The evidence for α-Linolenic acid and cardiovascular disease benefits: Comparisons with eicosapentaenoic acid and docosahexaenoic acid

Advances in Nutrition

Volumn 5, Issue 6, 2014, Pages 863S-876S

  Fleming, Jennifer A ^a   Kris Etherton, Penny M ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOCOSAHEXAENOIC ACID; ICOSAPENTAENOIC ACID; LINOLENIC ACID;

CARDIOVASCULAR DISEASES; COMPARATIVE STUDY; DIET; DIET SUPPLEMENTATION; DIETARY REFERENCE INTAKE; EVIDENCE BASED MEDICINE; HUMAN; INFLAMMATION; META ANALYSIS (TOPIC); OBSERVATIONAL STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ALPHA-LINOLENIC ACID; CARDIOVASCULAR DISEASES; DIET; DIETARY SUPPLEMENTS; DOCOSAHEXAENOIC ACIDS; EICOSAPENTAENOIC ACID; EVIDENCE-BASED MEDICINE; HUMANS; INFLAMMATION; META-ANALYSIS AS TOPIC; OBSERVATIONAL STUDIES AS TOPIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECOMMENDED DIETARY ALLOWANCES;

EID: 84910631338     PISSN: 21618313     EISSN: 21565376     Source Type: Journal    
DOI: 10.3945/an.114.005850     Document Type: Article

References (121)

1. Skeaff CM, Miller J. Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomised controlled trials. Ann Nutr Metab 2009;55:173-201.
2. Erkkilä A, de Mello VD, Riserus U, Laaksonen DE. Dietary fatty acids and cardiovascular disease: an epidemiological approach. Prog Lipid Res 2008;47:172-87.
3. Baum SJ, Kris-Etherton PM, Willett WC, Lichtenstein AH, Rudel LL, Maki KC, Whelan J, Ramsden CE, Block RC. Fatty acids in cardiovascular health and disease: a comprehensive update. J Clin Lipidol 2012; 6:216-34.
4. Willett WC. Dietary fats and coronary heart disease. J Intern Med 2012;272:13-24.
5. Rennison JH, Van Wagoner DR. Impact of dietary fatty acids on cardiac arrhythmogenesis. Circ Arrhythm Electrophysiol 2009;2:460-9.
6. Pan A, Chen M, Chowdhury R,Wu JH, Sun Q, Campos H,Mozaffarian D, Hu FB. a-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 2012;96:1262-73.
7. Connor SL, Gustafson JR, Sexton G, Becker N, Artaud-Wild S, Connor WE. The Diet Habit Survey: a new method of dietary assessment that relates to plasma cholesterol changes. J Am Diet Assoc 1992;92:41-7.
8. Benolken RM, Anderson RE, Wheeler TG. Membrane fatty acids associated with the electrical response in visual excitation. Science 1973;182:1253-4.
9. Bourre JM, Francois M, Youyou A, Dumont O, Piciotti M, Pascal G, Durand G. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 1989;119:1880-92.
10. Neuringer M, Connor WE, Van Petten C, Barstad L. Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest 1984;73:272-6.
11. Neuringer M, Connor WE, Lin DS, Barstad L, Luck S. Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci USA 1986;83:4021-5.
12. Wheeler TG, Benolken RM, Anderson RE. Visual membranes: specificity of fatty acid precursors for the electrical response to illumination. Science 1975;188:1312-4.
13. Astorg P, Arnault N, Czernichow S, Noisette N, Galan P, Hercberg S. Dietary intakes and food sources of n-6 and n-3 PUFA in French adult men and women. Lipids 2004;39:527-35.
14. Jeffrey BG, Weisinger HS, Neuringer M, Mitchell DC. The role of docosahexaenoic acid in retinal function. Lipids 2001;36:859-71.
15. Mitchell DC, Niu SL, Litman BJ. Enhancement of G protein-coupled signaling by DHA phospholipids. Lipids 2003;38:437-43.
16. Vinton NE, Heckenlively JR, Laidlaw SA, Martin DA, Foxman SR, Ament ME, Kopple JD. Visual function in patients undergoing longterm total parenteral nutrition. Am J Clin Nutr 1990;52:895-902.
17. Burdge GC, Calder PC. Dietary alpha-linolenic acid and health-related outcomes: a metabolic perspective. Nutr Res Rev 2006;19:26-52.
18. Mozaffarian D. Does alpha-linolenic acid intake reduce the risk of coronary heart disease? A review of the evidence. Altern Ther Health Med 2005;11(3):24-30; quiz 1, 79.
