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 13C-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 13C-DHA was in phosphatidylethanolamine (PE, 37%–56%), however, 75–80% of plasma 13C-DHA was found in triacylglycerols (TAG) at 14 ± 5 and 46 ± 12 nmol/g/day (p