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Test ID: FOL Folate, Serum

Reporting Name

Folate, S

Useful For

Investigation of suspected folate deficiency

Clinical Information

The term folate refers to all derivatives of folic acid. For practical purposes, serum folate is almost entirely in the form of N-(5)-methyl tetrahydrofolate.(1)


Approximately 20% of the folate absorbed daily is derived from dietary sources; the remainder is synthesized by intestinal microorganisms. Serum folate levels typically fall within a few days after dietary folate intake is reduced and may be low in the presence of normal tissue stores. RBC folate levels are less subject to short-term dietary changes.


Significant folate deficiency is characteristically associated with macrocytosis and megaloblastic anemia. Lower than normal serum folate also has been reported in patients with neuropsychiatric disorders, in pregnant women whose fetuses have neural tube defects, and in women who have recently had spontaneous abortions.(2) Folate deficiency is most commonly due to insufficient dietary intake and is most frequently encountered in pregnant women or in alcoholics.


Other causes of low serum folate concentration include:

-Excessive utilization (eg, liver disease, hemolytic disorders, and malignancies)

-Rare inborn errors of metabolism (eg, dihydrofolate reductase deficiency, formiminotransferase deficiency, 5,10-methylenetetrahydrofolate reductase deficiency, and tetrahydrofolate methyltransferase deficiency)


Serum folate is a relatively nonspecific test.(3) Low serum folate levels may be seen in the absence of deficiency, and normal levels may be seen in patients with macrocytic anemia, dementia, neuropsychiatric disorders, and pregnancy disorders.


Results below 4 mcg/L are suggestive of folate deficiency. The cutoff is based on consensus and was derived from the US NHANES III data.(4)


Evaluation of macrocytic anemias commonly requires measurement of the serum concentration of both vitamin B12 and folate; ideally they should be measured at the same point in time.


Serum folate measurement is preferred over RBC folate measurement due to considerable analytic variability (coefficient of variation) of assays. Both results give the same interpretation (internal Mayo study), therefore, RBC folate quantitation is not recommended. Additional serum testing with homocysteine and methylmalonic acid (MMA) determinations may help distinguish between vitamin B12 and folate deficiency states. In folate deficiency, homocysteine levels are elevated and MMA levels are normal. In vitamin B12 deficiency, the analytic variability of both serum and RBC folate assays is considerable. Homocysteine and MMA levels are alternate determinates of folate deficiency.


For more information, see Vitamin B12 Deficiency Evaluation.

Report Available

1 to 3 days

Day(s) Performed

Monday through Friday

Clinical Reference

1. Fairbanks VF, Klee GG: Biochemical aspects of hematology. In: Burtis CA, Ashwood ER, eds: Tietz Textbook of Clinical Chemistry. Saunders Company; 1999:1690-1698

2. George L, Mills JL, Johansson AL, et al: Plasma folate levels and risk of spontaneous abortion. JAMA 2002 October 16;288:1867-1873

3. Klee GG: Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem. 2000 August;46(8 Pt 2):1277-1283

4. Benoist BD: Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food and Nutrition Bulletin 2008 (volume 29, number 2) S238-S244

5. Roberts NB, Taylor A, Sodi R: Vitamins and trace elements. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:chap 37

Method Name

Competitive-Binding Receptor Assay

Specimen Type


Specimen Required

Specimen Required

Patient preparation:

1. Patient should be fasting for 8 hours.

2. Do not order on patients who have recently received methotrexate or other folic acid antagonists.


Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 0.6 mL

Collection Instructions: 

1. Serum gel tubes should be centrifuged within 2 hours of collection.

2. Red-top tubes should be centrifuged and the serum aliquoted within 2 hours of collection.

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 7 days
  Frozen  90 days

Special Instructions

Reference Values

≥4.0 mcg/L

<4.0 mcg/L suggests folate deficiency

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
FOL Folate, S 2284-8


Result ID Test Result Name Result LOINC Value
FOL Folate, S 2284-8


If not ordering electronically, complete, print, and send a Benign Hematology Test Request Form (T755) with the specimen.

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Behavioral, mml-Epilepsy, mml-Movement-Disorders, mml-Demyelinating-Diseases, mml-Neuromuscular, mml-Autonomic, mml-Pediatric, mml-Spinal-Cord, mml-Neurometabolic, mml-Neuro-ophthalmology