Last reviewed: 25 Dec 2021
Last updated: 29 Jun 2021



History and exam

Key diagnostic factors

  • presence of risk factors
  • old age
  • history of gastric surgery (gastrectomy, or bypass for obesity)

Other diagnostic factors

  • paraesthesias
  • vegan and strict vegetarian diet
  • chronic gastrointestinal disease (e.g., Crohn's disease or coeliac disease)
  • medicine (proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants)
  • ataxia
  • decreased vibration sense
  • positive Romberg's test
  • pallor
  • petechiae
  • glossitis
  • angular cheilitis
  • cognitive impairment

Risk factors

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

Diagnostic investigations

1st investigations to order

  • FBC
  • peripheral blood smear
  • serum vitamin B12
  • reticulocyte count

Investigations to consider

  • methylmalonic acid (MMA)
  • homocysteine
  • holotranscobalamin
  • intrinsic factor (IF) antibody
  • antiparietal cell (APC) antibody
  • serum gastrin (fasting)

Treatment algorithm



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

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.

Use of this content is subject to our disclaimer