What are the recommendations for taking Omega-3 (fatty acids) for the management of Hypertriglyceridemia?

From the Guidelines

For effective treatment of hypertriglyceridemia, take 2-4 grams of EPA+DHA omega-3 fatty acids daily, preferably through prescription products like Vascepa (icosapent ethyl) or Lovaza (omega-3 ethyl esters), as they provide more concentrated and purified forms, especially for severe hypertriglyceridemia (triglycerides >500 mg/dL) 1. When using over-the-counter supplements, it is crucial to check the label for actual EPA+DHA content and choose products that have been tested for purity. Taking omega-3s with meals can improve absorption and reduce fishy aftertaste. Starting with lower doses and gradually increasing can help minimize potential side effects like fishy taste, mild gastrointestinal discomfort, or burping. The mechanism of action of omega-3s involves decreasing the liver's production of triglycerides and VLDL cholesterol while enhancing triglyceride clearance from the bloodstream, as supported by studies such as the one published in Circulation 1. For optimal results, combining omega-3 supplementation with dietary changes (reducing refined carbohydrates and alcohol), regular exercise, and other medications if prescribed by your doctor is recommended. It's also important to note that prescription omega-3 fatty acids have been shown to lower very high triglyceride levels, but the potential net benefit should be evaluated, especially in patients at high risk of atrial fibrillation, as indicated in the 2021 ACC expert consensus decision pathway 1. Key points to consider include:

• The American Heart Association recommends 2 to 4 g of EPA plus DHA per day for patients who need to lower their triglyceride level 1.
• Prescription omega-3 products are preferred over nonprescription fish oil supplements due to their consistent content, purity, and efficacy verified by the FDA 1.
• The most recent and highest quality studies, such as REDUCE-IT, have demonstrated the effectiveness of omega-3 fatty acids, particularly EPA, in reducing cardiovascular events in patients with hypertriglyceridemia 1.

From the FDA Drug Label

LOVAZA (omega-3-acid ethyl esters) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (greater than or equal to 500 mg/dL) hypertriglyceridemia The daily dose of LOVAZA is 4 grams per day The daily dose may be taken as a single 4-gram dose (4 capsules) or as two 2-gram doses (2 capsules given twice daily) Patients should be advised to swallow LOVAZA capsules whole. Do not break open, crush, dissolve, or chew LOVAZA

Key Points:

• Indication: Omega-3 fatty acid (LOVAZA) is used to reduce triglyceride levels in adult patients with severe hypertriglyceridemia.
• Dosage: The daily dose is 4 grams per day, taken as a single 4-gram dose or as two 2-gram doses.
• Administration: Patients should swallow the capsules whole, without breaking, crushing, dissolving, or chewing them 2, 2.

From the Research

Omega-3 Fatty Acids for Hypertriglyceridemia

• Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been approved by the United States Food and Drug Administration as an adjunct to diet for the treatment of very high triglyceride levels 3.
• The recommended dose of EPA and DHA for triglyceride lowering is approximately 2-4 g/day, with a total of 0.84 g of these two active ingredients in every 1-g capsule of omega-3 fatty acids 3.
• Prescription omega-3 fatty acids have been shown to reduce triglyceride levels by 45% and very low-density lipoprotein cholesterol levels by more than 50% in patients with triglyceride levels above 500 mg/dl 3, 4.

Forms of Omega-3 Fatty Acids

• There are several prescription formulations of omega-3 fatty acids available, including omega-3 fatty acid ethyl esters (OM3EE), icosapent ethyl (IPE), and omega-3 carboxylic acids (OM3CA) 5.
• These formulations have been shown to be effective in reducing triglyceride and very-low-density lipoprotein levels, with some formulations also increasing low-density lipoprotein cholesterol 5.
• The bioavailability of OM3CA is up to 4-fold greater than that of OM3FA ethyl esters, and its absorption is not dependent on pancreatic lipase hydrolysis 5.

Safety and Efficacy

• Omega-3 fatty acids have been shown to be well tolerated, with a low rate of adverse events and treatment-associated discontinuations 3, 5.
• The use of omega-3 fatty acids for the treatment of hypertriglyceridemia has been supported by several studies, including the REDUCE-IT trial, which showed a 25% reduction in major adverse cardiovascular events in patients treated with EPA-only 6.
• Omega-3 fatty acids can be used as monotherapy or in combination with other lipid-lowering agents, such as statins and fibrates, to reduce triglyceride levels and improve cardiovascular outcomes 6, 7.