Plasma Unesterified Eicosapentaenoic Acid is Converted to Docosahexaenoic Acid (DHA) in the Liver and Supplies the Brain with DHA in the Presence or Absence of Dietary DHA

Recent meta-analyses suggest that high eicosapentaenoic acid (EPA, 20:5n-3) supplements may be beneficial in managing the symptoms of major depression. However, brain EPA levels are hundreds-fold lower than docosahexaenoic acid (DHA, 22:6n-3), making the potential mechanisms of action of EPA in the brain less clear. Using a kinetic model the goal of this study was to determine how EPA impacts brain DHA levels. Following 8 weeks feeding of a 2% alpha-linolenic acid (ALA, 18:3n-3) or DHA diet (2% ALA + 2% DHA), 11-week-old Long Evans rats were infused with unesterified C-EPA at steady-state for 3 h with plasma collected at 30 min intervals and livers and brains collected after 3 h for determining DHA synthesis-accretion kinetics in multiple lipid fractions. Most of the newly synthesized liver C-DHA was in phosphatidylethanolamine (PE, 37%-56%), however, 75-80% of plasma C-DHA was found in triacylglycerols (TAG) at 14 ± 5 and 46 ± 12 nmol/g/day (p < 0.05) in the ALA and DHA group, respectively. In the brain, PE and phosphatidylserine (PS) accreted the most C-DHA, and DHA compared to ALA feeding shortened DHA half-lives in most lipid fractions, resulting in total brain DHA half-lives of 32 ± 6 and 96 ± 24 (days/g ± SEM), respectively (p < 0.05). EPA was predominantly converted and stored as PE-DHA in the liver, secreted to plasma as TAG-DHA and accumulated in brain as PE and PS-DHA. In conclusion, EPA is a substantial source for brain DHA turnover and suggests an important role for EPA in maintaining brain DHA levels.