What are the effects of Omega-3 (n-3) fatty acids?

From the Guidelines

Omega-3 fatty acids, specifically prescription-grade omega-3 fatty acids, have been shown to lower very high triglyceride levels and reduce the risk of cardiovascular events, particularly in patients with established cardiovascular disease or diabetes mellitus and additional risk factors, and should be considered as an adjunct to maximally tolerated statin therapy or diet for these patients. When considering omega-3 fatty acid supplementation, it is essential to distinguish between nonprescription fish oil products and prescription omega-3 products, as the latter are FDA-approved to treat elevated triglyceride levels and have verified efficacy and consistent content and purity 1. The most recent and highest quality study, REDUCE-IT, demonstrated a 25% reduction in the primary composite endpoint of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina with 4 g of EPA (in the form of IPE) daily versus mineral oil placebo in patients with elevated triglyceride levels and established cardiovascular disease or diabetes mellitus and additional risk factors 1. Some key points to consider when prescribing omega-3 fatty acids include:

• Typical doses range from 250-1000mg combined EPA and DHA daily for general health, while higher therapeutic doses (2-4g daily) may be recommended for specific conditions like high triglycerides
• Prescription omega-3 products, such as IPE, are indicated as an adjunct to maximally tolerated statin therapy to reduce the risk of MI, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride levels and established cardiovascular disease or diabetes mellitus and additional risk factors
• Potential side effects of omega-3 fatty acid supplementation include eructation, dyspepsia, taste perversion, musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation, particularly at higher doses
• When choosing supplements, look for those containing both EPA and DHA in a ratio of approximately 3:2, and take them with meals containing some fat to improve absorption.

From the FDA Drug Label

The mechanism of action of omega-3-acid ethyl esters is not completely understood. Potential mechanisms of action include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal β-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity Omega-3-acid ethyl esters may reduce the synthesis of triglycerides in the liver because EPA and DHA are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit esterification of other fatty acids.

The effects of Omega-3 (n-3) fatty acids include:

• Reduced synthesis of triglycerides in the liver
• Inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase
• Increased mitochondrial and peroxisomal β-oxidation in the liver
• Decreased lipogenesis in the liver
• Increased plasma lipoprotein lipase activity 2

From the Research

Effects of Omega-3 Fatty Acids on Cardiovascular Health

• Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to have beneficial effects on cardiovascular health, including reducing serum triglycerides 3, 4, 5.
• However, the evidence for the effect of omega-3 fatty acids on major adverse cardiovascular events is inconsistent, with some studies showing a reduction in cardiovascular events and death, while others have found no benefit 3, 4, 5.
• Prescription-grade, EPA-only formulations have been shown to provide greater benefit than other omega-3 fatty acid formulations in reducing cardiovascular events in high-risk patients 5.

Effects of Omega-3 Fatty Acids on Bleeding Risk

• Omega-3 fatty acids have been found to affect haemostasis, but do not increase the risk of bleeding, even when used in combination with other agents that affect bleeding 6.
• The use of omega-3 fatty acids in several settings has been found to improve clinical outcomes, without increasing the risk of bleeding 6.

Recommendations for Omega-3 Fatty Acid Supplementation

• The American Heart Association has updated its recommendations for omega-3 fatty acid supplementation, based on the cumulative evidence from randomized controlled trials 7.
• Omega-3 fatty acid supplementation may be recommended for patients with prevalent coronary heart disease, as well as for patients with other clinical indications, such as diabetes mellitus and prediabetes, and those with high risk of cardiovascular disease 7.

Key Findings

• The REDUCE-IT trial demonstrated that a purified form of EPA ethyl esters (icosapent ethyl) at 4 g daily reduced cardiovascular events and death in patients with atherosclerotic cardiovascular disease (or diabetes and multiple cardiovascular risk factors) and elevated triglycerides on background statin therapy 3.
• The STRENGTH trial found that 4 g daily of omega-3 carboxylic acids (DHA and EPA) did not show a cardiovascular benefit in a similar population 3.
• EPA-only formulations have been shown to have distinct clinical efficacy compared to DHA and other omega-3 fatty acids, and may provide greater benefit in reducing cardiovascular events 5.