What is the role of fish oil in managing hypertriglyceridemia?

Role of Fish Oil in Managing Hypertriglyceridemia

Prescription omega-3 fatty acids are effective for treating hypertriglyceridemia, with icosapent ethyl (IPE) being the only FDA-approved omega-3 preparation for ASCVD risk reduction, while non-prescription fish oil supplements are not recommended due to inconsistent quality and lack of proven cardiovascular benefits. 1, 2

Treatment Algorithm Based on Triglyceride Levels

For Triglycerides 150-499 mg/dL:

• First implement comprehensive lifestyle modifications including weight loss, very low-fat diet, elimination of added sugars and alcohol, and addressing secondary causes 2
• Consider statin therapy based on ASCVD risk assessment 1
• If triglycerides remain elevated despite statin therapy, consider prescription omega-3 fatty acids, particularly IPE 2

For Triglycerides ≥500 mg/dL:

• Implement aggressive lifestyle modifications with very-low-fat diet (10-15% of calories from fat) 2
• Add prescription omega-3 fatty acids at 4 g/day 1, 2
• Consider fibrate therapy if response is inadequate 1

For Triglycerides ≥1,000 mg/dL:

• Implement extreme dietary fat restriction (<5% of calories) until levels decrease to <1,000 mg/dL 2
• Address secondary causes aggressively 2
• Add prescription omega-3 fatty acids and consider fibrate therapy 1, 2

Prescription vs. Non-Prescription Fish Oil Products

Prescription Omega-3 Products:

• FDA-approved for treating elevated triglyceride levels 1
• Consistent content and purity 1
• Generally well-tolerated 1
• IPE is indicated as adjunct to maximally tolerated statin therapy to reduce risk of cardiovascular events in adults with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease or diabetes with multiple risk factors 1, 2

Non-Prescription Fish Oil Supplements:

• Classified as dietary supplements, not FDA-approved for treating elevated triglycerides 1
• Variable content and quality; may contain impurities including saturated fat, oxidized lipids, and contaminants 1
• May require large quantities to achieve therapeutic doses, increasing caloric intake 1
• More likely to cause gastrointestinal side effects (burping, fishy taste, dyspepsia) 1
• Not recommended for ASCVD risk reduction 1

Efficacy of Omega-3 Fatty Acids

• Prescription omega-3 fatty acids at 4 grams per day have been shown to significantly lower very high triglyceride levels 1
• IPE has demonstrated cardiovascular outcome benefits in the REDUCE-IT trial 1
• Low-dose mixtures of EPA and DHA have not consistently shown cardiovascular benefits in recent large trials (ASCEND, VITAL, OMEMI) 1
• In patients with hypertriglyceridemia, fish oil can reduce triglyceride levels by 64-79% 3

Important Clinical Considerations and Side Effects

• Increased risk of atrial fibrillation is associated with higher doses (1.8-4 g daily) of prescription omega-3 preparations 1, 2
• In REDUCE-IT, more patients in the IPE group were hospitalized for atrial fibrillation or atrial flutter (3.1% vs 2.1%, P=0.004) 1
• Other common side effects include eructation, dyspepsia, taste perversion, musculoskeletal pain, peripheral edema, and constipation 1
• Omega-3 fatty acids may increase LDL cholesterol in some patients, particularly those with very high triglycerides, requiring monitoring 1
• The efficacy of fish oil may diminish over time if not maintained at appropriate doses 4

Special Populations

• In HIV-infected individuals receiving antiretroviral therapy with hypertriglyceridemia, fish oils are considered a third-line option (C-III recommendation) after fibrates and niacin 1
• For patients with severe hypertriglyceridemia associated with pancreatitis, fish oil may be considered as part of treatment, but the primary goal is to maintain triglyceride levels within normal range 1
• In diabetic patients, omega-3 supplements may be beneficial in lowering plasma triglyceride levels without adversely affecting glucose metabolism 1