Dietary Vitamin B12 is primarily found in meat, fish and dairy products. B12 forms a complex in the duodenum with intrinsic factor (produced in gastric parietal cells) and is absorbed in the terminal ileum. Deficiency can cause a macrocytosis with or without anaemia or pancytopenia. Neurological presentation can occur in the absence of haematological changes and early treatment is essential to avoid permanent neurological disability. Patients with strong clinical features of cobalamin deficiency can have levels that lie within the reference range, albeit at lower end of normal range. There is no “gold standard” test for the diagnosis of cobalamin deficiency so clinical features should always be considered alongside laboratory test results.

Causes of low B12 levels:

• pernicious anaemia
• vegan diet
• malabsorption syndromes (e.g. achlorhydria, gastric resection/bypass, Crohn’s disease, pancreatic insufficiency and gut infection e.g. giardiasis, fishtapeworm)
• prolonged proton pump inhibition
• pregnancy/combined oral contraceptive pill/HRT
• metformin
• rare congenital causes in infants and children.

• Macrocytosis +/- anaemia
• Pancytopenia
• Unexplained neurological/neuropsychiatric symptoms eg. peripheral neuropathy/sensory  ataxia/ambylopia/parasthesia; (newly diagnosed) dementia; visual loss
• Oral ulceration/ glossitis/ beefy tongue/ angular stomatitis
• Dietary deficiency (vegan diet)
• Malabsorption syndromes
• Oral B12 therapy, to check for effect, does not require longer term monitoring

• Tiredness is not an indication for testing.
• Lower B12 levels are seen in patients taking the combined oral contraceptive pill/HRT as well as in pregnancy. These levels are generally not clinically significant. Testing should not be undertaken in these situations unless one of the indications above is also present.
• Low B12 levels, mild macrocytosis and mild thrombocytopenia (plt 100-149) are not uncommon in pregnancy and can be due to normal physiological changes.
• If patient is on IM B12 replacement, repeat B12 testing is not indicated but FBC and reticulocyte response should be monitored initially.

• Tests should not be repeated within 3 months of previous test, repeat testing should be based around development of any of above indications.
• Initial assessment of response to oral B12 replacement at 3 months.

Devalia V, Hamilton MS, Molloy AM, on behalf of the British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology 2014 166(4): 496-513 Free full text