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Vitamin B12 deficiency

A Correction to this article was published on 20 July 2017

Abstract

Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age are also at high risk of deficiency in populations where dietary intake of B12-containing animal-derived foods is restricted. Deficiency is caused by either inadequate intake, inadequate bioavailability or malabsorption. Disruption of B12 transport in the blood, or impaired cellular uptake or metabolism causes an intracellular deficiency. Diagnostic biomarkers for B12 status include decreased levels of circulating total B12 and transcobalamin-bound B12, and abnormally increased levels of homocysteine and methylmalonic acid. However, the exact cut-offs to classify clinical and subclinical deficiency remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes and manifestations of B12 deficiency.

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Figure 1: Vitamin B12 and folate metabolism and function.
Figure 2: Prevalence of low and marginal vitamin B12.
Figure 3: Biomarkers of vitamin B12 status during pregnancy and lactation.
Figure 4: Absorption, enterohepatic circulation and intracellular metabolism of vitamin B12.
Figure 5: Mechanism and complications of autoimmune gastritis.
Figure 6: Blood and bone marrow morphological changes in vitamin B12 deficiency.
Figure 7: Determinants of vitamin B12 status.

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Acknowledgements

The authors thank N. DeGeorge and L. Texeira for their administrative and editing support. The authors also thank K. Eriksen (MRC Elsie Widdowson Laboratory, Cambridge, UK), S. Moore (MRC Unit The Gambia and Division of Women's Health, King's College London, UK), R. Wessells and S. Hess (Program in International and Community Nutrition, University of California, USA), and G. Kac (Nutritional Epidemiology Observatory, Rio de Janeiro Federal University, Brazil) for providing data from The Gambia, Niger and Brazil to construct Figure 2.

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Introduction (R.G.); Epidemiology (L.H.A., A.B., A.M.M., A.-L.B.-M., J.W.M. and P.M.U.); Mechanisms/pathophysiology (J.-L.G. and B.-H.T.); Diagnosis, screening and prevention (E.N. and C.Y.); Management (S.S.); Quality of life (S.S.); Outlook (R.G.); Overview of Primer (R.G.).

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Correspondence to Ralph Green.

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R.G. has previously served on speakers’ bureaus and as a consultant for Emisphere Technologies. J.W.M. has served on a scientific steering committee for Emisphere Technologies. A.M.M. received an honorarium as a speaker at the Abbott Transformation Forum, Manchester, UK. S.S. indirectly benefits from the activities of a company formed by the University of Colorado aimed at measuring vitamin B12-related metabolites. Otherwise she does not have any conflict of interest. All other authors declare no competing interests.

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Green, R., Allen, L., Bjørke-Monsen, AL. et al. Vitamin B12 deficiency. Nat Rev Dis Primers 3, 17040 (2017). https://doi.org/10.1038/nrdp.2017.40

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