Omega-3 and High Triglycerides: Evidence and Guideline Views

Terms used by the sources

• Triglycerides are a type of fat in the blood. NCCIH says excessive levels may raise the risk of heart disease. [3]
• Hypertriglyceridemia is the AHA advisory's term for triglycerides of 200 to 499 mg/dL. Very high means 500 mg/dL or higher. [2]
• US prescription labels use their own cut-offs: 150 mg/dL or higher for a heart-risk indication, and 500 mg/dL or higher for severe hypertriglyceridemia. [4]
• Units differ: US results are in mg/dL, and some countries use mmol/L. REDUCE-IT reports its entry range as 135 to 499 mg/dL (1.52 to 5.63 mmol/L). [5] Check the units on any report.

What the evidence found

1. Do EPA and DHA lower triglycerides in general?

   High certainty (Cochrane rating for this outcome)

   Cochrane 2020: about 15% reduction, dose-dependent; little or no effect on adiposity, other lipids or blood pressure. [1]

2. Same, in a review of 23 studies?

   Review summary

   NCCIH summarizing a 2020 review of 23 studies (43,998 people): about 15% lower, with no effect on body fat or other lipids. [3]

3. Very high triglycerides at 4 g a day

   Established for the lab number

   AHA advisory: EPA plus DHA prescription products lower triglycerides by 30% or more, with increases in LDL cholesterol. EPA-only did not raise LDL cholesterol in very high triglycerides. [2]

4. Triglycerides 200 to 499 mg/dL

   Established for the lab number

   AHA advisory: EPA plus DHA or EPA-only appear roughly comparable for lowering and do not raise LDL cholesterol as monotherapy or with a statin. [2]

5. Fewer heart events with a purified EPA product

   One prescription-product trial

   REDUCE-IT: 4 g a day icosapent ethyl, 17.2% vs 22.0% primary events (hazard ratio 0.75) in statin users with triglycerides 135 to 499 mg/dL. [5] The AHA advisory cites a 25% reduction in major adverse cardiovascular events. [2]

6. Fewer heart events with EPA plus DHA at 4 g a day

   No benefit shown

   STRENGTH vs corn oil: 12.0% vs 12.2% (hazard ratio 0.99); stopped early. [6]

7. Over-the-counter fish oil for triglycerides

   Proper evidence not found here

   The AHA advisory abstract we read covers pharmacological doses of more than 3 g a day of EPA plus DHA. It does not describe over-the-counter products; not described in the sources we read. [2]

What the AHA advisory concludes

The AHA advisory (Circulation, 2019) summarizes the lipid effects of pharmacological doses (more than 3 g a day total EPA plus DHA). It notes that a 2002 AHA statement had recommended 2 to 4 g a day for people with elevated triglycerides. Its conclusion: prescription omega-3 (EPA plus DHA, or EPA-only) at 4 g a day is "an effective and safe option" for reducing triglycerides alone or alongside other lipid-lowering medicines. [2] The advisory was published in 2019, and its abstract says results of a trial of 4 g a day of prescription EPA plus DHA in hypertriglyceridemia were anticipated in 2020. [2] The STRENGTH trial of an EPA and DHA product was published later, in 2020, and found no difference in cardiovascular events. [6]

Prescription vs over-the-counter

Prescription labels list use with diet to lower triglycerides of 500 mg/dL or higher, and for icosapent ethyl also a heart-risk use with a statin. [4][7] The EPA and DHA label advises periodic triglyceride and LDL cholesterol checks and ALT/AST checks in liver impairment. [7] NCCIH notes prescription products differ in composition, testing and regulation from supplements. [3] A supplement label states "fish oil 1000 mg" but the EPA plus DHA inside is a smaller number: see EPA and DHA per serving and prescription vs supplement.