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REMEDY : BNSSG referral pathways & Joint Formulary

Vitamin B12 - DRAFT

Checked: 13-12-2022 by Rob.Adams Next Review: 13-12-2023

Vitamin B12 deficiency - overview

For guidelines and suggested interpretation of test results please see page 15 of the  UHBristol Haematology Guidelines for Primary Care (PDF).

There is also an update on new reference ranges for Vitamin B12 on the NBT pathology website: Vitamin B12 | North Bristol NHS Trust (

Please note:

Do not send requests for vitamin B12 levels for patients already on replacement therapy.

Remedy notes that there is still some lack of consensus on appropriate testing for vitamin B12 and how it should be managed. Further national guidelines are due to be published in Summer 2022 and we will endeavour to keep this page updated with any developments.


Clinical features of Vitamin B12 deficiency are highly variable.

Mildly reduced B12 levels are common and not necessarily a pathological state.

Deficiency is suggested by:

  • Anaemia and blood film changes
  • Presence of neurological changes consistent with B12 deficiency

There is limited correlation between FBC abnormalities and the presence of neurological manifestations.

Measurement of Vitamin B12 should be considered if there are symptoms such as (1):

  • extreme tiredness
  • a lack of energy
  • pins and needles (paraesthesia)
  • a sore and red tongue
  • mouth ulcers
  • muscle weakness
  • disturbed vision
  • psychological problems, which may include depression and confusion 
  • problems with memory, understanding and judgement (including as part of dementia screen)

Monitoring of Vitamin B12 should also be considered in patients with the following: 

  • Malabsorption e.g known or suspected coeliac disease, Crohns disease, gastrectomy
  • Macrocytosis (MCV >99)
  • Long term use of drugs such as metformin, PPIs, OCP - but testing only advised if strong clinical suspicion.
  • Severe dietary restritions


Assessment & Investigations

Investigation of low B12 levels can be undertaken in primary care and should usually be done before starting treatment (unless severe neurology).


  • Anti-intrinsic factor antibodies should be tested if pernicious anaemia is suspected regardless of B12 level- may be found in up to 35% of cases of pernicious anaemia. Life-long replacement therapy is indicated.
  • Look for other evidence of malabsorption

B12 or folate deficiency does not normally require referral for haematology outpatient assessment.

Haematology advice and guidance can be requested if uncertainty regards management persist.

Special situations:

  • Pregnancy: Vitamin B12 testing should be avoided in pregnancy as results are unreliable (levels naturally decrease in pregnancy). If there is clinical suspicion of deficiency is strong, consider testing but interpret the results with caution. Discussion with the laboratory and additional tests may be needed. An alternative approach may be a short course of therapy and reassessment post-pregnancy.
  • Oral contraceptive pill: Only test if strong clinical suspicion as difficult to interpret vitamin B12 results. Asymptomatic women with mild reduction 145-190ng/l do not need replacement, review diet.
  • Food-B12 malabsorption e.g. gastric acid suppressants or metformin:  only test if strong clinical suspicion. Trial of oral cyanocobalamin could be considered and reviewed at 6 months.


  • Assess and perform relevant investigations before treating macrocytic anaemia or neurological symptoms unless there are features that are well established to be associated with vitamin B12 deficiency.
  • I.M. hydroxycobalamin as per BNF
  • High dose (1000micrograms daily) oral cyanocobalamin may be considered as an alternative. Approximately 1% is absorbed via gastrointestinal tract and is intrinsic factor independent. N.B. When clinical features of vitamin B12 deficiency are present ONLY parenteral replacement is appropriate.
  • A trial of low dose cyanocobalamin 50 micrograms daily can be considered in cases of low vitamin B12 assay results.

High vitamin B12 levels

This is often a non-pathological finding and rarely due to a haematological condition. The most common cause of high vitamin B12 in the absence of B12 replacement therapy is liver disease.  Vitamin B12 may be elevated in haematological malignancy including myeloproliferative disorders and these disorders are excluded by a normal FBC.

Assessment in Primary Care

Check that the patient has not been taking supplements that include vitamin B12.

Assess general health and for risk factors for liver disease.

Investigations in Primary care:

These will be determined by the clinical history examination and blood results. Unless a haematological malignancy is suspected from the FBC report discussion with or referral to Haematology is not required. Assessment for liver disease may be appropriate.


(1) Vitamin B12 & folate anaemia - Illnesses & conditions | NHS inform



Guidelines for the diagnosis and treatment of cobalamin and folate disorders Vinod Devalia, Malcolm S. Hamilton, and Anne M. Molloy on behalf of the British Committee for Standards in Haematology British Journal of Haematology, 2014, 166, 496–513. Available online at: