A, Terano T, Makuta H., Ozawa A, Fujita T, Tamura Y Yoshida S. Effect of oral administration of highly purified eicosapentaenoic acid and docosahexaenoic acid on platelet function and serum lipids in hyperlipidemic patients. Adv Prostaglandin Thromboxane Leukot Res 1989; 19: 627-630
132. Kobayashi S, Hamazaki T, Sawazaki S., Nakamura H. Reduction in the ADP release from shear-stressed red blood cells by fish oil administration. Thromb Res 1992; 65(3): 353-364
133. Lands WE, Culp BR, Hirai A, Gorman R. Relationship of thromboxane generation to the aggregation of platelets from humans: effects of eicosapentaenoic acid. Prostaglandins 1985; 30(5): 819-825 (Pubitemid 16199283)
134. Lorenz R, Spengler U, Fischer S., Duhm J, Weber PC Platelet function, thromboxane formation and blood pressure control during supplementation of the Western diet with cod liver oil. Circulation 1983; 67(3): 504-511 (Pubitemid 13144730)
135. Lox CD. The effects of dietary marine fish oils (omega-3 fatty acids) on coagulation profiles in men. Gen Pharmacol 1990; 21 (2): 241-246 (Pubitemid 20097410)
136. Lund EK, Harvey LJ, Ladha S, Clark D.C., Johnson IT Effects of dietary fish oil supplementation on the phospholipid composition and fluidity of cell membranes from human volunteers. Ann Nutr Metab 1999; 43(5): 290-300 (Pubitemid 30072407)
137. Nelson GJ, Schmidt PC, Corash L. The effect of a salmon diet on blood clotting, platelet aggregation and fatty acids in normal adult men. Lipids 1991; 26(2): 87-96
138. Nomura S, Kanazawa S, Fukuhara S. Effects of eicosapentaenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with Type 2 diabetes mellitus. J Diabetes Complications 2003; 17(3): 153-159 (Pubitemid 36547817)
139. Olivieri O, Negri M, De Gironcoli M, Bassi A, Guarini P., Stanzial AM, Grigolini L, Ferrari S, Corrocher R. Effects of dietary fish oil on malondialdehyde production and glutathione peroxidase activity in hyperlipidaemic patients. Scand J Clin Lab Invest 1988; 48(7): 659-665
140. Pschierer V, Richter WO, Schwandt P. Primary chylomicronemia in patients with severe familial hypertriglyceridemia responds to long-term treatment with (n-3) fatty acids. J Nutr 1995; 125(6): 1490-1494
141. Rylance PB, George MP, Saynor R, Weston MJ A pilot study of the use of MaxEPA in haemodialysis patients. Br J Clin Pract Suppl 1984; 31: 49-54
142. Rylance PB, Gordge MP, Saynor R, Parsons V., Weston MJ Fish oil modifies lipids and reduces platelet aggregability in haemodialysis patients. Nephron 1986; 43(3): 196-202 (Pubitemid 16084319)
143. Sakamoto N, Nishiike T, Iguchi H., Sakamoto K. Effects of eicosapentaenoic acid intake on plasma fibrinolytic and coagulation activity by using physical load in the young. Nutrition 2000; 16(1): 11-14 (Pubitemid 30050718)
144. Sanders TA, Hinds A. The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers. Br J Nutr 1992; 68(1): 163-173
145. Sanders TA, Hochland MC A comparison of the influence on plasma lipids and platelet function of supplements of omega 3 and omega 6 polyunsaturated fatty acids. Br J Nutr 1983; 50(3): 521-529 (Pubitemid 14243307)
146. 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; 50(1): 3-10 (Pubitemid 14224339)
147. Singer P, Berger I, Lück K, Taube C., Naumann E, Gödicke W. Long-term effect of mackerel diet on blood pressure, serum lipids and thromboxane formation in patients with mild essential hypertension. Atherosclerosis 1986; 62(3): 259-265 (Pubitemid 17208645)
148. Smith P, Arnesen H, Opstad T., Dahl KH, Eritsland J. Influence of highly concentrated n-3 fatty acids on serum lipids and hemostatic variables in survivors of myocardial infarction receiving either oral anticoagulants or matching placebo. Thromb Res 1989; 53(5): 467-474 (Pubitemid 19114480)
