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. 2002 Jan;6(4):203–209. doi: 10.1007/BF02897971

Omega-3 fatty acids and cardiovascular disease: The epidemiological evidence

Artemis P Simopoulos 1,✉
PMCID: PMC2723470  PMID: 21432336

Abstract

Epidemiological studies in the last 40 years suggest that omega-3 fatty acids derived from fish and fish oil decrease the risk of coronary heart disease, hypertension and stroke, and their complications. The beneficial effects of omega-3 fatty acids include effects on lipids, blood pressure, cardiac and vascular function, eicosanoids, coagulation, and immunological responses. However, not all population studies have shown that omega-3 fatty acids are associated with reduced rates of coronary mortality. Such studies suffer either from small numbers of subjects or the population already had a high intake of fish. When comparing the highest intake of fish to that of the lowest fish intake, the beneficial effects of omega-3 fatty acids have been shown. In population-based case-control studies, the patients consuming modest amounts of fish, the equivalent of one fatty fish meal per week, had a significant lower risk of primary cardiac arrest compared with those who did not eat fish at all. In case-control studies, the intake of eicosapentaenoic acid and docosahexaenoic acid as reflected in adipose tissue content is inversely associated with risk of myocardial infarction.

Key words: omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, coronary heart disease, hypertension

References

  • 1).Simopoulos AP. Historical perspective, conference conclusions and recommendations, and actions by federal agencies. In: Simopoulos AP, Kifer RR, Martin RE, editors. Health Effects of Polyunsaturated Fatty Acids in Seafoods. Orlando, FL; Academic Press, 1986: 3–29.
  • 2).Nelson AM. Diet therapy in coronary disease. Effect on mortalityof high-protein, high-seafood, fat-controlled diet. Geratrics 1972; 12: 103–116. [PubMed]
  • 3).Nelson AM, Douglas C. The effect of a fat-controlled diet on patients with coronary disease. Med. Welt. 1965; 36: 2063–2068. [PubMed]
  • 4).Pfeifer JJ, Janssen F, Muesing R. The lipid depressant activities of whole tish and their componentoils. J. Am. Oil Chem. Soc. 1962; 39: 292–296. [DOI]
  • 5).Bronte-Stewart B, Antonis A, Eales L, Brock JF. Effects of feeding different fats on serum cholesterol level. Lancet 1956; 1: 521–530. [DOI] [PubMed]
  • 6).Kinsell LW, Sinclair HM. Fats and disease. Lancet 1957; 1: 883–884. [DOI] [PubMed]
  • 7).Stansby ME. Nutritional properties of fish oils. World Rev. Nutr. Diet 1969; 11: 46–105. [DOI] [PubMed]
  • 8).Bierenbaum ML, Fleischman AI, Green DP, Raichelson RI, Hayton T, Watson PB, Caldwell AB. The 5-year experience of modified fat diets on younger men with coronary heart disease. Circulation 1970; 42: 943–952. [DOI] [PubMed]
  • 9).Dyerberg J. Linolenate-derived polyunsaturated fatty acids and prevention of atherosclerosis. Nutr. Rev. 1986; 44: 125–134. [DOI] [PubMed]
  • 10).Keys A, Anderson JT, Grande F. “Essential” fatty acids, degree of unsaturation and effect of corn (maize) oil on the serum cholesterol level in man. Lancet 1957; 1: 66–68. [DOI] [PubMed]
  • 11).Ahrens EH, Insull W, Hirsh J, et al. The effects on human serum lipids of a dietary fat, highly unsaturated, but poor in essential fatty acids. Lancet 1959; 1: 115–119. [DOI] [PubMed]
  • 12).Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic west coast Eskimos. Acta Med. Scand. 1972; 192: 85–94. [DOI] [PubMed]
  • 13).Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am. J. Clin. Nutr. 1975; 28: 958–966. [DOI] [PubMed]
