Folate (Folic Acid)

Folate (Folic Acid)

Number
	002014
CPT
	82746
Related Information
	Vitamin B₆, Plasma Vitamin B₁₂
Specimen
	Serum
Volume
	1 mL
Minimum Volume
	0.4 mL (Note: This volume does not allow for repeat testing.)
Container
	Red-top tube or gel-barrier tube
Collection
	If a red-top tube is used, transfer separated serum immediately to a plastic transport tube. Avoid hemolysis.
Storage Instructions
	Refrigerate
Causes for Rejection
	Plasma specimen; hemolysis
Reference Interval
	Normal: >5.4 ng/mL Deficit: <3.4 ng/mL Intermediate: 3.4-5.4 ng/mL
Use
	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
Limitations
	May be decreased in patients on oral contraceptives. Frequently measured with red cell folate and vitamin B₁₂ levels.
Methodology
	Immunochemiluminometric assay (ICMA)
Additional Information
	Naturally occurring folates are present widely in plant and animal foods taken in the diet and absorbed in the small intestine. Folic acid (pteroylglutamic acid) has a number of biologically active forms (largely conjugates of glutamic acid, eg, N-5-methyltetrahydrofolic acid and N-5-formyltetrahydrofolic acid - folinic acid) that function as coenzymes. Lack of folic acid inhibits DNA synthesis in rapidly dividing cells, thus producing megaloblastic anemia. While a specific folate-binding protein is present in the serum, some 90% of folate is unbound. The binding protein increases with folate deficiency and returns to normal with treatment. Serum levels are affected by present dietary intake. Drugs that are folate antagonists, such as methotrexate and pentamidine, may induce a deficiency state. Some drugs, such as oral contraceptives, phenytoin, and ethanol impair absorption of folate. In the pH range of physiologic significance, folate binds to aluminum hydroxide. Chronic use of antacids or H₂-receptor antagonists by patients with diets marginal in folate has been considered as a cause of folic acid deficiency.¹ Levels are commonly high in patients with B₁₂ deficiency since this vitamin is needed to allow incorporation of folate into tissue cells. Folate (folic acid) deficiency is present in some 33% of pregnant women, many alcoholics, patients with a wide variety of malabsorption syndromes including celiac disease, sprue, Crohn disease, and jejunal/ileal bypass procedure. Measurement of both serum and red cell folate levels constitutes a reliable means of determining the existence of folate deficiency. These tests are recommended for all patients who have megaloblastic anemia, as well as for patients who have anemia, hypersegmentation of the granulocytic nuclei, and coincident evidence of iron deficiency. The finding of a low serum folate means that the patient's recent diet has been subnormal in folate content and/or that recent absorption of folate has been subnormal, but does not prove that the patient either has or will develop tissue folate depletion requiring folate therapy. Therefore, serum folate assays have a very poor predictive value in diagnosis and should be interpreted with caution. A low red cell folate can mean either that there is tissue folate depletion due to folate deficiency requiring folate therapy, or alternatively, that the patient has primary vitamin B₁₂ deficiency blocking the ability of cells to take up folate. In the latter case, the proper therapy would be with vitamin B₁₂ rather than with folic acid. It is for these reasons that it is advisable to determine red cell folate in addition to serum folate, and thereby definitively determine that the diagnosis is folate deficiency for which the proper treatment is folic acid. For thoroughness, the serum vitamin B₁₂ level should also be determined, since >50% of all patients with significant megaloblastic anemia have primary deficiency of vitamin B₁₂ rather than of folic acid.² Folate deficient diets have been proposed for methotrexate responsive malignancy. It has also been suggested that plasma folate concentrations in patients who do and do not respond to folate deprivation/antagonism be compared and ratioed to methotrexate levels as part of tumor therapy regimes.³ The levels of serum and RBC folate may be significantly increased in hyperthyroidism.⁴
Footnotes
	Russell RM, Golner BB, Krasinski SD, et al, “Effect of Antacid and H₂ Receptor Antagonists on the Intestinal Absorption of Folic Acid,” J Lab Clin Med, 1988, 112(4):458-63. Bauer JD, Clinical Laboratory Methods, 9th ed, St Louis, MO: Mosby-Year Book Inc, 1982, 95-6. Cohen P and Dix D, “On the Role of Folate Deficiency in Cancer Therapy,” Clin Chem, 1988, 34(9):1945-6 (letter). Ford HC, Carter JM, and Rendle MA, “Serum and Red Cell Folate and Serum Vitamin B₁₂ Levels in Hyperthyroidism,” Am J Hematol, 1989, 31(4):233-6
References
	Chanarin I, “Megaloblastic Anaemia, Cobalamin, and Folate,” J Clin Pathol, 1987, 40(9):978-84 (review). Craig GM, Elliot C, and Hughes KR, “Masked Vitamin B₁₂ and Folate Deficiency in the Elderly,” Br J Nutr, 1985, 54(3):613-9. Davis RE and Nicol DJ, “Folic Acid,” Int J Biochem, 1988, 20(2):133-9 (review).