Cited by 409Fatty Acid Research and HealthNutritional Studies and DietCardiac Health and Mental Health

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Lack of benefit of dietary advice to men with angina: results of a controlled trial

Burr, M L, Ashfield-Watt, P A L, Dunstan, F D J, Fehily, A M, Breay, P, Ashton, T, Zotos, P C, Haboubi, N A A, Elwood, P C·2003·European Journal of Clinical Nutrition

DOI 10.1038/sj.ejcn.1601539

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Abstract

Objective To see whether mortality among men with angina can be reduced by dietary advice.Design A randomized controlled factorial trial.Setting Male patients of general practitioners in south Wales.Subjects A total of 3114 men under 70 y of age with angina.Interventions Subjects were randomly allocated to four groups: (1) advised to eat two portions of oily fish each week, or to take three fish oil capsules daily; (2) advised to eat more fruit, vegetables and oats; (3) given both the above types of advice; and (4) given no specific dietary advice. Mortality was ascertained after 3-9 y.Results Compliance was better with the fish advice than with the fruit advice. All-cause mortality was not reduced by either form of advice, and no other effects were attributable to fruit advice. Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised; the adjusted hazard ratio was 1.26 (95% confidence interval 1.00, 1.58; P=0.047), and even greater for sudden cardiac death (1.54; 95% CI 1.06, 2.23; P=0.025). The excess risk was largely located among the subgroup given fish oil capsules. There was no evidence that it was due to interactions with medication.Conclusions Advice to eat more fruit was poorly complied with and had no detectable effect on mortality. Men advised to eat oily fish, and particularly those supplied with fish oil capsules, had a higher risk of cardiac death. This result is unexplained; it may arise from risk compensation or some other effect on patients' or doctors' behaviour.

