Abstract 15894: Poor Bioavailability of Ethyl Ester Omega-3's on a Low-Fat Diet is Dramatically Improved With a Free Fatty Acid Formulation
Background: Ethyl esters (EE) of omega-3's require significant pancreatic lipase hydrolysis to be converted into a free fatty acid for intestinal absorption. Previous human trials have demonstrated that EE omega-3's require consumption with a high-fat meal to secrete pancreatic lipase and thereby enhance bioavailability. A novel free fatty acid (FFA) formulation of omega-3's with an enteric coating has been developed to maximize the bioavailability of EPA and DHA compared to the EE forms.
Objective: To compare the relative bioavailability of EPA and DHA from a single 4 g dose of Epanova® (Omega-3 free fatty acids) and Lovaza® (Omega-3-acid ethyl esters) during periods of low-fat and high-fat meal consumption.
Methods: This was a randomized, open-label, single dose, 4-way crossover, bioavailability study of 2 treatments: 4 g of Omega-3 free fatty acids (OM-3 FFA) or 4 g of Omega-3-acid ethyl esters (OM-3 EE) each administered under low-fat and high-fat diet conditions to 54 overweight adults.
Main Outcome Measures: The primary determinants of bioavailability were the ln-transformed area under the plasma concentration versus time curve (AUCt) over a 24-hour interval for baseline adjusted EPA and DHA.
Results: The baseline-adjusted AUCt for total EPA + DHA during the low-fat diet period, was 4.0-fold greater with OM-3 FFA compared to OM-3 EE (2650.2 versus 662.0 nmol•h/mL, respectively; p<0.0001). During the high-fat diet, AUCt for OM-3 FFA was 1.3-fold greater than with OM-3 EE (4604.0 versus 3589.5 nmol•h/mL respectively; p<0.0001). During the low-fat diet, 30 of 54 (56%) subjects on OM-3 FFA versus 3 of 52 (6%) on OM-3 EE maintained an AUCt that was ≥50% of the respective high-fat diet AUCt.
Conclusion: This comparative study showed that the FFA formulation of omega-3's provided dramatically improved bioavailability over the OM-3 EE in overweight patients on a low-fat diet. These findings suggest a potential significant therapeutic advantage of FFA omega-3's over the EE formulation in view of the NCEP recommendation to have patients with severe hypertriglyceridemia adhere to a low-fat diet during adjunct therapy.
- © 2011 by American Heart Association, Inc.