B12 deficiency testing and management

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This piece of guidance is new

These guidelines are being issued to provide nationally agreed advice for Scotland on appropriate requesting, of B12 testing. B12 testing is often performed indiscriminately as part of routine screening and can lead to unnecessary diagnostic and management quandaries

Causes of Low B12 levels
  • Pernicious anaemia
  • vegan diet
  • malabsorption syndromes
    • Coeliac
    • Sprue
    • Chron's
    • Ulcerative colitis (UC)
    • ”Food-bound Cobalamin Malabsorption syndrome” predisposing factors include atrophic gastritis, long term proton pump inhibitor or H2 antagonist use, chronic alcoholism, gastrectomy/ gastric bypass surgery, pancreatic exocrine failure, AIDS
  • myeloma (paraprotein related assay interference)
  • pregnancy
  • combined oral contraceptive pill/HRT
  • pancreatric insufficiency
  • metformin, acute phase situations
Indications for Vitamin B12 testing
  1. Macrocytosis (MCV greater than 104.1 on sample processsed within 24 hours) with or without anaemia
  2. Cytopenias
  3. Unexplained neurological / neuropsychiatric symptoms eg. peripheral neuropathy/ sensory ataxia/ ambylopia/parasthesia; (newlydiagnosed) dementia; visual loss.
  4. Oral ulceration/ glossitis/ ‘beefy’ tongue/ angular stomatitis.
  5. Malabsorption syndromes as above
  6. Oral B12 therapy
Cautions for Vitamin B12 testing
  1. Tiredness is NOT an indication for testing; please check FBC first.
  2. Lower B12 levels are seen in patients taking the combined oral contraceptive pill/ HRT. These levels are generally not clinically significant. Testing should NOT be undertaken in these situations unless one of the indications above is also present.
  3. Low B12 levels, mild macrocytosis and mild thrombocytopenia (PLT 100 to 149) are common in pregnancy and usually due to normal physiological changes. B12 replacement may be considered if PLT less than 100 or unexplained macrocytic anaemia is present (or unexplained paraesthesia or neuropathy).

If patient is on IM B12 replacement, repeat B12 testing is NOT indicated but FBC and reticulocyte response should be monitored.

B12 Testing Results, Interpretation and Management
  • Results out with laboratory normal ranges are flagged on reporting. Note that 2.5% of the population will have results a little below the reference range.
  • See flowchart for guidance on further advice on interpretation of results and management.
  • Intrinsic factor antibodies are positive in only 40 to 60% of cases of pernicious anaemia but with a high specificity. It is not possible to test for the antibody once B12 therapy has commenced.
  • Testing for gastric parietal cell antibodies is NOT recommended due to low specificity for the presence of pernicious anaemia.
  • Specialised testing for suspected vitamin B12 deficiency is currently under review in Scotland and is not available at this time.  Please discuss any specific cases with the haematology department.
  • In patients with anaemia, a rise in reticulocytes should be seen by day 7 to 10 of B12 therapy (ensure that the patient also has adequate levels of folate and ferritin).
  • Hydroxycobalamin is generally well tolerated. Side effects of the diluent can include itch, exanthema, chills, fever, hot flushes, nausea, dizziness and rarely anaphylaxis.  Acneiform eruptions have been reported rarely.  Occasionally steroid cover may be required, including hydrocortisone cover in a hospital setting in more severe cases.
  • Patients on metformin – use of metformin in type 2 diabetes is associated with low B12 levels. The mechanism is unknown but malabsorption may play a part.  This may be alleviated by an increased intake of calcium.  It is recommended that B12 levels are checked in patients who have symptoms and signs of deficiency as outlined above.  If the B12 level is reduced, check intrinsic factor antibody in case of co-existing pernicious anaemia.  If antibody negative and no neurological symptoms, consider a 1 month trial of oral therapy with further monitoring at 6 months and then annually.  If antibody positive or neurological symptoms then manage with IM B12 long term.
  • Patients on oral contraceptive pill/HRT – as above, testing should only be carried out where there is strong clinical suspicion of symptomatic B12 deficiency. If testing is carried out in the absence of symptoms and the B12 level is mildly reduced (150-200 picogram/mL), further investigation is not likely to be required but review diet and consider oral supplementation.  If B12 less than 150 consider alternative cause.
  • Pregnancy – as above, testing should only be carried out if there is strong clinical suspicion of symptomatic B12 deficiency. If the B12 level is low, check intrinsic factor antibody.  If antibody positive treat long term as for pernicious anaemia.  If antibody negative and there is strong clinical suspicion then the recommendation is for 3 injections of IM B12 to cover the pregnancy and then repeat testing at least 2 months post partum if symptoms persist.
  • Gastric/bariatric surgery – oral or IM supplementation may be required.
  • ‘Food bound cobalamin malabsorption’- consider oral supplementation.

Long-term therapy where B12 deficiency is due to dietary deficiency: either oral cyanocobalamin tablets 50-150 micrograms daily between meals (adults), or twice yearly hydroxycobalamin injection 1000 micrograms. This may need to be lifelong in vegans. 
In non-vegans, stop once vitamin B12 levels have been corrected and diet has improved, but monitor levels 6 monthly. Advise consumption of foods rich in B12 et. Fortified foods - some soy products, breakfast cereals and breads plus meat, eggs and dairy products.

  1. BSH Guidelines for the diagnosis and treatment of cobalamin and folate disorders. BJH, 2014, 166, 496-513
  2. Hunt A, Vitamin B12 deficiency, BMJ 2014;349:g5226
  3. Haematology and Transfusion Scotland draft guidelines on haematinic testing
Abbreviation Meaning
FBC Full blood count
HRT Hormone replacement therapy
IM Intramuscular
PLT Platelet 
MCV Mean corpuscular volume
Editorial Information

Last reviewed: 06 February 2020

Next review: 28 February 2023

Author(s): Consultant Haematologist

Approved By: TAM subgroup of ADTC

Reviewer Name(s): Consultant Haematologist

Document Id: TAM440