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Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial
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Blood Levels of Long-Chain n–3 Fatty Acids and the Risk of Sudden Death
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“Contrary to reports on the beneficial effects of fish oil, DART-2 reported that fish oil supplementation resulted in an increase in cardiac death in patients with angina pectoris [6].”
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Are dietary recommendations for the use of fish oils sustainable?
Jenkins, D. J. A., Sievenpiper, J. L., Pauly, D., Sumaila, U. R., Kendall, C. W. C., & Mowat, F. M. (2009) · Canadian Medical Association Journal · doi:10.1503/cmaj.081274 · Cited by 115
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Deane, K. H., Jimoh, F. O., Biswas, P., O'Brien, A. T., Hanson, S., Abdelhamid, A. S., Fox, C., & Hooper, L. (2019) · The British Journal of Psychiatry · doi:10.1192/bjp.2019.234 · Cited by 108
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“This could have contributed, among other factors, to the negative effect of fish intake in a study conducted in men with angina (Burr et al 2003).”
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“Conflicting reports arose as early as 9 years ago, when the DART-2 trial, discovered an apparent harmful effect of ω3 taken as fish oil supplements [3].”
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Potential impact of omega-3 treatment on cardiovascular disease in type 2 diabetes
Hartweg, J., Farmer, A. A., Holman, R. R., & Neil, A. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328321b3be · Cited by 100
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“In our meta-analysis, three trials with diet or dietary advice (8,13,15) and five trials with omega-3 fatty acid supplements (7,9,11,12,14) were reviewed.”
Method
Fatty acids and cardiovascular disease
Lecerf, J. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.2009.00194.x · Cited by 90
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“The DART-2 was a secondary prevention study conducted in men with stable angina (and not previous MI, unlike the first DART study) [44].”
BackgroundResultInfluential
Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure
den Ruijter, H. M., Berecki, G., Verkerk, A. O., Bakker, D., Baartscheer, A., Schumacher, C. A., Belterman, C. N. W., de Jonge, N., Fiolet, J. W. T., Brouwer, I. A., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.733329 · Cited by 78
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Oliver, M. F. (2006) · QJM · doi:10.1093/qjmed/hcl084 · Cited by 68
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BackgroundResult
n−3 Fatty acids, cardiac arrhythmia and fatal coronary heart disease
Brouwer, I. A., Geelen, A., & Katan, M. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.02.004 · Cited by 70
Nonstatin Therapies for Management of Dyslipidemia: A Review
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“More specifically, the majority of the larger early RCTs showed a reduction in cardiovascular risk or events with omega-3 FAs,(33,34,36,37) with the exception of 1 RCT that showed a higher risk of cardiac death.(35) Many of these studies were poorly designed, and lacked proper control group or blinding with ill-define…”
Background
The impact of EPA and DHA on blood lipids and lipoprotein metabolism: influence of apoE genotype
Anil, E. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005307 · Cited by 69
“(2002) meta-analysis may be the inclusion of the angina study (Diet and Reinfarction Trial 2 (Burr et al. 2003); see earlier discussion) in the Hooper et al.”
The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: A critical reassessment
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“However, more recent studies in patients with heart disease (Burr et al., 2003; Raitt et al., 2005; Brouwer et al., 2006b; Yokoyama et al., 2007; GISSI-HF investigators, 2008; Kromhout et al., 2010; Rauch et al., 2010) or animals (Coronel et al., 2007; Billman et al., 2012) have yielded conflicting…”
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Food and Western Disease Health and Nutrition from an Evolutionary Perspective
Lindeberg, S. (2009) · Cited by 64
Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts☆
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“However, in a trial in patients with angina pectoris without prior myocardial infarction, the incidence of sudden death tended to be increased [4].”
Background
Omega-3 Fatty Acids, Mercury, and Selenium in Fish and the Risk of Cardiovascular Diseases
Park, K., & Mozaffarian, D. (2010) · Current Atherosclerosis Reports · doi:10.1007/s11883-010-0138-z · Cited by 63
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Background
Effects of Moderate-Dose Omega-3 Fish Oil on Cardiovascular Risk Factors and Mood After Ischemic Stroke
Poppitt, S. D., Howe, C., Lithander, F. E., Silvers, K. M., Lin, R., Croft, J., Ratnasabapathy, Y., Gibson, R. A., & Anderson, C. S. (2009) · Stroke · doi:10.1161/strokeaha.109.555136 · Cited by 59
Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats
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“Moreover, in a trial of patients with stable angina pectoris without previous MI, a detrimental effect of n-3 PUFAs on sudden death was observed [4].”
Background
Serum β-carotene and the risk of sudden cardiac death in men: A population-based follow-up study
Karppi, J., Laukkanen, J. A., Mäkikallio, T. H., Ronkainen, K., & Kurl, S. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.10.077 · Cited by 59
Effectiveness of nonpharmacological secondary prevention of coronary heart disease
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Are n-3 fatty acids still cardioprotective?
Harris, W. S. (2012) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32835bf380 · Cited by 57
“There have been nine large (>2000 patients) randomized trials with n-3 fatty acids that may be grouped into four positive studies [8–11], four neutral studies [12 && ,13–15] (Table 1), and one negative study [16].”
BackgroundMethod
Effect of Dietary n-3 Polyunsaturated Fatty Acids on the Inducibility of Ventricular Tachycardia in Patients With Ischemic Cardiomyopathy
Metcalf, R. G., Sanders, P., James, M. J., Cleland, L. G., & Young, G. D. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.11.007 · Cited by 57
Omega-3 polyunsaturated fatty acid blood biomarkers increase linearly in men and women after tightly controlled intakes of 0.25, 0.5, and 1 g/d of EPA + DHA
Patterson, A. C., Chalil, A., Henao, J. J. A., Streit, I. T., & Stark, K. D. (2015) · Nutrition Research · doi:10.1016/j.nutres.2015.09.016 · Cited by 60
“However, in the past an increase in EPA + DHA in blood has been interpreted as an indication of compliance despite the fact that the size of the increase is too small relative to the dose prescribed [25].”
BackgroundResult
Pharmacologic treatment of hyperlipidemia.
Last, A. R., Ference, J. D., & Falleroni, J. (2011) · PubMed · Cited by 55
