Folate (Folic Acid)

• Vitamin B₁₂
• Vitamin B₆, Plasma

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

In patients receiving therapy with high biotin doses (ie, >5 mg/day), no sample should be taken until at least eight hours after the last biotin administration.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.

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 of less than 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

2. Miale JB, “Hematology,” Laboratory Medicine, St Louis, Mo: CV Mosby; 1982: 416-40.

3. Brewster MA, “Vitamins,” Clinical Chemistry: Theory, Analysis, and Correlation, Kaplan LA, Pesce AJ, eds, St. Louis, Mo: CV Mosby; 1989: 543-68.

4. Fairbanks VF, Klee GG, “Biochemical Aspects of Hematology,” Tietz Textbook of Clinical Chemistry, Burtis CA, Ashwood ER, eds, WB Saunders Co; 1999: 1642-710.

5. McNeely MD, “Folic Acid,” Methods in Clinical Chemistry, Pesce AJ, Kaplan LA, eds, St Louis, Mo: CV Mosby; 1987: 539-42.

6. Snow CF,”Laboratory Diagnosis of Vitamin B12 and Folate Deficiency: A Guide For the Primary Care Physician,” Arch Intern Med, 1999, 159(12):1289-1298. PubMed 21593497

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 4626525

8. “Nutritional Anemias, Reports of a WHO Group of Experts,” World Health Organ Tech Rep Ser 1972;503. PubMed 10386505

9. Wolff T, Witkop CT, Miller T, et al, “Folic Acid Supplementation for the Prevention of Neural Tube Defects: An Update of the Evidence For the U.S. Preventive Services Task Force,” Ann Interv Med, 2009:150(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 71(5 Suppl);1308S-1311S. PubMed 10799407

11. Choumenkovitch SF, Selhub J, Wilson PW, et al, “Folic Acid Intake from Fortification in United States Exceeds Predictions,” J Nutr. 2002 Sep;132(9):2792-8. 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;136:153-8. 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)718-27. PubMed 17823438