Cobalamin deficiency in elderly patients/One of the authors responds

• Published in: Canadian Medical Association journal (CMAJ) Vol. 172; no. 4; p. 448
• Main Authors: Ray, Joel G, Cole, David E C, Wetterberg, S Peter, Prousky, Jonathan E, Andrès, Emmanuel
• Format: Journal Article
• Language: English
• Published: Ottawa CMA Impact, Inc 15.02.2005
• ISSN: 0820-3946; 1488-2329

Second, the diagnostic algorithm for cobalamin deficiency proposed by Andres and colleagues (Fig. 3 in their article1) is unnecessarily complex, especially for seniors, in whom cobalamin malabsorption is commonly found because of age-related atrophic gastritis.4 Although serum methylmalonic acid (MMA) may have a place in a diagnostic algorithm, this indicator of cobalamin insufficiency is falsely elevated in the presence of modest renal impairment5 with advancing age. Furthermore, serum MMA is commonly elevated in elderly North Americans,6 but lowering it through vitamin B12 supplementation does not appear to affect blood hemoglobin concentration, neurological disability score or quality of life.7 Like homocysteine, MMA has not been fully validated as a routine clinical test of cobalamin deficiency,8 especially in the face of increased folate fortification,2 and MMA testing is not routinely available in Canadian centres and community laboratories. We propose a simpler and more direct diagnostic approach in elderly patients (Fig. 1), with 2 options for serum cobalamin concentrations in the "grey zone" of 150 to 200 pmol/L. Option A involves testing for serum holotranscobalamin - the complex formed by cobalamin and its transport protein, transcobalamin - the physiologically active form of vitamin B12 that is transported into cells.9 This inexpensive, simple radioimmunoassay-based test, which will become more readily available in Canada, displayed a sensitivity of 100% and a specificity of 89% for cobalamin deficiency in one study.9 Option B involves initial treatment with parenteral cobalamin according to the dosing schedule outlined by Anclres and colleagues,1 with assessment of the clinical response after 3 months. High-dose oral cobalamin (e.g., 1000 µg/day) can be used thereafter, as described by Andrès and colleagues.1 A therapeutic response validates not only the diagnosis, but also the treatment, which is otherwise safe and inexpensive. In a study of 5 patients with hypochlorhydria, all of the patients had decreased urinary excretion of protein-bound cobalamin.2 After receiving supplemental HCl, pepsin, gastric intrinsic factor or some combination of these, 4 of the 5 patients showed improvement in protein-bound cobalamin absorption. Another study examined the effect of water, cranberry juice (pH 2.5-2.6) or a 0.1N HCl solution (pH 1.2) on the absorption of protein-bound cobalamin in 3 groups of elderly subjects: healthy individuals, subjects pretreated with omeprazole to simulate the hypochlorhydria of atrophic gastritis and patients with diagnosed atrophic gastritis.3 Administration of diluted HCl increased the absorption of protein-bound cobalamin in all 3 groups, and this difference was statistically significant for both the omeprazole-treated and healthy subjects (p < 0.001). The authors noted that this improvement might have been the result of the acid's ability to augment the release of cobalamin from protein.