How we wish to be cited:
Norberg B. Safety and reliability of oral cobalamin [editorial]. Rondel 2004; 21. URL: http://www.rondellen.net

In a previous editorial, it was concluded that oral cyanocobalamin, 1 mg daily, and oral folic acid, 5 mg daily, provide safe and reliable treatment for most patients with deficiency states of cobalamin and/or folate (1). Now a B vitamin combination (cobalamin 0.5 mg, folic acid 0.8 mg, pyridoxine 3 mg) is launched for prevention of overt deficiency, that is for prophylactic management in the symptom-free pre-clinical stage of deficiency development. However, there is a fear that the B combination mentioned now is prescribed in Sweden on wrong indications due to a bushy and misleading marketing (2, 3).

With the Swedish experience in mind (2,3), it is suggested that the regulatory authorities of other countries should request a clinical trial designed to elucidate if the combination in question is safe and reliable in treating developing deficiency. The time-honored experimental model of pernicious anemia in relapse appears to be appropriate (cf 4). The design could be as follows.

About 400 patients with confirmed pernicious anemia on parenteral therapy are observed without maintenance therapy until relapse, defined as serum cobalamin approximately 300 pmol/L (400 pg/ml). Then treatment with the combination is started with an intention to maintain the regimen for one year with monthly monitoring. In cases of therapy failure, the patient is switched back to parenteral therapy.

Such a trial would show if the new combination is safe and reliable in cases of disturbed cobalamin absorption, defined by serum gastrin and serum pepsinogen A as "severe gastric body atrophy" according to the criteria of the Lindgren group (5); remaining parietal cell function would interfere with the interpretation of reuslts. This documentation is lacking at present; the documentation of the Swedish registration of the combination was performed on healthy persons (2), doubly checked for health prior to trial. About 50,000 patients suitable for the suggested trial are thought to be available in Sweden at present (cf 6).

1. Norberg B. Cobalamin and folate for better and worse [editorial]. Rondel 2004; 20. URL: http://www.rondellen.net/publisher20_eng.htm
2. Lökk J. Homocysteine lowering – from skunk to rose[debate]? Rondel 2003; 17. URL: http://www.rondellen.net/debate17_eng.htm
3. Rosenberg P, Hernborg A, Håkansson J, Skoglund I, Svartholm R, Söderström U, Wahlström L. B vitamins and dementia – lack of evidence in Cochrane analysis [debate]. Rondel 2004; 19. URL: http://www.rondellen.net/debate19_eng.htm
4. Nyholm E, Turpin P, Swain D, Cunningham B, Daly S, Nightingale P, et al. Oral vitamin B12 can change our practice. Postgraduate Medical Journal 2003;79(930):218-9.
5. Lindgren A, Lindstedt G, Killander AF. Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery. J Intern Med 1998; 244:341-9
6. Nilsson M, Norberg B, Hultdin J, Sandström H, Westman G, Lökk J. Medical intelligence in Sweden. Vitamin B12 – oral versus parenteral? Postgrad Med J 2004, in press

Published November 4, 2004