19. Campos H, Baylin A, Willett WC. Alpha-linolenic acid and risk of nonfatal acute myocardial infarction. Circulation 2008;118:339-45.
20. de Goede J, Verschuren WM, Boer JM, Kromhout D, Geleijnse JM. Alpha-linolenic acid intake and 10-year incidence of coronary heart disease and stroke in 20,000 middle-aged men and women in the Netherlands. PLoS ONE 2011;6:e17967.
21. Fretts AM, Mozaffarian D, Siscovick DS, Heckbert SR, McKnight B, King IB, Rimm EB, Psaty BM, Sacks FM, Song X, et al. Associations of plasma phospholipid and dietary alpha linolenic acid with incident atrial fibrillation in older adults: the Cardiovascular Health Study. J Am Heart Assoc 2013;2:e003814.
22. Virtanen JK, Mursu J, Voutilainen S, Tuomainen TP. Serum longchain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men. Circulation 2009;120:2315-21.
23. Mozaffarian D, Ascherio A, Hu FB, Stampfer MJ, Willett WC, Siscovick DS, Rimm EB. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation 2005;111:157-64.
24. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 2006;84:5-17.
25. HarrisWS, PostonWC, Haddock CK. Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 2007;193:1-10.
26. Kaul N, Kreml R, Austria JA, Richard MN, Edel AL, Dibrov E, Hirono S, Zettler ME, Pierce GN. A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr 2008;27:51-8.
27. Egert S, Kannenberg F, Somoza V, Erbersdobler HF, Wahrburg U. Dietary alpha-linolenic acid, EPA, and DHA have differential effects on LDL fatty acid composition but similar effects on serum lipid profiles in normolipidemic humans. J Nutr 2009;139:861-8.
28. Barceló-Coblijn G, Murphy EJ, Othman R, Moghadasian MH, Kashour T, Friel JK. Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid. Am J Clin Nutr 2008;88:801-9.
29. Sioen I, Hacquebard M, Hick G, Maindiaux V, Larondelle Y, Carpentier YA, De Henauw S. Effect of ALA-enriched food supply on cardiovascular risk factors in males. Lipids 2009;44:603-11.
30. Bloedon LT, Balikai S, Chittams J, Cunnane SC, Berlin JA, Rader DJ, Szapary PO. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr 2008;27:65-74.
31. Dodin S, Cunnane SC, Masse B, LemayA, JacquesH,Asselin G, Tremblay- Mercier J, Marc I, Lamarche B, Legare F, et al. Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial. Nutrition 2008;24:23-30.
32. Harris WS, Dayspring TD, Moran TJ. Omega-3 fatty acids and cardiovascular disease: new developments and applications. Postgrad Med 2013;125:100-13.
33. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, Deadman NM. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART). Lancet 1989;2:757-61.
34. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002;105:1897-903.
35. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090-8.
36. de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alpha-linolenic acidrich diet in secondary prevention of coronary heart disease. Lancet 1994;343:1454-9.
37. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999;99:779-85.
38. Kromhout D, Giltay EJ, Geleijnse JM. n-3 Fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010;363:2015-26.
39. Eussen SR, Geleijnse JM, Giltay EJ, Rompelberg CJ, Klungel OH, Kromhout D. Effects of n-3 fatty acids on major cardiovascular events in statin users and non-users with a history of myocardial infarction. Eur Heart J 2012;33:1582-8.
40. Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013;346:e8707.
41. Rose GA, Thomson WB, Williams RT. Corn oil in treatment of ischaemic heart disease. BMJ 1965;1:1531-3.
42. Frantz ID Jr., Dawson EA, Ashman PL, Gatewood LC, Bartsch GE, Kuba K, Brewer ER. Test of effect of lipid lowering by diet on cardiovascular risk: the Minnesota Coronary Survey. Arteriosclerosis 1989;9: 129-35.
43. Watts GF, Lewis B, Brunt JN, Lewis ES, Coltart DJ, Smith LD, Mann JI, Swan AV. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet 1992;339:563-9.
44. Dayton S, Pearce ML. Trial of unsaturated-fat diet. Lancet 1968;2: 1296-7.
45. Controlled trial of soya-bean oil in myocardial infarction. Medical Research Council Soy Study Report. Lancet 1968;2:693-9.
46. Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willett WC, Rimm EB. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 2003;108:155-60.
47. Lopez-Garcia E, Schulze MB, Manson JE, Meigs JB, Albert CM, Rifai N, Willett WC, Hu FB. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr 2004;134:1806-11.
