It’s no wonder there’s so much confusion about the value of fish and fish oil supplements. Several studies have suggested that omega-3 fatty acids such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) may play a role in heart disease prevention. But others have shown no benefit or even some evidence of harm. So where does the truth lie?

Landmark trials

A study called GISSI-Prevenzione supported the claims regarding omega-3 fatty acid benefits. It followed 11,000 patients after myocardial infarction. At a dosage of 1,000 mg/day of omega-3 fatty acids (fish oil) these patients showed a 15% decrease in cardiovascular (CV) events. Even greater benefits were seen in sudden death mortality with a decrease of 45% in patients taking fish oils.

Another study, GISSI-Heart Failure, was a large-scale randomized trial that investigated omega-3 fatty acids in patients with NYHA class 2-4 heart failure. Primary end points of mortality and all-cause mortality for CV causes were reduced in the omega-3 group, by 9% and 8%, respectively. The absolute risk reduction was small at 1.8%, suggesting that 56 patients would have to be treated to avoid one death and 44 to avoid one death or admission for CV reasons.

There was no difference in secondary outcomes such as sudden cardiac death, first MI, hospitalization for heart failure or stroke. The omega-3s appear to have a beneficial effect on the mechanisms leading to the progression of heart failure.

A randomized, controlled study called DART looked at people who ate fatty fish 3x/week. A 29% decrease in total mortality suggested that fatty acids may have a marked CV protective effect.

A well-oiled heart

Finally, a very large randomized trial (about 18,000 subjects) called Japan EPA Lipid Intervention Study, JELIS, found that patients with and without a history of coronary artery disease who were treated with EPA (1,800 mg/ day) had a 19% decrease in major coronary events. They found that unstable angina and nonfatal coronary events were reduced in the EPA group, though sudden cardiac death and coronary death were not. JELIS concluded that that EPA may be a potential treatment in the prevention of major coronary events, having the greatest effects on nonfatal coronary events in hypercholesterolemic Japanese patients.

These long chain polyunsaturated fatty acids (PUFAs) are thought to be beneficial in CV disease for several reasons. They’re believed to have anti-arrhythmic effects, to decrease heart rate and increase parasympathetic tone, to inhibit inflammation and to improve endothelial cell function.

Not so fast

That’s the good news. But there are plenty of trials with contrary results. A 2008 German study called OMEGA followed 3,827 patients who were randomized to treatment with omega-3 or olive oil for one year following a heart attack. This study found no end point differences between the two groups; neither primary (sudden cardiac death) nor secondary end points (total mortality, reinfarction, stroke, arrhythmic events and revascularization) differed. Total death in the placebo group (olive oil) was 3.7%, and 4.6% in the omega-3 group. The OMEGA study researchers pointed out that patients in their trial took aspirin, beta-blockers and statins, and 80% of their patients had received acute revascularization and 90% were on clopidogrel. The GISSI-Prevenzione study was done in an era when these therapies weren’t used to the same degree.

Similarly, studies such as SOFA and DART-2 have found no benefit to omega-3s. SOFA followed 546 patients with secondary prevention ICDs, randomized to receive either 2 g of fish oil or sunflower oil. They found no protective effect from fish oils in these patients. DART-2 (Diet and Reinfarction Trial) supplemented patients suffering from angina with polyunsaturated fatty acids. They actually saw a 26% increase in mortality. Other trials have found negative results for prevention of ventricular tachyarrhythmias in patients with previous ventricular tachycardia or ventricular fibrillation and implanted cardioverter defibrillators.

One potential negative to consuming too much fish is mercury content. Mercury is only highly present in fish such as swordfish, sharks, marlin, escolar (orange roughy) and albacore tuna. High mercury fish intake should be limited to 150 g per week for the average person. The limits are even lower for pregnant women and children (75-150 g/month). So anyone eating fish for their omega-3 content will need to mostly steer clear of high mercury species.

Net positive

How should we weigh the positive and negative data on the value of fish oil? The massive NIH VITAL study, set to get underway early this year, will be randomizing patients to receive either vitamin D supplements (1,000 IU) and fish oil placebo, fish oil supplements (1 g) and vitamin D placebo or placebos of both. This will hopefully give more insight than the contradictory existing data on the effectiveness of these supplements at reducing risk of heart disease, stroke and cancer.

For now, I think the trials do, on balance, show a benefit. My current recommendation is to eat fatty fish, such as salmon, sardines and mackerel, 4-5x/week. Those who don’t like fish and want to take a supplement can look at labels for the total content of DHA and EPA, aiming for 1,000 mg/ day. The AHA, European Society of Cardiology and WHO currently advise healthy individuals to aim for 500 mg/day of EPA/DHA (equivalent to two fatty fish meals per week), while those with known CHD or HF should consume 800-1,000 mg/day. Fish is simply a healthy food, it’s relatively high in protein, low in unhealthy fats, and certain fish are of course rich in omega-3s. Vegetable precursors to EPA, such as alpha-linolenic acid (ALA), found in flaxseeds and other plants, are also healthy foods but the data on additional vascular protection is much weaker and deserves more research.