Eating Fish to Prevent Sudden Death
March 2000; Volume 3: 25-28
By Matthew Sorrentino, MD
Increasing evidence suggests that a mediterranean diet rich in monounsaturated fatty acids and omega-3 fatty acids can help reduce cardiac mortality. The American Heart Association Nutrition Committee released a report in 1996 stating that the inclusion of marine sources of omega-3 fatty acids in the diet was reasonable and potentially highly beneficial.1 Recent studies have further clarified the role of cold water fatty fish, such as salmon, herring, mackerel, and tuna, in the diet.
Physiological Effects
Fish oils have effects. Such effects include an antiarrhythmic effect; favorable changes in some lipoprotein levels, especially serum triglyceride levels; improved vascular function; reduced thrombotic effect, probably by decreasing platelet aggregation; and lowered blood pressure.
Kang and Leaf reviewed a series of studies which showed that the intravenous administration of omega-3 fatty acids can prevent ischemia-induced malignant ventricular arrhythmias in an animal model.2 These investigators concluded that omega-3 fatty acids reduce the electrical excitability of myocytes, probably by binding to sodium channels, thus effecting an antiarrhythmic effect.
Numerous studies have evaluated the lipoprotein effects of fish oils. A meta-analysis and summary of the best designed trials showed that an average intake of 4 g/d of omega-3 fatty acids decreased triglyceride levels by 25% in normal individuals and 34% in hypertriglyceridemic subjects.3 Low-density lipoprotein (LDL) cholesterol rose 5-10% and high-density lipoprotein (HDL) cholesterol increased minimally by 1-3%. Further evaluation should determine if the triglyceride lowering effects of fish oils change the atherogenicity of LDL particles and if the increase in total LDL cholesterol is clinically important.
Fish oils may also have a direct effect on vascular function. An in vitro study of hypercholesterolemic individuals has shown a significant improvement in endothelial function of small arteries after three months of high-dose fish oil supplementation.4 This effect is probably independent of the lipoprotein effects because there was no statistically significant difference in lipoprotein values in this study.
Multiple studies have evaluated the effect of omega-3 fatty acids on platelet aggregation. A recent study attempted to determine the effects of dietary fat, dietary fish, and fish oil capsules on platelet function.5 All groups taking omega-3 fatty acids had reduced platelet aggregation. Dietary fish was found to have a greater effect on platelet function when fish was part of a low-fat diet. Since platelets play a critical role in thrombus formation in patients with atherosclerotic disease, omega-3 fatty acids may work in part like aspirin and prevent cardiac events by inhibiting the formation of a thrombus associated with plaque rupture.
The effect of fish oils on blood pressure has been variable. A meta-analysis of 31 trials showed a small but significant effect of fish oil, lowering blood pressure approximately 3 mm Hg systolic with a mean dose of 4.8 g/d of omega-3 fatty acids.6 This effect was more likely to be noted in hypertensive individuals.
Epidemiological Evidence
Early epidemiological studies have suggested that populations consuming higher levels of fish have lower coronary mortality than populations eating a typical North American diet.7 The mechanism of this apparent protective effect is unknown but may include favorable changes in lipoprotein profiles, antithrombotic effects, or antiarrhythmic effects.
Recently the Physicians’ Health Study group reevaluated the cohort of more than 20,000 U.S. male physicians and assessed their fish consumption to help clarify the potentially protective effects of fish in the diet.8
One hundred thirty-three sudden deaths were reported in the trial. Dietary fish was associated with a reduced risk of sudden death and total mortality. These benefits were noted with the consumption of one fish meal per week or greater. There was, however, no associated change in the risk of myocardial infarction or non-sudden cardiac death. These findings suggest that a component of fish may have antiarrhythmic qualities that may prevent cardiac arrest.
Clinical Studies
Prescribing a diet rich in fish oils may offer protection against sudden cardiac events. The GISSI investigators reported a secondary prevention trial of patients who had recently had a myocardial infarction.9
Patients were randomized to a daily dose of omega-3 fish oil capsules (850-882 mg eicosapentenoic acid and docosahexenoic acid) in addition to a Mediterranean diet (100 g [3.3 oz] of fatty fish per day). Treatment with the fish oil capsules significantly decreased the primary endpoints of death, nonfatal myocardial infarction, and stroke in treated individuals. The latter two benefits were primarily attributable to a decrease in the risk of death, again suggesting that an antiarrhythmic effect may be important.
