Folate, RBC

Detect folate deficiency; monitor therapy with folate; evaluate megaloblastic and macrocytic anemia.

Folates are compounds of pteroylglutamic acid (PGA) that function as coenzymes in metabolic reactions involving the transfer of single-carbon units from a donor to a recipient compound. Folate, with vitamin B12, is essential for DNA synthesis, which is required for normal red blood cell maturation.2 Humans obtain folate from dietary sources including fruits, green and leafy vegetables, yeast, and organ meats.3 Folate is absorbed through the small intestine and stored in the liver.

Low folate intake, malabsorption as a result of gastrointestinal diseases, pregnancy, and drugs such as phenytoin are causes of folate deficiency.4 Folate deficiency is also associated with chronic alcoholism.5 Folate and vitamin B12 deficiency impair DNA synthesis, causing macrocytic anemias. These anemias are characterized by abnormal maturation of red blood cell precursors in the bone marrow, the presence of megaloblasts, and decreased red blood cell survival.2

Since both folate and vitamin B12 deficiency can cause macrocytic anemia, appropriate treatment depends on the differential diagnosis of the deficiency. Serum folate measurement provides an early index of folate status3; however, folate is much more concentrated in red blood cells than in serum so the red blood cell folate measurement more closely reflects tissue stores.5,6 Erythrocytes incorporate folate as they are formed, and levels remain constant throughout the life span of the cell. RBC folate levels are less sensitive to short-term dietary effects than are serum folate levels. Red blood cell folate concentration is considered the most reliable indicator of folate status.3

Low serum folate during pregnancy has been associated with neural tube defects in the fetus.7,8

1. Folate on Elecsys 1010/2010 and Modular Analytics E170 [package insert]. 2007-02, V1. Indianapolis, Ind: Roche Diagnostics; 2007.

2. Miale JB. Laboratory Medicine Hematology. St Louis, Mo: CV Mosby;1982:416-440.

3. Brewster MA. Vitamins. In: Kaplan LA, Pesce AJ, eds. Clinical Chemistry: Theory, Analysis, and Correlation. St. Louis, Mo: CV Mosby;1989:543-568.

4. Fairbanks VF, Klee GG. Biochemical aspects of hematology. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. WB Saunders Co;1999:1642-1710.

5. McNeely MD. Folic acid. In: Pesce AJ, Kaplan LA, eds. Methods in Clinical Chemistry. St Louis, Mo: CV Mosby;1987:539-542.

6. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: A guide for the primary care physician. Arch Intern Med. 1999 Jun 28; 159(12):1289-1298. PubMed 10386505

7. Wolff T, Witkop CT, Miller T, Syed SB, US Preventive Services Task Force. Folic acid supplementation for the prevention of open neural tube defects: An update of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2009 May 5; 150(9):632-639. PubMed 19414843

8. McNulty H, Cuskelly GJ, Ward M. Response of red blood cell folate to intervention: Implications for folate recommendations for the prevention of neural tube defects. Am J Clin Nutr. 2000 May; 71(5 Suppl):1308S-1311S. PubMed 10799407