What are the clinical benefits of omega-3 (polyunsaturated fatty acid) supplementation?

From the Guidelines

Omega-3 fatty acid supplementation, particularly with EPA, has been shown to have significant clinical benefits in reducing cardiovascular risk, with a 25% reduction in the primary composite endpoint of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina, as demonstrated in the REDUCE-IT trial 1. The benefits of omega-3 supplementation are most pronounced in patients with elevated triglyceride levels, with prescription-grade omega-3 fatty acids, including mixtures of EPA and DHA, and purified EPA, at doses of 4 grams per day, shown to lower very high triglyceride levels 1. Some key points to consider when prescribing omega-3 supplements include:

• The dose and formulation of the supplement, with EPA-only supplements potentially offering more benefits than combination EPA and DHA supplements 1
• The patient's underlying cardiovascular risk factors, with those at higher risk potentially benefiting more from omega-3 supplementation 1
• The potential for interactions with other medications, such as anticoagulants, and the need for monitoring of bleeding risk 1
• The importance of choosing high-quality supplements that are tested for purity and oxidation 1 Overall, the evidence suggests that omega-3 fatty acid supplementation, particularly with EPA, can be a useful adjunctive therapy for reducing cardiovascular risk in patients with elevated triglyceride levels or other cardiovascular risk factors, as supported by the findings of the REDUCE-IT trial 1 and the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

From the Research

Clinical Benefits of Omega 3 Supplementation

• Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease 2.
• The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease 2.
• Omega-3 fatty acids are also used to treat hyperlipidemia and hypertension, with higher dosages required to reduce elevated triglyceride levels (2-4 g/day) 2, 3.
• Prescription omega-3 fatty acids (EPA+DHA or EPA-only) at a dose of 4 g/d are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents 3.
• The use of omega-3 fatty acids for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in the REDUCE-IT trial 3.

Dosage and Efficacy

• The lowest doses shown to be effective in raising the omega-3 index to recommended levels were >1,000 mg/d of combination DHA plus EPA for 12 weeks or longer 4.
• Supplements composed of triglycerides were more bioavailable and thus more effective than other formulas 4.
• Practical recommendations to improve the omega-3 index to ≥8% are consumption of 1,000-1,500 mg/d EPA plus DHA as triglycerides for at least 12 weeks 4.
• Dietary supplementation with omega-3 fatty acids significantly reduced the risk of cardiovascular deaths, sudden cardiac death, all-cause mortality, and nonfatal cardiovascular events 5.

Patient Groups

• Omega-3 fatty acid supplementation has been shown to be beneficial in patients with known coronary heart disease, hypertriglyceridemia, and those at high risk of cardiovascular disease 2, 3, 6.
• The mortality benefit of omega-3 fatty acid supplementation was largely due to the studies which enrolled high-risk patients, while the reduction in nonfatal cardiovascular events was noted in the moderate risk patients (secondary prevention only) 5.