Omega-3 long chain fatty acid "bioavailability": a review of evidence and methodological considerations

Prog Lipid Res. 2014 Oct;56:92-108. doi: 10.1016/j.plipres.2014.09.001. Epub 2014 Sep 16.


This review considers the bioavailability of different forms of omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), including ethyl esters (EEs), free fatty acids (FFAs), triacylglycerols (TAGs) and phospholipids (PLs). The retrieved studies include short-term and longer-term studies in humans, and a number of animal studies, which were highly heterogeneous in their design making it difficult to draw substantiated conclusions. The apparent bioavailability (as defined by the authors of these studies) seems to be lowest for the EE form and highest for the FFA form, whilst no conclusion can be made for TAG versus PL from human data. Animal studies suggest that there are substantial differences in the bioavailability of PL form of LC-PUFA compared with the TAG form. This apparent limited knowledge and understanding is fundamentally driven by methodological limitations of these studies. The major limitations with the studies to date include: (between studies) loose definition of the term "bioavailability", lack of standardisation of analytical methodology, and differences in which blood compartment was analysed; (within a study) failure to provide equal amounts the n-3 LC-PUFA of the different forms being compared, failure to provide the dose of n-3 LC-PUFA on a body weight basis, failure to measure fatty acid excretion, failure to control the total fat intake, and failure to adequately power the studies from a statistical point of view. This review has laid out a set of suggestions and criteria for conducting future studies on the bioavailability of different chemical forms of n-3 LC-PUFA.

Keywords: DHA; EPA; Ethyl esters; Krill oil; Phospholipids; Triacylglycerol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical / methods*
  • Dietary Supplements*
  • Esters / chemistry
  • Fatty Acids, Nonesterified / chemistry
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / chemistry
  • Fatty Acids, Omega-3 / pharmacokinetics*
  • Humans
  • Randomized Controlled Trials as Topic
  • Triglycerides / chemistry


  • Esters
  • Fatty Acids, Nonesterified
  • Fatty Acids, Omega-3
  • Triglycerides