  • 14).Bang HO, Dyerberg J, Hjorne N. The composition of food consumed by Greenland Eskimos. Acta Med. Scand. 1976; 200: 69–73. [DOI] [PubMed]
  • 15).Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 1978; 2: 117–119. [DOI] [PubMed]
  • 16).Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 1979; ii: 433–435. [DOI] [PubMed]
  • 17).Bang HO, Dyerberg J. Lipid metabolism and ischemic heart disease in Greenland Eskimos. In: Draper HH, editor. Advanced Nutrition Research. New York, Plenum Press, vol. 3, 1980; 1–22.
  • 18).Dyerberg J. The Eskimo experience. N-3 news. 1986; 1: 1–4.
  • 19).Hirai A, Hamazaki T, Terano T, et al. Eicosapentaenoic acid and platelet function in Japanese. Lancet 1980; 2: 1132–1133. [DOI] [PubMed]
  • 20).Hirai A, Terano T, Saito H, et al. Eicosapentaenoic acid and platelet function in Japanese. In: Goto Y, Homma Y, editors. Nutritional Prevention of Cardiovascular Disease. New York, Academic Press, 1984: 231–239.
  • 21).Kagawa Y, Nishizawa M, Suzuki M, et al. Eicosapentaenoic acids of serum lipids of Japanese Islanders with low incidence of cardiovascular disease. J. Nutr. Sci. Vitaminol. 1982; 28: 441–453. [DOI] [PubMed]
  • 22).Kromhout D, Bosschieter EB, Coulander C deL. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N. Engl. J. Med. 1985; 312: 1205–1209. [DOI] [PubMed]
  • 23).Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR. Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N. Engl. J. Med. 1985; 312: 1210–1216. [DOI] [PubMed]
  • 24).Lee TH, Hoover RL, Williams JD, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N. Engl. J. Med. 1985; 312: 1217–1224. [DOI] [PubMed]
  • 25).Glomset JA. Fish, fatty acids, and human health (editorial). N. Engl. J. Med. 1985; 312: 1253–1254. [DOI] [PubMed]
  • 26).Shekelle RB, Missell LV, Oglesby P, Shryock AM, Stamler J. Letter to the editor N. Engl. J. Med. 1985; 313: 820. 4033711
  • 27).Curb JD, Reed DM. Letter to the editor. N. Engl. J. Med. 1985; 313: 821.
  • 28).Vollset SE, Hench I, Bjelke E. Fish consumption and mortality from coronary heart disease. N. Engl. J. Med. 1985; 313: 820. [DOI] [PubMed]
  • 29).Simonsen T, Vartun A, Lyngmo V, Nordoy A. Coronary heart disease, serum lipids, platelets and dietary fish in two communities in northern Norway. Acta Med. Scand. 1987; 222: 237–245. [DOI] [PubMed]
  • 30).Hunter DJ, Kazda I, Chockallngam A, Fodor JG. Fish consumption and eardiovascular mortality in Canada: an inter-regional comparison. Am. J. Prev. Med. 1988; 4: 5–10. [PubMed]
  • 31).Burr ML, Fehily AM, Gibert JF, et al. Effect of changes in fat, fish and fibre intakes on death and myocardial reinfarction; diet and reinfarction trial (DART). Lancet 1989; ii: 757–761. [DOI] [PubMed]
  • 32).Dolecek TA, Grandits G. Dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial (MRFIT). World Rev. Nutr. Diet 1991; 66: 205–216. [DOI] [PubMed]
  • 33).Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 1995; 274: 1363–1367. [DOI] [PubMed]
  • 34).Simon JA, Hodgkins ML, Browner WS, Neuhaus JM, Bernert JT Jr, Hulley SB. Serum fatty acids and the risk of coronary heart disease. Am. J. Epidemiol. 1995; 142: 469–476. [DOI] [PubMed]
  • 35).de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alphalinolenic acid-rich diet in the secondary prevention of coronary heart disease. Lancet 1994; 343: 1454–1459. [DOI] [PubMed]
  • 36).Renaud S, de Lorgeril M, Delaye J, Guidollet J, Jacquard F, Mamelle N, Martin JL, Monjaud I, Salen P, Touboul P. Cretan Mediterranean diet for the prevention of coronary heart disease. Am. J. Clin. Nutr. 1995; 61 (supp): 1360S-1367S. [DOI] [PubMed]
