Clinical Drug Experience Knowledgebase

Supplemental Choline and Neurodevelopment in Humans

The development of brain during critical periods in embryogenesis is vulnerable to changes in diet, specifically changes in choline intake. Babies born of mothers eating more choline are smarter on memory testing. These effects of dietary choline have been repeatedly demonstrated in rodent models in a series of studies funded by the NIH during the last eight years. Specifically, prenatal choline supplementation in rats facilitates cognitive function and visuospatial memory, whereas choline deficiency impairs divided attention and accelerates the age-related decline in temporal processing. There are two sensitive periods in rat brain development during which treatment with choline produces long-lasting enhancement of spatial memory that is lifelong. The first occurs during embryonic days 12-17 (rats give birth on day 21) and the second, during postnatal days 16-30. Choline supplementation during these critical periods elicits a major improvement in memory performance at all stages of training on a 12-arm radial maze. These changes in memory are correlated with decreases in the threshold for induction of long-term potentiation and with biochemical changes. Choline supplementation in pregnant rats decreases choline acetyltransferase activity and increases phospholipase D (PLD) activity in the hippocampus of offspring. Also, it increases the size of the cell body of cholinergic neurons. In contrast choline deficiency increases the activity of cholinergic system, but does not affect the basal level of PLD activity in hippocampus. These long-lasting functional, anatomical, and biochemical alterations may be related to the changes in neurogenesis and differentiation in fetal hippocampus and septum, areas of brain that are important for normal spatial learning and memory.

It is not known if these findings in rodents are likely to be true in humans, as human and rat brains mature at different rates. Moreover, rat brain is comparatively more mature at birth than is the human brain, but in humans hippocampal development may start around 20 weeks gestation and continue for months after birth. However, everything we know about brain development tells us that the processes seen in rodents are the same as those that occur in the developing human brain. For this reason, it is extremely likely that the robust effects we observe for choline in rodent brain have importance in the human. The research is the first major study in humans to determine whether maternal diet and diet during the baby's first year influences brain function.