Folate (Folic Acid)

Overview:

Detect folate deficiency; monitor therapy with folate; evaluate megaloblastic and macrocytic anemia; evaluate alcoholic patients and those with prior jejunoileal bypass for morbid obesity or those with intestinal blind-loop syndrome.

Folate assays of samples from patients receiving therapy with certain pharmaceuticals (eg, methotrexate or leucovorin), are contraindicated because of the cross-reactivity of folate-binding protein with these compounds.1 Serum samples should not be altered with additives (biocides, antioxidants, or substances possibly changing the pH of the sample) in order to avoid erroneous folate recovery.

Hemolysis may significantly increase folate values due to high concentrations of folate in red blood cells; therefore, hemolyzed samples are not suitable for this assay.1

Samples with extremely high total protein concentrations (eg, patients suffering from Waldenström macroglobulinemia) are not suitable for use in this assay, since they may lead to the formation of protein gel in the assay cup.1

As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes.1 In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur.1 The test contains additives that minimize these effects.

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. A serum folate concentration <3 ng/mL is considered to represent clinical deficiency by the World Health Organization and numerous subsequent clinical studies.6,7 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.5,8 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.9,10

In the 1990s mandatory increased fortification of enriched cereal-grain products along with the requirement of folate-related health and nutrient content claims on food and dietary supplement products significantly increased the folic acid content of the US food supply.11-13 Several reports have shown that serum folate concentrations have increased in the general US population since these measures were implemented.11-13

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

2. Miale JB. Hematology. Laboratory Medicine. 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. Shane B. Folate status assessment history: Implications for measurement of biomarkers In NHANES. Am J Clin Nutr. 2011 Jul; 94(1):337S-342S. PubMed 10386505

8. Nutritional anemias. Report of a WHO group of experts. World Health Organ Tech Rep Ser. 1972; 503:1-29. PubMed 4626525

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

10. 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

11. Choumenkovitch SF, Selhub J, Wilson PW, Rader JI, Rosenberg IH, Jacques PF. Folic acid intake from fortification in United States exceeds predictions. J Nutr. 2002 Sep;132(9):2792-2798. PubMed 12221247

12. Ganji V, Kafai MR. Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: Analysis of data from National Health and Nutrition Examination Surveys, 1988-1994, 1999-2000, and 2001-2002. J Nutr. 2006 Jan; 136(1):153-158. PubMed 16365075

13. Pfeiffer CM, Johnson CL, Jain RB, et al. Trends in blood folate and vitamin B-12 concentrations in the United States, 1988 2004. Am J Clin Nutr. 2007 Sep; 86(3)718-727. PubMed 17823438