What are the effects of fatty acid (FA) supplements?

From the Guidelines

Fatty acid supplements, specifically omega-3 fatty acids, should be used with caution due to the increased risk of atrial fibrillation (AF), and their use should be individualized based on the patient's risk factors and medical history. When considering the use of fatty acid supplements, it is essential to weigh the potential benefits against the risks, particularly the risk of AF, which has been consistently demonstrated in recent studies 1. The American College of Cardiology expert consensus decision pathway recommends the use of prescription omega-3 fatty acid products, such as icosapent ethyl, for the treatment of elevated triglyceride levels, but also highlights the importance of evaluating the potential net benefit in patients at high risk of AF 1.

Key Considerations

• The use of nonprescription fish oil supplements is not recommended for ASCVD risk reduction due to the lack of FDA approval, inconsistent content and purity, and potential for adverse effects 1.
• Prescription omega-3 fatty acid products, such as icosapent ethyl, have been shown to reduce the risk of major adverse cardiovascular events, but may increase the risk of AF, particularly in patients with previous AF 1.
• The risk of AF associated with omega-3 fatty acid supplementation appears to be dose-dependent, with higher doses (> 1 g daily) increasing the risk of AF 1.

Recommendations

• Prescription omega-3 fatty acid products should be used under the guidance of a healthcare provider, and patients should be closely monitored for signs and symptoms of AF.
• Patients with elevated triglyceride levels and established cardiovascular disease or diabetes mellitus with additional risk factors for cardiovascular disease may benefit from prescription omega-3 fatty acid products, but the potential net benefit should be carefully evaluated 1.
• Nonprescription fish oil supplements should not be used as a substitute for prescription omega-3 fatty acid products, and patients should be advised of the potential risks and limitations of these supplements 1.

From the FDA Drug Label

LOVAZA is a combination of ethyl esters of omega 3 fatty acids, principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. The primary use of omega-3 fatty acid supplements, such as LOVAZA, is to reduce triglyceride levels in adults with severe hypertriglyceridemia [ 2 ].

• The indication is specifically for patients with triglyceride levels ≥500 mg/dL.
• The supplement is used as an adjunct to diet, implying that it should be used in conjunction with dietary changes.

From the Research

Fatty Acid Supplements

• Fatty acid supplements, particularly omega-3 fatty acids, have been shown to be effective in reducing triglyceride levels and managing hypertriglyceridemia 3, 4, 5.
• The mechanisms of action of omega-3 fatty acids include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation 3.
• Omega-3 fatty acid supplements have been found to be well-tolerated and effective in reducing triglyceride levels, with some studies showing a reduction of up to 30% in triglyceride levels 3, 5.

Types of Fatty Acid Supplements

• There are different types of omega-3 fatty acid supplements, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) 3, 5.
• EPA-only supplements have been found to be effective in reducing triglyceride levels without increasing low-density lipoprotein cholesterol 5.
• DHA-containing supplements may increase low-density lipoprotein cholesterol, but this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk 3.

Clinical Utilities

• Omega-3 fatty acid supplements have been found to be effective in reducing the risk of atherosclerotic cardiovascular disease (ASCVD) 5, 6.
• The use of omega-3 fatty acid supplements has been shown to reduce major adverse cardiovascular events in high-risk patients treated with a statin 5.
• Omega-3 fatty acid supplements have anti-inflammatory mechanisms that can help reduce the risk of ASCVD 6.