The traditional Mediterranean diet is rich in fish and plant fatty acids, and lean in red meat and saturated fats. The diet has been championed as cardioprotective. To test whether a Mediterranean diet compared with a Western diet may reduce the risk of cardiac events after a first myocardial infarction, investigators initiated and designed the Lyon Diet Heart Study—a randomized, single-blind secondary prevention trial.10 The combined outcome of cardiac death and nonfatal myocardial infarction was significantly reduced in the Mediterranean diet group as opposed to the Western diet group. This protective effect was maintained up to four years after the first heart attack. The study was not designed to determine which factor of the diet may have provided the benefit. These results support the recent findings of the GISSI study group.
Omega-3 fatty acids have been shown to:
a. reduce platelet aggregation.
b. decrease risk of nonfatal myocardial infarction and stroke.
c. lower triglyceride levels.
d. All of the above.
Dosage and Formulation
A minimum of one fish meal per week seems to give benefit. (See Table 1 for dietary sources of omega-3 fatty acids.) There is no evidence of a dose effect since the Health Professionals Follow-up Study found that increasing doses of fish did not further decrease the risk of heart disease.11 The GISSI trial is the first major trial to suggest that fish oil capsules at a reasonable dose of less than 1 g/d may give the same benefit as fish in the diet, although all patients in this trial were instructed to eat a Mediterranean diet as well.
| Table 1-Dietary sources of omega-3 fatty acids | ||
| Food Source | Omega-3 Fatty Acids per 100 g Serving | |
| Atlantic mackerel | 2.5 g | |
| Salmon | 1.2-1.4 g | |
| Canned sardine | 1.7 g | |
| Eel | 1.7 g | |
| Herring | 1.6 g | |
| Bluefish | 1.2 g | |
| Squid | 0.9 g | |
| Striped bass | 0.8 g | |
| Rainbow trout | 0.5-1.0 g | |
| Tuna | 0.3 g | |
| Flounder | 0.2 g | |
| Adapted from: Linder MC, ed. Nutritional Biochemistry and Metabolism. 2nd ed. Norwalk, CT: Appleton and Lange; 1991. | ||
Adverse Effects
Possible side effects of fish oil capsules are listed in Table 2.
| Table 2-Potential side effects of fish oil capsules | |
| • Fishy odor, gastrointestinal upset | |
| • May increase bleeding time | |
| • Increase caloric intake and weight gain | |
| • May increase LDL cholesterol in some individuals | |
| • May decrease immune response | |
| • Unrefined fish oil preparations may contain pesticides | |
| • Vitamin A and D toxicity with some preparations | |
| Source: Stone NJ. Fish consumption, fish oil, lipids, and coronary heart disease. Circulation 1996;94:2337-2340. | |
Conclusion
The GISSI trial and the Lyon Diet Heart Study support the recommendations of the American Heart Association Nutrition Committee.1 There is compelling evidence that a diet rich in omega-3 fatty acids is protective against sudden cardiac events. Omega-3 fatty acids may function as antiarrhythmic agents in patients with ischemic heart disease as well as lower triglyceride levels, improve endothelial function, decrease thrombogenicity, and slightly lower blood pressure.
Recommendation
We recommend inclusion of at least one to two marine fish meals per week in the diet of all patients with coronary heart disease or with risk factors for heart disease. We prefer fish in the diet to fish oil capsules since dietary fish appears to be effective, less expensive, and better tasting, and free of the potential side effects of the fish oil capsules. In addition, a Mediterranean diet may contain antioxidants and additional fatty acids (such as the monounsaturates within olive oil) that may offer further cardiovascular benefits.
Fish oil capsules have fewer side effects and are preferred over dietary fish.
a. True
b. False
References
1. Stone NJ. Fish consumption, fish oil, lipids, and coronary heart disease. Circulation 1996;94:2337-2340.
2. Kang JX, Leaf A. Antiarrhythmic effects of polyunsaturated fatty acids: Recent studies. Circulation 1996;94:1774-1780.
3. Harris WS. N-3 fatty acids and serum lipoproteins: Human studies. Am J Clin Nutr 1997;65(suppl): 1645S-1654S.
4. Goode GK, et al. Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients: A double-blind placebo-controlled study. Circulation 1997;96: 2802-2807.
5. Mori TA, et al. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997;17:279-286.
6. Morris MC, et al. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 1993;88:523-533.
7. Sorrentino M. Fish consumption and the risk of coronary artery disease. Altern Med Alert 1998;1:32-34.
8. Albert CM, et al. Fish consumption and the risk of sudden cardiac death. JAMA 1998;279:23-28.
9. 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.
10. De Lorgeril M, et al. 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.
11. Ascherio A, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977-982.
March 2000; Volume 3: 25-28
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