Editorial background The classical documentation of oral B12 is within the same patient –  deficiency diagnosis, treatment, recording of objective parameters of recovered health. Only two randomised studies have been published hitherto, which compare oral and parenteral B12 treatment. Thus, it is suggested that oral cyanocobalamin, 1 mg daily, is tested against parenteral hydroxocobalamin, 1 mg every third month, in a randomised Pan-European study of maintenance treatment for one year. The groups should be compared by haemoglobin levels, serum B12 levels, vibration sense in the distal joint of the first toe, plantar sensitivity, a simple test of balance, patient mood each quarter (before and after injection in the parenteral group), and doctor assessment of the treatment. (cf 1, 2).

Oral vitamin B12 therapy in Europe

Oral vitamin B12 seems to be experiencing a new revival. Despite oral vitamin B12 has been widely used in Sweden for more than 40 years to treat vitamin B12 deficiency (1,2), it is rarely prescribed in oral form in most other European countries. In the last decade, several groups of researchers in Sweden, Holland, France and Great Britain have renewed their interest in oral vitamin B12.

Our Cochrane review

In July 2005 we published a systematic review in The Cochrane Library showing that 2000 mcg doses of oral vitamin B12 daily was as efficient as intramuscular 1000 mcg doses initially daily and thereafter weekly and then monthly in achieving short-term haematological and neurological responses in B12 deficient patients (3).

During the systematic review we reviewed 797 abstracts and selected 41 abstracts for which the full paper was obtained but just two studies met the inclusion criteria. The two studies were randomised clinical trials comparing oral with intramuscular administration of vitamin B12 (4, 5). The trials recruited a total of 108 participants who received either high dose vitamin B12 or intramuscular vitamin B12 and followed up 93 of these participants from 90 days to four months.

During our literature search we also identified many studies assessing the effectiveness of oral vitamin B12, but they were not randomised. The studies, dating from the early 50’s to recently, were mainly before and after studies and all show that patients with vitamin B12 deficiency respond to oral vitamin B12 replacement therapy in clinical and/or laboratory terms.

A French contribution

Very recently, Professor Emmanuel Andres and his group, one of the most active groups researching on vitamin B12 at the moment, have published a study involving 92 elderly patients with food-cobalamin malabsorption (6). The researchers concluded that food-cobalamin malabsorption may be a leading cause of vitamin B12 deficiency in the elderly and that patients responded equally well to either oral or parenteral vitamin B12.

Andres et al. administered a daily dose of between 125 and 1000 mcg of oral crystalline cyanocobalamin to 30% of the patients participating in the study. Vitamin B12 levels were corrected in all patients treated orally, haematological abnormalities were corrected in at least two thirds of patients and one third of patient reported clinical improvement with oral treatment.

Conclusion

Researchers are providing more and more evidence of the effectiveness of oral vitamin B12 to treat vitamin B12 deficiency but all this evidence seems not sufficient to change current practice in most countries. Maybe the time has arrived for a collaborative Pan-european randomised trial of documented oral B12 maintenance therapy versus parenteral B12 therapy.

Dr Josep Vidal-Alaball
Public Health Medicine
National Public Health Service for Wales

E-mail:josepvidal@doctors.org.uk

References

1.   Nilsson M, Norberg B, Hultdin J, Sandstrom H, Westman G, Lokk J. Medical intelligence in Sweden. Vitamin B12: oral compared with parenteral? Postgraduate Medical Journal 2005(81):191-3

2.   Norberg B. Oral high-dose vitamin B12 and folate – breakthrough by broken hips [editorial]. Rondel 2005; 24. URL: http://www.rondellen.net/publisher24_eng.htm

3.   Vidal-Alaball J, Butler C, Cannings-John R, Goringe A, Hood K, McCaddon A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deciency (Review). The Cochrane Library 2005;Issue 3

4.   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. Clinical Therapeutics 2003;25(12):3124-34

5.   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

6.   Andres E, Affenberger S, Vinzio S, Kurtz J, Noel E, Kaltenbach G, et al. Food-cobalamin malabsorption in elderly patients: Clinical manifestations and treatment. American Journal of Medicine 2005;118(10):1154-9

Published October 26, 2005