Four positive quality studies (two cohort studies, one cross-sectional study, and one meta-analysis) provide evidence of a protective effect of consumption of fish and fish-derived omega-3 fatty acids on the risk of CVD events in patients with known CHD. In patients with CHD, higher plasma levels of DHA and EPA are associated with a reduction in arrhythmias and fatal heart disease. In post-menopausal women, regular weekly fish consumption is associated with reduced progression of coronary atherosclerosis. 

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

Consumption of one to two fish meals per week (total of four to eight ounces) is associated with reduced cardiac mortality from CHD or sudden death in American men. More studies are needed to assess the benefit of fish and fish-derived omega-3 fatty acids and the risk of CVD for women.  

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

Consumption of fish and fish-derived omega-3 fatty acids may or may not be associated with reduced incidence of arrhythmia in patients without CHD.

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

In populations that consume diets rich in fish (Finnish men, Alaska Natives, Japanese), the cardiovascular benefits of consuming additional fish and fish-derived omega-3 fatty acids are not evident at this time. 

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

One RCT and one case-control study, both of neutral quality, indicate that higher intakes of plant-derived omega-3 fatty acids in patients with CHD, are associated with a decreased rate of cardiac death and non-fatal myocardial infarction. The experimental group in the RCT also had a significantly lower intake of total lipids, saturated fats and increased intake of oleic, linoleic and alpha-linolenic fatty acids.

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

Two large positive quality studies (one a cohort and one a cross-sectional), indicate that higher intakes of alpha-linolenic acid (ALA) in men and women without CHD are associated with a lower risk of fatal ischemic heart disease (IHD) (plasma level used as biomarker) and prolonged repolarization (mean intake 0.74g per day of ALA; source of ALA was not specified). Two positive quality case-control studies indicate that ALA lowers the risk of IHD in men and women in one study (amount of ALA from mustard oil not specified) and sudden cardiac death in women (median intake 1.16g per day ALA; source of ALA was not specified) in the second study. Alpha-linolenic acid, however, was not related to other non-sudden fatal CVD events or to non-fatal myocardial infarction. 

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

The majority of studies with supplemental omega-3 fatty acids (n-3FA) (varied doses and n-3FA composition) reduced CVD events (sudden death and re-infarction) and mortality. These included four positive quality research publications, one of which was a meta-analysis of 11 randomized controlled trials.

However, results vary in certain populations. In patients with angina, one neutral quality study showed an increase in cardiac death. In patients with implantable cardioverter defibrillators (ICDs), the effects were variable in two positive quality studies. In a population with a high consumption of fish, one positive quality, small, short-term study reported no benefit. 

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

No evidence exists to describe the relationship between consumption of omega-3 fatty acid supplements and the risk of CVD events in patients without CHD.

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

The ADA Disorders of Lipid Metabolism workgroup concurs with the following statement and grade from the USDA Nutrition Evidence Library (NEL): 

Alpha-linolenic acid (ALA) intake of 0.6-1.2% of total calories will meet current recommendations and may lower cardiovascular disease (CVD) risk, but new evidence is insufficient to warrant greater intake beyond this level. Limited, but supportive evidence suggests that higher intake of n-3 from plant sources may reduce mortality among persons with existing CVD. 
 

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

• Detail
• Worksheets
  • 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 Nov 22;112(21):3232-8.
  • Baylin A, Kabagambe EK, Ascherio A, Spiegelman D, Campos H. Adipose tissue a-linolenic acid and nonfatal acute myocardial infarction in Costa Rica. Circulation. 2003 Apr; 107(12): 1,586-1,591.
  • 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: 779-785.
  • Folsom AR, Demissie Z. Fish intake, marine omega-3 fatty acids, and mortality in a cohort of postmenopausal women. Am J Epidemiol. 2004, Nov 15; 160(10): 1005-1010.
  • Lemaitre RN, King IB, Sotoodehnia N, Rea TD, Raghunathan TE, Rice KM, Lumley TS, Knopp RH, Cobb LA, Copass MK, Siscovick DS. Red blood cell membrane alpha-linolenic acid and the risk of sudden cardiac arrest. Metabolism. 2009 Apr;58(4):534-40.
  • Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. N-3 polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2003 Feb; 77 (2): 319-325.
  • 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 Jan 18; 111(2): 157-164. Epub 2005 Jan 3.
  • Rastogi T, Reddy KS, Vaz M, Spiegelman D, Prabhakaran D, Willett WC, Stampfer MJ, Ascherio A. Diet and risk of ischemic heart disease in India. Am J Clin Nutr. 2004 Apr; 79(4): 582-592. PMID: 15051601
  • Virtanen JK, Mozaffarian D, Chiuve SE, Rimm EB. Fish consumption and risk of major chronic disease in men. Am J Clin Nutr. 2008 Dec;88(6):1618-25.
  • 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 Jul;84(1):5-17.

