Use of dietary fish oils for the prevention and treatment of heart disease

an analysis by Ping Zhang, Ph.D.

Heart disease is still the number one killer in the United States and other Westernized societies. About half of the deaths from heart disease are from coronary heart disease (CHD), which includes heart attack. Heart attack happens when one or more of the coronary arteries supplying blood to the heart muscle are blocked. This is usually caused by the build up of plaques (deposits of fat-like substances), a process called atherosclerosis (2). One of the first approaches to treatment of cardiovascular disease (CVD), including heart disease, is dietary intervention to reduce saturated fat and cholesterol intake.

In addition, an increase of fatty fish consumption or the use of fish oil supplement is recommended to reduce the risk of premature heart disease. The beneficial effects of dietary fish oil on cardiovascular disease have been well-documented from both epidemiology and randomized clinical trials.

The concept that dietary fish oil protects against cardiovascular disease was based on epidemiological studies in the 1970's on disease patterns of Greenland Eskimos (4). Even though the Greenland Eskimos had a high fat diet, they exhibited very low cardiovascular mortality compared with their counterparts in Denmark. The protective effect of fish oil was attributed to the high content of two highly unsaturated omega-3 fatty acids, EPA and DHA. Following this initial observation, an epidemiological study in Japan also showed that the Japanese population, which has a higher intake of EPA/DHA in the diet relative to that of North Americans, exhibited considerably lower rates of acute myocardial infarctions (MI) (3). In addition, many epidemiological studies within populations also reported that men who ate at least some fish weekly had a lower CHD mortality rates compared to that of men who ate none (1). A recent study conducted with women in the Nurses' Health Study reported an inverse association between omega-3 fatty acids from fish and CHD death (8).

Numerous randomized trials in humans have also shown a cardio-protective role of dietary fish oil for both primary prevention and secondary prevention. The Physicians' Health Study which followed 20,551 subjects for 12 years reported an approximately 50 percent overall relative risk reduction even with a small amount of fish intake (eat fish once a month) (5). The Diet and Reinfarction Trial results indicated a 29% reduction in all-cause mortality over a two year period in male MI survivors advised to increase their fatty fish intake (6). In the GISSI-Prevention Study, 11,324 patients with preexisting CHD were randomized to fish oil, vitamin E, both, or neither treatment groups. After the follow-up for 3.5 years, the fish oil group had a 20% reduction in all-cause mortality and a 45% reduction in sudden death compared to controls (7).

Multiple mechanisms have been proposed for the cardio protective benefits of dietary fish oil. One of the most consistent observations associated with consumption of fish oil is a reduction in plasma triglycerides (TG). Dietary omega-3 fatty acids also reduce the postprandial TG response following a high fat meal. Dietary fish oil has also been shown to reduce blood pressure, decrease thrombosis, decrease arrhymias, decrease inflammation, and decrease endothelial function.

Increasing dietary fatty fish intake or taking fish oil supplements results in elevated levels of EPA and DHA in tissues. Levels of EPA and DHA in serum phospholipids reflect dietary intake and overall physiological status. Evidence has shown an inverse correlation between omega-3 fatty acids, particularly DHA levels, and the development of CHD in men. Higher DHA and total serum omega-3 fatty acids levels (more than 7.2% of total serum fatty acids) was estimated to result in an approximately 30% overall lower risk of CHD (3).

Overall most studies reported so far show evidence that consumption of fish oil reduces various CVD outcomes such as sudden death, cardiac death, non-sudden death from MI, and MI. However, some studies have not reported a beneficial association of fish oil consumption and CHD mortality. The explanation for the conflicting results is not clear by may be related to the different contents of methyl mercury and other organic toxic compound such as PCBs in certain fish that may attenuate the protective effects of dietary fish oil on cardiovascular health (1, 9).

The current dietary intake of total omega-3 fatty acids in the United States is about 1.6 g/d (about 0.7% of total energy). Of this, a-linolenic acid accounts for 1.4 g/d and only 0.1-0.2 g/d comes from EPA or DHA. Although a-linolenic acid can be converted into EPA and DHA in the body, the extent of conversion is very limited. All fish contain EPA and DHA, however the quantity varies among species and sources. The American Heart Association suggests that healthy adults eat two fatty fish meals a week for positive cardiovascular benefits (1).

Patients with CHD are encouraged to increase consumption of EPA and DHA to about 1 g/d. This level of omega-3 fatty acid consumption can be achieved through diet, but for people who do not eat fish, a fish oil supplement may be considered. Most common fish oil capsules in the United States provide 180 mg of EPA and 120 mg of DHA, thus three 1-g capsules will be roughly enough to provide 1g/d of omega-3 fatty acids (1).

Consumers should be aware of both the benefits and risks of fish and fish oil consumption. Children and women who are pregnant or lactating are at increased risk for mercury toxicity from fish consumption but are also at low risk for CHD. For this group, avoiding potentially contaminated fish is a higher priority. Men beyond middle-age and postmenopausal women are at higher risk for CHD. The benefits of consuming more fish far outweigh the risks of mercury contamination if the contaminations of fish are within FDA and EPA limits. Consumption of a wide variety of fish with contaminations within the guidelines is advised to increase omega-3 fatty acid intake.

Literature cited:

1. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002. 106:2747-57.


2. Lusis, AJ. Atherosclerosis. Nature 2000. 407: 233-241.


3. Holub DJ, Holub BJ. Omega-3 fatty acids from fish oils and cardiovascular disease. Mol Cell Biochem 2004. 263:217-225.


4. Dyerberg J, Bang HO. A hypothesis on the development of acute myocardial infarction in Greenlanders. Scand. J. Clin. Invest. 1982. 42:7-13.


5. Albert CM, Hennekens CH, O'Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998. 279:23-28.


6. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, Deadman NM. Effects of changes in fat, fish and fiber intakes on death and myocardial infarction: diet and reinfarction (DART). The Lancet 1989. 2: 757-761.


7. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. The Lancet 1999. 354: 447-455.


8. Hu FB, Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE. Fish and Omega-3 fatty acids and the risk of coronary heart diseasein women. JAMA 2002. 287: 1815-1821.


9. Virtanen JK, Voutilainen S, Rissanen TH, Mursu J, Tuomainen TP, Korhonen MJ, Valkonen VP, Seppanen K, Laukkanen JA, Salonen JT. Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland. Arterioscler Thromb Vasc Biol. 2005. 25(1):228-33.