VITAMIN [B.sub.12] OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.
Vitamin [B.sub.12] or cobalamin deficiency occurs frequently among elderly patients, (1) but it is often unrecognized or not investigated because the clinical manifestations are subtle. However, the potential seriousness of the complications (particularly neuropsychiatric and hematological) (1-4) requires investigation of all patients who present with vitamin or nutritional deficiency. We summarize the current state of knowledge on cobalamin deficiency, with a particular focus on deficiency in elderly people.
In gathering information for this article, we systematically searched PubMed for articles published from 1990 to July 2003 (the search strategy is outlined in online Appendix 1 [www.cmaj.ca/cgi/content/full/171/3/xxx/DC1]). We have also included unpublished data from our working group, the Groupe d'etude des carences en vitamine [B.sub.12] des Hopitaux Universitaires de Strasbourg.
Defining cobalamin deficiency
Cobalamin deficiency is defined in terms of the serum values of cobalamin and of homocysteine and methylmalonic acid, 2 components of the cobalamin metabolic pathway. High homocysteine levels (hyperhomocysteinemia) may also be caused by folate or vitamin [B.sub.6] deficiencies, and these should be excluded as causes of cobalamin deficiency before a diagnosis is made. To obtain cutoff points of cobalamin serum levels, patients with known complications are compared with age-matched control patients without complications. Because different patient populations have been studied, several serum concentration definitions have emerged. (5-7) Varying test sensitivities and specificities result from the lack of a precise "gold standard." The definitions of cobalamin deficiency used in this review are shown in Box 1. Based in part on the work of Klee (7) and in part on our own work, (8) they are calculated for elderly patients. The first definition is simpler to interpret, but it requires that blood samples be drawn on 2 separate days.Box 1: Definitions of cobalamin (vitamin [B.sub.12]) deficiency in elderly people * Serum cobalamin level < 150 pmol/L on 2 separate occasions OR * Serum cobalamin level < 150 pmol/L AND total serum homocysteine level > 13 [micro]mol/L OR methymalonic acid > 0.4 [micro]mol/L (in the absence of renal failure and folate and vitamin [B.sub.6] deficiencies)
New serum cobalamin (holotranscobalamin) assay kits have replaced older assay kits in most countries and should become the standard for testing. (9)
Epidemiological studies show a prevalence of cobalamin deficiency of around 20% (between...