From the Guidelines
High EPA levels on a lipid profile are generally not dangerous and may actually be beneficial for cardiovascular health, as evidenced by the most recent and highest quality study, REDUCE-IT 1. EPA is an omega-3 fatty acid found in fatty fish and fish oil supplements that has been shown to reduce triglycerides, decrease inflammation, and potentially lower the risk of heart disease. When EPA appears elevated on a lipid profile, it typically reflects either a diet rich in fatty fish (such as salmon, mackerel, or sardines) or the use of fish oil or prescription omega-3 supplements. For those taking supplements, typical over-the-counter fish oil doses range from 1-3 grams daily, while prescription omega-3 products like Vascepa (icosapent ethyl) are prescribed at 2-4 grams daily for high triglycerides. Very high EPA levels are rarely associated with adverse effects, though some people might experience minor side effects like fishy taste, mild gastrointestinal discomfort, or slightly increased bleeding risk. The cardiovascular benefits of EPA are thought to come from its anti-inflammatory properties, ability to reduce blood clotting, and favorable effects on blood vessel function. Unless specifically advised otherwise by a healthcare provider, elevated EPA levels are considered a positive finding on a lipid profile, as supported by studies such as REDUCE-IT 1 and JELIS 1, which demonstrated a reduction in cardiovascular events with EPA supplementation. Key findings from these studies include:
- A 25% reduction in the primary composite endpoint of non-fatal myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization with EPA supplementation 1
- A 19% reduction in major coronary events, including sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina, percutaneous coronary intervention, and coronary artery bypass grafting, with EPA supplementation 1 Overall, the current evidence suggests that high EPA levels on a lipid profile are not only safe but also potentially beneficial for cardiovascular health, and patients with elevated EPA levels should be reassured and encouraged to continue their current regimen, unless otherwise advised by their healthcare provider.
From the Research
Effects of High EPA on Lipid Profile
- High doses of EPA have been shown to have varying effects on lipid profiles, with some studies suggesting that DHA may have stronger serum triglyceride-lowering effects than EPA 2.
- EPA supplementation has been found to increase the lipogenic index and δ13C-16:0, indicating increased lipogenesis, whereas DHA supplementation reduces blood triglycerides without changing the lipogenic index or δ13C-16:0 2.
- The impact of EPA and DHA on blood lipids and lipoprotein metabolism may be influenced by apoE genotype, with recent evidence suggesting that apoE genotype may be responsible for the highly-heterogenous response of LDL-cholesterol to fish oil intervention 3.
Safety of High EPA Consumption
- Studies have investigated the safety of consuming high doses of EPA, particularly in combination with other medications such as aspirin and clopidogrel.
- One study found that high-dose fish oil (mean dose 3 +/- 1.25 g) is safe in combination with aspirin and clopidogrel and does not increase the risk of bleeding compared with that seen with aspirin and clopidogrel alone 4.
- Another study analyzed 8 clinical intervention studies and found no evidence of increased risk of bleeding with use of n-3 LC-PUFAs, even at short-term doses up to 10 g/day of EPA + DHA or consumed for up to 52 weeks above 1.5 g/day 5.
Cardiovascular Benefits of EPA and DHA
- Omega-3 fatty acids, including EPA and DHA, have been shown to reduce cardiovascular disease risk, with epidemiologic data suggesting that they reduce cardiovascular disease 6.
- A systematic review of prospective, randomized, placebo-controlled clinical trials found that dietary supplements of EPA and DHA decrease cardiovascular events across a spectrum of patients, including those at high and moderate risk of cardiovascular events 6.