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Managing Patients with Evidence of a Vitamin B12 Deficiency

“A caregiver must manage a subclinically deficient patient with pernicious anemia as a cause quite differently and pay closer attention than to a similar patient without it.” - Carmel, 2006

Clinical Vitamin B12 Deficiency

Cobalamin replacement is effective because crystalline forms of B12 can be absorbed even when animal protein bound forms cannot be digested.

Options available for treating a clinical vitamin B12 deficiency include oral and parenteral (intramuscular or subcutaneous) preparations. Intravenous dosing is not recommended because this will result in most of the vitamin being lost in the urine.74

The response of the patient with vitamin B12 deficiency anemia to treatment is usually rapid, with reticulocytosis occurring within 2 - 5 days, and the hematocrit normalizing within weeks.10 Treatment with cobalamin effectively halts progression of the deficiency process but might not fully reverse more advanced neurologic effects.39,42 If the underlying cause of the vitamin B12 deficiency is treatable (e.g., fish tapeworm infection or bacterial overgrowth), then treatment should include addressing the underlying etiology.7

Vitamin B12 is not carcinogenic, teratogenic, or mutagenic. It is considered safe even at 1,000 times the RDA.

Baik and Russell, 1999

Vitamin B12 is considered safe, even at levels much higher than the recommended dose. It has not been shown to be toxic or cause cancer, birth defects, or mutations.10,75 Be aware, however, that patients who have a vitamin B12 deficiency with associated megaloblastic anemia might experience hypokalemia and fluid overload early in treatment due to increased erythropoiesis, cellular uptake of potassium, and increased blood volume. 76,77

While the route, dosage, treatment timing, and follow-up might vary somewhat, there is no question about the decision to treat patients with pernicious anemia or with a low serum B12 level and hematologic or neurologic signs or symptoms without pernicious anemia (clinical vitamin B12 deficiency). Once treated for a vitamin B12 deficiency due to pernicious anemia or other irreversible severe problems with absorption, patients need to continue some form of cobalamin therapy for life.7

Parenteral (Intramuscular or Subcutaneous)

Administration of parenteral crystalline cobalamin has been the standard treatment protocol for decades.78,79 Few side effects have been reported, and patient acceptance is generally high. Anecdotally, the subcutaneous route causes less burning than does the intramuscular route (Carmel RA, New York Methodist Hospital [personal communication] 2006-2007). Regimens for parenteral administration vary. An approach suggested by Stabler and Allen is 1 milligram (1,000 µg) weekly for 8 weeks, then once monthly for life.7

Some providers have used quarterly injections after the initial dosing protocol. However, experts state that in pernicious anemia or severe malabsorptive deficiency, quarterly injections are not sufficient, noting that cobalamin levels start to fall prior to the 1 month follow-up (Allen RH. University of Colorado [personal communication] 2006-2007).


Large daily oral replacement doses might be an acceptable alternative if patients are compliant.7 Sufficient amounts of vitamin B12 are absorbed via passive diffusion in the small intestine.2,11 A study by Eussen et al. demonstrates a linear response in the reduction of metabolites and increased serum B12 levels with increasing dosages of oral cyanocobalamin.80 A common therapy is 1 milligram (1,000 µg) of vitamin B12 consumed daily.2,11,14


A relatively new vehicle for vitamin B12 therapy is a cyanocobalamin gel for intranasal use. However, absorption can be inconsistent, limited studies have been done to determine efficacy, and it is expensive.

Treatment approaches by clinicians vary somewhat in the initial treatment and the route used.7,77,81 Given the long-term nature of cobalamin therapy, consideration of the patient’s condition (e.g., cognitive impairment), convenience of getting the treatment, and ease of administration should heavily influence the method and dosage selected.7,11 For example, oral therapy is less painful and can be self-administered. However, because cognitive impairment is a frequent reason for noncompliance, patients might be more compliant with clinic or home health nurse-administered injections. Additionally, Carmel observed that many patients prefer the convenience of monthly injections to daily consumption of pills.11

Examples of treatment regimens from different sources for clinical vitamin B12 deficiency are listed in Table 6.

Subclinical Vitamin B12 Deficiency

The far more prevalent patient presentation is by an asymptomatic individual with borderline serum B12 levels and elevated homocysteine or methylmalonic acid levels, or both. These patients pose a dilemma for providers because there are no guidelines for the treatment of patients with subclinical vitamin B12 deficiency. Some providers prefer to treat these patients and check to see that metabolite markers have normalized, while others prefer to "wait and watch". For patients in the subclinical vitamin B12 deficiency category, taking a vitamin with B12 (usual dosages are 6 to 25 µg) is not sufficient to correct the metabolites. Two recent studies have suggested that the lowest dose of oral cyanocobalamin needed to normalize metabolites in subclinical vitamin B12 deficiency is 500-1,000 µg daily.80,82 The providers who test for and treat patients with subclinical vitamin B12 deficiency, especially those patients with possible pernicious anemia or elevated metabolites, or both, can prevent potential subsequent hematologic and neurologic manifestations. Whether treating or "waiting and watching", you should remember that routine monitoring of and educating the patient are important.


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  • Page last updated: June 29, 2009 The U.S. Government's Official Web PortalDepartment of Health and Human Services
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