How
we wish to be cited:
Schneede
J. Vitamin B12 and folate depletion in the elderoly. Diagnosis, clinical
correlates and causes [evaluation]. Rondel 2007; 27. URL: http://www.rondellen.net
Vitamin B12 and folate depletion in the
elderoly
Diagnosis, clinical correlates and causes
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Background
The
primary working hypothesis of the dissertation was the impression that subnormal
cobalamin and/or folate status is common among the elderly, even in assumed
healthy individuals, but that the condition often is undiagnosed and untreated.
The
improvement of the diagnostic tools for B-vitamins has made it possible to
identify atypical and subclinical deficiency states at an earlier stage. This is
especially important as B-vitamin deficiencies are easily treatable, and the
costs and risks of intervention are presumed to be low. This has led to a new
clinical practice of prophylactical supplementation of patients primarily based
on abnormal laboratory test outcomes rather than on typical clinical signs and
symptoms. This approach may be justified taking into consideration the potential
risks of untreated B-vitamin deficiency which can result in reduced cognitive
performance, irreversible neurological damage and reduced quality of life in
general.
On
the other hand, also doubts have been raised that the new diagnostic markers
could be confounded by other clinical or physiological conditions, which could
result in over-diagnosis and over-treatment of B-vitamin deficiency. Even though
short-term treatment with B12 in individuals is cheap, over-treatment may
represent a considerable cost for the health care systems as treatment often is
life-long and large proportions of populations may need to be supplemented. Thus,
the controversy of over-treatment or under-diagnosis of
B-vitamin deficiency still is of immediate interest (2,3). Only
placebo-controlled intervention studies of adequate size and duration may solve
this dilemma.
The
present dissertation
In
her thesis, Lewerin pointed out that the fraction of elderly subjects who might
benefit from B-vitamin supplementation could be considerably higher than the
prevalence of traditional pernicious anaemia which accounts for 1-2% of the
elderly Swedish population. Based on data from the literature the number of
subjects suffering from sub-optimal B12-status could be as high as 15-20%,
depending on the population of elderly tested and the diagnostic criteria for
B-vitamin deficiency.
To
examine the situation in
A
population of “free-living” elderly (70-93 years old), n=209, residing in
central Gothenburg was investigated. The socio-economic state of people living
in this area is higher than average. Even though this population could also be
considered healthier than average, Lewerin et al. found, in agreement with many
earlier studies in elderly populations, that a high proportion of subjects had
plasma tHcy and serum MMA levels above the reference limits of the local
laboratory. However, when Lewerin et al. adjusted for renal function, the
proportion of individuals with abnormal Hcy values was reduced from 53% to 10%.
The number of patients with abnormal MMA-values was not affected by
adjustment for renal function.
Even
when using Hcy-/MMA-values from a subgroup of the tested population - after
exclusion of “non-healthy” subjects and after vitamin supplementation –
for definition of specific upper cut-off values for the metabolites, about 7.2%
of the total study population had biochemical signs of B12-deficiency at
baseline, 11% of showed signs of folate deficiency and 1.4% of
combined deficiency (the definition of deficiency was based on a
combination of abnormal metabolite concentrations and certain cut-off values for
the respective vitamins in blood). These are high numbers taking into
consideration that individuals in the present study might be regarded healthier
than in the average Swedish population of this age.
Lewerin
et al. defined atrophic gastritis (AG) as a pepsinogen I/II ratio of below 2,9.
Twenty-six subjects (14%) fulfilled the criteria of AG and among these,
twenty-two were positive for H. pylori antibodies. Interestingly, subjects with
AG but without H. pylori antibodies showed higher MMA and tHcy-values, even
after adjustment for cystatin C. AG explained part of the variation of MMA, but
not that of Hcy. No associations between markers of AG and neuro-cognitive
performance were found. Subjects with AG showed better biochemical responses to
vitamin supplementation than those without and thus treatment of patients with
AG with oral B-vitamin supplements is feasible.
The
clinical consequences of suboptimal vitamin status were assessed with
haematological and neurocognitive investigations. There were no signs of
macrocytic anaemia at baseline and MCV-values did not change significantly upon
vitamin supplementation. As regards neuro-cognitive examinations, a
comprehensive set of cognitive tests, and tests of motor and coordination
ability (postural-locomotor-manual test, PLM) were applied. Lewerin et al. found
independent correlations between the metabolites and cognitive function and PLM
performance at baseline. Four months of vitamin therapy failed to improve
neuro-cognitive performance.
Lewerin
et al. proposed several explanations for their observation that vitamin
supplementation only resulted in biochemical but not in clinical responses.
Firstly, the sample size was possibly too small to achieve sufficient
statistical power. Secondly, the observation length could have been too short,
the vitamin doses too low, the route of application and formulation not optimal
(oral vs. parenteral therapy, cyano-cobalamin vs. hydroxo-/methyl-cobalamin).
Thirdly, most patients were clinically non-symptomatic, and it was thus
difficult to monitor clinical effects. Lastly, neuro-cognitive decline could
have had causes other than vitamin deficiency, or may have been irreversible,
and thus was unlikely to respond to vitamin supplementation.
Conclusions
In
summary, Lewerin et al. found that a large proportion of the investigated
free-living elderly population showed elevated concentrations of Hcy and MMA.
They could demonstrate that both vitamin and metabolite assays for B-vitamin
deficiency are subject to confounding and show other inherent limitations. Age-
and gender specific reference ranges should be applied. Furthermore, especially
Hcy measurements should be adjusted for renal function. Otherwise, the
prevalence of “biochemical” B-vitamin deficiencies could be overestimated.
Still, even after these adjustments, there was a substantial proportion of
elderly left showing biochemical signs of impaired B-vitamin status. At the same
time, Lewerin et al. could show that atrophic gastritis was common and
represented a cause of suboptimal B12-status. This could mean that a substantial
proportion of the elderly could benefit from increased intake of B-vitamins.
However, four months of oral supplementation with B-vitamins brought about only
a considerable reduction of subjects with abnormal homocysteine, but did not
result in clinical responses. The reason for this remains obscure. Further
research is necessary to allow guidelines for how to deal with subjects with
“subclinical” or atypical B-vitamin deficiency, showing only metabolic
evidence of impaired B-vitamin status.
Medical Bioscience, Clinical
SE-901 85
E-mail: jorn.schneede@medbio.umu.se
References
Published January 30, 2007
Context