Immigrant Health Service

Vitamin B12

  • Background

    • Vitamin B12 (cobalamin) is synthesised by microorganisms and found in animal products (meat, organ meat, fish, seafood, dairy and eggs). Some packaged cereals and soy milk are also fortified with B12. 
    • B12 is important in haematopoiesis and the central nervous system and is an enzyme cofactor.
    • Recommended daily requirements range from 0.4 mcg (infants) to 2.4 mcg (>14 years age)
    • Most diets containing animal products contain a much higher intake than this. B12 is safe in doses up to 1000 times the RDI. See B12 content of common foods 

    Causes of low vitamin B12

    • Exclusively breastfed infants of mothers with B12 deficiency may develop deficiency and typically present from 4-6 months of age
    • Malabsorption - causes include: parasites (including Giardia intestinalis), bacterial overgrowth, tropical sprue, possibly H. pylori, inflammatory bowel disease, ileal resection, medication (e.g. proton pump inhibitors)
    • Vegan/vegetarian diet - due to low intake
    • Pernicious anaemia - autoimmune atrophic gastritis causes loss of intrinsic factor
    • Rare metabolic disorders - including TCII deficiency, cobalamin C/D defects

    Causes by age

    • Birth - 6 months severe maternal deficiency, consider metabolic causes, especially if severe metabolic disturbance (acidosis/vomiting) and neurological features
    • 6 months – mid childhood dietary deficiency, maternal deficiency (causing deficiency in breast fed infants), malabsorption 
    • Mid childhood onwards Juvenile pernicious anaemia, gastritis, malabsorption, medication

    In refugee populations the most common cause is low intake - typically a diet low in animal products, due to chronic food insecurity in the country of origin.


      • A recent study of refugees presenting to Australian health centres for screening found the prevalence of low B12 (total serum B12 <150 pmol/L) was 
        • 17 % overall, including 12% of children aged under 14 yrs. 
        • The highest rates were in people from Bhutan, Iran, Iraq and Afghanistan (up to 20-30%). 
        • Lower rates were found in refugees from Africa (4-11%) and Burma (2%)
      • There are no data for the Australian population overall.
      • Globally very high prevalence of B12 deficiency are reported in Kenyan schools (including Sudanese refugees: up to 40%) and pregnant women in Nepal (including Bhutanese refugees: up to 50%) 


      B12 deficiency can cause life threatening disease due to megaloblastic anaemia with cytopaenias or neurological abnormalities (regression/seizures). Findings in children include delay or regression of developmental milestones, feeding difficulties, hypotonia, lethargy or hyperirritability, microcephaly and coma. Other patients may be asymptomatic or diagnosed incidentally. There are associations with decreased cognitive function, mental health and long-term cardiovascular outcomes.


      • Dietary intake current and previous. Consumption of animal products more often than weekly should be protective – consider malabsorption in children with clinical symptoms and apparent adequate intake. Check maternal dietary history in breast fed infants.
      • Symptoms of anaemia or other cytopaenias
      • Developmental and neurological symptoms - regression, seizures, floppy /hypotonia
      • Underlying disorders causing malabsorption, symptoms of malabsorption (diarrhoea, failure to thrive)


      • Pallor, Jaundice, bruising
      • Neurological – reduced tone in infants, defects in vibration sense, proprioception, cutaneous sensation, ataxia, weakness, abnormal reflexes, choreoathetoid movements, gait abnormalities
      • Microcephaly
      • Skin pigmentation changes and oedema in infants.


      • Routine measurement of B12 is not recommended for all refugees
      • Consider B12 screening in people from Bhutan, Iran, Iraq and Afghanistan, especially where there is a history of poor food access. Screening is generally not required for asymptomatic individuals with an adequate dietary intake, or those who have been in Australia for > 6 months and consume animal products.
      • Complete screening in exclusively breastfed babies where there has been poor maternal food access or where deficiency is suspected clinically or based on initial blood test results
      • An FBE (and ferritin) is part of initial refugee health screening although this is not adequate screening for B12 deficiency

      Where B12 deficiency is suspected:

      • Active B12 (holotranscobalamin) is more sensitive and the appropriate initial investigation (used at RCH) 
        • Measurement of total serum B12 (Note: this test is not available at RCH) 
          • Not sensitive or specific for clinical deficiency 
          • Total serum B12 <150 pmol/L is usually consistent with significant clinical deficiency , however results at the lower end of the normal range may in fact be deficient (false negative)
      • Full blood examination and film - macrocytic red cells, hypersegmented neutrophils. Note: Macrocytosis can be masked by concomitant iron deficiency and thalassemia, and is not a useful screening test. Leukopaenia/thrombocytopenia/pancytopaenia are all possible associations.

      If B12 deficiency is confirmed:

      • Urinary Methylmalonic acid (MMA) and serum homocysteine are useful to confirm tissue deficiency. One or both are elevated in almost all patients with clinical deficiency, but decrease immediately after treatment. Homocysteine may also be elevated in folate deficiency. 
      • Haemolysis screen - Increased LDH (often very high), bilirubin and AST, decreased haptoglobin
      • Iron studies and red cell folate for coexisting deficiency
      • Bone marrow aspirate is not usually necessary
      • If history does not suggestive dietary deficiency, consider other causes and investigate as appropriate


      Seek specialist advice for patients with symptomatic B12 deficiency. At RCH management is usually in consultation with the Haematology and/or the Metabolic units. 

      For infants and those with neurological involvement, standard replacement is intramuscular B12 (cyanocobalamin). Although oral doses are poorly absorbed (0.5-4% absorbed), high doses can be effective for lower-risk cases - i.e. older children/adults without evidence of tissue deficiency (i.e. no clinical features and normal homocysteine/MMA)

      Regimens vary:

      • Infants with clinical deficiency (macrocytic anaemia or neurological involvement) - one approach would be:
        • 250 - 1000mcg intramuscular B12, on alternate days for 1-2 weeks, then 250mcg weekly 
        • Short term parenteral therapy is often sufficient, especially if maternal deficiency is proven. 
        • Switch to oral supplements once child is well, no diarrhoea, feeding improved, and maternal stores are replaced. 
        • If diagnosis is unclear, where a metabolic cause is possible, or there are ongoing symptoms, seek ongoing specialist advice. 
      • Older children with mild disease an alternative would be: 
        • 1000mcg oral daily 
      • Subclinical, dietary deficiency 
        • 50-200 mcg oral daily (generally as 100mcg tablets, also available as sublingual sprays/tablets).
        • Increase dietary intake
      • Supplement (not deficient, no dietary intake)
        • 50-100mcg daily or alternate daily


      • In infants and children with severe deficiency, repeat homocysteine and MMA levels 1-2 weeks after commencement of treatment, (levels should normalise quickly). Once established on oral therapy, repeat B12 levels after 3 months, then regularly until several months after completing treatment. 
      • Patients with deficiency due to metabolic causes require individual and specialised management.
      • In patients with subclinical deficiency: Repeat B12 levels at 3 months, treat for 3 – 6 months total.

      Rapid clinical improvement is usually seen with replacement, but neurological impairment may persist if there has been prolonged deficiency.
      Long term developmental follow-up may be required if presentation included neurological features (seizures and neurocognitive deficits are common). 

      Immigrant health resources Author: Daniel Engelman. November 2013. Contact: