n‐3 PUFA Esterified to Glycerol or as Ethyl Esters Reduce Non‐Fasting Plasma Triacylglycerol in Subjects with Hypertriglyceridemia: A Randomized Trial

To date, treatment of hypertriglyceridemia with long‐chain n‐3 polyunsaturated fatty acids (n‐3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non‐fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long‐chain n‐3 PUFA on non‐fasting triacylglycerol levels and to compare the effects of n‐3 PUFA formulated as acylglycerol (AG‐PUFA) or ethyl esters (EE‐PUFA). The study was a double‐blinded randomized placebo‐controlled interventional trial, and included 120 subjects with non‐fasting plasma triacylglycerol levels of 1.7–5.65 mmol/L (150–500 mg/dL). The participants received approximately 3 g/day of AG‐PUFA, EE‐PUFA, or placebo for a period of eight weeks. The levels of non‐fasting plasma triacylglycerols decreased 28 % in the AG‐PUFA group and 22 % in the EE‐PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega‐3 index (EPA + DHA content in erythrocyte membranes). The omega‐3 index increased 63.2 % in the AG‐PUFA group and 58.5 % in the EE‐PUFA group (P < 0.001). Overall, the heart rate in the AG‐PUFA group decreased by three beats per minute (P = 0.045). High‐density lipoprotein (HDL) cholesterol increased in the AG‐PUFA group (P < 0.001). Neither total nor non‐HDL cholesterol changed in any group. Lipoprotein‐associated phospholipase A2 (LpPLA2) decreased in the EE‐PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long‐chain n‐3 PUFA lowered non‐fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG‐PUFA, and EE‐PUFA are equally effective in reducing non‐fasting triacylglycerol levels.