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Etiology and clinical manifestations of vitamin B12 and folate deficiency

Stanley L Schrier, MD
Section Editor
William C Mentzer, MD
Deputy Editor
Jennifer S Tirnauer, MD


Nutritional megaloblastic anemias were characterized over one hundred years ago. This term identifies patients with anemia and macroovalocytic red cells (ie, mean corpuscular volume greater than 100 fL). The bone marrow shows intense erythroid hyperplasia with abnormal (megaloblastic) morphology. The megaloblast, the morphologic hallmark of the syndrome, is a product of impaired DNA formation, which in turn is due to deficiencies of vitamin B12 (cobalamin, Cbl) or folate [1,2].

This topic will review the major causes and clinical manifestations of Cbl and folate deficiency. In this review, the terms B12, Cbl, and cobalamin will be used interchangeably. The terms "folate" and "folic acid" are sometimes used interchangeably; however, the vitamin is found in nature as a folate while folic acid (FA) is the synthetic, therapeutic form.

The physiology of these vitamins, how lack of availability leads to a megaloblastic anemia with ineffective erythropoiesis, and the diagnosis and treatment of these disorders are discussed separately. (See "Physiology of vitamin B12 and folate deficiency" and "Diagnosis and treatment of vitamin B12 and folate deficiency".)

Deficiencies of Cbl and FA may also be present in the elderly and in those with alcohol abuse. These are discussed separately. (See "Anemia in the older adult", section on 'Search for treatable disorders' and "Hematologic complications of alcohol use".)


Dietary intake and absorption — Animal products (meat and dairy products) provide the only dietary source of Cbl for humans. The usual Western diet contains 5 to 7 mcg of cobalamin per day, while the minimum daily requirement is listed as 6 to 9 mcg per day [3]. Total body stores of Cbl are 2 to 5 milligrams (2000 to 5000 mcg), approximately one-half of which are in the liver. As a result, it takes years to develop vitamin B12 deficiency after absorption of dietary B12 ceases [3].


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Literature review current through: Sep 2016. | This topic last updated: Jul 15, 2016.
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