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Vitamin B12 deficiency

Last reviewed: 20 Aug 2025
Last updated: 16 Jul 2025

Summary

Definition

History and exam

Key diagnostic factors

  • old age
  • history of gastric surgery (gastrectomy, or bypass for obesity)
Full details

Other diagnostic factors

  • paresthesias
  • vegan and strict vegetarian diet
  • chronic gastrointestinal disease (e.g., Crohn disease or celiac disease)
  • drug (proton-pump inhibitors [PPIs], H2 receptor antagonists, metformin, anticonvulsants)
  • ataxia
  • decreased vibration sense
  • positive Romberg test
  • pallor
  • petechiae
  • glossitis
  • angular cheilitis
  • cognitive impairment
Full details

Risk factors

  • age >65 years
  • gastric surgery (bypass or resection)
  • chronic gastrointestinal (GI) disease
  • vegan or strict vegetarian diet
  • metformin use
  • H2 receptor antagonist or proton-pump inhibitor (PPI) use
  • Helicobacter pylori infection
  • anticonvulsant use
  • nitrous oxide misuse
  • diabetes mellitus
  • pregnancy
Full details

Diagnostic tests

1st tests to order

  • CBC
  • peripheral blood smear
  • serum vitamin B12
  • reticulocyte count
Full details

Tests to consider

  • methylmalonic acid (MMA)
  • homocysteine
  • holotranscobalamin (hTC)
  • anti-intrinsic factor antibody (anti-IFAB)
  • antiparietal cell (APC) antibody
  • serum gastrin (fasting)
Full details

Treatment algorithm

ACUTE

symptomatic

asymptomatic or borderline deficiency

Contributors

Authors

Robert C. Oh, MD, MPH, CAQSM
Robert C. Oh

Chief Wellbeing Officer

VA Palo Alto Health Care System

Palo Alto

CA

Declarações

RCO declares that he has no competing interests.

Revisores

Thein Hlaing Oo, MD, FRCP Edin, FACP

Professor of Internal Medicine

Consultant Hematologist

The University of Texas MD Anderson Cancer Center

Houston

TX

Declarações

THO declares that he has no competing interests.

Rebecca Connor, MD

Chief Fellow

Section of Hematology and Oncology

Department of Internal Medicine

Wake Forest University Baptist Medical Center

Winston-Salem

NC

Declarações

RC declares that she has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

Referências

Nossas equipes internas de editoria e de evidências trabalham em conjunto com colaboradores internacionais especializados e pares revisores para garantir que forneçamos acesso às informações o mais clinicamente relevantes possível.

Principais artigos

Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014 Aug;166(4):496-513.Texto completo  Resumo

Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med. 1999 Jun 28;159(12):1289-98.Texto completo  Resumo

Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013 Jan 10;368(2):149-60. Resumo

National Institutes of Health, Office of Dietary Supplements. Vitamin B12: fact sheet for health professionals. Mar 2024 [internet publication].Texto completo

Guidelines and Protocols Advisory Committee, British Columbia. Cobalamin (vitamin B12) and folate deficiency. Apr 2024 [internet publication].Texto completo

Artigos de referência

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