48. Ferrucci L, Cherubini A, Bandinelli S, Bartali B, Corsi A, Lauretani F, Martin A, Andres-Lacueva C, Senin U, Guralnik JM. Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 2006;91:439-46.
49. Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res 2008;52:885-97.
50. Calder PC. n-3 Polyunsaturated fatty acids and inflammation: from molecular biology to the clinic. Lipids 2003;38:343-52.
51. Calder PC, Ahluwalia N, Brouns F, Buetler T, Clement K, Cunningham K, Esposito K, Jonsson LS, Kolb H, Lansink M, et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr 2011;106 Suppl 3:S5-78.
52. Zhao G, Etherton TD, Martin KR, Vanden Heuvel JP, Gillies PJ, West SG, Kris-Etherton PM. Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells. Biochem Biophys Res Commun 2005;336: 909-17.
53. Zhao G, Etherton TD, Martin KR, West SG, Gillies PJ, Kris-Etherton PM. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 2004;134:2991-7.
54. Paschos GK, Rallidis LS, Liakos GK, Panagiotakos D, Anastasiadis G, Votteas V, Zampelas A. Background diet influences the antiinflammatory effect of alpha-linolenic acid in dyslipidaemic subjects. Br J Nutr 2004;92:649-55.
55. Zhao G. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr 2007;85:385-91.
56. Poudyal H, Panchal SK, Diwan V, Brown L. Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. Prog Lipid Res 2011;50:372-87.
57. Rallidis LS, Paschos G, Liakos GK, Velissaridou AH, Anastasiadis G, Zampelas A. Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 2003;167:237-42.
58. Rallidis LS, Paschos G, Papaioannou ML, Liakos GK, Panagiotakos DB, Anastasiadis G, Zampelas A. The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients. Atherosclerosis 2004;174:127-32.
59. Paschos GK, Zampelas A, Panagiotakos DB, Katsiougiannis S, Griffin BA, Votteas V, Skopouli FN. Effects of flaxseed oil supplementation on plasma adiponectin levels in dyslipidemic men. Eur J Nutr 2007;46: 315-20.
60. Dewell A, Marvasti FF, Harris WS, Tsao P, Gardner CD. Low- and high-dose plant and marine (n-3) fatty acids do not affect plasma inflammatory markers in adults with metabolic syndrome. J Nutr 2011;141:2166-71.
61. Chiuve SE, Rimm EB, Sandhu RK, Bernstein AM, Rexrode KM, Manson JE, Willett WC, Albert CM. Dietary fat quality and risk of sudden cardiac death in women. Am J Clin Nutr 2012;96:498-507.
62. Albert CM, Oh K, Whang W, Manson JE, Chae CU, Stampfer MJ, Willett WC, Hu FB. Dietary alpha-linolenic acid intake and risk of sudden cardiac death and coronary heart disease. Circulation 2005; 112:3232-8.
63. de Oliveira Otto MC, Wu JH, Baylin A, Vaidya D, Rich SS, Tsai MY, Jacobs DR Jr., Mozaffarian D. Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2013;2: e000506.
64. Sabaté J, Fraser GE, Burke K, Knutsen SF, Bennett H, Lindsted KD. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med 1993;328:603-7.
65. Bassett CM, Rodriguez-Leyva D, Pierce GN. Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed. Appl Physiol Nutr Metab 2009;34(5):965-74.
66. Hooper L, Thompson RL, Harrison RA, Summerbell CD, Moore H, Worthington HV, Durrington PN, Ness AR, Capps NE, Davey Smith G, et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev 2004;(4): CD003177.
67. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSIHF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1223-30.
68. Jacobson TA. Beyond lipids: the role of omega-3 fatty acids from fish oil in the prevention of coronary heart disease. Curr Atheroscler Rep. 2007;9(2):145-53.
69. Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, et al. n-3 Fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 2012;367:309-18.
70. Harris WS. Are n-3 fatty acids still cardioprotective? Curr Opin Clin Nutr Metab Care 2013;16:141-9.
71. Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet 2010;376:540-50.
72. Dietary Guidelines Advisory Committee. Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans. Washington, D.C.: USDA; 2010.
73. Panel on Dietary Reference Intakes for Macronutrients. Dietary References Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington: The National Academies Press, 2005.
74. Burdge GC, Calder PC. Conversion of alpha-linolenic acid to longerchain polyunsaturated fatty acids in human adults. Reprod Nutr Dev 2005;45:581-97.
75. Kris-Etherton PM, Taylor DS, Yu-Poth S, Huth P, Moriarty K, Fishell V, Hargrove RL, Zhao G, Etherton TD. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 2000;71(1 Suppl): 179S-88S.
