How we wish to be
cited:
Liedholm H. Clinical effects of overfilling – vitamin B12 and folate repletion
in non-deficient elderly [debate]. Rondel 2007; 27. URL:
http://www.rondellen.net
Clinical effect of overfilling
Vitamin B12 and folate repletion in non-deficient elderly
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The costs of vitamin B12 and folate in pharmacological dosage in Sweden (10 miljon inhabitants) in 2005 (3). |
Editorial background |
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Preparation |
Euro in millions |
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Tablet B12, 1 mg |
10 |
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Tablet folic acid, 5 mg |
6 |
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Injectabile B12 |
3 |
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Tablet TrioBea |
13 |
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Total |
32 |
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a. Cyanocobalamin 0.5 mg, folic acid 0.8
mg, pyridoxine 3 mg. The cost of the tablet is at present approximately twice the corresponding costs of adequate doses of oral cyanocobalamin as one pill and oral folic acid as one pill. |
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Homocysteine lowering in Sweden 1998-2007
Sweden was blessed by a B vitamin combination for the prevention of symptomatic deficiency of vitamin B12 and folate in 1998, the brand TrioBe from Recip AB, Stockholm, Sweden. The formula of the combination is cyanocobalamin, 0.5 mg, folic acid 0.8 mg, and pyridoxine, 3 mg. The approved dosage is one tablet daily and the actual indication (translated from Swedish) is “prophylaxis of symptom-giving deficiency of vitamin B6, vitamin B12, and folic acid in conditions of insufficient food intake and malabsorption, especially in the elderly”.
By means of an unscrupulous marketing and an exorbitant price, TrioBe devoured 40% of the costs in Sweden for the central B vitamins in pharmacological dosage during 2005 (3).
The owner of TrioBe was remarkably reluctant to consider objections against its marketing from regulatory authorities and experts - by now, it has been fined about ten times for irrelevant marketing, one of the fines the heaviest possible at present in Sweden (4).
Up to now, it has been difficult to obtain reliable documentation about TrioBe for us who worked within the pharmacological committees and the pharmacological boards of the county councils, which foot a main part of drug costs. The documentation for registration of the preparation was gathered during 1997. However, it was not fully available for examination in relation to marketing. Now most of the basic documentation is finally available as a dissertation (1,2).
The documentation of TrioBe
The documentation of TrioBe is based on a randomized, double-blind, prospective clinical trial during four months. The treatment group comprised 115 participants, of whom 11 had probable B12 and/or folate deficiency, as defined by a homocysteine level above 25 mikromol/L at baseline. Five of these probands had MMA levels in the range 0.35 – 0.45 micromol/L. Four other participants had MMA levels in the range 0.45 – 0.50, one alone approximately 0.70. Thus, most of the participants were healthy or at least without deficiency of vitamin B12 and/or folate.
The selection of the patients was clearly defined, the first adequate description in 10 years (1). The mean age was 76 years, range 70-88. The cognition and the motor function of the patients were subject to advanced analysis by methods, previously applied in two dissertations in geriatrics in Gothenburg.
The cognitive performance and the motility of the participants did not improve during TrioBe treatment (1,2). The repletion of vitamin B12 and folate to already satisfactory body stores corresponds to a mean amount of 600 microgram of vitamin B12 as an average supplementation to each participant (cf 5).
It should be emphasised that the participants of the present trial had no signs and symptoms of B12-folate deficiency at start – with a few possible exceptions. Thus, possible deficient-dependent neuron lesions are expected to be mild, of short standing, and rapidly reversible during treatment.
An average supplementation of 600 microgram vitamin B12 in combination with folic acid during four months was expected to produce measurable improvement of cognitive performance and motility in the present participants, in case deficiency-dependent impairment was present at start. Instead, the actual results support the classical concept that overfilling of adequate body stores with cobalamin and folate does not improve physiological functions.
There were some additional findings of international interest in the present dissertation (1). One such finding was that homocysteine appears to be unreliable in the monitoring of oral treatment with vitamin B12 and folate; even slightly impaired renal function could mimick treatment failure. Another interesting finding was that atrophic gastritis appeared to be more rare and mild in the actual participants than expected from previous studies (1).
Conclusions
The present dissertation (1) on the documentation of TrioBe provides a reproducible but truly inconclusive clinical trial; TrioBe supports its eaters with the expected amounts of vitamin B12 and folate. The study also confirms the old concept that there is no immediate health profit in the “prevention” of cobalamin and folate deficiency in elderly people, who lack signs of deficiency. The study is inconclusive about the benefits and draw-backs of long-term feeding of non-deficient elderly people with vitamin B12 and folate (cf 6).
It is evident from Table 1 that TrioBe provides half the B12 activity needed for approximately twice the cost of adequate B12 treatment (3,5). The positive facet of this fact is that the economical profits will probably stimulate competition. It is reasonable to assume that a manufacturer which offers the prescribers a TrioBe analogue with improved vitamin B12 content – 1 mg – is likely to win the market.
Dr Hans Liedholm
Möllevångsvägen 37
SE-22240 Lund, Sweden
E-mail:
hans.liedholm@med.lu.se
References
Published May 07, 2007