The ADA Disorders of Lipid Metabolism workgroup concurs with the following statement and grade from the USDA Nutrition Evidence Library (NEL):

Moderate evidence shows that consumption of two servings of seafood per week (4oz per serving), which provide an average of 250mg per day of long-chain n-3 fatty acids, is associated with reduced cardiac mortality from coronary heart disease (CHD) or sudden death in persons with cardiovascular disease (CVD).
 

• Grade I means there is Good/Strong evidence supporting the statement;
• Grade II is Fair;
• Grade III is Limited/Weak;
• Grade IV is Expert Opinion Only;
• Grade V is Not Assignable.
• High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
• Moderate (B) means we are moderately confident in the effect estimate;
• Low (C) means our confidence in the effect estimate is limited;
• Very Low (D) means we have very little confidence in the effect estimate.
• Ungraded means a grade is not assignable.

• Detail
• Quality Rating Summary
  For a summary of the Quality Rating results, click here.
• Worksheets
  • Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC, Ma J. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002; 346 (15): 1,113-1,118.
  • Brouwer IA, Heeringa J, Geleijnse JM, Zock PL, Witteman JC. Intake of very long-chain n-3 fatty acids from fish and incidence of atrial fibrillation. The Rotterdam Study. Am Heart J. 2006 Apr; 151 (4): 857-862. PMID: 16569549.
  • Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: A meta-analysis of randomized controlled trials. Am J Med. 2002 Mar; 112(4): 298-304.
  • Erkkila AT, Lehto S, Pyorala K, and Uusitupa MIJ. N-3 fatty acids and five-year risks of death and cardiovascular disease events in patients with coronary artery disease. Am J Clin Nutr 2003 July; 78 (1): 65-71.
  • Erkkila AT, Lichtenstein AH, Mozaffarian D, Herrington DM. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr. 2004 Sep; 80(3): 626-632  
  • Erkkilä AT, Matthan NR, Herrington DM, Lichtenstein AH. Higher plasma docosahexaenoic acid is associated with reduced regression of coronary atherosclerosis in women with CAD. J Lipid Res. 2006; 47: 2,814-2,819.
  • Folsom AR, Demissie Z. Fish intake, marine omega-3 fatty acids, and mortality in a cohort of postmenopausal women. Am J Epidemiol. 2004, Nov 15; 160(10): 1005-1010.
  • Frost L, Vestergaard P. n-3 Fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer and Health Study. Am J Clin Nutr. 2005; 81: 50-54.
  • He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Greenland P. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies.Circulation. 2004 Jun 8;109(22):2705-11. PubMed PMID: 15184295
  • Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S; JPHC Study Group. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: The Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation. 2006; 113(2): 195-202.
  • (no title)
  • Järvinen R, Knekt P, Rissanen H, Reunanen A. Intake of fish and long-chain n-3 fatty acids and the risk of coronary heart mortality in men and women. Br J Nutr. 2006 Apr; 95(4): 824-829.
  • Konig A, Bouzan C, Cohen JT, et al. A quantitative analysis of fish consumption and coronary heart disease mortality. Am J Prev Med. Nov 2005;29(4):335-346.
  • Lankinen M, Schwab U, Erkkilä A, Seppänen-Laakso T, Hannila ML, Mussalo H, Lehto S, Uusitupa M, Gylling H, Oresic M. Fatty fish intake decreases lipids related to inflammation and insulin signaling--a lipidomics approach. PLoS One. 2009;4(4):e5258. Epub 2009 Apr 23.
