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

• Published in: The American journal of clinical nutrition 2009-02, Vol.89 (2), p.697S-701S
• Main Authors: Thompson, Miles D, Cole, David EC, Ray, Joel G
• Format: Article
• Language: English
• Subjects: Adult; Biological Availability; biomarkers; Biomarkers - blood; Canada; Clinical trials; cohort studies; Dietary supplements; epidemiological studies; Epidemiology; Female; fetal development; fetus; Flour; folic acid; Folic Acid - administration & dosage; food additives; food fortification; Food, Fortified; Humans; literature reviews; maternal nutrition; methylmalonic acid; Methylmalonic Acid - blood; neural tube defects; Neural Tube Defects - epidemiology; Neural Tube Defects - etiology; Neural Tube Defects - prevention & control; nutrient availability; nutrient intake; nutrient-nutrient interactions; Nutrition; nutrition assessment; Nutritional Status; Pregnancy; pregnant women; protective effect; Randomized Controlled Trials as Topic; risk factors; Studies; Transcobalamins; Vitamin B; Vitamin B 12 - administration & dosage; Vitamin B 12 - blood; Vitamin B 12 - pharmacokinetics; Vitamin B 12 Deficiency - complications; Vitamin B 12 Deficiency - epidemiology; Vitamin B Complex - administration & dosage; Vitamin B Complex - blood; vitamin B12; Vitamin deficiency
• ISSN: 0002-9165; 1938-3207
• DOI: 10.3945/ajcn.2008.26947B

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.