Effect of supplementation with methyl-donor nutrients on neurodevelopment and cognition: considerations for future research

Pregnancy represents a critical period in fetal development, such that the prenatal environment can, in part, establish a lifelong trajectory of health or disease for the offspring. Poor nutrition (macro- or micronutrient deficiencies) can adversely affect brain development and significantly increase offspring risk for metabolic and neurological disease development. The concentration of dietary methyl-donor nutrients is known to alter DNA methylation in the brain, and alterations in DNA methylation can have long-lasting effects on gene expression and neuronal function. The decreased availability of methyl-donor nutrients to the developing fetus in models of poor maternal nutrition is one mechanism hypothesized to link maternal malnutrition and disease risk in offspring. Animal studies indicate that supplementation of both maternal and postnatal (early- and later-life) diets with methyl-donor nutrients can attenuate disease risk in offspring; however, clinical research is more equivocal. The objective of this review is to summarize how specific methyl-donor nutrient deficiencies and excesses during pre- and postnatal life alter neurodevelopment and cognition. Emphasis is placed on reviewing the current literature, highlighting challenges within nutrient supplementation research, and considering potential strategies to ensure robust findings in future studies.