76. Hulshof KF, van Erp-Baart MA, Anttolainen M, Becker W, Church SM, Couet C, Hermann-Kunz E, Kesteloot H, Leth T, Martins I, et al. Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study. Eur J Clin Nutr 1999; 53:143-57.
77. Ollis TE,Meyer BJ,Howe PR.Australian food sources and intakes of omega-6 and omega-3 polyunsaturated fatty acids. Ann Nutr Metab 1999;43:346-55.
78. Innis SM, Elias SL. Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women. Am J Clin Nutr 2003;77:473-8.
79. USDA, Agricultural Research Service. What we eat in America. [cited 2010 Jul 24]. Available from: http://www.ars.usda.gov/Services/docs. htm?docid=13793.
80. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic impact goal through 2020 and beyond. Circulation 2010;121:586-613.
81. Vannice G, Rasmussen H. Position of the Academy of Nutrition and Dietetics: dietary fatty acids for healthy adults. J Acad Nutr Diet 2014;114:136-53.
82. Undercurrent News. Shrimp still US' favorite food [cited 2014 Jun 10]. Available from: http://www.undercurrentnews.com/2012/09/25/shrimpstill- us-favorite-seafood/.
83. National Fisheries Institute. Top 10 consumed seafoods [cited 2014 Jun 10]. Available from: http://www.aboutseafood.com/about/aboutseafood/ top-10-consumed-seafoods.
84. Blok WL, Deslypere JP, Demacker PN, van der Ven-Jongekrijg J, Hectors MP, van der Meer JW, Katan MB. Pro- and anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year. Eur J Clin Invest 1997;27:1003-8.
85. Abe Y, El-Masri B, Kimball KT, Pownall H, Reilly CF, Osmundsen K, Smith CW, Ballantyne CM. Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion. Arterioscler Thromb Vasc Biol 1998;18:723-31.
86. Seljeflot I, Arnesen H, Brude IR, Nenseter MS, Drevon CA, Hjermann I. Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers. Eur J Clin Invest 1998;28:629-35.
87. Johansen O, Seljeflot I, Hostmark 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;19:1681-6.
88. Sampson MJ, Davies IR, Brown JC, Morgan V, Richardson T, James AJ, Sampson AP, Hughes DA. n-3 Polyunsaturated fatty acid supplementation, monocyte adhesion molecule expression and pro-inflammatory mediators in type 2 diabetes mellitus. Diabet Med 2001;18:51-8.
89. Thies F, Miles EA, Nebe-von-Caron G, Powell JR, Hurst TL, Newsholme EA, Calder PC. Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 2001;36:1183-93.
90. Chan DC, Watts GF, Mori TA, Barrett PH, Beilin LJ, Redgrave TG. Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Eur J Clin Invest 2002;32:429-36.
91. Berstad P, Seljeflot I, Veierod MB, Hjerkinn EM, Arnesen H, Pedersen JI. Supplementation with fish oil affects the association between very long-chain n-3 polyunsaturated fatty acids in serum non-esterified fatty acids and soluble vascular cell adhesion molecule-1. Clin Sci (Lond) 2003;105:13-20.
92. Ciubotaru I, Lee YS, Wander RC. Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT. J Nutr Biochem 2003;14:513-21.
93. Madsen T, Christensen JH, Blom M, Schmidt EB. The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a doseresponse study. Br J Nutr 2003;89:517-22.
94. Grundt H, Nilsen DW, Mansoor MA, Hetland O, Nordoy 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;33:88-95.
95. Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, Beilin LJ. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic Biol Med 2003;35:772-81.
96. 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;166:85-93.
97. Eschen O, Christensen JH, De Caterina R, Schmidt EB. Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids. Nutr Metab Cardiovasc Dis 2004;14:180-5.
98. Jellema A, Plat J, Mensink RP. Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial state. Eur J Clin Invest 2004;34:766-73.
99. Hjerkinn EM, Seljeflot I, Ellingsen I, Berstad P, Hjermann I, Sandvik L, Arnesen H. Influence of long-term intervention with dietary counseling, long-chain n-3 fatty acid supplements, or both on circulating markers of endothelial activation in men with long-standing hyperlipidemia. Am J Clin Nutr 2005;81:583-9.
100. Cazzola R, Russo-Volpe S, Miles EA, Rees D, Banerjee T, Roynette CE, Wells SJ, Goua M, Wahle KW, Calder PC, et al. Age- and dose-dependent effects of an eicosapentaenoic acid-rich oil on cardiovascular risk factors in healthy male subjects. Atherosclerosis 2007;193:159-67.
