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Oral B12 Treatment
- Sally Stabler (13 November 2006)
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Oral B12 Treatment
- Josep Vidal-Alaball (13 November 2006)
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Sally Stabler, Professor of Medicine UCHSC, 4200 E. 9th Ave., B170, Denver, CO 80262
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To the Editor, Doctor Butler and Co-authors reviewed two randomized controlled trials of oral vs. intramuscular vitamin B12 replacement therapy (1). In one trial oral vitamin B12, 2000 mcg, was continued daily for 4 months with a resulting 3 fold higher level of serum vitamin B12 when compared to the monthly intramuscular injection (2). The other trial started with daily oral vitamin B12 1000 mcg for 10 days then decreased to only once a week for 4 weeks and then only once a month (3). At 90 days, the vitamin B12 levels in that trial were quite low at 213.8 and 225.5 pg/mL for oral and intramuscular dosing respectively. Butler, et al. state in their Discussion that “high doses of oral vitamin B12 (1000 ug) initially daily and thereafter weekly and then monthly are also as affective as intramuscular vitamin B12.” This statement could be misinterpreted because this study (3) followed the patients for only 90 days, and there is no data, to show what the later risk of relapse of symptomatic megaloblastic anemia will be. Relapse after total interruption of B12 therapy in pernicious anemia may take more than 2 years (4). Thus, only a long term follow up will show whether such a regimen will be adequate treatment. It is likely that monthly oral treatment will not provide optimum B12 status since only 1% of an oral dose can be absorbed i.e. 10 ug out of the 1000 ug dose. Over 30 days this would only be 0.33 ug/daily dose, which is considerably less than the obligatory loss of biliary B12, 2-9 ug/day. Even parenteral administration of 1000 ug, wherein a much greater proportion (10%) of B12 is retained does not completely prevent modest elevations of methylmalonic acid in some individuals, probably due to these obligatory losses (3). Until a long term study with monitoring of serial serum B12 levels along with some other measure of functional status is performed, it would seem prudent to provide oral treatment on a daily basis. Such treatment as pointed out by the authors (1) has been successful for 40 years in Sweden. 1. Butler CC, Vidal-Alaball J, Cannings-John R, McCaddon A, Hood K, Papaioannou A, Mcdowell I, Goringe A. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 23:279-285, 2006. 2. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 92:1191-1198, 1998. 3. Bolaman Z, Kadikoylu G, Yukselen V, Yavasoglu I, Barutca S, Senturk T. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clin Ther 25:3124-3134, 2003. 4. Savage D, Lindenbaum J. Relapses after interruption of cyanocobalamin therapy in patients with pernicious anemia. Am J Med 74:765-772, 1983. Conflict of Interest:None declared |
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Josep Vidal-Alaball, General Practitioner and Specialist Registrar in Public Health Medicine Swansea, UK, SA1 5AQ
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To Dr Stabler, Thank you for your comments. We recognised that our systematic review has limitations, one of which is that it included “only two open studies with relatively short follow-up periods”. The study published at Family Practice is a shorter version of a more detailed review that we published in The Cochrane Database of Systematic Reviews(1) where we also stated that “the length of follow up was probably too short to demonstrate effectiveness of the oral treatment” and that “the length of follow up ranged from 90 days to four months. We consider this as insufficient because of the long biological half-life of body stores of vitamin B12. This is estimated to be more than 30 months(2)". We also advocated for a large pragmatic randomised controlled trial in Primary Care settings to resolve some of the uncertainties surrounding oral treatment with vitamin B12. I agree that until such study is conducted, daily oral treatment with Vitamin B12 seems a prudent option. (1). Vidal-Alaball J, Butler CC, Cannings-John R et al. Oral vitamin B12 versus parenteral vitamin B12 for vitamin B12 deficiency. The Cochrane Database of Systematic Reviews 2005; issue 3. (2). Basu TK, Dickerson JWT. Vitamins in human health and disease. Wallingford: CAB International, 1996. Dr Josep Vidal-Alaball General Practitioner and Specialist Registrar in Public Health Medicine National Public Health Service for Wales 36 Orchard Street, Swansea, SA1 5AQ E-mail: Josep.Vidal-Alaball@nphs.wales.nhs.uk Conflict of Interest:None declared |
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