Comparison of pharmacokinetics of omega-3 fatty acid supplements in monoacylglycerol or ethyl ester in humans: a randomized controlled trial

Eur J Clin Nutr. 2021 Apr;75(4):680-688. doi: 10.1038/s41430-020-00767-4. Epub 2020 Oct 3.


Background: A diet low in omega-3 fatty acids (n-3 FA) results in low plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main long chain n-3 FA. n-3 FA supplements on the market are esterified in triglycerides (TG) or ethyl ester (EE); the latter is absorbed less than other esterification forms. The objective of this study was to test and compare the pharmacokinetics of n-3 FA esterified in monoacylglycerides (MAG), a predigested form, with the EE form.

Methods: This study was a randomized, double-blind, crossover, controlled, clinical trial. Ten men and ten women between 18 and 60 years old were recruited. Participants received a single oral dose of 3 g of n-3 FA esterified in EE or MAG. Eleven blood samples were collected over 24 h post-dose. Plasma total lipids were extracted, methylated, and analyzed using gas chromatography.

Results: After receiving the MAG form, plasma EPA and DHA peaked at a concentration 3 and 2.5 times higher, respectively, than with the EE form. When provided in MAG form, n-3 FA plasma concentration during the absorption phase was on average 3-5 times higher than in EE form. When n-3 FAs were provided esterified in MAG, their concentration 24 h post-dose was higher than in EE. Males had a lower n-3 FA plasma concentration than females when n-3 FAs were provided in EE but there was no sexe difference when provided in MAG.

Conclusions: Plasma concentration of DHA and EPA was higher when provided in MAG than EE form.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Dietary Supplements
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Esters
  • Fatty Acids, Omega-3*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monoglycerides*
  • Young Adult


  • Esters
  • Fatty Acids, Omega-3
  • Monoglycerides
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid