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Vitamin B12 Deficiency Glos Care Overview

Gloucestershire CCG is aware that the majority of B12 testing is undertaken for patients with non-specific symptoms.  The current assay also does not offer complete certainty in diagnosing true deficiency (specificity of <80%).  The local reference range in Gloucestershire is 180-1000ng/L and a recent audit of B12 results showed that around 20% of samples had levels below 180ng/L – around 1/3 of these were in the ‘deficient’ range (<150ng/L) with the rest being indeterminate (150-180ng/L).  Spuriously low B12 levels are commonly seen as a result of alterations in protein binding in pregnancy, use of the oral contraceptive pill etc. Studies have shown that the B12 levels within an individual patient can show large fluctuations (by up to 23%) within a period of weeks.

Furthermore there is growing evidence that for some patients requiring B12 supplementation, oral treatment is as effective as IM injections.  Current prescribing approaches are also not in line with the NHS England guidance ‘Conditions for which over the counter items should not routinely be prescribed in primary care’ which advises that treatment to correct deficiencies will be prescribed, and that supplements for ongoing maintenance or prevention of deficiency should be self-funded. However, it should be noted that for some people being treated via the oral route, self-purchasing their treatment dose over the counter may be cheaper than paying the NHS prescription charge and this should be discussed with the patient.

This pathway seeks to offer guidance on appropriate testing and treatment options and whilst it has been drafted to support GPs with a range of clinical scenarios we acknowledge that there may still be the occasional patient who is not accounted for within the pathway.  In these instances we would encourage GPs to use their own clinical judgement to determine the most suitable testing and treatment options and using the relevant clinical support available to them. 


Vitamin B12 is water-soluble and is predominantly found in meat, milk (including milk products), fish, eggs and fortified breakfast cereals. Pure dietary deficiency is very unusual except in strict vegans. The dietary requirement is only 1-2 micrograms per day and the body stores represent 2-5mg (predominantly in the liver).

Most B12 absorption is an active process in the terminal ileum. This relies on the formation of a complex of B12 with Intrinsic Factor (secreted by gastric parietal cells). Around 1% of ingested B12 is absorbed passively throughout the digestive tract. 

Causes of low B12 levels can be found here.

Please click the relevant flowchart box to be taken directly to textual information


Causes of low B12 levels

Causes of low B12 level – (see algorithm below for treatment options)

  • Inadequate diet – strict vegan
  • Reduced protein bound B12 (reduced transcobalamin) active B12 unchanged
    • Pregnancy
    • oral contraceptive pill
    • anticonvulsants
    • HIV drugs
    • Myeloma
  • Malabsorption:
    • Pernicious anaemia
    • Long-term Proton pump inhibitor or H2-antagonist: Review to prn/STOP if possible.  
    • Biguanide (Metformin): Only assess vitamin B12 levels in patients on metformin if evidence of deficiency is apparent e.g. peripheral neuropathy or macrocytic anaemia.
    • Gastrectomy / bariatric surgery: - Recommendations for B12 replacement after gastric / bariatric surgery should follow the British Obesity and Metabolic Surgery Society guidelines,
    • Terminal ileum disease / surgery
    • Generalised malabsorption
    • Fish tapeworm (Scandinavia / poorly prepared Sushi)
    • other meds e.g. colchicine, colestyramine, Slow-K,  may also cause Vit B12 deficiency.
  • Rare – Nitrous oxide – although this may be seen more frequently with increased recreational misuse and increased use in the clinical setting; disorders of cobalamin transport / inborn errors of metabolism

NB The Schilling test is no longer available.

Initial Primary Care Assessment

Indications for measuring B12 level

There is no need to monitor serum B12 levels in patients receiving 3 monthly parenteral vitamin B12 treatment.

If the below indications are present then request B12 levels.

  • Unexplained macrocytosis +/_ anaemia or pancytopenia
  • Neurological signs – including peripheral neuropathy and optic neuritis
  • Cognitive change
  • Post gastric / bariatric surgery
  • Investigation of malabsorption
  • Failure to thrive, movement disorders and developmental delay in infants
  • Glossitis (sore beefy red tongue).

Haematological manifestations can present in the absence of neurological problems and vice versa.

If the patient has non-specific symptoms, consider waiting and retest at a later date if considered appropriate. The ‘Fatigue/Tired All The Time (TATT) pathway on G-care should be followed for patients in which fatigue is the main presenting symptom.  The finding of modestly reduced levels in patients with non-specific symptoms is usually of dubious significance.

Secondary tests for B12 deficiency (Homocysteine, MethylMalanoic Acid and Holotranscobalamin) need careful interpretation and are not routinely available locally. MethylMalanoic Acid levels can be accessed as a ‘send away’ test via the Biochemistry laboratory if a good clinical case for the investigation can be made (e.g. a patient with a strong clinical suspicion of B12 deficiency with a borderline /normal B12 level in whom a trial of B12 replacement is not thought appropriate – this should be an unusual occurrence).

Primary Care Management – Treatment Algorithm


Supporting guidance

Due to variations in pricing and the potential cost implications of prescribing 50-100mcg supplements we recommend that if prescribing oral B12 supplements for the initial correction of the deficiency, 1000mcg only are prescribed e.g. CyanocoB12 1mg tablets (TrioOn Pharma Ltd). There are no known adverse effects to prescribing higher doses of B12 than are clinically required.  However, for a small number of people who are being treated via the oral route, self-purchasing their treatment dose over the counter may be cheaper than paying the NHS prescription charge and this should be discussed with the patient.

In line with NHS England guidance ‘Conditions for which over the counter items should not routinely be prescribed in primary care’, Gloucestershire CCG will fund the initial treatment to correct B12 deficiency and then patients should be asked to purchase ongoing maintenance supplementation OTC (with the exception of those patients requiring ongoing IM B12 who will continue to be prescribed this).

As described above, the oral maintenance dose will be either 1000mcg or 100mcg. The patient should be counselled as to which one they will require. On the high street, the lower doses are typically cheaper than the higher dose (which differs from the prescribing costs), with the cost ranging from approximately £4-£8 for 3 month’s supply of 100mcg and £7-£14 for 3 month’s supply of 1000mcg. On-line outlets may have cheaper products available and patients who are able to may wish to explore this option.

Gloucestershire CCG’s implementation of NHSE’s guidance on Over The Counter (OTC) items advises that patients will receive initial treatment on the NHS for vitamin and mineral deficiencies, but the ongoing maintenance or prevention of deficiency should be purchased OTC. This will be applicable for those who are considered suitable for oral B12. 1000mcg oral B12 is readily available to purchase OTC at costs much lower than the NHS would incur.

Those on oral replacement may need intermittent monitoring to assure compliance / effectiveness of therapy. Vitamin B12 replacement should be given in line with the recommendations of the British National Formulary.

When to Refer
  • Consider discussing patients with a significantly abnormal Full Blood Count that does not respond to B12 replacement with a Haematologist.
  • For patients with non-responding neurological problems consider discussion with a Neurologist.
  • If patient does not respond to therapy.
Ongoing Primary Care
  • Monitoring of B12 levels is not routinely required or recommended beyond initial checking of treatment response.
  • Intermittent monitoring may be required in those receiving oral therapy to ensure compliance/effectiveness.
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