Ethyl esters of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are well-established pharmaceutical agents used to lower high triglyceride levels. Prescription omega-3 ethyl ester formulations, such as Lovaza (US) or Omacor (EU), have been extensively studied in randomized controlled trials. Multiple meta-analyses and clinical guidelines confirm that high-dose omega-3 ethyl esters (generally 2-4 grams per day) can reduce serum triglyceride levels by 20-50% in individuals with hypertriglyceridemia.

The mechanism involves reduced hepatic synthesis of triglycerides and increased clearance of triglyceride-rich lipoproteins. These effects are dose-dependent and most pronounced at prescription-level dosages, which are higher than typical over-the-counter fish oil supplements. The US Food and Drug Administration (FDA) has approved omega-3 ethyl esters as a treatment for severe hypertriglyceridemia, underscoring the scientific validation of their use for this purpose.

While omega-3 fatty acids can be administered as triglycerides or ethyl esters, most large clinical trials demonstrating triglyceride lowering have used the ethyl ester form. Therefore, the use of ethyl ester omega-3s for treating high triglycerides is firmly supported by high-quality scientific evidence and is reflected in medical guidelines worldwide.