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Am J Clin Nutr. 2009 Feb;89(2):697S-701S. doi: 10.3945/ajcn.2008.26947B. Epub 2008 Dec 30.

Vitamin B-12 and neural tube defects: the Canadian experience.

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  • 1Department of Laboratory Medicine and Pathobiology, Banting Institute, University of Toronto, Toronto, ON, Canada.


Although early epidemiologic studies showed a protective effect of adequate maternal folic acid (FA) status against neural tube defects (NTDs), the role of adequate vitamin B-12 nutrition in the putative reduction of NTD frequency has remained uncertain. Evaluating vitamin B-12 status was complicated by the need to control for altered FA status after fortification in Canada. More recent studies have made use of better biomarkers of vitamin B-12 status, including methylmalonic acid and holotranscobalamin (holoTC). HoloTC provides a useful measure of vitamin B-12 status because it represents the bioavailable fraction of circulating vitamin B-12. By assessing bioavailable vitamin B-12 status in a large Canadian cohort accrued before and after FA fortification, we found a 3-fold increase in the risk of NTDs in mothers who had vitamin B-12 status in the lower quartile, regardless of FA fortification. Our work suggests that vitamin B-12 fortification, analogous to the FA fortification program, may reduce NTDs more than FA fortification alone. A multicenter randomized controlled trial comparing periconceptional vitamin B-12 in combination with FA against FA alone is warranted.

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