One-carbon metabolism in neurodevelopmental disorders: Using broad-based nutraceutics to treat cognitive deficits in complex spectrum disorders

Folate and choline, two nutrients involved in the one-carbon metabolic cycle, are intimately involved in regulating DNA integrity, synthesis, biogenic amine synthesis, and methylation. In this review, we discuss evidence that folate and choline play an important role in normal cognitive development, and that altered levels of these nutrients during periods of high neuronal proliferation and synaptogenesis can result in diminished cognitive function. We also discuss the use of these nutrients as therapeutic agents in a spectrum of developmental disorders in which intellectual disability is a prominent feature, such as in Fragile-X, Rett syndrome, Down syndrome, and Autism spectrum disorders. A survey of recent literature suggests that nutritional supplements have mild, but generally consistent, effects on improving cognition. Intervening with supplements earlier rather than later during development is more effective in improving cognitive outcomes. Given the mild improvements seen after treatments using nutrients alone, and the importance of the genetic profile of parents and offspring, we suggest that using nutraceutics early in development and in combination with other therapeutics are likely to have positive impacts on cognitive outcomes in a broad spectrum of complex neurodevelopmental disorders.