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Although diets rich in marine lipids and fish-oil supplements have staked a claim to heart disease prevention, controversy remains. A recent study examining the role of omega-3-enriched margarine as a functional food for secondary prevention of heart attacks yielded negative results;1 publication of the study spawned skeptical and even derisive headlines in the popular press: Omega-3 Fats Offer No Protection Against Heart Disease—Study and Low Doses of Omega-3s Don’t Help with Heart Disease: Say it Ain’t So, Fish Oil!.

Are the results of this study (perhaps somewhat prematurely titled “The Alpha Omega Trial”) definitive? How do clinicians reconcile these negative findings with the vast body of references that support the cardiovascular benefits of fish consumption and omega-3 supplementation? And most important, what are the implications for consumers and for potential advocacy by health-care professionals?

The current regulatory climate for fish-oil claims underscores this uncertainty. Lovaza (omega-3-acid ethyl esters), the only FDA-approved fish-oil supplement, is indicated only for its pharmacologic effect of lowering elevated triglycerides. FDA labeling specifically qualifies that “The effect of Lovaza on cardiovascular mortality and morbidity in patients with elevated triglyceride levels has not been determined.”2

No comparable approval, either explicit or tacit, exists in the United States for the application of fish-oil supplements to primary or secondary prevention of cardiovascular disease (CVD). But a considerable proportion of the population consumes these supplements, and a high percentage of health-care providers embrace such recommendations—if not for their patients, then for themselves and their families.

While the exact proportions are not known, a recent investigation showed that 62% of U.S. doctors surveyed agreed that one of their roles as a health-care professional is to provide information to patients about appropriate dietary supplements.3 The most popular supplements among cardiologists were multivitamins, omega-3s/fish oil, and vitamin C.

Even regulatory language governing claims for cardioprotection via consumption of omega-3-rich foods remains highly circumscribed. In September 2004, the FDA announced permission for “qualified health claims on omega-3 fatty acids” to the effect that, “Supportive but not conclusive research shows that consumption of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] omega-3 fatty acids may reduce the risk of coronary heart disease.”4

Compounding the controversy are international discrepancies vis a vis the prescription of fish-oil supplements. A front-page article in The New York Times pointed out that while 57% of family clinicians in Washington State acknowledged fish oil’s potential benefits in preventing a second heart attack, only 17% identified themselves as frequent prescribers of fish oil.5

The situation in the United States stood in contrast with that in Europe where, according to Dr. Massimo Santini, chief of cardiology at Rome’s San Filippo Neri hospital, a doctor’s failure to prescribe fish oil to a heart patient “would be considered tantamount to malpractice.”5

The article concluded that in the United States, “community doctors do not learn how to use [fish oil],” while insurers will not pay for cardiovascular prevention via fish-oil supplementation because it is not specifically approved by the FDA for that indication.5

In its scientific statement on fish consumption, fish oil, omega-3 fatty acids, and CVD, the American Heart Association (AHA) acknowledges that: “[Randomized controlled trials] have demonstrated that omega-3 fatty acid supplements can reduce cardiac events (e.g., death, nonfatal MI, nonfatal stroke) and decrease progression of atherosclerosis in coronary patients. However, additional studies are needed to confirm and further define the health benefits of omega-3 fatty acid supplements for both primary and secondary prevention.”6

After some equivocation to the effect that dietary approaches to omega-3 supplementation are preferable, the AHA allows that certain individuals, whose dietary preferences preclude adequate intake from natural sources, “in consultation with their physician, could consider supplements for coronary heart disease [CHD] risk reduction.”6

What lines of evidence support fish-oil supplementation for cardiovascular prevention? Early impetus came from epidemiologic studies. As early as 1944, Sinclair noted the decreased prevalence of CVD in Arctic Eskimos who subsisted largely on omega-3-rich fish and aquatic mammals.7 In the 1970s, Danish researchers noted improved cardiovascular profiles and lower MI mortality among Greenland Eskimos consuming a low-carbohydrate, fat-rich diet when compared with subjects consuming a Western diet on the Danish mainland.8

Three large randomized trials have documented the effects of omega-3 polyunsaturated fatty acid (PUFA) in primary and especially in secondary prevention of CHD.9 More than twenty years ago, the Diet and Reinfarction Trial demonstrated a 29% reduction in mortality—almost entirely attributable to decreased cardiovascular death—in subjects consuming high amounts of omega-3 from fish sources or supplements.10 The reduction in cardiovascular events was particularly impressive in individuals consuming fish-oil capsules.