AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of 13C-labeled DHA after oral intake of a single dose of 13C-AceDoPC®, in comparison with 13C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the 13C enrichment of DHA-containing lipids. 13C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, 13C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the 13C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion.

Docosahexaenoic acid (DHA, 22:6n-3) is an omega-3 polyunsaturated fatty acid (PUFA) essential for neural development, learning, and vision. Although DHA can be provided to humans through nutrition and synthesized in vivo from its precursor alpha-linolenic acid (ALA, 18:3n-3), deficiencies in cerebral DHA level were associated with neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases. The aim of this review was to develop a complete understanding of previous and current approaches and suggest future approaches to target the brain with DHA in different lipids’ forms for potential prevention and treatment of neurodegenerative diseases. Since glycerophospholipids (GPs) play a crucial role in DHA transport to the brain, we explored their biosynthesis and remodeling pathways with a focus on cerebral PUFA remodeling. Following this, we discussed the brain content and biological properties of phospholipids (PLs) and Lyso-PLs with omega-3 PUFA focusing on DHA’s beneficial effects in healthy conditions and brain disorders. We emphasized the cerebral accretion of DHA when esterified at sn-2 position of PLs and Lyso-PLs. Finally, we highlighted the importance of DHA-rich Lyso-PLs’ development for pharmaceutical applications since most commercially available DHA formulations are in the form of PLs or triglycerides, which are not the preferred transporter of DHA to the brain.