Methyl Donors, Epigenetic Alterations, and Brain Health: Understanding the Connection

Methyl donors such as choline, betaine, folic acid, methionine, and vitamins B6 and B12 are critical players in the one-carbon metabolism and have neuroprotective functions. The one-carbon metabolism comprises a series of interconnected chemical pathways that are important for normal cellular functions. Among these pathways are those of the methionine and folate cycles, which contribute to the formation of S-adenosylmethionine (SAM). SAM is the universal methyl donor of methylation reactions such as histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and play roles in human health and disease. Epigenetic mechanisms have been considered a bridge between the effects of environmental factors, such as nutrition, and phenotype. Studies in human and animal models have indicated the importance of the optimal levels of methyl donors on brain health and behavior across the lifespan. Imbalances in the levels of these micronutrients during critical periods of brain development have been linked to epigenetic alterations in the expression of genes that regulate normal brain function. We present studies that support the link between imbalances in the levels of methyl donors, epigenetic alterations, and stress-related disorders. Appropriate levels of these micronutrients should then be monitored at all stages of development for a healthier brain.