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Subnormal Vitamin B12 Concentrations and Anaemia in Older Persons Wendy PJ den Elzen1

and Jacobijn Gussekloo2 1. Senior Researcher; 2. General Practitioner and Professor of Primary Care, Department of Public Health and Primary Care, Leiden University Medical Centre


Pernicious anaemia is a form of anaemia that is undeniably associated with vitamin B12 deficiency. However, evidence of a positive association between subnormal vitamin B12 concentrations and anaemia in older persons in the general population is limited and inconclusive. Well-designed intervention studies of appropriate size and duration with timely follow-up periods are needed to determine whether subnormal vitamin B12 concentrations are a risk factor for anaemia in older persons in the general population.

Keywords Vitamin B12, vitamin B12 deficiency, anaemia, aged

Disclosure: The authors have no conflicts of interest to declare. Acknowledgement: We thank BioMed Central (BMC Geriatrics, 2010;10:42) and the American Medical Association (Archives of Internal Medicine, 2008;168(20):2241). Copyright © 2008. All rights reserved for granting permission for reproduction of previously published data. Received: 27 January 2011 Accepted: 23 March 2011 Citation: European Oncology & Haematology, 2011;7(2):136–9 Correspondence: Wendy PJ den Elzen, Department of Public Health and Primary Care, Leiden University Medical Centre, Post zone V-0-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E:

Anaemia in Older Persons

Anaemia is very common in older individuals. The reported prevalence ranges from <3% in healthy persons aged 65 years and over to 61% in older patients newly admitted to geriatric wards.1,2

These numbers

differ not only because of varying definitions of anaemia, but also because of large differences in study populations with respect to gender, age, race, living situation and health status.1,2

In the Third

National Health and Nutrition Examination Survey (NHANES III), a nationally representative study of non-institutionalised civilian adults in the US, the overall prevalence of anaemia among adults aged 65 years and over was 11% in men and 10.2% in women.3

In this study, anaemia

Interestingly, the prevalence of anaemia increased significantly with age, up to 26.1% in men and 20.1% in women aged 85 years and over.3

was defined according to World Health Organization criteria (haemoglobin concentration less than 12g/dl in women and less than 13g/dl in men).4

In older persons, anaemia is associated with impaired survival,5–10 decreased physical performance, disability in daily living, cognitive impairment, depression, diminished quality of life and an increased number of hospital admissions.1,11–21

Considering the steep increase in

the prevalence of anaemia in older individuals, and the exponential rise in the number of older individuals in our ageing society, anaemia in older individuals may have a significant effect on healthcare needs and costs in the decades to come.22

Adequate diagnosis and treatment of anaemia in older persons is therefore of vital importance.

Vitamin B12 Deficiency in Pernicious Anaemia – An Undeniable Cause of Anaemia

In 1849, Thomas Addison described patients with a ‘very remarkable form of general anaemia’. This severe type of anaemia, for which no treatment was available, was later called anaemia perniciosa (fatal


anaemia) by Anton Biermer.23,24

Apart from severe haematological

abnormalities, patients with pernicious anaemia also had a sore tongue, neuropathy of the hands and extremities and subacute combined degeneration of the spinal cord.24

After many years of

research, it appeared that patients with pernicious anaemia produce antibodies against ‘intrinsic factor’, a molecule in the stomach that is needed to bind and transport vitamin B12 through the gastrointestinal tract.23,24

Undoubtedly, patients with very low vitamin B12 concentrations (in case of pernicious anaemia) have to be treated: several studies showed large increases in haemoglobin after vitamin B12 administration in patients with pernicious anaemia or food vitamin B12 malabsorption.30–34

Subnormal Vitamin B12 Concentration – Also a Cause of Anaemia?

Due to the clear aetiology of pernicious anaemia, the outcomes of studies in patients with pernicious anaemia are often extrapolated to patients with subnormal vitamin B12 concentrations in the general population. As a result, subnormal vitamin B12 concentrations are considered to be associated with (mild) anaemia in general, but also with other conditions such as dementia, neuropathy and subacute combined degeneration of the spinal cord.35–38

Therefore, physicians

routinely measure vitamin B12 in patients with anaemia, and individuals with low serum concentrations of vitamin B12 (and normal folate concentrations) are frequently given intramuscular vitamin B12 supplements, often for many years.37–39

Also, since low serum

vitamin B12 concentrations are very common in older individuals,40 screening older people for vitamin B12 deficiency has often been recommended.41,42


Therefore, pernicious anaemia is a form of anaemia that is undeniably associated with severe vitamin B12 deficiency. Finding the cure for pernicious anaemia even led to the discovery of vitamin B12.23–29

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