Vitamin B12 Therapy

Vitamin B12 Therapy That's Easy to Swallow


Is oral B12 therapy an effective substitute for monthly injections?

Vitamin B12 deficiency is common; the estimated prevalence is about 15%. It can also be cumbersome to treat. The "gold standard" for therapy has been monthly intramuscular injections of 1000 µg of vitamin B12. The hidden costs of this treatment are the pain of the injections and the travel requirements for either the patient (who is often an older adult) or the visiting nurse.

What the data show. Butler and colleagues1 suggest that 2000 µg of oral vitamin B12 daily or a daily dose of 1000 µg initially followed by the same dose weekly, and finally monthly, is as effective as intramuscular B12 for preventing the anemic and neurological complications of B12 deficiency.1,2 Their conclusions are based on the results of 2 studies that qualified for inclusion in their systematic review of randomized controlled trials of B12 therapy.

The first study included 26 patients who received oral therapy and 34 who had intramuscular injections; the second included a total of 33 participants who were given intramuscular B12 followed by oral therapy.3,4 Primary outcomes in the 2 studies were similar; they included serum cobalamin (B12) levels, hemoglobin levels, mean cell volumes, white blood cell counts, platelet counts, Mini-Mental State Examination results, neurological examination results, side-effect profiles of the 2 treatments, and methylmalonic acid (MMA) and homocysteine levels.

MMA levels were measured because determination of B12 levels alone does not provide complete accuracy in the diagnosis of deficiency. Of patients with an established B12 deficiency, 3% to 5% have a normal B12 level (95% to 97% sensitivity); 25% to 40% of patients with a low B12 level may not have deficiency (60% to 75% specificity). In contrast, measurement of MMA has greater than 90% sensitivity and probably higher than 90% specificity for detecting vitamin B12 deficiency. Recent data have shown, however, that renal insufficiency can raise the MMA level in the absence of true B12 deficiency.5

A few caveats. Although the data from these trials are promising, only the short-term effectiveness of oral therapy was addressed. In addition, the 2 studies included a total of only 93 patients.

If you choose to switch from parenteral B12 to an oral preparation, careful follow-up is mandatory because neurological damage can result from B12 deficiency. Oral B12 replacement is probably most appropriate for patients who do not want intramuscular injections, who find travel a hardship (although they must still visit the office 3 or 4 times a year for monitoring while taking oral B12), and who are reliable in follow-up.

Measurement of MMA is probably the best test for the adequacy of replacement. If the level rises, a return to intramuscular dosing is necessary.


1. Butler CC, Vidal-Alaball J, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract. 2006;23:279-285.
2. Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655.
3. Bolaman Z, Kadikoylu G, Yukselen V, et al. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clin Ther. 2003;25:3124-3134.
4. Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92:1191-1198.
5. Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency—an update. Haematologica. 2006;91:1506-1512.