Cardiovascular Diseases, Depression Disorders and Potential Effects of Omega-3 Fatty Acids
Trebatická, J., Dukát, A., Ďuračková, Z., & Muchová, J. (2017) · Physiological Research · doi:10.33549/physiolres.933430 · Cited by 56
US dietary guidelines: is saturated fat a nutrient of concern?
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de Lorgeril, M., Salen, P., Defaye, P., & Rabaeus, M. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-5 · Cited by 53
“One trial published in 2003 in secondary prevention (DART-2) was not incorporated in the present analysis because of major design issues [30].”
Fish intake and acute coronary syndrome
Bjerregaard, L. J., Joensen, A. M., Dethlefsen, C., Jensen, M. K., Johnsen, S. P., Tjønneland, A. M., Rasmussen, L. H., Overvad, K., & Schmidt, E. B. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp375 · Cited by 53
“In contrast, patients with stable angina pectoris randomized to fatty fish twiceweekly had an increased risk of coronary mortality and sudden cardiac death.(28) There are many explanations for the discordant results obtained, not least differences in study design and methodology.”
Result
Secondary prevention of CHD in UK men: the Diet and Reinfarction Trial and its sequel
Burr, M. L. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005241 · Cited by 53
“Third, a factorial design would again be utilized, but this time to test the effect of advice to eat more fruit, vegetables and oats (Burr et al. 2003).”
Method
Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to the safety assessment of wild and farmed fish
(EFSA), E. F. S. A. (2005) · EFSA Journal · doi:10.2903/j.efsa.2005.236 · Cited by 55
Pitfalls in the use of randomised controlled trials for fish oil studies with cardiac patients
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“Advice or comments relevant to non-study n-3 intake in randomised controlled trials with fish or fish oil Recruitment period and criteria Follow-up Comments relevant to n-3 intake DART-1(1) 1983–1987 2 years 3-fold increase in EPA intake in the fish advice v. the control group and comment ‘there was little spontaneous…”
BackgroundInfluential
Advice to eat fish and mood: a randomised controlled trial in men with angina
Ness, A. R., Gallacher, J. E. J., Bennett, P. D., Gunnell, D. J., Rogers, P. J., Kessler, D., & Burr, M. L. (2003) · Nutritional Neuroscience · doi:10.1080/1028415021000056069 · Cited by 50
“(Burr et al., 2002) From April 1990 until August 1991, 452 men aged 37–70 with treated angina were recruited from 30 general practices in South Wales.”
BackgroundSelf-citation
Public health perspectives on aquaculture
Gormaz, J. G., Fry, J. P., Erazo, M., & Love, D. C. (2014) · Current Environmental Health Reports · doi:10.1007/s40572-014-0018-8 · Cited by 50
Effects of n−3 Polyunsaturated Fatty Acids on Cardiac Ion Channels
Moreno, C., Macías, Á., Prieto, Á., de la Cruz, A., González, T., & Valenzuela, C. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00245 · Cited by 53
“, 2010), and a deleterious effect due to an increased risk of cardiac death was reported in men with stable angina (without myocardial infarction) who were advised to eat fish (Burr et al., 2003), and in patients with implantable cardioverter defibrillators (ICDs; Raitt et al.”
Influential
Serum long-chain n-3 polyunsaturated fatty acids, mercury, and risk of sudden cardiac death in men: a prospective population-based study.
Virtanen, J. K., Laukkanen, J. A., Mursu, J., Voutilainen, S., & Tuomainen, T.-P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041046 · Cited by 48
“Benefits have not been observed in all trials, however [15,16].”
Background
ω-3 Fatty acids, atherosclerosis progression and cardiovascular outcomes in recent trials: new pieces in a complex puzzle
Wu, J. H. Y., & Mozaffarian, D. (2014) · Heart · doi:10.1136/heartjnl-2013-305257 · Cited by 47
Antiarrhythmic effects of n-3 fatty acids: evidence from human studies
Geelen, A., Brouwer, I. A., Zock, P. L., & Katan, M. (2004) · Current Opinion in Lipidology · doi:10.1097/00041433-200402000-00006 · Cited by 47
Highly Purified Omega-3 Fatty Acids for Secondary Prevention of Sudden Cardiac Death After Myocardial Infarction—Aims and Methods of the OMEGA-Study
Rauch, B. H., Schiele, R., Schneider, S., Gohlke, H., Diller, F., Gottwik, M. G., Steinbeck, G., Heer, T., Katus, H. A., Zimmer, R., et al. (2006) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-006-0495-6 · Cited by 45
(n-3) Fatty Acid Content of Red Blood Cells Does Not Predict Risk of Future Cardiovascular Events following an Acute Coronary Syndrome
Aarsetoey, H., Pönitz, V., Grundt, H., Staines, H., Harris, W. S., & Nilsen, D. W. T. (2009) · Journal of Nutrition · doi:10.3945/jn.108.096446 · Cited by 45
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“For example, Burr et al. (2003) demonstrated no benefits of dietary advice (eating more fish, fruits and vegetables) on allcause mortality after 3–9 years’ follow-up in elderly men with angina, which was probably attributable to poor compliance.”
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BackgroundResultInfluential
Antiarrhythmic Mechanisms of n-3 PUFA and the Results of the GISSI-Prevenzione Trial
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Red Blood Cell Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Socioeconomic Status in Patients with Established Coronary Artery Disease: Data from the Heart and Soul Study
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Authors: Burr, M. L., Ashfield-Watt, P. A. L., Dunstan, F. D. J., Fehily, A. M., Breay, P., Ashton, T., Zotos, P. C., Haboubi, N. A. A., & Elwood, P. C.
Affiliations: Cardiff University (GB)
Corresponding author: Burr, M L
ORCID: Ashfield-Watt, P A L
Dunstan, F D J
Elwood, P C
Venue: European Journal of Clinical Nutrition
Publisher: Springer Science and Business Media LLC
Published: 2003-02-01
Volume: 57
Issue: 2
Pages: 193-200
ISSN: 0954-3007 (ISSN-L)
1476-5640
DOI: 10.1038/sj.ejcn.1601539
OpenAlex: W2095073323
Cited by: 409
References: 30
Citations by year: 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 10 · 2018: 19 · 2017: 11 · 2016: 18 · 2015: 17 · 2014: 14 · 2013: 22 · 2012: 27
FWCI: 30.10
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: European Journal of Clinical Nutrition (publishedVersion)
PubMed (publishedVersion)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders: British Heart Foundation
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
Keywords: angina pectoris, dietary recommendations, oily fish, fish oil capsules, fruit and vegetable intake, oat, all-cause mortality, cardiovascular mortality, sudden cardiac death, dietary adherence, risk compensation, men
MeSH terms: Angina Pectoris, Diet, Fatty Acids, Unsaturated, Fish Oils, Fruit, Humans, Male, Middle Aged, Time Factors, Vegetables, Wales, Eicosapentaenoic Acid, Survival Analysis, Avena, beta Carotene, Nutritional Sciences

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Lack of benefit of dietary advice to men with angina: results of a controlled trial

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