Eicosapentaenoic acid (EPA) is a long-chain omega-3 polyunsaturated fatty acid found predominantly in oily fish such as salmon, mackerel, and sardines. EPA plays a vital role in cardiovascular health, particularly in reducing triglyceride levels and lowering cardiovascular risk when used as prescription-strength icosapent ethyl alongside statin therapy. Once consumed, EPA becomes incorporated into cell membranes, where it influences inflammation, cellular signalling, and the production of bioactive compounds. Available both as dietary supplements and licensed medicines in the UK, EPA's therapeutic applications extend beyond heart health to include potential benefits in inflammatory conditions and mental health, though evidence varies across these indications.

What Is Eicosapentaenoic Acid (EPA)?

Eicosapentaenoic acid (EPA) is a long-chain omega-3 polyunsaturated fatty acid predominantly found in marine sources such as oily fish, including salmon, mackerel, sardines, and herring. Unlike alpha-linolenic acid (ALA), EPA is not considered essential as the body can synthesise it in limited amounts from ALA. However, dietary intake or supplementation is typically needed to achieve significant levels. Structurally, EPA contains 20 carbon atoms and five double bonds, which classifies it as a highly unsaturated fatty acid with significant biological activity.

EPA serves as a crucial precursor for various bioactive compounds within the body. Once consumed, it becomes incorporated into cell membranes throughout the body, where it influences membrane fluidity and cellular signalling processes. EPA works through multiple mechanisms, including conversion into eicosanoids (signalling molecules such as prostaglandins, thromboxanes, and leukotrienes of the 3-series), production of specialised pro-resolving mediators called resolvins, and effects on gene expression. These compounds generally exhibit anti-inflammatory properties, contrasting with the more pro-inflammatory eicosanoids derived from omega-6 fatty acids.

In clinical practice, EPA is available both as a component of standard fish oil supplements (typically combined with docosahexaenoic acid or DHA) and as a prescription medicine. In the UK, icosapent ethyl (Vazkepa), a highly purified EPA ethyl ester, is licensed for specific cardiovascular indications. The MHRA regulates these medicinal products, whilst dietary supplements containing EPA fall under food supplement regulations. Understanding the distinction between food supplements and licensed medicines is important, as prescription formulations contain standardised, pharmaceutical-grade EPA at higher concentrations than typical over-the-counter products.

Health Benefits and Clinical Uses of EPA

EPA exerts multiple physiological effects that contribute to cardiovascular health and metabolic function. Cardiovascular benefits represent the most extensively researched area, with evidence demonstrating that EPA can reduce triglyceride levels, a recognised risk factor for cardiovascular disease. NICE Technology Appraisal 805 specifically recommends icosapent ethyl with statin therapy for reducing cardiovascular risk in adults with established cardiovascular disease, elevated triglycerides (≥1.7 mmol/L), and LDL-cholesterol controlled by statins. It's important to note that general omega-3 fish oil supplements and other prescription omega-3 products containing both EPA and DHA are not recommended by NICE for cardiovascular disease prevention.

The anti-inflammatory properties of EPA have generated interest in various inflammatory conditions. EPA competes with arachidonic acid (an omega-6 fatty acid) for incorporation into cell membranes and for metabolism by cyclooxygenase and lipoxygenase enzymes. This competition results in reduced production of pro-inflammatory mediators. Some research suggests potential benefits in rheumatoid arthritis, with patients reporting reduced joint pain and stiffness, though evidence quality varies and EPA should not replace conventional disease-modifying treatments. UK guidelines do not currently recommend EPA for rheumatoid arthritis management.

Mental health applications have also been investigated, particularly in depression. Some studies indicate that EPA supplementation may provide modest benefits as an adjunct to standard antidepressant therapy. However, NICE guidelines do not recommend omega-3 supplements as a treatment for depression, and patients should not discontinue prescribed medications without medical supervision.

Other areas of ongoing research include EPA's potential role in cognitive function, skin health, and inflammatory bowel disease. Whilst preliminary findings appear promising in some contexts, the evidence base remains insufficient for definitive clinical recommendations. Patients considering EPA for conditions beyond established cardiovascular indications should discuss this with their GP or specialist to ensure appropriate, evidence-based management of their condition.

