Many patients are taking fish oil supplements, which contain omega-3 fatty acids, either on their own initiative or on their physician’s advice. Driving this trend are accumulating data from observational and epidemiologic studies and clinical trials that these lipids actually reduce cardiovascular risk.
In the following article, we review available studies of omega-3 fatty acids in cardiovascular disease.
WHAT ARE OMEGA-3 FATTY ACIDS?
Omega-3 fatty acids are a class of polyunsaturated fatty acids. Their name means that they all have a double carbon-to-carbon bond in the third position from the omega (or methyl, or n) end of the fatty acid chain.
Most of the cardiovascular research on the omega-3 family has been on eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA). EPA and DHA are found primarily in fatty fish; ALA is abundant in flaxseed, walnuts, and soybeans.1 The human body can convert small amounts of ALA into EPA and DHA: only about 5% of ALA is converted to EPA and less than 0.5% is converted to DHA. Currently, it is not known whether ALA is active itself or only via these metabolites. In this review, the term omega-3 fatty acid refers to EPA and DHA only.
GETTING ENOUGH FISH OIL
Healthy people should consume fish (preferably oily fish) at least twice a week, according to the American Heart Association.1 However, not all fish contain the same amount of oil. Some, such as cod and catfish, contain only 0.2 g of EPA/DHA per 100-g serving; others, such as Atlantic salmon, contain about 10 times as much (Table 1).2
People with known coronary artery disease should take in 1 g of EPA/DHA per day, according to the American Heart Association.1 This recommendation is based on clinical trials that found omega-3 fatty acids to have beneficial effects.
For most people with coronary artery disease, this means taking supplements. However, buyers need to carefully examine the label of over-the-counter fish oil supplements to see if they contain the recommended amounts of both DHA and EPA. Generic 1-g fish oil supplements may contain variable amounts of DHA and EPA, and some may have less than 300 mg.
People with hypertriglyceridemia. The US Food and Drug Administration (FDA) has approved Lovaza (formerly Omacor), which contains EPA/DHA in higher concentrations than over-the-counter preparations, for the treatment of hypertriglyceridemia in people with triglyceride levels higher than 500 mg/ dL, along with a regimen of diet and regular exercise.3 It is currently the only FDA-approved prescription form of omega-3 fatty acid ethyl esters. Each 1-g capsule contains 375 mg of DHA and 465 mg of EPA; the recommended dose is 2 to 4 g/day. To take in an equivalent amount of these substances with over-the counter-preparations, patients might have to take many capsules a day.
Safety of omega-3 fatty acids
Generally, omega-3 fatty acids are very well tolerated, and their adverse effects are limited to gastrointestinal complaints (discomfort, upset stomach) and a fishy odor. Common ways to prevent these effects are to freeze the capsules or take them at bedtime or with meals.
Mercury advisory on fish. Nursing or pregnant women should limit their consumption of certain fish, as some fish (but not fish oil) contain high levels of mercury. The highest levels of mercury are usually found in the larger, older predatory fish such as swordfish, tilefish, and mackerel, and the FDA advises women who are nursing or pregnant to avoid these fish completely. Tuna, red snapper, and orange roughy are lower in mercury, but nursing or pregnant women should still limit consumption of these fish to 12 oz per week.4
Theoretical risk of bleeding. In theory, high doses of omega-3 fatty acids may increase the bleeding time by inhibiting the arachidonic acid pathway. Clinically, this effect is minimal. In a trial in 511 patients undergoing coronary artery bypass grafting who were receiving aspirin or warfarin (Coumadin), the bleeding time and the number of bleeding episodes were no higher in those who were randomized to receive 4 g/day of omega-3 fatty acids daily than in a control group.5
Harris6 reviewed 19 studies of omega-3 fatty acids in patients undergoing coronary artery bypass grafting, carotid endarterectomy, or femoral artery catheterization, and none of the studies found a significantly increased risk of bleeding.