Steven H. Zeisel, M.D., Ph.D.
Kenan Distinguished University Professor of Nutrition and Pediatrics
Director, UNC Nutrition Research Institute
Director, UNC Clinical Nutrition Research Center
Director, UNC Center of Excellence in Children’s Nutrition
Gillings School of Global Public Health and School of Medicine
University of North Carolina at Chapel Hill
Nutrition Research Institute at Kannapolis
Choline: Its Importance in Intrauterine and Neonatal Development
Choline is an essential nutrient in humans, needed for the structural integrity of cell membranes; for normal cholinergic neurotransmission; and as the major source of methyl-groups in the diet. This nutrient is derived not only from the diet, but as well from de novo synthesis. The gene for the enzyme (PEMT) that catalyzes endogenous choline biosynthesis is induced by estrogen. Almost half the population has a single nucleotide polymorphism in PEMT that makes them insensitive to induction by estrogen, and thereby more dependent on dietary intake. The amount of choline eaten in the diet varies at least two-fold in the U.S., and this difference in intake is enough to increase by four times the risk that a woman will have a baby with a neural tube defect. Women evolved to have increased capacity for endogenous synthesis of choline because this nutrient is critical during fetal development, when, via epigenetic mechanisms (DNA methylation and histone methylation), it influences neural progenitor cell proliferation and apoptosis in the fetal hippocampus. This results in permanent changes in hippocampal structure and function. The effect of choline on hippocampus is limited to a critical period (in the mouse days 12-17 of gestation) when the primordial hippocampus is formed. Extra choline during this period results in a 30% enhancement in spatial memory that lasts lifelong. Too little choline during this period results in decreased memory function. Restoration of choline after the critical period does not reverse the deficit.
This work was funded by grants from the National Institutes of Health (DK55865, AG09525). Support for this work was also provided by grants from the NIH to the UNC Clinical Nutrition Research Unit (DK56350) and to the UNC General Clinical Research Center (RR00046).