Lipid-modifying agents. Omega-3 polyunsaturated fatty acids
ATC code: C10AX06 (Omega-3 triglycerides incl. other esters and acids)
Brand names – drugs
Vascepa, Lovaza
Brand names – supplements
Nordic Naturals Ultimate Omega, Carlson Elite Omega-3, NOW Foods Ultra Omega-3
Supplements are not tested in clinical trials and are not registered as medications.
Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids reduce hepatic triglyceride synthesis by inhibiting acyl-CoA carboxylase and stimulating fatty acid β-oxidation. They decrease VLDL secretion and enhance chylomicron clearance. Additional effects include cardiomyocyte membrane stabilisation, antiarrhythmic action, and anti-inflammatory effects via reduced pro-inflammatory eicosanoid synthesis.
First line
High-dose omega-3 PUFA (2–4 g EPA+DHA daily) reduces triglycerides by 20–50% in patients with severe hypertriglyceridaemia. The 2019 Science Advisory lists high-dose omega-3 as a first-line option when triglycerides exceed 500 mg/dL (5.6 mmol/L) to reduce acute pancreatitis risk. Omacor and similar products with at least 84% EPA+DHA content are registered for this indication.
Over-the-counter supplements with lower EPA+DHA content are not used for this indication – the therapeutic dose would require 6–8 capsules of standard fish oil daily, which is impractical.
Sources
Individual decision
Evidence is conflicting. REDUCE-IT (NEJM 2019, 8,179 patients) showed a 25% reduction in major cardiovascular events with icosapent ethyl 4 g daily in statin-treated patients with triglycerides 150–500 mg/dL. However, STRENGTH (JAMA 2020, 13,078 patients) with a similar design but a different formulation (EPA+DHA) showed no benefit. The role of the mineral oil placebo in REDUCE-IT is debated. In both trials and in OMEMI (Circulation 2021), high-dose omega-3 therapy increased atrial fibrillation incidence by 30–70% depending on formulation. A meta-analysis of 5 large RCTs (Circulation 2021, Lombardi et al.) confirmed a dose-dependent atrial fibrillation risk. 2021 includes icosapent ethyl for a narrow patient group with residual hypertriglyceridaemia. EPA+DHA mixtures (Omacor) are not indicated for cardiovascular risk reduction when triglycerides are normal.
In patients on maximally tolerated statins with residual hypertriglyceridaemia, icosapent ethyl is considered – not over-the-counter fish oil. Baseline cardiac rhythm and history of atrial fibrillation are assessed before prescribing.
Sources
Not recommended
In adults without established CVD, omega-3 PUFA capsules do not reduce cardiovascular or all-cause mortality. The 2020 Cochrane review (86 RCTs, more than 162,000 participants) found no clinically meaningful effect. The OMEMI trial (Circulation 2021) in older adults after myocardial infarction also showed no MACE reduction and increased atrial fibrillation. 2021 does not recommend omega-3 for primary prevention. An evidence-based exception is the JELIS trial (Lancet 2007) in a Japanese population with high baseline fish intake: adding EPA 1.8 g daily to statins reduced MACE by 19%. This effect has not been reproduced in populations with low baseline fish intake. Over-the-counter supplements with 300–500 mg EPA+DHA per capsule do not affect cardiovascular risk and can increase atrial fibrillation risk with long-term high-dose use.
Fatty marine fish in the diet (2 servings per week) remains the baseline recommendation by the and . Dietary omega-3 is the only form with robust evidence for reduced CVD mortality in healthy adults. Fish versus capsules is a comparison with fundamentally different evidence strength.
Sources
Not recommended
— Anti-aging and longevity: The VITAL-ancillary RCT (BMJ 2022) tested the combination of omega-3 1 g daily and vitamin D and found no significant effect on all-cause mortality or biological age markers. International guidelines do not recommend omega-3 for slowing ageing. For anti-ageing use, omega-3 is not recommended in healthy individuals.
Controlled pregnancy data are limited. Dietary omega-3 sources are encouraged in pregnancy by ACOG. High-dose pharmaceutical forms for hypertriglyceridaemia treatment are used only when clearly indicated.
Transfers into breast milk. Breast milk DHA supports infant brain development. Supplementation during breastfeeding is acceptable at supplement-level doses (up to 1 g daily) without special precautions.
omega-3 triglycerides (EPA and DHA) is evaluated for the following indications with varying evidence strength: Severe hypertriglyceridaemia (evidence tier A), Secondary cardiovascular prevention on statin therapy (evidence tier C), Primary cardiovascular prevention in individuals without established CVD (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of omega-3 triglycerides (EPA and DHA) (≥ 1 in 100): Dyspepsia, fish-flavoured eructation, Nausea, epigastric discomfort, Flatulence. See the Safety section for uncommon and serious reactions.
FDA category C. Controlled pregnancy data are limited. Dietary omega-3 sources are encouraged in pregnancy by ACOG. High-dose pharmaceutical forms for hypertriglyceridaemia treatment are used only when clearly indicated.
Transfers into breast milk. Breast milk DHA supports infant brain development. Supplementation during breastfeeding is acceptable at supplement-level doses (up to 1 g daily) without special precautions.
omega-3 triglycerides (EPA and DHA) is contraindicated in: Hypersensitivity to fish or seafood components; Haemorrhagic diathesis, haemophilia; Active clinically significant bleeding; Age under 18 months for drug formulations. Full list in the Safety section.
in healthy people with normal triglycerides, capsules do not reduce cardiovascular risk. The 2020 Cochrane review (162,000 participants) and VITAL 2019 confirmed this. Benefit is demonstrated only in narrow groups: severe hypertriglyceridaemia and statin-treated patients with residual hypertriglyceridaemia (icosapent ethyl).
large observational studies (Mozaffarian & Rimm JAMA 2006, 2018 AHA Advisory) show that regular fatty fish intake of 2 servings weekly reduces CVD mortality. Capsule fish oil at equivalent doses in healthy adults has not shown this effect. The single exception is the 2007 Japanese JELIS trial in patients with high baseline fish intake.
high-dose therapy (2–4 g daily) increases atrial fibrillation risk in a dose-dependent manner. REDUCE-IT, STRENGTH, OMEMI, and the 2021 Circulation meta-analysis documented a 30–70% increase in atrial fibrillation incidence.
systematic reviews have not confirmed an effect in adults without dementia. Some paediatric society recommendations address DHA in infants under 2 years – but not in adults.
Omacor contains 84% EPA+DHA as ethyl esters and is registered as a medicine. Mass-market fish oil contains 18–30% EPA+DHA and is registered as a supplement. A therapeutic 4 g EPA+DHA dose requires 4 capsules of Omacor or 12–15 capsules of a supplement.