debate22

Figure legend
To regret time lost
is to loose more time.

Opinion of The Rondel

The discussion between Herman Nilsson-Ehle (1) and Bo Norberg (2) is whether oral cyanocobalamin, 0.5 mg daily, is a safe and reliable treatment for vitamin B12 deficiency. The historical evidence for present practice, 1 mg daily, has not been questioned since 1968 (2). In any case, the burden of proof rests with the advocate of new guidelines. The reply by Nilsson-Ehle below maintains that 0.5 mg might be sufficient for some patients. Lars Brattström and Anders Lindgren have also announced contributions on the subject. Then the debate is closed in The Rondel for the time being. /The Editors

The article "High homocysteine – prophylaxis and treatment" [1] triggered sharp reactions from the editor of this journal, Bo Norberg (BN). In addition to a strongly argumentative "Editorial orientation", the article was extensively commented upon in the next volume, as an editorial published 2005-01-23 [2]. Now, three months later, an opportunity to reply is being offered. The key issue relates to passive absorption of cobalamin, making oral treatment with high doses of cyanocobalamin feasible both for remission therapy and maintenance (secondary prophylaxis) in patients with severe cobalamin malabsorption [1]. BN does not quote me correctly regarding means and variability of the Berlin data [3], and the figures provided do not add any clarity to the discussion [2]. Figure 1 is an inferior variant of Fig 8 from Berlin´s original paper [3], also reproduced above my article [1]. Here, the observant reader will notice that none of the subjects displayed borderline or subnormal serum cobalamin concentrations at the end of follow up according to criteria set up by the investigators based on the methods and standards of that time; all had "normal values". Figure 2 is an oversimplification, hiding the true range of absorption data clearly stated in my article [1]. Since the interpretation of the old studies is controversial, I encourage the reader to scrutinize the original papers and data, mainly [3, 4]. It´s in my view highly questionable to apply newly designed efficacy criteria, both arbitrary and derived from totally different methodology, on the original study group treated several decades before. I have not stated that an oral daily dose of 0.5 mg would be sufficient for all stages and cases of cobalamin deficiency [1]. Further, I have not stated that all pernicious anemia patients in remission should receive 0.5mg cyanocobalamin without compromise, merely that the early absorption and clinical data [3] indicate that this might be sufficient. A daily oral dose of 1mg cyanocobalamin is documented as a safe and reliable treatment for patients in remission according to well performed studies. However, oral treatment with vitamin B₁₂ does, at all dose levels, carry a risk for bad compliance, and should therefore be carefully monitored with both laboratory and clinical measures [1], irrespective of the indication (primary prophylaxis for risk groups, remission treatment, maintenance/secondary prophylaxis). In such a sound clinical setting, there should be no risk of therapeutic failure.

Herman Nilsson-Ehle, MD, PhD, associate professor
Department of Internal Medicine
Section of Haematology
Sahlgrenska University Hospital
SE-413 45 Göteborg, Sweden
New email: herman.n-ehle@vgregion.se

[3]. Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med Scand 1968;184:247-58.

[4]. McIntyre PA, Hahn R, Masters JM, Krevans JR. Treatment of pernicious anemia with orally administered cyanocobalamin (vitamin B12). Arch Intern Med 1960;106:280-92.