In praise of high-dose oral B12


“Is high-dose oral B12 a safe and effective alternative to B12 injection?” (Clinical Inquiries, J Fam Pract. 2012;61:162-163) is a well-documented and practical review. I would like to present additional data that may be of interest to family physicians.

Cobalamin (vitamin B12) is absorbed by intrinsic factor-independent passive diffusion. High-dose oral B12 (≥1000 mcg/d) can cure cobalamin deficiency, and may also induce and maintain remission in patients with megaloblastic anemia.1

Two prospective, randomized controlled studies comparing oral and intramuscular (IM) vitamin B12 documented the efficacy of oral B12 as a curative treatment.2,3 One study involved 38 patients, several of whom had pernicious anemia (PA), who showed improvement in hematological parameters and vitamin B12 levels after 4 months of oral cyanocobalamin therapy using a higher dose (2000 mcg/d) of cobalamin.2 Another involved 60 patients, and reported significant improvement of hematological parameters and vitamin B12 levels after 3 months of oral cyanocobalamin therapy (1000 mcg/d).3

A Cochrane review also supports the efficacy of oral B12 as a curative treatment, with a dose between 1000 and 2000 mcg, initially taken daily and then weekly.4 In this analysis, serum vitamin B12 levels increased significantly in patients receiving oral B12, and those taking oral B12 and the IM group showed an improvement in neurological symptoms.4

Our working group (CARE B12, Hôpitaux Universitaires de Strasbourg) has developed an effective oral curative treatment for patients presenting with food-cobalamin malabsorption (FCM) and PA, using crystalline cyanocobalamin.1 In a first study, we prospectively followed 10 patients with cobalamin deficiency and well-established FCM who received 3000 or 5000 mcg oral crystalline cyanocobalamin once a week for at least 3 months. After 3 months, all had increased hemoglobin levels and decreased erythrocyte cell volume. However, 2 patients had only minor, if any, response. Serum cobalamin levels were increased in all 8 patients in whom it was measured.

We also conducted an open study of 10 patients with well-documented cobalamin deficiency related to PA who received 1000 mcg/d oral crystalline cyanocobalamin for at least 3 months. After 3 months, serum cobalamin levels were increased in all 9 patients in whom it was measured; 8 patients also had increased hemoglobin levels, and all 10 had decreased mean erythrocyte cell volume. Three patients experienced clinical improvements.

Analysis of several other studies has shown that all patients treated with oral B12 corrected their levels of the vitamin and at least two-thirds corrected hematologic abnormalities,1 and one-third experienced clinical improvement.

We currently recommend that patients with PA take 1000 mcg/d oral cyanocobalamin for life. Oral B12 allows patients to avoid the inconvenience and discomfort of injections. It is less expensive than IM B12 and can be particularly useful for the elderly, and for patients on anticoagulants or antiplatelet agents, for whom IM injections are prohibited.

Emmanuel Andrès, MD
Strasbourg, France

1. Andrès E, Fothergill H, Mecili M. Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opin Pharmacother. 2010;11:249–256.

2. Kuzminski AM, Del Giacco EI, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92:1191–1198.

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. 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.

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