Vitamin B12 deficiency

Last reviewed: 30 Aug 2023
Last updated: 22 Aug 2023



History and exam

Key diagnostic factors

  • old age
  • history of gastric surgery (gastrectomy, or bypass for obesity)
More key diagnostic factors

Other diagnostic factors

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

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 use
  • Helicobacter pylori infection
  • anticonvulsant use
  • nitrous oxide misuse
  • diabetes mellitus
  • pregnancy
More risk factors

Diagnostic investigations

1st investigations to order

  • CBC
  • peripheral blood smear
  • serum vitamin B12
  • reticulocyte count
More 1st investigations to order

Investigations to consider

  • methylmalonic acid (MMA)
  • homocysteine
  • holotranscobalamin (hTC)
  • anti-intrinsic factor antibody (anti-IFAB)
  • antiparietal cell (APC) antibody
  • serum gastrin (fasting)
More investigations to consider

Treatment algorithm



asymptomatic or borderline deficiency



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

Associate Chief of Staff, Education

VA Puget Sound Health Care System




RCO declares that he has no competing interests.

Peer reviewers

Thein Hlaing Oo, MD, FRCP Edin, FACP

Professor of Internal Medicine

Consultant Hematologist

The University of Texas MD Anderson Cancer Center




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




RC declares that she has no competing interests.

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