149. Tagawa H, Shimokawa H, Tagawa T., Kuroiwa-Matsumoto M, Hirooka Y, Takeshita A. Long-term treatment with eicosapentaenoic acid augments both nitric oxide-mediated and non-nitric oxide-mediated endothelium-dependent forearm vasodilatation in patients with coronary artery disease. J Cardiovasc Pharmacol 1999; 33(4): 633-640 (Pubitemid 29164828)
150. Takimoto G, Galang J, Lee G.K., Bradlow BA Plasma fibrinolytic activity after ingestion of omega-3 fatty acids in human subjects. Thromb Res 1989; 54(6): 573-582 (Pubitemid 19170992)
151. Tamura Y, Hirai A, Terano T., Kumagai A, Yoshida S. Effects of eicosapentaenoic acid on hemostatic function and serum lipids in humans. Adv Prostaglandin Thromboxane Leukot Res 1985; 15: 265-267
152. Tamura Y, Hirai A, Terano T., Yoshida S, Takenaga M, Kitagawa H. Anti-thrombotic and anti-atherogenic action of eicosapentaenoic acid. Jpn Circ J 1987; 51(4): 471-477 (Pubitemid 17150211)
153. 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; 46(3): 321-331 (Pubitemid 13148186)
154. Thorngren M, Gustafson A. Effects of 11-week increases in dietary eicosapentaenoic acid on bleeding time, lipids, and platelet aggregation. Lancet 1981; 2(8257): 1190-1193 (Pubitemid 12228352)
155. Thorngren M, Shafi S, Born GV Delay in primary haemostasis produced by a fish diet without change in local thromboxane A2. Br J Haematol 1984; 58(4): 567-578 (Pubitemid 15175996)
156. Tremoli E, Mosconi C, Maderna P., Colli S, Stragliotto E, Sirtori C.R., Galli C. Effects of EPA and DHA ethylesters on plasma fatty acids and on platelets, PMN and monocytes in healthy volunteers. Adv Prostaglandin Thromboxane Leukot Res 1991; 21A: 233-236
157. Tsuruta K, Ogawa H, Yasue H., Sakamoto T, Miyao Y, Tanae H., Kaiga K. Effect of purified eicosapentaenoate ethyl ester on fibrinolytic capacity in patients with stable coronary artery disease and lower extremity ischaemia. Coron Artery Dis 1996; 7 (11): 837-842 (Pubitemid 27020357)
158. Turini ME, Powell WS, Behr S.R., Holub BJ Effects of a fsh-oil and vegetable-oil formula on aggregation and ethanolamine-containing lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils. Am J Clin Nutr 1994; 60(5): 717-724
159. Vanschoonbeek K, Feijge MA, Paquay M, Rosing J., Saris W, Kluft C, Giesen P.L., de Maat MP, Heemskerk JW Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol 2004; 24(9): 1734-1740 (Pubitemid 39180903)
160. Yao JK, Magan S, Sonel A.F., Gurklis JA, Sanders R, Reddy RD Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia. Prostaglandins Leukot Essent Fatty Acids 2004; 71(3): 171-176 (Pubitemid 38903062)
161. Yosefy C, Viskoper JR, Varon D, Ilan Z., Pilpel D, Lugassy G, Schneider R., Savyon N, Adan Y, Raz A. Repeated fasting and refeeding with 20:5, n-3 eicosapentaenoic acid (EPA): a novel approach for rapid fatty acid exchange and its effect on blood pressure, plasma lipids and hemostasis. J Hum Hypertens 1996; 10 Suppl 3: S135-S139 (Pubitemid 26312946)
162. Yoshimura T, Matsui K, Ito M., Yunohara T, Kawasaki N, Nakamura T., Okamura H. Effects of highly purified eicosapentaenoic acid on plasma beta thromboglobulin level and vascular reactivity to angiotensin II. Artery 1987; 14(5): 295-303 (Pubitemid 17119028)
163. Baumann KH, Hessel F, Larass I., Müller T, Angerer P., Kiefl R, von Schacky C. Dietary omega-3, omega-6, and omega-9 un-saturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study. Arterioscler Thromb Vasc Biol 1999; 19 (1): 59-66 (Pubitemid 29031913)
164. Eritsland J, Seljeflot I, Abdelnoor M., Arnesen H. Long-term influence of omega-3 fatty acids on fibrinolysis, fibrinogen, and serum lipids. Fibrinolysis 1994; 8(2): 120-125 (Pubitemid 24095971)
165. Gazso A, Kaliman J, Horrobin D., Sinzinger H. Effects of omega-3 fatty acids on the prostaglandin system in healthy volunteers. Prog Clin Biol Res 1989; 301: 517-521