B12 Deficiency

Updated 10/2012

What is B12 Deficiency?

Vitamin B12 (cobalamin) deficiency is common in the population over 80, affecting approximately 10% of this age group. It can be a cause of unsteady gait (ataxia), sometimes accompanied by anemia (macrocytic), and loss of position sense. When associated with spinal cord disease, it is sometimes termed “subacute combined degeneration”. The ataxia is called a “sensory ataxia”, because it appears to be related to loss of position sensation from the feet. Other diseases that can produce similar symptoms include:

  • Subacute combined degeneration (B12 deficiency)
  • Tabes Dorsalis (syphilis)
  • Fredriech’ ataxia
  • Peripheral neuropathy
  • Thoracic cord lesions

The term subacute combined degeneration was coined by Russell, Batten and Collier in 1900 to describe pathological changes in the spinal cord. While changes in the posterior columns are emphasized in clinical accounts, pathologically the lateral and anterior columns are also often affected. The peripheral nerves are generally unaffected.

In addition to ataxia and anemia, patients with B12 deficiency may have fatigue, weight loss, numbness and weakness in the extremities or mental status changes including dementia and depression.

Causes of B12 deficiency

The liver stores enough B12 to last several years, and conditions that lead to B12 deficiency must be ongoing for at least 2 years before symptoms appear. B12 is bound to animal protein when it is ingested, from which it is released by gastric acid. Afterwards, B12 binds to intrinsic factor, a protein secreted by the stomach that allows B12 to be absorbed in the ileum.

Bowel conditions contributing to B12 deficiency include pancreatic deficiency states, ileal disease (e.g. Crohn’s disease), and surgery such as gastrectomy, or removal of the small bowel. Pernicious anemia accounts for 15-70% of B12 deficiency. In this situation autoimmune antibodies are produced against intrinsic factor, preventing its production in the stomach.

Food-cobalamin malabsorption is the inability of stomach secretions to release B12 from the animal protein it is bound to upon ingestion. Recent research has shown that in older adults, food-cobalamin malabsorption is the most common cause of B12 deficiency.

Drugs that reduce stomach acidity and gastritis (inflammation of the stomach) can also lead to B12 deficiency by decreasing absorption. B12 is available only from animal sources and thus strict vegetarians or people with poor diets are at risk of deficiency.

Infants who are breastfed by vitamin B12 deficient mothers can develop B12 deficiency themselves. Lov levels of B12 in infants can produce severe complications including developmental abnormalities, growth retardation and anemia.


B12 deficiency is usually detected through measurement of the serum B12 level. Typical lower limits of normal are 200 pg/ml, but some patients with symptomatic B12 deficiency may have normal levels. Measurements between 150 and 300 are nondiagnostic. Plasma levels of holotranscobalamin (holoTC) detect the amount of B12 that is available for absorption by the cells, and recent research has suggested that it is a more sensitive method of detecting B12 deficiency than measurment of serum B12 alone.

B12 or holotranscobalamin levels that re nondiagnostic should be confirmed with secondary surrogate markers. Surrogate markers include methylmalonic acid (MMA) and homocysteine. MMA is elevated in 90-98% of patients with B12 deficiency. This test may be overly sensitive as 25-20% of patients over the age of 70 have elevated levels of MMA, but 25-33% of them do not have B12 deficiency. For this reason, MMA is not routinely recommended in the elderly. Homocysteine is also elevated in B12 deficiency.

Serum antibodies against intrinsic factor or parietal cells (which produce intrinsic factor) can also be measured to diagnose pernicious anemia.

In the past, the Shilling’s test was advocated as a method of determining whether oral or intramuscular B12 supplementation will be required. In the Shillings test it can be determined whether or not oral B12 is absorbable using a radioassay. The Shillings test is, however, somewhat expensive and certainly inconvenient. Some authors advocate simply providing B12 to the patient via an oral or nasal route, and then retesting the patient after a few months as a simpler and more direct method of determining whether shots will be needed.

While B12 deficiency can cause a macrocytic anemia, this is not required for diagnosis, and the absence of anemia should not dissuade the physician from considering B12 deficiency.


There are presently a variety of options. Oral therapy involves giving 250 ug to 1 mg of B12 daily. Monthly injections of B12 are traditional. Nasal B12 is also now available. One small trial found administration of B12 in combination with synthetic intrinsif factor to increase absorption, but this is currently an investigational treatment only.

All modes of treatment should include a method of checking for response. If clinical syndromes do not improve on oral B12 supplementation, physicians should assess surrogate markers (MMA, homocysteine), or perform a Shilling test to determine the ability of the gastrointestinal tract to absorb B12.

Some researchers have claimed to show a relationship between B12 deficiency and a variety of medical conditions, including dementia, cardiovascular disease, rheumatoid arthritis, macular degeneration and mood disorders. The true effect of B12 deficiencies on these condition is still poorly understood and no clear link has been established.

A recent case study indicated that B12 dificiency may go unnoticed in elderly populations, and should be suspected if neuropsychiatric symptoms are present (Singh and Arora, 2010).

Case Example:

A 45-year-old man presented with dizziness. The usual tests including audiometry, ENG and an MRI were all normal. In the course of an evaluation for gastritis it was determined that he was infected with H-pylori. B12 levels were checked and found to be low (100). His dizziness eventually resolved with injections of B12.


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