EPA and DHA Supplementation Increases HDL Content in n-3 Fatty Acids and Improves Endothelial Function in Hypertriglyceridemic Patients

This small controlled clinical trial enrolled 18 hypertriglyceridemic patients and assessed the effect of combined EPA and DHA supplementation on HDL composition and endothelial function as measured by flow-mediated dilation and biochemical markers.

Supplementation significantly increased EPA and DHA content within HDL particles, improved the EPA-to-arachidonic acid (EPA:AA) ratio, and enhanced endothelial function measures in vivo. The findings suggest that omega-3 fatty acids are incorporated into HDL and may modulate its functional properties — relevant because HDL function (rather than HDL-C concentration) increasingly appears to be the more important determinant of cardiovascular protection.

The study is mechanistically interesting but severely limited by its sample size of 18 patients and lack of hard cardiovascular outcomes. The endothelial function improvement is a surrogate endpoint with uncertain prognostic significance in this population. The finding that EPA+DHA modifies HDL composition adds to the mechanistic literature, but the combined EPA+DHA formulation tested here is the same type that failed to reduce cardiovascular events in STRENGTH — suggesting that these biochemical improvements do not necessarily translate to clinical benefit.

We rate the evidence limited. A very small mechanistic study of interest for understanding omega-3 effects on HDL composition, but too underpowered and surrogate-endpoint dependent for clinical inference.