EPA Dosage and How to Take It Safely

The appropriate EPA dosage varies considerably depending on whether it is being used for general health maintenance or specific therapeutic purposes. For cardiovascular risk reduction, the UK-licensed icosapent ethyl (Vazkepa) is prescribed at a dose of 2 g twice daily with food (total 4 g/day). This high-dose formulation requires medical supervision and is prescribed following assessment of cardiovascular risk factors and triglyceride levels. By contrast, prescription omega-3-acid ethyl esters (containing both EPA and DHA) are used at doses of 2-4 g daily for severe hypertriglyceridaemia but are not licensed for cardiovascular event reduction. Over-the-counter fish oil supplements generally contain much lower EPA concentrations, often 180–500 mg per capsule, combined with DHA.

For general dietary intake, the NHS recommends consuming two portions of fish per week, one of which should be oily fish (approximately 140 grams per portion). This provides omega-3 fatty acids, including EPA, as part of a balanced diet. Those who do not consume fish regularly may consider supplements, though whole food sources are generally preferable due to additional nutritional benefits.

Administration guidance includes taking EPA supplements with food to enhance absorption and reduce gastrointestinal side effects. The fat content of meals facilitates the absorption of these lipid-soluble compounds. Capsules should be swallowed whole with water and not chewed, as this may cause an unpleasant fishy taste. Some formulations use enteric coating to minimise aftertaste and reduce gastrointestinal discomfort.

Patients should inform their GP or pharmacist about all EPA-containing supplements they are taking. Those on prescribed EPA should not discontinue treatment before surgery without consulting their surgeon or anaesthetist. Patients taking anticoagulant medications (such as warfarin) or antiplatelet drugs (such as clopidogrel or aspirin) should be aware of potential increased bleeding risk with EPA. For prescription-strength EPA products, regular monitoring of lipid profiles is recommended to assess therapeutic response, and liver function tests should be monitored, particularly in patients with hepatic impairment.

Side Effects and Safety Considerations

EPA is generally well tolerated at recommended doses, though several side effects may occur, particularly with higher-dose formulations. Common adverse effects include:

• Gastrointestinal symptoms: Nausea, diarrhoea, indigestion, and abdominal discomfort affect approximately 5–10% of users. These effects are typically mild and often resolve with continued use or by taking supplements with meals.

• Fishy aftertaste or burping: This occurs frequently with standard fish oil preparations. Enteric-coated or highly purified formulations may reduce this effect.

• Loose stools: Higher doses (above 3 grams daily) may cause softer or more frequent bowel movements.

More significant concerns include potential effects on bleeding time. Clinical evidence shows increased bleeding risk with icosapent ethyl, particularly when used with anticoagulants or antiplatelet medications. Patients should seek medical advice rather than routinely discontinuing treatment before procedures.

Atrial fibrillation or flutter is another important risk, particularly with high-dose icosapent ethyl. Patients should seek medical advice if they experience palpitations or irregular heartbeat.

Precautions should be taken in patients with fish or shellfish allergies. While not an absolute contraindication for icosapent ethyl, caution is advised, and patients should check the product information and discontinue if allergic reactions occur. There is insufficient data on EPA use during pregnancy and breastfeeding; women should consult their healthcare provider and avoid fish liver oil supplements (which contain vitamin A) during pregnancy.

When to seek medical advice: Contact your GP if you experience persistent gastrointestinal symptoms, unusual bruising or bleeding, palpitations, allergic reactions (rash, swelling, breathing difficulties), or if you develop new symptoms after starting EPA. Patients taking prescription EPA should attend scheduled monitoring appointments to assess treatment efficacy and safety. Quality assurance is important when selecting supplements—choose products certified by reputable organisations to ensure purity and absence of contaminants such as heavy metals or environmental pollutants commonly found in marine sources.

If you suspect you have experienced a side effect from an EPA product, you can report this through the MHRA Yellow Card scheme.

Frequently Asked Questions