  • 37).de Lorgeril M, Salen P, Martin J-L, Monjaud I, Boucher P, Mamelle N. Mediterranean dietary pattern in a randomized trial. Prolonged survival and possible reduced cancer rate. Arch. Intern. Med. 1998; 158: 1181–1187. [DOI] [PubMed]
  • 38).de Lorgeril M, Salen P. Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer. World Rev. Nutr. Diet 2000; 87: 1–23. [DOI] [PubMed]
  • 39).Singh RB, Rastogi SS, Verma R, Laxmi B, Singh R, Ghosh S, Niaz MA. Randomized controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of a one year follow up. BMJ 1992; 304: 1015–1019. [DOI] [PMC free article] [PubMed]
  • 40).Singh RB, Niaz MA, Sharma JP, Kumar R, Rastogi V, Moshiri M. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction. The Indian experiment of infarct survival-4. Cardiovasc. Drugs Ther. 1997; 11: 485–491. [DOI] [PubMed]
  • 41).GISSI-Prevenzione Investigators: Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999; 354: 447–455. [DOI] [PubMed]
  • 42).Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am. J. Clin. Nutr. 1991; 54: 438–463. [DOI] [PubMed]
  • 43).Weber PC, Fischer S, von Schacky C, et al. Dietary omega-3 polyunsaturated fatty acids and eicosanoid formation in man. In: Simopoulos AP, Kifer RR, Martin RE, editors. Health Effects of Polyunsaturated Fatty Acids in Seafoods. Orlando, FL: Academic Press, 1986: 49–60.
  • 44).Weber PC, Leaf A. Cardiovascular effects of ω3 fatty acids. Atherosclerosis risk factor modification by ω3 fatty acids. Vorld Rev. Nutr. Diet 1991; 66: 218–232. [PubMed]
  • 45).Simopoulos AP, Visioli F, editors. Mediterranean Diets. World Rev. Nutr. Diet, vol. 87 Basel: Karger, 2000.
  • 46).Simopoulos AP, editor. The Return of ω3 Fatty Acids into the Food Supply. 1. Land-Based Animal Food Products and Their Health Effects. World Rev. Nutr. Diet, vol. 83, Basel: Karger, 1998.
  • 47).Simopoulos AP, Robinson J. The Omega Diet. The Lifesaving Nutritional Program Based on the Diet of the Island of Crete. New York: HarperCollins, 1999.
  • 48).Singer P, Jaeger W, Wirth M, et al. Lipid and blood pressurelowering effect of mackerel diet in man. Atherosclerosis 1983; 44: 99–108. [DOI] [PubMed]
  • 49).Lerenz R, Spengler U, Fisher 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: 504–511. [DOI] [PubMed]
  • 50).Mortensen JZ, Schmidt EB, Nielsen AH, Dyerberg J. The effect of n-6 and n-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure. Throm. Heamost. 1983; 50: 543–546. [PubMed]
  • 51).Singer P, Berger L, Luck K, Taube C, Naumann E, Godicke W. Long-term effect of mackerel diet on blood pressure, serum lipids and thromboxane formation in patients with mild essential hypertension. Atherosclerosis 1986; 62: 259–265. [DOI] [PubMed]
  • 52).Rogers S, James KS, Butland BK, Etherington MD, O'Brien JB, Jones JG. Effects of a fish oil supplement on serum lipids, blood pressure, bleeding time, haemostatic and rheological variables. A double blind randomised controlled trial in healthy volunteers. Atherosclerosis 1987; 63: 137–143. [DOI] [PubMed]
  • 53).Knapp HR, FitzGerald GA. The antihypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension. N. Engl. J. Med. 1989; 320: 1037–1043. [DOI] [PubMed]
  • 54).Singer P, Wirth M, Voigt S, et al. Blood pressure- and lipidlowering effect of mackerel and herring diet in patients with mild essential hypertension. A therosclerosis 1985; 56: 223–235. [DOI] [PubMed]
  • 55).Norris PG, Jones CJH, Weston MJ. Effect of dietary supplementation with fish oil on systolic blood pressure in mild essential hypertension. Br. Med. J. 1986; 293: 104–105. [DOI] [PMC free article] [PubMed]
