The cardioprotective benefits of marine-derived omega-3 fatty acids in persons with cardiovascular disease (CVD) as well as in healthy persons have been documented in recent randomized, controlled clinical trials. The results confirm that these acids have positive effects on cardiac rhythm, hemodynamics, and arterial endothelial function.
Despite the benefits, however, concerns have arisen because of the presence of environmental pollutants in several species of fish. The American Heart Association (AHA) has recently issued a statement that presents its recommendations and addresses contamination concerns.1 Highlights are summarized here.
CORONARY HEART DISEASE AND STROKE
Earlier prospective epidemiologic studies showed that men who ate some fish every week had a lower coronary heart disease (CHD) rate than men who ate none.2-4 A more recent study confirmed that fish consumption reduced CHD mortality in men by about one third and the risk of nonsudden death from myocardial infarction (MI) by two thirds.5 Reduced CHD mortality with fish consumption has also been shown in women.6 Other studies have demonstrated a reduced risk of sudden coronary death with fish consumption.
Evidence from randomized, controlled trials. A recent meta-analysis of randomized, controlled trials found that the consumption of marine-derived omega-3 fatty acids significantly reduced the risk of overall mortality, mortality from MI, and sudden death in patients with CHD.7 Other important recent trial results include the following:
Nearly 400 patients admitted to the hospital with suspected MI were assigned to either fish oil capsules, mustard oil (high in α-linolenic acid), or placebo.8 After 1 year, 25% of patients in the fish oil group and 28% in the mustard oil group experienced a cardiac event, compared with 35% in the placebo group. There were significantly fewer nonfatal MIs in the fish oil and mustard oil groups.
In the GISSI-Prevention Study for secondary prevention of CHD, more than 11,000 patients with CHD who were receiving standard cardiac pharmacotherapy were randomized to vitamin E, omega-3 fatty acids, both, or neither.9 After 3Z\x years of follow-up, there was a 15% reduction in mortality, nonfatal MI, and nonfatal stroke; a 20% reduction in all-cause mortality; and a 45% reduction in sudden death in the omega-3 fatty acids group. A follow-up analysis found significant reductions in total mortality after 3 months of treatment and the risk of sudden death after 4 months of treatment.10
Other randomized trials have demonstrated that patients who take omega-3 fatty acids show less angiographic progression of atherosclerotic plaque, more regression, and fewer clinical events than those taking placebo and that omega-3 fatty acids lower the vein graft occlusion rates in patients undergoing coronary artery bypass grafting.11,12
Stroke. Although relatively little information exists about the relationship between omega-3 fatty acids and stroke, some epidemiologic studies have shown that the risk of stroke among fish eaters is about half that of persons who do not eat fish. Other studies, however, have failed to find a relationship.
POSSIBLE MECHANISMS OF ACTION
Although precise mechanisms are not yet known, omega-3 fatty acids are thought to work in a number of ways to reduce the risk of CVD.
Triglyceride reduction. Marine-derived omega-3 fatty acids have a well-established, dose-dependent hypotriglyceridemic effect in patients with and without diabetes. Therapeutic doses of fish oil (3 to 5 g/d) can reduce serum triglyceride concentrations by about 25% to 30%. Such doses can be achieved only through supplementation, and patients who take more than 3 g/d of fish oil should do so only under a physician's care. In contrast, dosages of about 1 g/d are cardioprotective, can be achieved through diet, and have almost no potential for adverse effects.
Blood pressure reduction. Omega-3 fatty acids appear to have a small, dose-dependent hypotensive effect, especially in patients with severe hypertension. However, because high doses are required to achieve a relatively modest effect and other modalities are more effective, the role of omega-3 fatty acids in reducing blood pressure appears limited.
Thrombosis and hemostasis. Omega-3 fatty acids decrease platelet aggregation, but their effect on thrombosis is unknown. Trials of the effect of omega-3 fatty acids on fibrinolysis have yielded conflicting results.
Arrhythmia. Omega-3 fatty acids are thought to reduce the risk of sudden death through a novel stabilizing effect on the myocardium. They also reduce resting heart rate and increase left ventricular filling capacity. Animal experiments and cell culture studies have shown that fish oil has significant antiarrhythmic effects.
Other physiologic effects. Studies have shown that omega-3 fatty acids increase acetylcholine-stimulated relaxation of small arteries, improve endothelial function, and increase arterial compliance. These acids also contribute to antiatherogenesis by reducing inflammatory processes, vasoconstriction, and platelet aggregation.
Healthy persons. The approximate intake of omega-3 fatty acids in the United States is 1.6 g/d, of which α-linolenic acid (from nuts and nut and vegetable oils) accounts for 1.4 g. Only 0.1 to 0.2 g/d comes from marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
Current recommendations for healthy persons are 0.3 to 0.5 g/d of EPA plus DHA and 0.8 to 1.1 g/d of α-linolenic acid. Adults can achieve this by consuming 2 fish meals per week-especially fatty fish (eg, salmon, herring, and mackerel)-and by using vegetable oils that contain α-linolenic acid (such as olive, canola, and walnut oils). Commercially prepared fried fish (such as that offered in restaurants and fast-food establishments) and many frozen, convenience-type fried fish products are best avoided because they are low in omega-3 fatty acids and high in trans-fatty acids.
Persons with CHD. The AHA recommends that these patients consume about 1 g/d of EPA and DHA. This can be achieved with plentiful fish consumption or with the use of up to three 1-g fish oil capsules daily (the number needed to provide about 1 g/d of omega-3 fatty acids).
Persons at risk for CHD. These persons are advised to consume plant- and marine-derived omega-3 fatty acids, although optimal amounts are not known. Consumption of 0.5 to 1.8 g/d (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality. Intakes of about 1.5 to 3 g/d of α-linolenic acid appear to be beneficial.
1. Kris-Etherton PM, Harris WS, Appel LJ, for the Nutrition Committee. AHA Scientific Statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106: 2747-2757.
2. Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312:1205-1209.
3. Kromhout D, Feskens EJ, Bowles CH. 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.
4. 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.
5. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336:1046-1053.
6. Hu FB, Bronner L, Willett WC, et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA. 2002;287:1815-1821.
7. 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;112:298-304.
8. Singh RB, Niaz MA, Sharma JP, et al. 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.
9. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999;354:447-455.
10. Marchioli R, Barzi F, Bomba E, 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.
11. von Schacky C, Angerer P, Kothny W, et al. The effect of dietary omega-3 fatty acids on coronary atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;130:554-562.
12. Eristland J, Arnesen H, Gronseth K, et al. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol. 1996;77:31-36.
13. US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Seafood. Mercury levels in seafood species. May 2001. Available at: http://www.cfsan.fda.gov/~frf/sea-mehg. html. Accessed March 21, 2003.