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Clinical Implications and Implications for Future Research

The findings mentioned above do not at all imply that patients with pernicious anaemia or malabsorption of vitamin B12 from food (with tissue depletion of vitamin B12 and very low vitamin B12 concentrations) should not receive vitamin B12 supplementation.31,32 However, apart from the undisputed case of pernicious anaemia, the clinical impact of subnormal vitamin B12 concentrations in older persons in the general population remains unclear. The fact that several observational studies and randomised controlled trials also showed no effect of vitamin B12 administration on cognitive function raises even more doubt about the consequences of subnormal vitamin B12 concentrations in older persons in the general population.72–74

Taking this into account, many older persons in primary care may receive vitamin B12 supplementation without evidence of clinical improvement. Although the cost of treatment with vitamin B12 in older individuals may be considered limited compared with other types of medical treatment, this does not justify initiation and continuation of treatment with vitamin B12 in older persons if not supported by medical evidence. These findings also raise doubt about the value of vitamin B12 measurements in diagnostic guidelines for anaemia as they may distract attention from other possible underlying causes.

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Additional proof of the (lack of) effectiveness of treatment with vitamin B12 in older patients with anaemia and subnormal vitamin B12 concentrations would be provided by a randomised double-blind placebo-controlled trial in which older patients with anaemia and subnormal vitamin B12 concentrations either receive usual care with vitamin B12 or placebo. However, before such a trial has been performed, the accumulating evidence suggests that clinicians should at least reconsider the risks of low vitamin B12 concentrations before starting cyanocobalamin or hydroxocobalamin supplementation in older individuals.75

The subnormal vitamin B12 concentrations may not be the cause of the anaemia, and supplementation with vitamin B12 may therefore not lead to a rise in haemoglobin concentrations.


Despite the undisputed case of pernicious anaemia, evidence of a positive association between subnormal serum vitamin B12 concentrations and anaemia in older persons is limited and inconclusive. If anything, given the high clinical relevance of anaemia in old age, we recommend more well-designed intervention studies of appropriate size and duration with timely follow-up periods to determine whether supplementation of older persons with subnormal vitamin B12 concentrations has a beneficial effect on haematological parameters. n

J Am Geriatr Soc, 2005;53(12):2106–11.

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