Marine-Derived Omega-3 Fatty Acids (EPA and/or DHA) at 2-4 Grams Daily for Elevated Triglycerides
For patients with elevated triglycerides, prescribe marine-derived omega-3 fatty acids containing EPA and/or DHA at a dose of 2-4 grams per day under physician supervision, with 4 grams daily being optimal for maximal triglyceride reduction. 1, 2
Formulation Requirements
Only marine-derived omega-3 fatty acids (EPA and DHA) are effective for triglyceride lowering. 1
Plant-based omega-3 fatty acids (α-linolenic acid from flaxseed, walnuts, chia) have not demonstrated consistent triglyceride reductions due to very low conversion rates to the active compounds EPA and DHA. 1
Prescription omega-3 products are required for consistent dosing and purity—over-the-counter fish oil supplements have variable content, quality, and may contain impurities. 2, 3, 4
Dosing Algorithm by Clinical Context
For Severe Hypertriglyceridemia (≥500 mg/dL)
- Prescribe 4 grams daily of prescription EPA+DHA to reduce triglycerides by 25-45% and lower pancreatitis risk. 2, 3, 4, 5
- Implement very low-fat diet (10-15% of calories from fat) concurrently. 3
For Moderate Hypertriglyceridemia (150-499 mg/dL) with Cardiovascular Disease or Diabetes
- Prescribe icosapent ethyl (pure EPA) 4 grams daily as adjunct to maximally tolerated statin therapy if patient has established cardiovascular disease or diabetes with ≥2 additional risk factors. 2, 3, 5
- This regimen reduces major cardiovascular events by 25% based on the REDUCE-IT trial. 2, 3, 5
For Moderate Hypertriglyceridemia Without High-Risk Features
- Prescribe 2-4 grams daily of prescription EPA+DHA under physician supervision for triglyceride reduction of 20-30%. 1, 2, 6, 7
Expected Lipid Effects
Triglyceride reduction: 20-50% depending on baseline levels, with greater reductions in patients with higher baseline triglycerides. 1, 2
LDL-C may increase by 5-10% with EPA+DHA formulations in patients with very high triglycerides, requiring periodic monitoring. 2, 3, 5
Pure EPA formulations (icosapent ethyl) do not raise LDL-C at any dose, making them preferable when LDL elevation is a concern. 2, 5
HDL-C typically increases modestly by 1-3%. 1
Mechanisms of Action
Omega-3 fatty acids reduce triglycerides through decreased VLDL triglyceride secretion from the liver via preferential shunting into phospholipid synthesis, reduced SREBP-1 expression, enhanced peroxisomal β-oxidation, and upregulation of lipoprotein lipase facilitating VLDL clearance. 1, 2
Critical Safety Monitoring
Monitor for atrial fibrillation, particularly at doses ≥1.8 grams daily—risk increases by approximately 25% at therapeutic doses. 2, 3, 5
Monitor LDL-C levels periodically when using EPA+DHA formulations, as levels may rise by 5-10%. 2, 3, 5
Evaluate for gastrointestinal disturbances (most common adverse effect), skin changes, and bleeding risk. 2, 3
Dietary Sources (Adjunctive to Pharmacotherapy)
For patients preferring dietary approaches, fatty fish provide EPA and DHA: 1
- Anchovy, herring, farmed Atlantic salmon: ~2.1 grams per 3.5-oz serving
- Wild Atlantic salmon: ~1.8 grams per 3.5-oz serving
- Sardines, trout: ~1.0-1.4 grams per 3.5-oz serving
However, achieving therapeutic doses of 2-4 grams daily through diet alone is impractical and requires prescription formulations. 2, 3, 4
Common Pitfalls to Avoid
Do not prescribe over-the-counter fish oil supplements for therapeutic triglyceride lowering—they lack FDA approval, have variable content, and inconsistent quality. 2, 3
Do not use omega-3s for LDL cholesterol lowering—they typically increase LDL-C by 5-10% and are indicated specifically for triglyceride reduction. 2, 8
Do not use plant-based omega-3s (α-linolenic acid) for triglyceride lowering—they are ineffective due to poor conversion to EPA and DHA. 1
Do not initiate high-dose omega-3s without evaluating atrial fibrillation risk, especially in patients with prior arrhythmia history. 2, 3, 5