Should Everyone Be on Fish Oils?

Abstract & Commentary

By Harold L. Karpman, MD, FACC, FACP. Dr. Karpman is Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study. This article originally appeared in the November 29, 2010 issue of Internal Medicine Alert. At that time it was reviewed by Gerald Roberts, MD, Assistant Professor of Medicine, Albert Einstein College of Medicine, New York, NY. Dr. Roberts reports no financial relationships to this field of study.

Synopsis: Marine n-3 PUFAs act as pleiotropic agents on the cardiovascular system with a diverse range of effects most of which are beneficial for patients with known cardiovascular disease and possibly, they may even have beneficial effects with regard to the primary prevention of cardiovascular disease.

Source: Saravanan P, et al. Cardiovascular effects of marine omega-3 fatty acids. Lancet 2010;376:540-550.

The marine omega-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid and docosahexaenoic acid are present mainly in all the fish and commercially available supplements that are available either over the counter as fish oils or as concentrated pharmaceutical preparations. Fish oil supplements have been becoming increasingly popular because several health benefits have been attributed to them in both the medical and lay literature. Substantial benefits have been reported in relation to diseases of the cardiovascular system and, in fact, published medical guidelines recommend use of these agents in some cardiac disorders.1,2 Although much research had been focused on this area during the past three decades, such basic issues as the appropriate doses needed to achieve beneficial reduction in cardiovascular events are still unclear.

Commentary

Numerous prospective epidemiological studies have reported that high fish consumption was associated with a lowered mortality from coronary artery heart disease,3-6 and this hypothesis has been supported by findings of the landmark DART study,7 a randomized secondary prevention trial concerned with long-term dietary intervention in men who had suffered myocardial infarctions (MI). A 30% reduction in total mortality and morbidity related to coronary artery heart disease (CAD) was reported in patients who were randomly assigned to consumption of fatty fish twice weekly. Another large intervention trial of secondary prevention after MI demonstrated a substantial reduction in all-cause and cardio-vascular mortality in patients who were treated with only 1 g per day of n-3 PUFA supplementation.8 Data on the effects of these agents on the risk of development of CAD in healthy participants are inconsistent; however, the available evidence in primary prevention of CAD suggests that those patients with hyperlipidemia and/or diabetes might benefit the most by using fish oil. The main benefit reported for secondary prevention relates to the reduction in occurrence of sudden cardiac death, especially in patients with previous MI.9 Much research has been devoted to the antiarrhythmic effects of these agents and it has been suggested that the conflicting findings may be attributable to differences in the mechanisms of arrhythmia initiation in subsets within the study populations. Finally, it must be noted that no significant reduction in sudden cardiac death or CAD events was reported in a cohort of patients who had received optimal use of conventional therapy such as beta blockers, statins, and angiotensin converting enzyme inhibitors and even in patients who had a high rate of revascularization procedures performed,10 suggesting that n-3 PUFA therapy may be of no additional value in patients who already are receiving maximum medical therapy for their cardiac condition.

The risk of heart failure appears to be inversely related to fish consumption and, in a large study with 60,000 participants who were followed for up to 13 years, there was a reduction in deaths attributable to heart failure in those participants who reported an increase in fish intake.11,12 Thus far, no significant data are available regarding the effect of n-3 PUFA on the prevention or reduction of stroke in symptomatic or asymptomatic patients with or without atherosclerotic carotid arterial disease. A consistent effect of these agents is their ability to lower plasma triglyceride concentrations by reducing the hepatic synthesis of triglycerides and by increasing clearance of circulating triglycerides.13 Because prior studies have demonstrated significant benefit in the reduction of cardiovascular events in patients with type 2 diabetes, large prospective studies assessing the role of n-3 PUFA intake on risk reduction for cardiovascular events are underway.14

It has been suggested that the dietary intake of fish is the most desirable way to increase the n-3 PUFA intake, but it must be recognized that 1 g per day of the supplement is equivalent to the fish oil present in about 55-85 g of fresh tuna, sardines, salmon, or trout and in 652 g of Atlantic cod fish. These high intakes of fish are extremely difficult to achieve in most parts of the world; therefore, an argument can be made for prescribing supplements to all patients for whom reliable increases in n-3 PUFA are indicated.15 Finally, it should be noted that the joint American College of Cardiology and American Heart Association guidelines statement on the use of n-3 PUFA currently recommends an intake of at least two fish meals per week in patients with known CAD and supplemental therapy for 1 year with 1 g per day of a combination of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for those patients who have had a prior myocardial infarction.1 The evidence for these recommendations have been lent support by the results of many observational studies, although the recommendation for treatment of patients post MI were derived from only one study;8 therefore, further large-scale investigations are needed in this patient group as well as in the overall area of primary prevention.

In conclusion, marine n-3 PUFAs act as pleiotropic agents on the cardiovascular system and appear to be associated with beneficial anti-inflammatory, anti-atherosclerotic, anti-immunomodulatory, and anti-arrhythmic effects. However, assessment of the effectiveness of these agents in the setting of optimum conventional drug therapy and elucidation of the mechanisms of action of the perceived benefits needs to be established on a larger scale in carefully controlled, double-blind trials and with issues of sustainable fishing practices at the forefront.

References

1. Kris-Etherton PM, et al; for the American Heart Association Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acid, and cardiovascular disease. Circulation 2002;106:2747-2757.

2. NICE. Secondary prevention in primary and secondary care for patients following a myocardial infarction. NICE clinical guideline 48, 2002. London: National Institute for Health and Clinical Excellence; 2002.

3. Kromhout D, at al. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205-1209.

4. Kromhout D, et al. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol 1995;24:340-345.

5. Dolecek TA, Granditis G. Dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial (MRFIT). World Rev Nutr Diet 1991;66:205-216.

6. Albert CM, et al. Fish consumption and risk of sudden cardiac death. JAMA 1998;279:23-28.

7. Burr ML, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and reinfarction trial (DART). Lancet 1989;2:757-761.

8. GISSI-Prevenzione investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione trial. Lancet 1999; 354:447-455.

9. Marchioli R, 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;105:1897-1903.

10. Senges S, et al; for the OMEGA study group. Randomized trial of Omega three fatty acids on top of modern therapy after acute myocardial infarction: The OMEGA trial. Oral presentation at the annual scientific sessions of the American College of Cardiology. Orlando FL; March 2009.

11. Mozaffarian D, et al. Fish intake and risk of incident heart failure. J Am Coll Cardiol 2005;45:2015-2021.

12. Yamagishi K, et al; for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Study Group. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular disease in a nationwide community-based cohort of Japanese men and women. J Am Coll Cardiol 2008;52:988-996 .

13. Harris WS, et al. Omega-3 fatty acids and coronary heart disease risk: Clinical and mechanistic perspectives. Atherosclerosis 2008;197:12-24.

14. De Caterina R, et al. n-3 fatty acids in the treatment of diabetic patients: Biological rationale and clinical data. Diabetes Care 2007;30:1012-1026.

15. Wood DA, et al; for the EUROACTION study group. Nurse-coordinated multidisciplinary, family-based cardiovascular disease prevention programme (EUROACTION) for patients with coronary heart disease and asymptomatic individuals at high risk of cardiovascular disease: A paired, cluster-randomised controlled trial. Lancet 2008;371:1999-2012.