Vitamin B12 deficiency

Green, Ralph; Allen, Lindsay H.; Bjørke-Monsen, Anne-Lise; Brito, Alex; Guéant, Jean-Louis; Miller, Joshua W.; Molloy, Anne M.; Nexo, Ebba; Stabler, Sally; Toh, Ban-Hock; Ueland, Per Magne; Yajnik, Chittaranjan

doi:10.1038/nrdp.2017.40

Cited by 970Folate and B Vitamins ResearchPorphyrin Metabolism and DisordersHematological disorders and diagnostics

Vitamin B12 deficiency

Green, Ralph, Allen, Lindsay H., Bjørke-Monsen, Anne-Lise, Brito, Alex, Guéant, Jean-Louis, Miller, Joshua W., Molloy, Anne M., Nexo, Ebba +4 more·2017·Nature Reviews Disease Primers

DOI 10.1038/nrdp.2017.40

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Abstract

Vitamin B 12 (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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Folate and vitamin B12 act synergistically in one-carbon metabolism, and deficiency of vitamin B12 can impair folate-dependent DNA synthesis and methylation, potentially masking megaloblastic anemia while exacerbating epigenetic dysregulation during fetal development.
“Folate and vitamin B12 act synergistically in one-carbon metabolism, and deficiency of vitamin B12 can impair folate-dependent DNA synthesis and methylation, potentially masking megaloblastic anemia while exacerbating epigenetic dysregulation during fetal development [110,155].”
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Vitamin C is needed for two dioxygenase enzymes involved in the biosynthesis of carnitine, an essential cofactor in the transport of long-chain fatty acids into the mitochondria.
“Vitamin C is needed for two dioxygenase enzymes involved in the biosynthesis of carnitine, an essential cofactor in the transport of long-chain fatty acids into the mitochondria.”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [52]
Impaired carnitine metabolism, including through insufficient vitamin C supply, can be responsible for weakness or muscle aching.
“It thus plays an important role in the production of energy via beta-oxidation (Figure 1, part A) so impaired carnitine metabolism, including through insufficient vitamin C supply, can be responsible for weakness or muscle aching [52,53].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [52]

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Authors: Green, R., Allen, L. H., Bjørke-Monsen, A.-L., Brito, A., Guéant, J.-L., Miller, J. W., Molloy, A. M., Nexo, E., Stabler, S., Toh, B.-H., Ueland, P. M., & Yajnik, C.
Affiliations: University of California, Davis (US)
Western Human Nutrition Research Center (US)
Inserm (FR)
Rutgers, The State University of New Jersey (US)
Trinity College Dublin (IE)
University of Colorado Denver (US)
Monash Institute of Medical Research (AU)
Haukeland University Hospital (NO)
King Edward Memorial Hospital Research Centre (IN)
Corresponding author: Green, Ralph
ORCID: Green, Ralph
Allen, Lindsay H.
Guéant, Jean-Louis
Miller, Joshua W.
Molloy, Anne M.
Stabler, Sally
Ueland, Per Magne
Yajnik, Chittaranjan
Venue: Nature Reviews Disease Primers
Publisher: Springer Science and Business Media LLC
Published: 2017-06-29
Volume: 3
Issue: 1
Pages: 17040-17040
ISSN: 2056-676X (ISSN-L)
DOI: 10.1038/nrdp.2017.40
OpenAlex: W52603844
Cited by: 970
References: 239
Citations by year: 2026: 106 · 2025: 115 · 2024: 135 · 2023: 117 · 2022: 111 · 2021: 112 · 2020: 83 · 2019: 74 · 2018: 45 · 2017: 16 · 2016: 17 · 2015: 19 · 2014: 12 · 2013: 8
FWCI: 9.65
Type: journal article
Language: en
Update notices: correction (2017-07-20)
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Disease Primers (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
Health Sciences › Medicine › Emergency Medicine › Hematological disorders and diagnostics
Keywords: vitamin B12 deficiency, vitamin B12, subclinical deficiency, hematologic manifestations, neurological symptoms, homocysteine, methylmalonic acid, vitamin B12 supplementation, dietary restriction, older adults, DNA synthesis, methylation, mitochondrial metabolism
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Homocysteine, Humans, Male, Methylmalonic Acid, Middle Aged, Risk Factors, Transcobalamins, Vitamin B 12, Vitamin B 12 Deficiency, Biomarkers, Prevalence, Young Adult

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