  • Lara JJ, Economou M, Wallace AM, Rumley A, Lowe G, Slater C, Caslake M, Sattar N, Lean ME. Benefits of salmon eating on traditional and novel vascular risk factors in young, non-obese healthy subjects. Atherosclerosis. 2007 Jul; 193(1): 213-221. Epub 2006 Oct 27.
  • Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. N-3 polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2003 Feb; 77 (2): 319-325.
  • Lindqvist HM, Langkilde AM, Undeland I, Sandberg AS. Herring (Clupea harengus) intake influences lipoproteins but not inflammatory and oxidation markers in overweight men. Br J Nutr. 2009 Feb;101(3):383-90. Epub 2008 Jul 18.
  • Mozaffarian D. Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death. Am J Clin Nutr. 2008 Jun;87(6):1991S-6S.
  • Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006 Oct 18;296(15):1885-99.
  • 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 Jan 18; 111(2): 157-164. Epub 2005 Jan 3.
  • Mozaffarian D, Psaty BM, Rimm EB, Lemaitre RN, Burke GL, Lyles MF, Lefkowitz D, Siscovick DS. Fish intake and risk of incident atrial fibrillation. Circulation, 2004 Jul 27; 110 (4): 368-373. Epub 2004 Jul 19. PMID: 15262826.
  • Panagiotakos DB, Zeimbekis A, Boutziouka V, Economou M, Kourlaba G, Toutouzas P, Polychronopoulos E. Long-term fish intake is associated with better lipid profile, arterial blood pressure, and blood glucose levels in elderly people from Mediterranean islands (MEDIS epidemiological study). Med Sci Monit. 2007 Jul;13(7):CR307-12.
  • (no title)
  • Panagiotakos DB, Antonogeorgos G, Papadimitriou A, Anthracopoulos MB, Papadopoulos M, Konstantinidou M, Fretzayas A, Priftis KN. Breakfast cereal is associated with a lower prevalence of obesity among 10-12-year-old children: the PANACEA study. Nutr Metab Cardiovasc Dis. 2008 Nov;18(9):606-12.
  • Seierstad SL, Seljeflot I, Johansen O, Hansen R, Haugen M, Rosenlund G, Frøyland L, Arnesen H. Dietary intake of differently fed salmon; the influence on markers of human atherosclerosis. Eur J Clin Invest. 2005 Jan;35(1):52-9.
  • Streppel MT, Ocké MC, Boshuizen HC, Kok FJ, Kromhout D. Long-term fish consumption and n-3 fatty acid intake in relation to (sudden) coronary heart disease death: the Zutphen study. Eur Heart J. 2008 Aug;29(16):2024-30. Epub 2008 Jul 18.
  • Turunen AW, Verkasalo PK, Kiviranta H, Pukkala E, Jula A, Männistö S, Räsänen R, Marniemi J, Vartiainen T. Mortality in a cohort with high fish consumption. Int J Epidemiol. 2008 Oct;37(5):1008-17. Epub 2008 Jun 25.
  • Virtanen JK, Mozaffarian D, Chiuve SE, Rimm EB. Fish consumption and risk of major chronic disease in men. Am J Clin Nutr. 2008 Dec;88(6):1618-25.
  • Virtanen JK, Mursu J, Voutilainen S, Tuomainen TP. Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men. Circulation. 2009 Dec 8;120(23):2315-21. Epub 2009 Nov 23.PMID: 19933935
  • 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 Jul;84(1):5-17.
  • Whelton SP, He J, Whelton PK, Muntner P. Meta-analysis of observational studies on fish intake and coronary heart disease. Am J Cardiol. 2004;93(9):1119-23.
  • Yamagishi K, Iso H, Date C, Fukui M, Wakai K, Kikuchi S, Inaba Y, Tanabe N, Tamakoshi A; Japan Collaborative Cohort Study for Evaluation of Cancer Risk Study Group. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women.   The JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J Am Coll Cardiol. 2008 Sep 16;52(12):988-96.