My patients often ask me if they should try one or the other supplement. Often times my answer is ambiguous because for most supplements we simply don’t have enough evidence to give an unequivocal answer. This does not mean that a particular patient may not benefit from a particular supplement. It just means I don’t have standardized research to guide my recommendations. Unfortunately, this also applies to omega-3 fatty acid supplements. The results of studies on omega-3 supplements have been inconsistent and have led both doctors and patients to wonder what to do.

Omega-3 fatty acids show benefits in the REDUCE-IT study and receive FDA approval

Two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are mainly found in fish and fish oil. Omega-3 fatty acids from fish and fish oil have been recommended by the American Heart Association (AHA) for 20 years to help reduce cardiovascular events such as heart attacks or strokes in people with pre-existing cardiovascular disease (CVD). I’ve written about it and been a strong advocate of getting omega-3s through diet and sometimes through the use of supplements.

Over the past year, I have prescribed an omega-3 drug, sold under the brand name Vascepa, to my patients at high risk for CVD based on evidence of cardiovascular benefits. Vascepa contains purified EPA and its use is based on good clinical data from the REDUCE-IT study. This study included over 8,000 patients with increased cardiovascular risk and high blood triglyceride levels. They instructed half of the study participants to receive 2 grams of Vascepa twice a day, and the other participants were given a placebo (a pill filled with mineral oil). The results showed a significant benefit from Vascepa over placebo. Vascepa reduced triglyceride levels in the blood, but more importantly, it reduced the number of heart attacks and strokes, the need for a cardiac stent procedure to open clogged arteries, and death.

A subsequent meta-analysis, which included data from over 10 studies, found that omega-3 supplements made from fish oil lower the risk of heart attack and death from coronary artery disease.

In December 2020, the FDA approved the use of Vascepa to reduce the risk of cardiovascular events in certain patients at or at high risk for CVD.

The STRENGTH study casts doubt on the benefits of omega-3

However, a recent study has raised some questions. The STRENGTH study published in JAMA looked at a different formulation of omega-3 fish oil – a combination of EPA and DHA – to see if it would also reduce cardiovascular risk. This study enrolled over 13,000 patients who were randomized to receive either the EPA / DHA combination pill or placebo (a pill filled with corn oil). The study was terminated prematurely because an interim analysis showed no difference between the two treatment groups.

We don’t know exactly why the REDUCE-IT study showed omega-3 fatty acids benefit while the STRENGTH study didn’t. One possibility is that the different results are due to the different drugs studied. REDUCE-IT studied a purified formulation of high dose EPA, which resulted in higher EPA levels. This was similar to the results of another study that also found that pure EPA reduced the risk of cardiac events. A combination of EPA and DHA was tested in the STRENGTH study. No large study has ever looked at the effects of purified DHA on cardiovascular outcomes alone, so we have to wonder if DHA might counteract EPA’s benefits.

Where are we standing?

Back to my patients who want to know if they should be taking an omega-3 supplement. Given the availability of data today, I would recommend an EPA-only supplement or one that contains more EPA than DHA. But don’t stop there. Eat a healthy heart, exercise regularly, and pursue other lifestyle changes that have been shown to be beneficial for cardiovascular health. In the meantime, my colleagues and I are waiting for more detailed data on the benefits of omega-3 fish oil and who could benefit most from it.

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