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Physiology of vitamin B12 and folate deficiency

Stanley L Schrier, MD
Section Editor
Kathleen J Motil, MD, PhD
Deputy Editor
Jennifer S Tirnauer, MD


Vitamin B12 (cobalamin, Cbl) and/or folate deficiency can cause a characteristic megaloblastic anemia with ineffective erythropoiesis [1,2]. The anemia of Cbl deficiency may be accompanied by characteristic neurologic abnormalities. This topic will review the normal physiologic functions of Cbl and folate and the mechanisms by which deficiency of these vitamins can lead to clinical disease. The causes and clinical manifestations of these disorders are discussed separately. (See "Etiology and clinical manifestations of vitamin B12 and folate deficiency".)

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 megaloblastic features are identical in deficiencies of FA and Cbl. The two vitamins are intertwined biochemically so that the final common pathway that impairs DNA synthesis in hematopoietic cells is the same when either vitamin is deficient (figure 1). As will be described below, however, neuropathy occurs only with Cbl deficiency, indicating that additional mechanisms are involved in the central nervous system.

Folate — Folate occurs in animal products and in leafy vegetables in the polyglutamate form [1,3]. The daily folate requirement for unstressed adults is estimated to be approximately 50 mcg/day; the estimated requirement for infants and children ranges from 5 to 50 mcg/day. On a more practical level, however, the Recommended Dietary Allowance (RDA) for adults is 400 mcg of dietary folate equivalents per day; for lactating and pregnant women, RDA includes an additional 100 and 200 mcg per day, respectively, of dietary folate equivalents [4]. The RDA for children in the toddler stage through adolescence ranges from 50 to 200 mcg/day.

Dietary folate in the form of the polyglutamates is cleaved to the monoglutamate in the jejunum where it is absorbed [3]. Folates enter plasma and are rapidly cleared by entering hepatocytes and other cells. Surgical biliary drainage results in a reduction in serum folate within six hours, whereas dietary restriction does not produce a comparable fall for three weeks, presumably because total body stores of folate are estimated to be between 500 to 20,000 mcg [5]. This observation indicates that there is a large enterohepatic circulation of folate.


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Literature review current through: Apr 2017. | This topic last updated: May 10, 2016.
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