  • 56).von Houwelingen R, Nordoy A, van der Beck E, Houtsmuller U, de Metz M, Hornstra G. Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males. Am. J. Clin. Nutr. 1987; 46: 424–436. [DOI] [PubMed]
  • 57).Demke DM, Peters GR, Linet OI, Metzler CM, Klott KA. Effects of a fish oil concentrate in patients with hypercholesterolemia. Atherosclerosis 1988; 70: 73–80. [DOI] [PubMed]
  • 58).Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromso study. N. Engl. J. Med. 1990; 322: 795–801. [DOI] [PubMed]
  • 59).Dusing R, Struck A, Scherg H, Pietsch R, Kramer HJ. Dietary fish oil supplements: effects on renal hemodynamics and renal excretory function in healthy volunteers. Kidney Int. 1987; 31: 268.
  • 60).Fischer S, Weber PC. Prostaglandin I3 is formed in vivo in man after dietary eicosapentaenoic acid. Nature 1984; 307: 165–168. [DOI] [PubMed]
  • 61).Knapp HR, Reilly IAG, Alessandrini P, FitzGerald GA. In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis. N. Engl. J. Med. 1986; 314: 937–942. [DOI] [PubMed]
  • 62).McMillan DE. Antihypertensive effects of fish oil. N. Engl. J. Med. 1989; 321: 1610–1611. [DOI] [PubMed]
  • 63).Bao DQ, Mori TA, Burke V, Puddey IB, Beilin LJ. Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives. Hypertension 1998; 32(4): 710–717. [DOI] [PubMed]
  • 64).Eritsland J, Arnesen H, Gronseth K, Fjeld NB, Abdelnoor M. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am. J. Cardio. 1996; 77: 31–36. [DOI] [PubMed]
  • 65).Sellmayer A, Witzgall H, Lorenz RL, Weber PC. Effects of dietary fish oil on ventricular premature complexes. Am. J. Cardiol. 1995; 76: 974–977. [DOI] [PubMed]
  • 66).Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study. Lancet 1994; 344: 1383–1389. [DOI] [PubMed]
  • 67).Shepherd J, Cobbe SM, Ford I, Isles C, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastation in men with hypercholesterolemia. N. Engl. J. Med. 1995; 333: 1301–1307. [DOI] [PubMed]
  • 68).Pharoah PDP, Hollingworth W. Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population. Brit. Med. J. 1996; 312: 1443–1448. [DOI] [PMC free article] [PubMed]
  • 69).Simopoulos AP. Evolutionary aspects of omega-3 fatty acids in the food supply. Prostaglandins, Leukotrienes and Essential Fatty Acids. 1999: 60(5&6): 421–429. [DOI] [PubMed]
  • 70).Simopoulos AP. Overview of evolutionary aspects of ω3 fatty acids in the diet. In: Simopoulos AP, ed. The Return of ω3 Fatty Acids into the Food Supply. I. Land-Based Animal Food Products and Their Health Effects. World Rev Diet. Karger, Basel, 1998, vol. 83, pp. 1–11.
  • 71).Von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary ω-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 1999; 130: 554–562. [DOI] [PubMed]
  • 72).Simopoulos AP, Leaf A, Salem N Jr. Essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Ann. Nutr. Metab. 1999; 43: 127–130. [DOI] [PubMed]
  • 73).Pedersen JI, Ringstad J, Almendingen K, Haugen TS, Stensvold I, Thelle DS. Adipose tissue fatty acids and risk of myocardial infarction—a case-control study. Eur. J. Clin. Nutr. 2000; 54: 618–625. [DOI] [PubMed]
  • 74).Simopoulos AP. ω-3 fatty acids in the prevention-management of cardiovascular disease. Can. J. Physiol. Pharmacol. 1997; 75: 234–239. [DOI] [PubMed]
  • 75).Nordoy A, Hatcher L, Goodnight S, FitzGerald GA, Connor 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: 914–920. [PubMed]
  • 76).Bairati I, Roy L, Meyer F. Double blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Circulation 1992; 85: 950–956. [DOI] [PubMed]
  • 77).Simopoulos AP. The role of fatty acids in gene expression: health implications. Ann. Nutr. Metab. 1996; 40: 303–311. [DOI] [PubMed]

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