expert opinion

The role of vitamin B12 in fetal growth and the programming of chronic disease

January 15, 2014

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Elaine Rush, PhD, Child Health Centre, Auckland University of Technology, Faculty of Health and Environmental Science, New Zealand

“Across the life course, the dietary supplies of the methyl donors, such as folate and vitamin B12, are essential for normal growth, development and physiological func- tions. One-carbon metabolism refers to a network of interrelated biochemical path- ways that donate and regenerate one-carbon units, including the methyl group. The maternal diet is the primary source of nutrient availability to the embryo and the placenta has a vital regulatory role. The developmental pathway of the child defines its phenotype and the balance between future health and disease. Critical periods of cell division and diffe- rentiation occur in utero. Optimal organogenesis, growth and the development of the fetus is dependent on the maternal diet and supply of nutrients, including the methyl donors.

Folate, the key methyl donor, has been extensively studied and there is a world-wide recommendation for the supplementation in women who plan to become pregnant. In more than 50 countries, fortification of the food supply with folic acid is mandated but the extent of implementation and effectiveness vary. On the other hand, vitamin B12 is often deficient in pregnant women who are ovo-lacto vegetarians or eat little or no meat, and this continues to be a major nutritional problem in parts of the world where the population is predominantly vegetarian (1). Vitamin B12 is only derived from animal and microbial foods, and a vegetarian diet therefore contains little vitamin B12. Even in countries where fortification has been effective, such as Canada, there remains a residual problem with vitamin B12 deficiency (2).

The importance of dietary methyl donors, and in particular vitamin B12, requires a broad understanding of the interrelationship of one-carbon metabolism, which describes reactions, including the addition, transfer or removal of one-carbon units in cellular metabolic pathways. Vitamin B12 acts as a cofactor of the enzyme methionine synthase, which is involved in the central methylation cycle. When concentrations of available vitamin B12 are insufficient the following occurs: first, the folate, which is needed for purine and pyrimidine nucleotide synthesis and therefore essential for the formation and stability of DNA and RNA, becomes trapped. Second, the regeneration of methionine is inhibited, which interferes with the methylation of DNA nucleotides. As an important epigenetic mechanism for the control of gene expression, this is particularly important during critical periods of fetal growth and development. Third, the concentrations of homocysteine and its metabolites increase within the cell, which is toxic and may increase the risk of chronic diseases such as cancer (3).

Genetic stability is related to the supply of dietary one-carbon nutrients in critical periods of growth. One such period is the developmental phase within the uterus. There is increasing evidence for the importance of maternal-fetal vitamin B12 status with regard to the growth and programming of offspring (potentially affec- ting body composition, neurodevelopment and the risk of developing insulin resistanceobesitycardiovas- cular disease, fatty liver disease and/or cancer later in life). Associations of low maternal vitamin B12 con- centrations and raised homocysteine with impaired fetal growth have been demonstrated in diverse popu- lations (4). Throughout the life cycle, cognitive and neurological deficits are traditionally recognized as hallmark signs of vitamin B12 deficiency (5, 6). Neural tube defects are arguably the most severe effect that has been linked to vitamin B12 deficiency (7). There is also some evidence that a low vitamin B12 status in children is associated with increased lipogenesis, obesity and insulin resistance (8).”

Based on: Rush E. C. et al. Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease. European Journal of Clinical Nutrition. Published online November 2013.
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3.    Sinclair K. D. et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci USA. 2007; 104:19351–19356. 
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