Timothy C. Hain, MD Page last modified: June 18, 2009Vitamin B12 deficiency is common in the population over 80 (about 10%). 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. A list of diseases that can present with a similar picture is given below:
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. B12 deficiency is a risk factor for cognitive decline (i.e. dementia) according to Tagney et al (2009).
B12 is available only from animal sources and thus strict vegetarians are at a risk of deficiency. B12 is bound to animal protein and released by gastric acid. When taken as part of food, B12 is released from food by a combination of gastric acid and pepsin (an enzyme). It then binds to "R" binders, released by the stomach. Intrinsic factor (IF) is also released by the stomach. Next, pancreatic enzymes degrade the R-binder/B12 complex and allow formation of the IF/B12 complex. The intrinsic factor/B12 complex is absorbed in the terminal ileum (the end of the small bowel, just prior to the large bowel).
A medication for diabetes, Metformin, reduces absorption of B12 (Tagney et al, 2009).
Gastric conditions contributing to B12 deficiency include various stomach diseases that impair release of B12 from food or production of intrinsic factor (such as gastrectomy, antacid medications or gastritis), pancreatic deficiency states which impair formation of the b12/intrinsic factor complex, ileal disease (e.g. Crohn's disease), bacterial overgrowth in the bowel, and other miscellaneous causes of malabsorption.
Pernicious anemia (PA) accounts for 15-70% of B12 deficiency. This an autoimmune disorder where antibodies are made to intrinsic factor. Oral supplements are generally less effective in PA than other modes of administration.
B12 deficiency is usually detected through a B12 level. Typical lower limits of normal are 200 pg/ml. Levels between 150 and 300 should be confirmed with secondary surrogate markers (see following). A CBC test may show macrocytic anemia. This is not required for diagnosis, and the absence of anemia should not dissuade the physician from considering B12 deficiency.
Because B12 is stored in the liver, it takes about 2 years following a sudden cessation of intake for signs of deficiency to arise.
Bacterial overgrowth syndrome may be detected via upper GI, serum D-lactate, and blood alcohol level. A small bowel biopsy is occasionally helpful in ruling out Celiac disease (as is anti-Gliaden antibodies) as well as Whipples disease. Celiac may be particularly relevant as some patients with celiac have unsteadiness too. H-pylori infection can be assayed for with a blood test. Intrinsic factor and parietal cell antibody tests are available.
Surrogate markers for B12 deficiency 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.
In the past, the Shilling's test was advocated as a method of determining whether oral vs nasal 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. One microgram of radioactive B12 is given by mouth. One hour later, 1 mg of non-radioactive B12 is given as a "flushing dose", to prevent further absorption. Radioactive B12 is counted in the blood and urine. The test can be also done with the addition of intrinsic factor, pancreatic extract, and after therapeutic attempts to improve absorption (such as gluten free diet, use of antibiotics).
The Shillings test is somewhat expensive and inconvenient. Recently there has been a shortage of the needed radioisotope (2004). The clinical benefit of the Shillings test is also sometimes difficult to follow, as the cost of the test greatly exceeds the cost of supplementing B12 and rechecking B12 later. 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.
There are presently a variety of options.
All modes of treatment should include a method of checking for response (i.e. a B12 level, clinical followup). If clinical syndromes do not improve on oral B12 supplementation, and B12 level is normalized (we would look for a level of about 500) assess surrogate markers (MMA, homocysteine).
In situations where there is a treatable cause of malabsorption, treatment should also be directed towards this cause.
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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