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http://dx.doi.org/10.4163/jnh.2013.46.3.226

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  

Jeong, Sewon (Biofood CRO Co., Ltd.)
Kim, Ji Yeon (Department of Food Science and Technology, Seoul National University of Science and Technology)
Paek, Ju Eun (Biofood Network Center, Ewha Womans University)
Kim, Joohee (Biofood Network Center, Ewha Womans University)
Kwak, Jin Sook (Biofood CRO Co., Ltd.)
Kwon, Oran (Biofood Network Center, Ewha Womans University)
Publication Information
Journal of Nutrition and Health / v.46, no.3, 2013 , pp. 226-238 More about this Journal
Abstract
Omega-3 polyunsaturated fatty acids are essential fatty acids because humans cannot synthesize them de novo and must obtain them in their diet. Fish and fish oil are rich sources of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Significant evidence of the beneficial role of dietary intake of omega-3 fatty acids in blood flow has been reported and putative mechanisms for improvement of blood flow include anti-thrombotic effects, lowered blood pressure, improved endothelial function, and anti-atherogenic effects. Edible oils containing omega-3 fatty acids were registered as functional ingredients in the Korea Health Functional Food Code. Although omega-3 fatty acids have been evaluated by the Korea Food and Drug Administration (KFDA) based on scientific evidence, periodic re-evaluation may be needed because emerging data related to omega-3 fatty acids have accumulated. Therefore, in this study, we re-evaluated scientific evidence for the effect of omega-3 fatty acids as a functional ingredient in health functional food on improvement of blood flow. A comprehensive literature search was conducted for collection of relevant human studies using the Medline and Cochrane, KISS, and IBIDS databases for the years 1955-2012. Search keywords were used by combination of terms related to omega-3 fatty acids and blood flow. The search was limited to human studies published in Korean, English, and Japanese. Using the KFDA's evidence based evaluation system for scientific evaluation of health claims, 112 human studies were identified and reviewed in order to evaluate the strength of the evidence supporting a relation between omega-3 fatty acids and blood flow. Among 112 studies, significant effects on improvement of blood flow were reported in 84 studies and the daily intake amount was ranged from 0.1 to 15 g. According to this methodology of systematic review, we concluded that there was possible evidence to support a relation between omega-3 fatty acid intake and blood flow. However, because inconsistent results have recently been reported, future studies should be monitored.
Keywords
systematic review; omega-3 fatty acids; blood flow; DHA; EPA; health functional food; re-evaluation;
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1 Baldassarre D, Amato M, Eligini S, Barbieri SS, Mussoni L, Frigerio B, Kozakova 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   DOI   ScienceOn
2 Blonk MC, Bilo HJ, Nauta JJ, 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
3 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   DOI
4 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   DOI
5 Finnegan YE, Howarth D, Minihane AM, 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
6 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
7 Grundt H, Nilsen DW, Hetland O, Mansoor MA. Clinical outcome and atherothrombogenic risk profile after prolonged washout following long-term treatment with high doses of n-3 PUFAs in patients with an acute myocardial infarction. Clin Nutr 2004; 23(4): 491-500   DOI   ScienceOn
8 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   DOI   ScienceOn
9 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   DOI   ScienceOn
10 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
11 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
12 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   DOI   ScienceOn
13 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   DOI   ScienceOn
14 Takimoto G, Galang J, Lee GK, Bradlow BA. Plasma fibrinolytic activity after ingestion of omega-3 fatty acids in human subjects. Thromb Res 1989; 54(6): 573-582   DOI   ScienceOn
15 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
16 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   DOI
17 Hawthorne AB, Filipowicz BL, Edwards TJ, 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   DOI   ScienceOn
18 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   DOI   ScienceOn
19 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   DOI   ScienceOn
20 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   DOI   ScienceOn
21 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
22 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   DOI   ScienceOn
23 Brox J, Olaussen K, Osterud B, Elvevoll EO, Bjornstad E, Brattebøg G, Iversen H. A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. Lipids 2001; 36 (1): 7-13   DOI   ScienceOn
24 Nelson GJ, Schmidt PS, Bartolini GL, 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   DOI   ScienceOn
25 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   DOI   ScienceOn
26 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   DOI
27 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
28 Hwang DH, Chanmugam PS, Ryan DH, 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
29 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
30 Conquer JA, Cheryk LA, Chan E, Gentry PA, 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   DOI   ScienceOn
31 Turini ME, Powell WS, Behr SR, Holub BJ. Effects of a fish-oil and vegetable-oil formula on aggregation and ethanolaminecontaining lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils. Am J Clin Nutr 1994; 60(5): 717-724
32 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   DOI   ScienceOn
