Is It Time to Rethink Omega-3 Supplements?

Background

I received lots of questions about recent headlines reporting an increased risk of atrial fibrillation in individuals taking omega-3 supplements.  In the US alone, over $1.2 billion dollars is spent on the consumption of fish oil supplements.  On an individual basis, many of my patients are spending $50-60 or more a month on high quality omega-3 supplements and it’s time to evaluate whether this is a worthwhile investment, especially based on recent studies.

A few key points to help you while you read this post.  First let’s start with some common terms and abbreviations:

• I’m going to abbreviate omega-3 supplements as O3s
• The two major O3 subtypes will be referred to as DHA and EPA, which stand for eicosapentaenoic acid and docosahexaenoic acid respectively
• Atrial fibrillation is the most common heart arrhythmia (abnormal heart rhythm) disorder and I will abbreviate this as AF 

Let’s now get an understanding of some of the key studies on O3 supplements before I make some general recommendations.

Key Studies

I’ve split the trials below into those that include EPA only and those that combine DHA and EPA.  This distinction may be important as we’ll discuss later in this post.  A reminder that I’m using AF to represent the heart arrhythmia, atrial fibrillation.

EPA ONLY TRIALS

These are studies that used supplements containing EPA only, and the primary ones are the REDUCE-IT and JELIS trials.  REDUCE-IT was a higher quality study enrolling over 8,000 participants on statin who either had established heart disease or diabetes and an additional heart disease risk, and assigned half to receive the EPA supplement called Vascepa (2 grams twice daily) and assigned the other half to placebo (mineral oil pill).  The absolute risk reduction in cardiovascular events at nearly 5 years was about 5% in these high risk patients and the risk reduction in those without these risks was more modest.

The JELIS trail was run in Japan on participants also taking statins who were randomized in an open-label manner to treatment with EPA+statin or statin alone.  Similar to REDUCE-IT, there was a small, but significant reduction in heart disease events in the EPA+statin group using a lower dose of EPA (1.8g daily) compared to the REDUCE-IT trial.  Like REDUCE-IT, in individuals without existing heart disease, the benefits were not significant.

Without going into further details, both studies show a small, but significant reduction in heart disease events when EPA is added to statins in individuals with existing heart disease which becomes less significant in those without heart disease.

Side effect profiles in both studies showed that the EPA only supplement is well tolerated with a modest increase in side effects on the higher doses.

DHA + EPA TRIALS

These are studies that use a combination of both DHA and EPA, and the primary studies cited to date are the STRENGTH trial, the OMEMI trial, and the VITAL Rhythm study.  In all these studies there was no significant reduction in heart disease events, with a small increase in the risk of AF.  Somehow it appears in these studies that the addition of DHA might counteract some of the heart protective benefits of EPA alone.  The overall dose of purified EPA is also less in these trials compared to the EPA only trials.

Overall Thoughts on O3s for Heart Protection

Let’s break this down into risk categories:

1. Individuals with existing heart disease (aka secondary prevention):  EPA only supplementation has a small, but significant impact on heart disease risk reduction.  Adding EPA only to statin therapy to further reduce heart disease risk seems like a reasonable strategy and should be discussed with your physician.

As of now, using a DHA+EPA supplement does not appear to confer risk reduction and the small increase in risk of AF does not seem to make this a reasonable strategy.

2. Low risk Individuals without existing heart disease (aka primary prevention):  Right now available studies do not make a strong case for using O3s in either formulation for the prevention of heart disease.

3. High risk individuals without existing heart disease:  The REDUCE-IT trial shows small, but significant risk reduction in heart disease events for the EPA only supplement which can be considered in addition to statin therapy.  Using a DHA+EPA formulation does not have strong evidence to date in this subgroup.

The risk of AF that was highlighted in several news headlines is overall small, but given that AF is a condition that can potentially cause stroke, lead to surgical interventions, and requires being on lifelong blood thinners, I don’t think the small reduction in heart disease risk is worth it, especially for individuals in the low risk category without existing heart disease.

There are multiple lifestyle changes most of us can implement that would have a far greater impact on lowering heart disease risk than taking O3 supplements, without increasing the risk of AF.

For those of you taking O3s to lower triglycerides, keep in mind that the triglyceride lowering effects typically require much higher doses, and again there is no significant reduction in cardiovascular events which is what we really care about.

Taking higher doses of O3s to lower triglycerides also further increases the risk of AF, which is a dose-dependent side effect.   The most significant risk of AF is at daily doses of 4g/day or more, intermediate risk is at 1.8g/day, and no significant risk at 840 mg/day.

What About O3s for Non-Heart Reasons?

I do have patients who take O3s for various other non-cardiac reasons, like for autoimmune and inflammatory disorders, arthritis, and/or prevent or manage cognitive decline (memory loss, dementia, etc.).  You will need to weigh the risks and benefits in order to decide whether you should continue your supplement.

If you have experienced a benefit in your symptoms from O3s or are willing to accept the small potential risk of AF in order to prevent against other conditions, then you might decide to continue your supplements.

However, keep in mind that other than anecdotal reports and lesser quality studies, I have not seen any solid studies to show that O3s are truly effective against major chronic health conditions.

I’m also not aware of any high quality studies looking at the health impact of DHA only supplements.  Just like we are linking EPA to heart protection, DHA is theoretically linked to brain protection.  Many individuals take O3s specifically to prevent cognitive decline and also as a mood enhancer.  We will need to await further studies to see if this is a safe and effective strategy for these types of conditions.

Closing Thoughts

If your diet allows it, I would encourage you to get most of your O3s from fish.  This is one of many examples of how a nutrient (in this case O3s) exerts its therapeutic effects best when presented in the context of a whole food, rather than an isolated supplement.

The natural blend of DHA and EPA along with marine protein and multiple micronutrients found naturally in fish is a combination that purified, extracted supplements do not match.

The relatively high intake of fish might be one of the primary reasons why we see such low rates of heart disease and overall chronic disease in populations that consume high levels of fish, like with the traditional Japanese, the Inuit Eskimo, and Mediterranean diets.

Of course not all individual diets prefer or permit regular servings of fish weekly, so further studies need to be assessed to find the right dose and formulation of O3s to enhance human health.  For vegetarians, there are similarly no high quality studies available yet showing that vegetarian-based O3 supplements reduce heart disease and other chronic disease risks.

Finally, we must also pay attention to the risks of lower quality fish oil supplements as the global burden of toxins like PCBs , heavy metals (arsenic, lead, mercury, cadmium), and pesticides continues to increase in our fish supply.  The purest O3 supplements are costly and not easily accessible to the average consumer who often turn to lower quality products.

It may have sounded like I’ve mostly written off O3 supplements in this blog post.  That’s not the case.  I think they play a critical role in human health, specifically at the level of the cell membrane.  I discuss the science of Omega 3s in detail in my prior blog post here.

I think ongoing and future studies will likely identify more specific use cases for when O3 supplements can have potential benefit.  In the mean time, health care providers and consumers need to take a more thoughtful approach to weighing the risks, benefits, and cost of O3 supplements as a preventive and therapeutic strategy.