Vitamin B12 (cobalamin) is a water-soluble vitamin that is found in foods of animal origin, such as meat, dairy products and eggs. It is the only vitamin not found in vegetables. Absorption of vitamin B12 occurs in the terminal ileum and requires intrinsic factor to be present. IF is a glycoprotein secreted by the gastric parietal cells that facilitates the transport of vitamin B12 across the intestinal mucosa.


Aetiology of vitamin B12 deficiency

The majority of cases of vitamin B12 deficiency are caused by autoimmune pernicious anaemia (approximately 80%). Other causes include the following:

  • Inadequate dietary intake, e.g. strict vegan diet
  • Gastric causes, e.g. gastrectomy, atrophic gastritis, Helicobacter pylori infection, Zollinger-Ellison syndrome
  • Intestinal causes, e.g. Crohn’s disease, ileal resection, tropical sprue
  • Drugs, e.g. colchicine, anticonvulsants, H2-receptor antagonists, PPIs


Pernicious anaemia

Pernicious anaemia is a disease of the stomach characterised by loss of gastric parietal cells and impaired secretion of IF. It is most commonly an autoimmune process that occurs as a result of antibodies that attack the gastric parietal cells that secrete intrinsic factor and gastric acid. In addition to a lack of IF, achlorhydria (lack of gastric hydrochloric acid) is invariably present. It is associated with other autoimmune disorders such as vitiligo and myxoedema. Less commonly, Helicobacter pylori infection and Zollinger-Ellison syndrome may also cause non-autoimmune gastritis that can lead to pernicious anaemia.

Pernicious anaemia usually occurs in the middle-aged and elderly and is more common in women. The peak age at diagnosis is 60. The UK incidence is estimated to lie in the range of 1-5/100,000 per annum.


Clinical features of vitamin B12 deficiency

The most common present6ing features of pernicious anaemia are tiredness and lethargy. Other clinical features include:

  • Weight loss and anorexia
  • Diarrhoea
  • ‘Lemon-yellow’ skin colour (due to a combination of haemolytic jaundice and the pallor of anaemia)
  • Glossitis and oral ulceration
  • Yellow-blue blindness can occur
  • Psychiatric symptoms in advanced cases


Neurological features may include subacute combined degeneration of the spinal cord and peripheral neuropathy. Peripheral loss of position and vibratory sense is often the earliest indicator of central nervous system involvement. The lack of vitamin B12 results in patchy loss of myelin in the dorsal and lateral columns which causes:

  • Weakness of arms and legs
  • Progressively worsening parasthesia
  • Reduced joint position and vibration sense
  • Hyperreflexia
  • Extensor plantar response
  • Eventual spastic paraparesis


Investigations in vitamin B12 deficiency

Investigations in vitamin B12 deficiency can reveal the following:

  • Macrocytic anaemia
  • Neutropaenia
  • Thrombocytopaenia
  • Blood film: anisocytosis, poikilocytosis
  • Low serum B12
  • Raised serum bilirubin (haemolysis)
  • Intrinsic factor antibodies (in pernicious anaemia)
  • Positive Schilling test (rarely available now)


Folic acid levels should always be measured together with vitamin B12 levels, as folate deficiency can co-exist. B12 deficiency may result in increased serum folate levels but reduced red cell folate levels, because of the effect on intracellular folate metabolism, so red cell folate is the test of choice.


Treatment of vitamin B12 deficiency

NICE recommends that B12 deficiency is managed as follows:


Patients with neurological involvement:

  • Seek urgent specialist advice from a haematologist.
  • Ideally, management should be guided by a specialist, but if specialist advice is not immediately available, consider the following:
  • Initially administer hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then administer hydroxocobalamin 1 mg intramuscularly every 2 months.


Patients without neurological involvement:

  • Initially administer hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks.
  • The maintenance dose depends on whether the deficiency is diet related or not. For people with B12 deficiency that is:
    • Not thought to be diet related – administer hydroxocobalamin 1 mg intramuscularly every 3 months for life.
    • Thought to be diet related – advise people either to take oral cyanocobalamin tablets 50-150 micrograms daily between meals, or have a twice-yearly hydroxocobalamin 1 mg injection.
    • In vegans, treatment may need to be life-long, whereas in other people with dietary deficiency replacement treatment can be stopped once the vitamin B12 levels have been corrected and the diet has improved.
  • Give dietary advice about foods that are a good source of vitamin B12 – good sources of vitamin B12 include:
    • Eggs
    • Foods which have been fortified with vitamin B12 (for example some soy products, and some breakfast cereals and breads) are good alternative sources to meat, eggs, and dairy products.
    • Meat
    • Milk and other dairy products.
    • Salmon and cod.



Further reading:

NICE Clinical Knowledge Scenario on B12 and folate deficiency



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Thank you to the joint editorial team of for this article.