33 Tremoli E, Mosconi C, Maderna P, Colli S, Stragliotto E, Sirtori CR, 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
34 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   DOI
35 Vanschoonbeek K, Feijge MA, Paquay M, Rosing J, Saris W, Kluft C, Giesen PL, 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   DOI   ScienceOn
36 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
37 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   DOI
38 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
39 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
40 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   DOI
41 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
42 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
43 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   DOI   ScienceOn
44 Brown AJ, Roberts DC. Fish and fish oil intake: effect on haematological variables related to cardiovascular disease. Thromb Res 1991; 64(2): 169-178   DOI   ScienceOn
45 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   DOI
46 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   DOI   ScienceOn
47 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   DOI
48 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
49 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   DOI   ScienceOn
50 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   DOI   ScienceOn
51 Harris WS, Rothrock DW, Fanning A, Inkeles SB, Goodnight SH Jr, Illingworth DR, Connor WE. Fish oils in hypertriglyceridemia: a dose-response study. Am J Clin Nutr 1990; 51(3): 399-406
52 Goodfellow J, Bellamy MF, Ramsey MW, 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   DOI   ScienceOn
53 Demke DM, Peters GR, Linet OI, Metzler CM, Klott KA. Effects of a fish oil concentrate in patients with hypercholesterolemia. Atherosclerosis 1988; 70(1-2): 73-80   DOI
54 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
55 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   DOI   ScienceOn
56 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
57 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
58 Haines AP, Sanders TA, Imeson JD, 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   DOI   ScienceOn
59 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   DOI
60 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   DOI
61 Phang M, Sinclair AJ, Lincz LF, Garg ML. Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation. Nutr Metab Cardiovasc Dis 2012; 22(2): 109-114   DOI   ScienceOn
62 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   DOI   ScienceOn
63 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   DOI   ScienceOn
64 Berrettini M, Parise P, Ricotta S, Iorio A, Peirone C, Nenci GG. Increased plasma levels of tissue factor pathway inhibitor (TFPI) after n-3 polyunsaturated fatty acids supplementation in patients with chronic atherosclerotic disease. Thromb Haemost 1996; 75(3): 395-400
65 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
66 Haberka M, Mizia-Stec K, Mizia M, Janowska J, Gieszczyk K, Chmiel A, Zahorska-Markiewicz B, Gąsior 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   DOI   ScienceOn
67 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   DOI
68 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   DOI   ScienceOn
69 Rizza S, Tesauro M, Cardillo C, Galli A, Iantorno M, Gigli F, Sbraccia P, Federici M, Quon MJ, Lauro D. Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Atherosclerosis 2009; 206(2): 569-574
70 Vognild E, Elvevoll EO, Brox J, Olsen RL, 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   DOI   ScienceOn
71 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   DOI   ScienceOn
72 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   DOI
73 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 NIDDM. Diabetes Care 1993; 16(5): 683-688   DOI   ScienceOn
74 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   DOI   ScienceOn
75 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   DOI   ScienceOn
76 Park Y, Harris W. EPA, but not DHA, decreases mean platelet volume in normal subjects. Lipids 2002; 37(10): 941-946   DOI   ScienceOn
77 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
78 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   DOI   ScienceOn
79 Freese R, Mutanen M. Alpha-linolenic acid and marine longchain 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
80 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   DOI   ScienceOn
81 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   DOI
82 Baumann KH, Hessel F, Larass I, Müller T, Angerer P, Kiefl R, von Schacky C. Dietary omega-3, omega-6, and omega-9 unsaturated 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   DOI   ScienceOn
83 Yao JK, Magan S, Sonel AF, 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   DOI   ScienceOn
84 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
85 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
86 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
87 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
88 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   DOI   ScienceOn
89 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   DOI   ScienceOn
90 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
91 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   DOI   ScienceOn
92 Lund EK, Harvey LJ, Ladha S, Clark DC, 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   DOI   ScienceOn
93 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   DOI   ScienceOn
94 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   DOI   ScienceOn
95 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   DOI
96 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
97 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   DOI
98 Poppitt SD, Howe CA, Lithander FE, 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   DOI   ScienceOn
