IMPROVING OMEGA-3 FATTY ACID SUPPLEMENTATION WITH MICROENCAPSULATION

The consumption of 3 fatty acid-rich foods is associated with multiple health benefits, including theprevention of cardiovascular and neurologic diseases. However, while the dietary consumption of these fattyacids often shows benefits, the use of fish-oil containing capsules and other supplements to augment theintake of ?-3 fatty acids has produced largely negative results on these health outcomes in clinical trials. Thereasons accounting for the reduced benefits of the supplements are unclear, but one possibility could be alower bioavailability of the ?-3 fatty acids in the supplements due to factors including differences in fatty acidesterification, the presence of other lipids, and the size of the oil droplets. In addition, while currently poorlystudied, there may also be important differences in the presence of ?-3 fatty acids oxidation products, knownas oxylipins, between the dietary and supplement sources. Importantly, these oxylipins can have biologicactions that are independent of those produced by the parent ?-3 fatty acid, so their presence or absencecould alter the effects or effectiveness of a specific source of ?-3 fatty acid intake. For example, in ourresearch we found that the treatment of the nematode C. elegans with the ?-3 fatty acid ?-linoleic acid (ALA)increases lifespan in part through the activation of the SKN-1/Nrf2 transcription factor, which coordinatesresponses to oxidative stress. The activation of SKN-1 occurs through the accumulation of oxidation product9S-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9(S)-HpOTrE) after ALA is exposed to air. Based in parton our findings, we hypothesize that the reduced health benefits of supplement versus dietary intake of ?-3fatty acids reflects critical differences in lipid bioavailability and also the blend of oxylipins present in these twosources. Furthermore, research involving the treatment of lab animals, such as mice, with ?-3 fatty acidssuffers from the same issues with the absorption and oxidation status of the ?-3 fatty acids, as well aschanges in the texture and palatability of the food for the animals due to the direct addition of an oil containingthe ?-3 fatty acids to a dry animal diet. To overcome these barriers, we propose to use two approaches, whichare the preparative technique microencapsulation and the novel combined supplementation with oxylipins, toimprove the absorption, palatability, and activity of ?-3 fatty acids with the immediate goal of enhancing thesupplementation of mice diets. In particular, we will prepare and then compare diets containing ALA inmicroencapsulated form or diets containing microencapsulated ALA along with one of two microencapsulatedoxylipins also added on outcomes including changes in gene expression and the brain injury produced in anexperimental stroke model. The research will be carried out by a team including members with expertise insynthetic chemistry, microencapsulation, lipidomics, and stroke research. If this approach is successful,microencapsulation can be used in the production of novel supplements for human use, including the deliveryof optimized blends of specific oxylipins along with the ?-3 fatty acids.