B₁₂ deficiency: A look beyond pernicious anemia

IM injection is customary, though dosages vary

The classic treatment for B₁₂ deficiency, particularly when the cause is not a dietary deficiency, is parenteral administration—usually by intramuscular injection—of cyanocobalamin (and in rare occasions, hydroxocobalamin).^7,11,16,35 In the US and UK, dosages range from 100 to 1000 mcg per month (or every 2–3 months when hydroxocobalamin is given). The patient will receive this treatment for the rest of his life.^1,35

In France, the recommended practice is to build up the tissue stores of the vitamin quickly and correct serum B₁₂ hypovitaminosis, particularly in the case of pernicious anemia. The treatment involves administering 1000 mcg of cyanocobalamin per day for 1 week, followed by 1000 mcg per week for 1 month, followed by 1000 mcg per month, normally for the rest of the patient’s life.^2,3,20

Oral therapy is a well-kept secret

In cases of B₁₂ deficiency that don’t involve nutritional deficiency, alternative routes of cobalamin administration, including the oral^16,35-42 and nasal^43,44 routes have been used. These alternative routes offer patients a way to avoid the discomfort, inconvenience, and cost of an office visit for monthly injections.

Our research team has developed an effective oral treatment of food-B₁₂ malabsorption^38-41 and for pernicious anemia⁴⁵ using crystalline cobalamin (cyanocobalamin). Our principal studies of oral B₁₂ treatment (open, not randomized studies) are described in TABLE 2.^38-41,45 Our data confirm the previously reported efficacy of oral crystalline cyanocobalamin, especially in food-B₁₂ therapy.^6,16,36 All of our patients who received oral therapy corrected their B₁₂ levels and at least two thirds corrected their hematological abnormalities.^38-41,45 Moreover, one third of patients experienced a clinical improvement on oral treatment. In most cases of food-B₁₂ malabsorption, a “low” B₁₂ dose (ie, 125–1000 mcg of oral crystalline cyanocobalamin per day) was used.

These data are in line with the results of the 2 prospective randomized controlled studies comparing oral B₁₂ with intramuscular B₁₂ therapy.^35,37 An evidence-based analysis by the Vitamin B₁₂ Cochrane Group supports the efficacy of oral B₁₂ therapy, with doses between 1000 and 2000 mcg given daily in the beginning, and then weekly.⁴⁶ In this analysis, serum B₁₂ levels increased significantly in patients receiving oral vitamin B₁₂ and both groups of patients (receiving oral and intramuscular treatment) had neurological improvement.

In a randomized, parallel-group, double-blind, dose-finding trial, Eussen et al showed that the lowest dose of oral cyanocobalamin required to normalize mild B₁₂ deficiency is more than 200 times the recommended dietary allowance of approximately 3 mcg daily (ie, >500 mcg/day).⁴⁷ The procedure for oral B₁₂ treatment has, however, not been completely validated yet in “real life,” particularly as it relates to long-term efficacy.⁴⁸ Nonetheless, several authors suggest that oral B₁₂ therapy remains one of medicine’s “best-kept secrets.”⁴⁹

Acknowledgements

We are indebted to Professor Marc Imler and Jean-Louis Schlienger who initiated this work and to Helen Fothergill who kindly edited the text for publication in this English-language journal.

Correspondence
Prof. E. Andrès, Service de Médecine Interne, Diabète et Maladies Métaboliques, Clinique Médicale B, Hôpital Civil–Hôpitaux Universitaires de Strasbourg, 1 porte de l’Hôpital, 67091 Strasbourg Cedex, France; emmanuel. andres@chru-strasbourg.fr