From the Guidelines
EPA and DHA omega-3 fatty acids are generally safe, but high doses may increase the risk of atrial fibrillation (AF) and other adverse effects in specific situations, as evidenced by recent studies such as STRENGTH 1 and OMEMI 2.
Safety Profile of EPA and DHA
The safety profile of EPA and DHA is well-established, with most individuals tolerating these fatty acids without significant adverse effects. However, high doses (typically above 3 grams daily) may increase the risk of AF, as seen in studies such as STRENGTH 1 and OMEMI 2. Additionally, prescription omega-3 fatty acid preparations may cause eructation, dyspepsia, taste perversion, musculoskeletal pain, peripheral edema, constipation, gout, and AF 1.
Potential Negative Health Impacts
Some studies have suggested that omega-3 supplements might increase prostate cancer risk, though this evidence remains controversial and inconclusive. Fish oil supplements containing EPA and DHA can sometimes cause minor side effects like fishy aftertaste, bad breath, heartburn, nausea, and loose stools. People with seafood allergies should be cautious with marine-derived omega-3 supplements.
Benefits and Risks
Despite these concerns, for most healthy individuals, the cardiovascular and anti-inflammatory benefits of moderate EPA and DHA consumption (250-500mg daily) generally outweigh these potential risks. The American College of Cardiology recommends the use of prescription omega-3 fatty acid preparations, such as icosapent ethyl (IPE), as an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride levels and established cardiovascular disease or diabetes mellitus with additional risk factors 1.
Key Considerations
When prescribing or recommending EPA and DHA supplements, clinicians should evaluate the potential net benefit in patients at high risk of AF and consider the following:
- High doses (above 3 grams daily) may increase the risk of AF
- Prescription omega-3 fatty acid preparations may cause adverse effects such as eructation, dyspepsia, and musculoskeletal pain
- Patients with seafood allergies should be cautious with marine-derived omega-3 supplements
- The benefits of moderate EPA and DHA consumption generally outweigh the potential risks for most healthy individuals.
From the Research
Adverse Health Impacts of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA)
- There is evidence to suggest that high doses of EPA and DHA may be associated with an increased risk of bleeding and atrial fibrillation 3, 4.
- However, other studies have found that EPA and DHA may not be associated with an increased risk of atrial fibrillation, and may even have a protective effect against ischemic brain infarcts 5, 6.
- The relationship between EPA and DHA and cardiovascular risk reduction is complex, and further research is needed to define their role in this area 7.
- Some studies have suggested that EPA may be more effective than DHA in reducing cardiovascular risk, but higher doses of EPA may also be associated with more side effects 7.
Specific Findings
- A study published in the Journal of the American Heart Association found that higher plasma levels of EPA and EPA+DHA were associated with significantly fewer hospitalized bleeding events, and higher DHA levels were associated with fewer incident atrial fibrillation events 3.
- A study published in Pharmacotherapy found that low-dose omega-3 fatty acids (DHA and EPA) did not reduce cardiovascular events or death in patients with or without established atherosclerotic cardiovascular disease, but that a purified form of EPA ethyl esters (icosapent ethyl) at 4g daily reduced cardiovascular events and death in patients with elevated triglycerides on background statin therapy 4.
- A study published in Nutrients found that EPA correlated inversely with the prevalence of ischemic brain infarcts in patients with atrial fibrillation, but that DHA and total n-3 FAs did not have a significant association 5.
- A study published in the Journal of the American College of Cardiology found that in vivo levels of omega-3 fatty acids, including EPA, DPA, DHA, and EPA+DHA, were not associated with an increased risk of incident atrial fibrillation 6.