99 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   DOI   ScienceOn
100 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   DOI   ScienceOn
101 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
102 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   DOI   ScienceOn
103 Din JN, Harding SA, Valerio CJ, Sarma J, Lyall K, Riemersma RA, Newby DE, Flapan AD. Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. Atherosclerosis 2008; 197(1): 290-296
104 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   DOI   ScienceOn
105 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   DOI   ScienceOn
106 Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D, Maturi J, Wittkowski KM, 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   DOI   ScienceOn
107 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
108 Solomon SA, Cartwright I, Pockley G, Greaves M, Preston FE, Ramsay LE, 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   DOI
109 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
110 Woodman RJ, Mori TA, Burke V, Puddey IB, 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
111 McVeigh GE, Brennan GM, Cohn JN, Finkelstein SM, Hayes RJ, Johnston GD. Fish oil improves arterial compliance in noninsulin- dependent diabetes mellitus. Arterioscler Thromb 1994; 14(9): 1425-1429   DOI
112 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
113 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
114 Lindman AS, Pedersen JI, Hjerkinn EM, 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
115 Mehta JL, Lopez LM, Lawson D, Wargovich TJ, 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
116 Moertl D, Berger R, Hammer A, Hutuleac R, Koppensteiner R, Kopp CW, 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   DOI
117 Landgraf-Leurs MM, 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   DOI
118 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   DOI   ScienceOn
119 Wright SA, O'Prey FM, McHenry MT, Leahey WJ, Devine AB, Duffy EM, Johnston DG, Finch MB, 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   DOI   ScienceOn
120 Woodcock BE, Smith E, Lambert WH, 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   DOI
121 Zucker ML, Bilyeu DS, Helmkamp GM, 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   DOI
122 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   DOI   ScienceOn
123 Cobiac L, Clifton PM, Abbey M, Belling GB, 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
124 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
125 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   DOI   ScienceOn
126 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   DOI   ScienceOn
127 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
128 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   DOI
129 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   DOI   ScienceOn
130 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   DOI
131 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   DOI
132 Coates AM, Sioutis S, Buckley JD, Howe PR. Regular consumption of n-3 fatty acid-enriched pork modifies cardiovascular risk factors. Br J Nutr 2009; 101(4): 592-597
133 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   DOI
134 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   DOI
135 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
136 Grundt H, Nilsen DW, Mansoor MA, 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   DOI   ScienceOn
137 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   DOI   ScienceOn
138 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
139 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   DOI   ScienceOn
140 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
141 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   DOI   ScienceOn
142 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   DOI   ScienceOn
143 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
144 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   DOI
145 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
146 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   DOI   ScienceOn
147 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   DOI   ScienceOn
148 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   DOI   ScienceOn
149 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
150 Hendra TJ, Britton ME, Roper DR, Wagaine-Twabwe D, Jeremy JY, Dandona P, Haines AP, Yudkin JS. Effects of fish oil supplements in NIDDM subjects. Controlled study. Diabetes Care 1990; 13(8): 821-829   DOI   ScienceOn
151 Holub BJ. Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. CMAJ 2002; 166(5): 608-615
152 Grundt H, Nilsen DW, Hetland O, Mansoor MA, 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
153 Kris-Etherton PM, 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   DOI   ScienceOn
154 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   DOI   ScienceOn
155 Connor WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr 2000; 71(1 Suppl): 171S-175S
156 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/GuidanceDocuments RegulatoryInformation/LabelingNutrition/ucm073332.htm
157 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 (CAC/ 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
158 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/
159 Mesa MD, Buckley R, Minihane AM, 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
160 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   DOI   ScienceOn
161 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   DOI   ScienceOn
162 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   DOI
163 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
164 Serebruany VL, Miller M, Pokov AN, 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   DOI   ScienceOn
165 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