Vitamin B12 (Cobalamin) Deficiency

Vitamin B12 (cobalamin) is a coenzyme required for various metabolic functions in the body, including fat metabolism, carbohydrate metabolism, and protein synthesis. It plays an additional critical roles in hematopoiesis and a significant role in the synthesis and maintenance of myelin in both the central and peripheral nervous system.

Vitamin B12 deficiency is an important cause of reversible neuropsychiatric symptoms and often overlooked.[1][2][3] Many case reports and series have reported psychosis,[4] hallucinations,[5][6] mood, irritability, dementia, catatonia,[7] delirium, hallucinations, and other neuropsychiatric symptoms in B12 deficiency.[8][9] The specific association between the role of B12 deficiency and neuropsychiatric symptoms is not well understood due to the lack of studies.

Causes of B12 deficiency include:

  • Dietary insufficiency - B12 can be low in vegetarians, or in the elderly when there is malnutrition. B12 can generally be found in meat and dairy products
  • Decreased absorption - can be caused by:
    • Deficiency of intrinsic factor (IF), leading to pernicious anemia
    • GI dysfunction such as hypochlorhydria
    • Long-term use of proton pump inhibitors
  • Inadequate utilization - Vitamin B12 is binds to the transport protein, transcobalamin II. In individuals with a transcobalamin II deficiency, this process is disrupted, and B12 cannot be delivered to sites of utilization and storage.
  • Inhalant Use Disorder - Nitrous oxide is a commonly abused inhalant drug and can precipitate vitamin B12 deficiency when used chronically and acutely, especially in individuals with pre-existing low vitamin B12 reserve.[10][11]
  • Serum B12 level should be ordered first, if B12 levels are borderline low, then you should also order:
    • Serum methylmalonic acid (normal level, <400), elevated level of methylmalonic acid is more sensitive and specific for the diagnosis of B12 deficiency
    • Serum homocysteine (normal level, <14)

Although laboratory norms and ranges may show that a serum vitamin B12 level between 200 pg/mL and 900 pg/mL is considered normal, a minimum level of 300 to 350 pg/mL is desirable in the elderly.[12]

If an individual is hospitalized, unable to take medications by mouth, or have severe neurological/psychiatric symptoms, then intramuscular (IM) administration of synthetic B12 (cyanocobalamin) is the treatment of choice. Otherwise, oral intake should be encouraged.[13]

Vitamin B12 Dosing

Oral • Cyancobalamin 1000mcg PO daily
• Ranges from 300 to 2000mcg have been commonly used with no evidence of toxicity
IM • Cyancobalamin 100 mcg for 5 to 10 days to saturate B12 stores
• Then 100 to 200 mcg qmonthly until normalization of the hemoglobin and hematocrit
• Then 100 mcg monthly to maintain remission