New insights into erythropoiesis: the roles of folate, vitamin B12, and iron

Annu Rev Nutr. 2004:24:105-31. doi: 10.1146/annurev.nutr.24.012003.132306.


Erythropoiesis is the process in which new erythrocytes are produced. These new erythrocytes replace the oldest erythrocytes (normally about one percent) that are phagocytosed and destroyed each day. Folate, vitamin B12, and iron have crucial roles in erythropoiesis. Erythroblasts require folate and vitamin B12 for proliferation during their differentiation. Deficiency of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis. Erythroblasts require large amounts of iron for hemoglobin synthesis. Large amounts of iron are recycled daily with hemoglobin breakdown from destroyed old erythrocytes. Many recently identified proteins are involved in absorption, storage, and cellular export of nonheme iron and in erythroblast uptake and utilization of iron. Erythroblast heme levels regulate uptake of iron and globin synthesis such that iron deficiency causes anemia by retarded production rates with smaller, less hemoglobinized erythrocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Apoptosis
  • Erythropoiesis / physiology*
  • Folic Acid / metabolism
  • Folic Acid / physiology*
  • Humans
  • Iron / metabolism
  • Iron / physiology*
  • Vitamin B 12 / metabolism
  • Vitamin B 12 / physiology*


  • Folic Acid
  • Iron
  • Vitamin B 12