“The term ‘Vitamin B12’ is usually restricted to cyanocobalamin, which is the most chemically stable and unnatural form of cobalamin, but Vitamin B12 refers to all potentially biologically active cobalamins.”1
Vitamin B12 and folate are cofactors in metabolic processes to do with DNA synthesis in the human body.2 Recommended daily requirements are 0.4ug for infants and 2.4ug for teenagers and adults, and there is a huge safety margin (over 1000-fold the recommended daily requirement) for overdose.3 Dietary vitamin B12 is obtained from animal products (dairy, meat, eggs, fish and seafood). A small amount may be obtained from bacteria found on unwashed, unpeeled, dried shitake mushrooms (as opposed to most other sorts), fermented soybean (specifically tempe), and dried purple laver (nori, or algae).1
Macrocytosis and megaloblastic anaemia are the typical haematological changes caused by vitamin B12 deficiency, but pancytopaenia may occur. Other signs and symptoms include fatigue, concentration and memory defects, depression, dementia, personality change, peripheral neuropathy, paraesthesia, decreased reflexes, ataxia and restless legs.
Several guidelines recommend testing vitamin B12 levels to investigate the following clinical indications.2
In the initial evaluation of anaemia in chronic kidney disease.
In the initial evaluation of mild cognitive impairment or dementia in elderly patients. The incidence of low vitamin B12 levels in Australia appears to increase with age (> 65 years).
Patients with polyneuropathy.
Patients with Crohn’s disease with macrocytic anaemia or who do not respond to iron treatment.
Patients with symptoms or signs of macrocytic anaemia.
Patients with chronic fatigue syndrome or myalgic encephalopathy, if they have already undergone pre-test investigations (such as full blood examinations).
It is unclear whether other special populations should be tested for B12 deficiency (e.g. patients with suspect neuropsychiatric abnormalities).
Interestingly and surprisingly, patients with other malabsorption conditions (other than Crohn’s disease), vegans and people addicted to alcohol are not mentioned in these guidelines. Patients taking phenytoin, metformin and proton pump inhibitors may also have reduced levels of vitamin B12.4
Serum vitamin B12 levels do not correspond well with tissue vitamin B12 concentrations (e.g. pregnancy, simple gastritis).1 In addition to this, different laboratories have different cut-offs for vitamin B12 deficiency and there is lack of a gold standard.
“Internationally, the cut-off for vitamin B12 varies markedly between < 130 pmol/L and < 258 pmol/L.”5
Symptoms of deficiency may be apparent with vitamin B12 levels under 258pmol/L, but in Australia most pathology laboratories suggest a lower level of 220pmol/L.5 Between 15% and 40% of patients with low vitamin B12 levels do not have actual vitamin B12 deficiency on further investigation.4 To improve the reliability in cases of low normal range vitamin B12 levels and possible deficiency, a relatively new assay now measures active vitamin B12 levels in this situation.4
It is important to note that a diagnosis of vitamin B12 deficiency should prompt investigation to determine not just the cause, but also possible malabsorption of other nutrients (iron, red cell folate).
“Pernicious anaemia” is megaloblastic anaemia caused by an autoimmune gastritis, resulting in less intrinsic factor produced in the stomach. The vitamin B12 normally binds to intrinsic factor in the upper small bowel and then is absorbed in the ilium. Pernicious anaemia is associated with type 1 diabetes, autoimmune thyroiditis, the development of gastric cancer and carcinoid tumours.4
Generally, vitamin B12 will need to be replaced parenterally via intramuscular injections as malabsorption is the most common cause. Replacement regimens vary according to the degree of deficiency, but for symptomatic patients or those with very low active B12 levels 1000ug intramuscularly may be used alternate daily for the first two weeks and then weekly until stabilised, then every three months for maintenance. It should be noted that oral vitamin B12 is normally poorly absorbed (0.5 to 4% of dietary intake), so high doses (1000ug daily) should be used.3
1. Watanabe F., et al. Vitamin B12-Containing Plant Food Sources for Vegetarians. Nutrients, May 2014; 6(5): 1861–1873.
2. NPS MedicineWise, Vitamin B12 Tests, National Prescribing Service, Nov 2014
3. Engelman, D. Vitamin B12. Immigrant Health Service, The Royal Children’s Hospital, Melbourne, Nov 2013
4. Sacks, S. Vitamin B12 Deficiency: New Diagnostic Assay, Clinipath Pathology
5. Zeuschner C. L., et al. Vitamin B12 and vegetarian diets. MJA Open 2012; 1 Suppl 2: 27-32.