evaluation

Clinical evaluation

How we wish to be cited:
Norberg B. A prospective placebo-controlled trial – tablets for suspected vitamin B12 deficiency [evaluation]. Rondel 2011; 31. URL: http://www.rondellen.net

A prospective placebo-controlled trial
Tablets for suspected vitamin B12 deficiency

Variable	Baseline	One month
Age, years	76 (31-91)	76 (31-91)
S-B12^a	164 (127-203)	263*
S-MMA^b	0.32 (0.19-1.1)	0.23*
S-Hcy^c	18.1 (9.8-31.5)	16.5*
Haematocrit^d	39,5 (32-46)	39.6*
MCV^e	90 (63-100)	90*

Table 1: Oral treatment, 1 mg daily, of suspected vitamin B12 deficiency for one month (N=26, median values and range).

a. Serum vitamin B12, pmol/L
b. Serum methylmalonic acid, mikromol/L
c. Serum homocysteine, micromol/L
d. Packed red cells, percentage of blood volume
e. Mean corpuscular volume, fL
*Only mean values were reported

Summary

A prospective, randomised and placebo-controlled trial of oral treatment, 1 mg daily, for vitamin B12 deficiency in western Switzerland is evaluated (1). Within the first month of treatment, serum vitamin B12 rose and serum methylmalonic acid fell. The effect vanished during the subsequent three months without vitamin B12 supplementation. The observations are in agreement with the time-honoured concept that vitamin B12 treatment for deficiency must be life-long, whether oral or parenteral.

Background

There is still some doubts in most countries about the efficacy of oral treatment for vitamin B12 deficiency, despite favourable experience in isolated societies (2-6).

Restrictions of the present evaluation

The trial evaluated (1) was placebo-controlled (N=24 versus N=26 in the intervention group). The outcomes were obvious and expected. Thus, only changes in the intervention group are analysed in the present evaluation.

Objective

The purpose of the present study (1) was to test oral vitamin B12 treatment, 1 mg daily, versus placebo in patients with suspected deficiency of vitamin B12 in a prospective, randomised and double-blinded clinical trial.

Settings

The study took place in western Switzerland. It was multicentric with participation of 13 general practices, two nursing homes, and one primary care centre. The study was conducted between October 2002 and September 2004.

Selection of patients

Consecutive patients (N=50) with serum levels of vitamin B12 between 125-200 pmol/L were recruited to the study. Suspicion of vitamin B12 deficiency was based on clinical signs and symptoms, mainly neurological and psychiatric. Exclusion criteria were folate deficiency, renal insufficiency, and treatment with vitamin B12 and/or folate during the preceding six months.

Methods

The trial was prospective, pragmatic, placebo-controlled and double-blinded. Treatment duration was one month. After three more months, the outcome measures were repeated again.

Results

It is evident from Table 1 that treatment with oral vitamin B12 had the expected influence on serum vitamin B12, MMA, and homocysteine. Without further supplementation of vitamin B12, the initial effect vanished during the following three months.

Discussion

The present study (1) illustrates the dilemmas of modern trials on vitamin B12 deficiency; for ethical reasons, such studies may only be performed in borderline deficiency during a short time period. Otherwise, some patients might develop permanent nerve lesions.

One limitation of the present paper (1) is the lag between conduction and publication. Thus, the discussion of the paper has not been updated since about 2005. Homocysteine is a sensitive marker of deficiency of vitamin B12 and/or folate. But it is no longer regarded as a causal risk factor for vascular disease.

It should be emphasised that the results of the present paper (1) are restricted to the initial stages of deficiency treatment, remission induction (cf 5). Adequate remission treatment in moderate deficiency corresponds to five weekly injections of one mg cobalamin or oral cobalamin, 1 mg daily, for 200 days (6). Such treatment provides about 50% refilling of body stores (2).

Conclusions

It is reasonable to assume that the present study (1) will support health care authorities within Europe to approve oral treatment of vitamin B12 deficiency. Like parenteral treatment for vitamin B12 deficiency, oral treatment has to be life-long.

References

1. Favrat B, Vaucher P, Herzig L, Burnand B, Ali G, Boulat O, Bischoff T, Verdon F. Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial. BMC Family Practice 2011, 12:2doi:10.1186/1471-2296-12-2

2. Lee GR, Bitchell TC, Forster J, Athens JW, Lukens JN (eds). Wintrobe´s Clinical Hematology, pp.777-9 Ed 9, Philadelphia: Lea & Febiger; 1993

3. Norberg B. Deficiency of vitamin B12 and folate – the branded generic for optimal oral therapy [editorial]. Rondel 2008; 28. URL: http://www.rondellen.net/publisher28_eng.htm

4. Drugs and Therapeutics Bulletin. Oral or intramuscular vitamin B12? DTB 2009; 47(2):19-21

5. Liedholm H. Clinical effects of overfilling – vitamin B12 and folate repletion in non-deficient elderly [debate]. Rondel 2007; 27. URL: http://www.rondellen.net/debate27_eng.htm

6. Magnus EM. Cobalamin and unsaturated cobalamin values in pernicious anaemia: Relation to treatment. Scand J Haematol 1986; 36:457-65

Published October 31, 2011