Choline and Its Companions: Inter-Related Roles of Choline and B Vitamins in Fetal Development and Offspring Health

Background/Objectives: Previous publications have primarily examined the individual roles of nutrients during fetal development. However, growing evidence suggests that one-carbon (1C) metabolism nutrients, including choline and key B vitamins, act synergistically within interconnected metabolic pathways that modulate epigenetic regulation and may have implications for the health of future generations. Methods: This narrative integrative review examined evidence relating to the roles of choline and B vitamins (B1, B2, B6, folate (B9) and B12) in fetal development and offspring health. Peer-reviewed literature was identified through PubMed, Science Direct and Semantic Scholar. Results: Current evidence indicates that periconceptional and maternal intake and status of 1C metabolism nutrients are associated with DNA methylation processes involved in developmental programming and the risk of non-communicable diseases (NCDs) in childhood and adulthood. Habitual intakes of several 1C metabolism nutrients are frequently below recommended levels during pregnancy and lactation, particularly for choline and folate. Inadequate intakes, each contributing differently to 1C metabolism, may disrupt 1C metabolic pathways and alter DNA methylation patterns during critical windows of fetal programming. Homocysteine metabolism is intricately linked to 1C metabolism and is modulated by choline and B vitamins. Collectively, these pathways have potential implications for the health of the next generation, including effects on growth, neural tube closure, brain development and increased susceptibility to diseases later in life, e.g., cardiovascular disease, diabetes, obesity and other chronic conditions. Adequate maternal intakes of choline and B vitamins may help mitigate the 'early life origin' of certain NCDs by promoting healthy neurodevelopment, reducing inflammation, and regulating central metabolic pathways. Conclusions: Greater awareness of the roles and importance of 1C metabolism nutrients, including choline and key B vitamins (B1, B2, B6, folate and B12), during the early life course is warranted. Furthermore, there is also a need for organizations and policy makers to formalize intake recommendations for 1C metabolism nutrients beyond the individualized simplicity of folate/folic acid, and to extend this to include other methyl-donor nutrients with epigenetic effects, such as choline and key B vitamins, given their interconnected roles in 1C metabolism and fetal development.