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Subclinical cobalamin deficiency

Carmel, Ralph

Current Opinion in Gastroenterology: March 2012 - Volume 28 - Issue 2 - p 151–158
doi: 10.1097/MOG.0b013e3283505852
NUTRITION: Edited by David H. Alpers and William F. Stenson

Purpose of review This review focuses on recent developments and controversies in the diagnosis, consequences, and management of subclinical cobalamin deficiency (SCCD), which affects many elderly persons.

Recent findings Diagnosis of SCCD depends exclusively on biochemical tests whose individual limitations suggest that combinations of tests are needed, especially in epidemiologic research. The causes of SCCD are unknown in more than 60% of cases, which limits prognostic predictions and identification of health consequences. After years of varying, often inconclusive associations, new clinical trials suggest that homocysteine reduction by high doses of folic acid, cobalamin, and pyridoxine may reduce progression of structural brain changes and cognitive impairment, especially in predisposed individuals. The causative or contributory roles, if any, of SCCD itself in cognitive dysfunction require direct study. If the findings are confirmed, high-dose supplementation with three vitamins will probably be more effective than fortification of the diet.

Summary The story of SCCD, which is severalfold times more common in the elderly than clinical cobalamin deficiency but also differs from it in arising only infrequently from severe malabsorption and thus being less likely to progress, continues to evolve. Preventive benefits need to be confirmed and expanded, and will require fuller understanding of SCCD pathophysiology, natural history, and health consequences.

Department of Medicine, New York Methodist Hospital, Brooklyn and Weill Cornell Medical College, New York, New York, USA

Correspondence to Dr Ralph Carmel, New York Methodist Hospital, 506 Sixth Street, Brooklyn, NY 11215, USA. Tel: +1 718 780 3253; fax: +1 718 780 6333; e-mail:

© 2012 Lippincott Williams & Wilkins, Inc.