[Tidigare debattartiklar]

How we wish to be cited:
Vidal-Alaball J, Butler CC. Critical review: oral high-dose cobalamin [debatt]? Rondellen 2003; 15. URL: http://www.rondellen.net

The study by Nyholm and colleagues is a prospective case series of 50 patients (of 108 eligible) switched from intramuscular to daily oral Vitamin B12 (1000 mcg cyanocobalamin). Patients entered in the study were known to have vitamin B12 deficiency as a consequence of gastrointestinal surgery, pernicious anaemia or because they were intrinsic factor negative. Patients too unwell or with cognitive impairment were excluded. The study was set in U.K. Primary Care Centres with a combined population of 19,000 patients.

All consenting patients received 1000 mcg of intramuscular Vitamin B12 at the beginning of the study. They were followed with monthly blood tests and when their Vitamin B12 levels fell below 418 pg/ml, they were started on oral daily vitamin B12.

Ten patients withdrew for various reasons. Of the 40 patients who completed the study, all achieved acceptable levels of Vitamin B12 with the oral preparation.

The study has the obvious limitations of not being a Randomized Control Trial (RCT) and not being double blinded. We do not know the reasons why patients choose to participate in the study, but probably they were the most motivated to comply with the oral regime. This suggests that extrapolation from this study about compliance after conversion to oral therapy should be treated with caution. Also the patients took the treatment for variable periods of time, from 3 to 18 months. 3 months may be not enough to show a possible fall in vitamin B12 levels associated with oral therapy.

This study is one of the first to asses levels of satisfaction among people switching to oral vitamin B12. The study reports 83% of patients who agreed to be changed to oral treatment preferred oral vitamin B12 to the injections and 87% of those found the tablets highly acceptable. How satisfaction was measured is not described. It would be important to study the reasons behind these preferences. Of note is that only 50 of the 108 eligible patients agreed to take part on the study and switch to oral treatment. Less than 40% of eligible patients completed the study, and as this was not blinded, those satisfaction data are even more prone to bias. Why did the remaining 58 patients decline participation? The author’s conclusions that patients much prefer oral medication could be therefore disproportionate.

Conclusions

This is another study showing that oral B12 taken by those who choose to switch from intramuscular therapy is as effective as the intramuscular route. However, this non-randomised study is unlikely to change 50 years of practice, and oral vitamin B12 probably will remain as one of "medicine’s best kept secrets".

What do we need to change practice? Is more than 30 years of experience using oral vitamin B12 in Sweden not enough ? In addition, more than a dozen of case series since the earlier fifties have shown equivalence of both routes of administration, and a recent RCT showed that oral Vitamin B12 is as effective as intramuscular vitamin B12 or even superior .

Unfortunately, the answer seems to be that all this evidence is not enough for many doctors and a big RCT with double blinding may be necessary to convince sceptics.

Or perhaps the answer lies in unwrapping the reasons behind the majority of patients declining to participate in this study. Indeed, why was this not a randomised study? It could be that a significant number of patients are happy with the intramuscular route and do not want to try oral therapy. Clinicians may perceive this reluctance, and do not want to generate headaches for themselves by trying to switch patients over.

A deep understanding of patient’s preferences, explaining possible psychotropic effects of intramuscular Vitamin B12 therapy, and developing effective ways of reaching shared decisions with patients is probably the way forward.

Josep Vidal-Alaball
Clinical Academic GP Fellow

Chris Butler
Professor of Primary Care Medicine

Department of General Practice
University of Wales College of Medicine
Llanedeyrn Health Centre
Cardiff
CF23 9PN

1. 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.
2. Lederle FA. Oral cobalamin for pernicious anemia. Medicine's best kept secret? Journal of the American Medical Association 1991;265(1):94-95.
3. Norberg B. Oral high-dose cyanocobalamin - a contagious concept [editorial]. Rondel 2001; 8. URL: http://www.rondellen.net/publisher08_eng.htm
4. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191-8.

Publicerat 2003-06-10