Review article
Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy,☆☆,

https://doi.org/10.1016/j.ejim.2007.02.013Get rights and content

Abstract

The aim of this work was to review the literature concerning cobalamin deficiency in elderly patients. Articles were identified through searches of PubMedMEDLINE (January 1990 to June 2006), restricted to: English and French language, human subjects, elderly patients (> 65 years), clinical trial, review and guidelines. Additional unpublished data from our cohort with cobalamin deficiency at the University Hospital of Strasbourg, France, were also considered. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. In elderly people, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. The recently identified food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or from its binding proteins. This syndrome is usually the consequence of atrophic gastritis, related or not to Helicobacter pylori infection, and of the long-term ingestion of antacids and biguanides (in around 60% of the patients). Management of cobalamin deficiency has been well established with the use of cobalamin injections. However, new routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption.

Introduction

Cobalamin, or vitamin B12, deficiency is frequent in elderly patients [1], but it is often unrecognized or not investigated because the clinical manifestations are subtle. However, because of the potential seriousness of the complications, particularly neuropsychiatric and hematological [1], [2], [3], [4], investigation of all patients who present with vitamin or nutritional deficiency is required. Classic disorders, such as pernicious anemia, are the cause of cobalamin deficiency in only a limited proportion of elderly patients [4]. The main cause of cobalamin deficiency is food-cobalamin malabsorption, a disorder characterized by the inability to release vitamin B12 from food or from its binding proteins [4].

We summarize here the current state of knowledge on clinical aspects of cobalamin deficiency in the elderly, with a special focus on food-cobalamin malabsorption and particularly on oral cobalamin therapy.

Section snippets

Definition of cobalamin deficiency

In the recent literature, several definitions of cobalamin deficiency in elderly patients have emerged, depending mainly on the populations studied and on the particular test assay kits used [5], [6], [7]. Varying test sensitivities and specificities have resulted from this lack of a precise ‘gold standard’, especially in elderly patients. The definitions of cobalamin deficiency used in this review are shown in Table 1 [7], [8]. Currently, cobalamin deficiency is often defined in terms of the

Epidemiology of cobalamin deficiency

Epidemiological studies have shown a prevalence of cobalamin deficiency of around 20% in the elderly population of industrialized countries (between 50% and 60%, depending on the definition of cobalamin deficiency used in the study). The Framingham study demonstrated a prevalence of 12% among elderly people living in the community [11]. Other studies focusing on elderly people, particularly those who are in institutions or who are sick, have suggested a higher prevalence of 30–40% [12], [13].

Cobalamin metabolism and functions

Cobalamin metabolism is complex and requires many processes, any one of which, if not present, may lead to cobalamin deficiency [4], [14], [15], [16]. The different stages of cobalamin metabolism and corresponding causes of cobalamin deficiency are shown in Table 2 [14], [16]. Once metabolized, cobalamin is a cofactor and coenzyme in many biochemical reactions, including DNA synthesis, methionine synthesis from homocysteine, and conversion of propionyl into succinyl coenzyme A from methyl

Causes of cobalamin deficiency

Fig. 1 presents the principal causes of cobalamin deficiency in 172 elderly patients (median age 70 years) hospitalized in the University Hospital of Strasbourg, France [15]. Historically, in elderly patients, cobalamin deficiency was associated with pernicious anemia (or Biermer's or Addison's disease) [1], [12]. The principal characteristics of pernicious anemia have been reported in detail in several recent reviews [20], [21], [22]. Cobalamin deficiency caused by dietary deficiency or

Food-cobalamin malabsorption syndrome

First described by Carmel in 1995 [23], food-cobalamin malabsorption is a syndrome characterized by the inability of the body to release cobalamin from food or intestinal transport proteins, particularly in the presence of hypochlorhydria, where the absorption of “unbound” cobalamin is normal. This syndrome is characterized by cobalamin deficiency in the presence of sufficient food-cobalamin intake and a normal Schilling test, ruling out malabsorption or pernicious anemia [15], [23], [24]. The

Clinical manifestations of cobalamin deficiency

The primary clinical manifestations of cobalamin deficiency in elderly patients are described in Table 5. They are highly polymorphic and of varying severity, ranging from milder conditions such as tiredness, common sensory neuropathy, and isolated anomalies of macrocytosis or hypersegmentation of neutrophils, to severe disorders, including combined sclerosis of the spinal cord, hemolytic anemia, and even pancytopenia [2], [15], [33], [34], [35]. In the aforementioned series of 92 patients with

Classical treatment of cobalamin deficiency

The standard treatment of cobalamin deficiency, particularly when the cause is not dietary deficiency, is parenteral administration – usually by intramuscular injection – of cyanocobalamin or hydroxocobalamin [1], [18], [19], [33]. In France, the recommended practice to build up the body stores of the vitamin quickly and to correct serum cobalamin hypovitaminosis, particularly in the case of pernicious anemia, involves the administration of 1000 μg of cyanocobalamin per day for 1 week, followed

Oral cobalamin therapy

In the absence of nutritional deficiency etiology, two alternative routes of cobalamin administration have recently been proposed: oral [18], [19], [39], [40], [41], [42], [43], [44] and nasal [45], [46]. Our working group has developed an effective oral treatment for both food-cobalamin malabsorption [41], [42], [43], [44] and pernicious anemia [47] using a crystalline cobalamin (cyanocobalamin). The main results of our oral cobalamin treatment studies (open, not randomized) are summarized in

Learning points

  • Cobalamin, or vitamin B12, deficiency is frequent in elderly patients, but it is often unrecognized or not investigated because the clinical manifestations are subtle.

  • In elderly people, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption, a disorder characterized by the inability to release cobalamin from food or its binding proteins.

  • In elderly people, food-cobalamin malabsorption syndrome is usually the consequence of atrophic gastritis, related or

Acknowledgements

The authors are indebted to Professor Marc Imler and Jean-Louis Schlienger, who initiated this work.

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    Funding: The research on cobalamin deficiency was supported by a grant from the Fondation de France (Prix Robert et Jacqueline Zittoun 2004).

    ☆☆

    Contributors: Drafting of the article: E. Andrès and J. Vidal-Alaball. Final approval of the manuscript: E. Andrès, L. J. Vidal-Alaball, Federici, N.H. Loukili, J. Zimmer and G. Kaltenbach.

    Competing interests: No author has any conflict of interest.

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