Omega-3 Fatty Acids

Omega-3 fatty acids, at a dosage of 2 to 4 g per day, lower triglycerides and are therefore primarily used in cases of primary hypertriglyceridemia. In mixed hyperlipidemias, omega-3 fatty acids can be combined with statins or fibrates to lower triglycerides, but the results are inconsistent.

It is believed that omega-3 fatty acids reduce cardiovascular risk. Early studies showed that low doses (1 g per day) reduced cardiovascular risk. However, these studies were conducted in Italy and Japan, where the populations already consume a high amount of omega-3 fatty acids through diet. In those settings, an additional 1 g per day was sufficient to have a positive effect.

Studies in the USA and Europe were unable to reproduce these results, and the protective effect of low-dose omega-3 fatty acids on cardiovascular events could not be confirmed. Higher doses of 2 to 4 g per day of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) produced conflicting results.

However, a highly purified ester of EPA (Icosapent Ethyl), at a dose of 4 g per day, significantly reduced both triglycerides and cardiovascular event risk, including cardiovascular death, with a Number Needed to Treat (NNT) of 21.

Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., … & Ballantyne, C. M. (2019).
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.
New England Journal of Medicine, 380(1), 11–22. https://doi.org/10.1056/NEJMoa1812792

It was subsequently discovered that the different components of omega-3 fatty acids—EPA and DHA—have distinct mechanisms of action at the cellular level. The debate remains ongoing. Still, EPA clearly reduces cardiovascular risk.

However, omega-3 fatty acids increase the risk of atrial fibrillation, with a Number Needed to Harm (NNH) of about 100. This effect appears independent of the formulation used, meaning the increase in atrial fibrillation risk is small.

For patients with very high cardiovascular risk, omega-3 fatty acids can therefore still be considered as an add-on therapy to existing lipid-lowering treatment.

The main side effects are gastrointestinal symptoms, including nausea and diarrhea.