Supplements for Elevated Triglycerides
Prescription Omega-3 Fatty Acids Are the Only Evidence-Based Supplement
Prescription omega-3 fatty acids (specifically icosapent ethyl 2-4g daily) are the only supplement with proven cardiovascular benefit for elevated triglycerides, while over-the-counter fish oil supplements lack equivalent efficacy and should not be substituted. 1, 2
When to Use Prescription Omega-3 Fatty Acids
Icosapent ethyl (prescription EPA) is indicated as an adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL who have either established cardiovascular disease OR diabetes with ≥2 additional risk factors. 1, 2 The REDUCE-IT trial demonstrated a 25% reduction in major adverse cardiovascular events with this therapy (number needed to treat = 21). 2, 3
Specific Dosing and Indications
For moderate hypertriglyceridemia (135-499 mg/dL) on statin therapy: Add icosapent ethyl 2g twice daily if cardiovascular disease or diabetes with additional risk factors is present. 2, 3
For severe hypertriglyceridemia (≥500 mg/dL): Prescription omega-3 fatty acids (2-4g daily) can be added as adjunctive therapy to fibrates, but fibrates remain first-line to prevent acute pancreatitis. 1, 2, 4
Critical Distinction: Prescription vs Over-the-Counter
Over-the-counter fish oil supplements are NOT equivalent to prescription formulations and should not be substituted. 2 Prescription omega-3 preparations contain standardized, purified forms of EPA (icosapent ethyl) or EPA/DHA combinations at therapeutic doses, while OTC supplements have variable content and lower concentrations. 1, 2
FDA-Approved Prescription Omega-3 Products
Icosapent ethyl (pure EPA): The ONLY triglyceride-lowering therapy approved by the FDA for cardiovascular risk reduction. 1, 2
Omega-3 carboxylic acid and omega-3-acid ethyl esters (EPA + DHA combinations): FDA-approved only for severe hypertriglyceridemia (≥500 mg/dL) as adjunct to diet, NOT for cardiovascular risk reduction. 1
Important Safety Considerations
Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids at doses of 2-4g daily. 1, 2 In REDUCE-IT, 3.1% of patients on icosapent ethyl were hospitalized for atrial fibrillation versus 2.1% on placebo (P = 0.004). 1 This risk appears consistent across all high-dose omega-3 preparations. 1
Dietary Omega-3 Fatty Acids from Food
Consuming ≥2 servings (8+ ounces) per week of fatty fish (salmon, trout, sardines, anchovies) is recommended for moderate hypertriglyceridemia as part of lifestyle modification. 2, 4 Marine-derived omega-3 fatty acids from food reduce triglycerides by 20-50% when combined with other dietary interventions. 2
Treatment Algorithm by Triglyceride Level
Mild to Moderate Hypertriglyceridemia (150-499 mg/dL)
First-line: Lifestyle modifications including weight loss (5-10% body weight), carbohydrate restriction, increased omega-3 intake from fatty fish, and regular aerobic exercise. 2, 4
Second-line: Statin therapy if 10-year ASCVD risk ≥7.5% or elevated LDL-C is present. 2, 5
Third-line: Add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) if triglycerides remain >200 mg/dL after 3 months of optimized statin therapy AND patient has established cardiovascular disease or diabetes with ≥2 additional risk factors. 2, 3
Severe Hypertriglyceridemia (≥500 mg/dL)
Immediate intervention: Fibrates (fenofibrate 54-200 mg daily) as first-line therapy to prevent acute pancreatitis. 2, 4, 5
Adjunctive therapy: Prescription omega-3 fatty acids (2-4g daily) can be added if triglycerides remain elevated after fibrate therapy and lifestyle optimization. 1, 2, 4
Why Other "Supplements" Are Not Recommended
Niacin should generally not be used, as it showed no cardiovascular benefit when added to statin therapy in clinical trials (AIM-HIGH, ACCORD), with increased risk of new-onset diabetes and gastrointestinal side effects. 2, 6 While niacin can lower triglycerides by 20-30%, the lack of cardiovascular benefit and significant side effects make it a poor choice. 6, 7, 8
Common Pitfalls to Avoid
Do not rely on over-the-counter fish oil supplements as a substitute for prescription omega-3 fatty acids—they lack proven cardiovascular benefit and have inconsistent dosing. 2
Do not add prescription omega-3 fatty acids before maximizing statin therapy in patients with moderate hypertriglyceridemia—statin intensification should come first. 2, 3
Do not use prescription omega-3 fatty acids as monotherapy—they are indicated only as adjunctive therapy to maximally tolerated statins in appropriate patient populations. 1, 2
Do not overlook secondary causes of hypertriglyceridemia (uncontrolled diabetes, hypothyroidism, excessive alcohol, certain medications) before adding supplements—treating these conditions may be more effective than any supplement. 2, 4, 5