101. Fujioka S, Hamazaki K, Itomura M, Huan M, Nishizawa H, Sawazaki S, Kitajima I, Hamazaki T. The effects of eicosapentaenoic acid-fortified food on inflammatory markers in healthy subjects-a randomized, placebo-controlled, double-blind study. J Nutr Sci Vitaminol (Tokyo) 2006;52:261-5.
102. Krebs JD, Browning LM, McLean NK, Rothwell JL, Mishra GD, Moore CS, Jebb SA. Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. Int J Obes (Lond) 2006;30:1535-44.
103. Sanders TA, Lewis F, Slaughter S, Griffin BA, Griffin M, Davies I, Millward DJ, Cooper JA, Miller GJ. Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP study. Am J Clin Nutr 2006;84:513-22.
104. Kabir M, Skurnik G, Naour N, Pechtner V, Meugnier E, Rome S, Quignard-Boulange A, Vidal H, Slama G, Clement K, et al. Treatment for 2 mo with n-3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 2007;86:1670-9.
105. Browning LM, Krebs JD, Moore CS, Mishra GD, O'Connell MA, Jebb SA. The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes Obes Metab 2007;9:70-80.
106. Rasic-Milutinovic Z, Perunicic G, Pljesa S, Gluvic Z, Sobajic S, Djuric I, Ristic D. Effects of n-3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients. Ren Fail 2007; 29:321-9.
107. Madsen T, Christensen JH, Schmidt EB. C-reactive protein and n-3 fatty acids in patients with a previous myocardial infarction: a placebo-controlled randomized study. Eur J Nutr 2007;46:428-30.
108. Murphy KJ, Meyer BJ, Mori TA, Burke V, Mansour J, Patch CS, Tapsell LC, Noakes M, Clifton PA, Barden A, et al. Impact of foods enriched with n-3 long-chain polyunsaturated fatty acids on erythrocyte n-3 levels and cardiovascular risk factors. Br J Nutr 2007; 97:749-57.
109. Yamada H, Yoshida M, Nakano Y, Suganami T, Satoh N, Mita T, Azuma K, Itoh M, Yamamoto Y, Kamei Y, et al. In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid. Arterioscler Thromb Vasc Biol 2008;28:2173-9.
110. Yusof HM, Miles EA, Calder P. Influence of very long-chain n-3 fatty acids on plasma markers of inflammation in middle-aged men. Prostaglandins Leukot Essent Fatty Acids 2008;78:219-28.
111. Kelley DS, Siegel D, Fedor DM, Adkins Y, Mackey BE. DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr 2009;139: 495-501.
112. Pot GK, Brouwer IA, Enneman A, Rijkers GT, Kampman E, Geelen A. No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-aged individuals. Eur J Clin Nutr 2009;63: 1353-9.
113. Trøseid M, Arnesen H, Hjerkinn EM, Seljeflot I. Serum levels of interleukin-18 are reduced by diet and n-3 fatty acid intervention in elderly high-risk men. Metabolism 2009;58:1543-9.
114. Junker R, Pieke B, Schulte H, Nofer R, Neufeld M, Assmann G, Wahrburg U. Changes in hemostasis during treatment of hypertriglyceridemia with a diet rich in monounsaturated and n-3 polyunsaturated fatty acids in comparison with a low-fat diet. Thromb Res 2001;101:355-66.
115. Bemelmans WJ, Lefrandt JD, Feskens EJ, van Haelst PL, Broer J, Meyboom-de Jong B, May JF, Tervaert JW, Smit AJ. Increased alpha- linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. Eur J Clin Nutr 2004;58:1083-9.
116. Lopes C, Aro A, Azevedo A, Ramos E, Barros H. Intake and adipose tissue composition of fatty acids and risk of myocardial infarction in a male Portuguese community sample. J Am Diet Assoc 2007;107:276-86.
117. HeK,RimmEB,MerchantA,RosnerBA, StampferMJ,WillettWC,Ascherio A. Fish consumption and risk of stroke in men. JAMA 2002;288:3130-6.
118. Larsson SC, Virtamo J, Wolk A. Dietary fats and dietary cholesterol and risk of stroke in women. Atherosclerosis 2012;221:282-6.
119. Dolecek TA. Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial. Proc Soc Exp Biol Med 1992;200: 177-82.
120. Hu FB, Stampfer MJ, Manson JE, Rimm EB, Wolk A, Colditz GA, Hennekens CH, Willett WC. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 1999;69:890-7.
121. Laaksonen DE, Nyyssonen K, Niskanen L, Rissanen TH, Salonen JT. Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Arch Intern Med 2005;165:193-9.