FOL - Overview: Folate, Serum (2023)

Useful For

Suggests clinical disorders or settings where the test may be helpful

Investigation of suspected folate deficiency

Testing Algorithm

Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For more information, see Vitamin B12 Deficiency Evaluation.

Special Instructions

Library of PDFs including pertinent information and forms related to the test

  • Vitamin B12 Deficiency Evaluation

Method Name

A short description of the method used to perform the test

Competitive-Binding Receptor Assay

NY State Available

Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name

Lists a shorter or abbreviated version of the Published Name for a test

Folate, S


Lists additional common names for a test, as an aid in searching

Folate, Serum

Folic Acid

Pteroylglutamic Acid

Folate and Vitamin B12 (Order FB12)

Testing Algorithm

Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

(Video) Folate ( Vitamin B9) and folate deficiency

For more information, see Vitamin B12 Deficiency Evaluation.

Specimen Type

Describes the specimen type validated for testing


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.

Special Instructions

Library of PDFs including pertinent information and forms related to the test

  • Vitamin B12 Deficiency Evaluation


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

Specimen Minimum Volume

Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.5 mL

Reject Due To

Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK

Specimen Stability Information

Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

(Video) Overview of Folate and Vitamin B12

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

Useful For

Suggests clinical disorders or settings where the test may be helpful

Investigation of suspected folate deficiency

Testing Algorithm

Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For more information, see Vitamin B12 Deficiency Evaluation.

Clinical Information

Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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)

Reference Values

Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

> or =4.0 mcg/L

<4.0 mcg/L suggests folate deficiency


Provides information to assist in interpretation of the test results

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) determinationsmay 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.


Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

(Video) Folate deficiency | What are the symptoms of low folic acid? | Harmful effects of Folate deficiency

Patients with combined deficiency of folate and iron may not demonstrate the erythrocyte macrocytosis that is typical of folate deficiency anemia. In these patients, however, the red cell distribution width (RDW) will typically be elevated.

Nonfasting specimens yield falsely elevated results.

Recent folic acid administration or dietary folate intake could result in normal or elevated values and possibly mask an underlying folate deficiency.

Folates other than N-(5)-methyltetrahydrofolate and folic acid antagonists (such as methotrexate) may, under some circumstances, be present in serum and will also be measured by this method.

Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.

Clinical Reference

Recommendations for in-depth reading of a clinical nature

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

Special Instructions

Library of PDFs including pertinent information and forms related to the test

  • Vitamin B12 Deficiency Evaluation

Method Description

Describes how the test is performed and provides a method-specific reference

The instrument used is a Beckman Coulter DXI 800. The Access Folate assay is a competitive-binding receptor assay. A serum specimen is treated to release folate from endogenous binding proteins. After neutralization of the reaction mixture, folate-binding protein, mouse antifolate-binding protein, folic acid-alkaline phosphatase conjugate, and goat antimouse capture antibody coupled to paramagnetic particles are added to the reaction vessel. Folate in the sample competes with the folic acid-alkaline phosphatase conjugate for binding sites on a limited amount of folate-binding protein. Resulting complexes bind to the solid phase via mouse antifolate binding protein. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field, while unbound materials are washed away. The chemiluminescent substrate Lumi-Phos 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is inversely proportional to the concentration of folate in the sample. The amount of analyte in the sample is determined from a stored, multipoint calibration curve. The assay is standardized to the World Health Organization (WHO) International Standard 03/178.(Beckman Coulter Assay Manual 2011, Beckman Coulter Inc., Fullerton, CA)

PDF Report

Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) Performed

Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available

The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 3 days

Specimen Retention Time

(Video) Vitamin B9 (Folate) 🥬 | Structure, Function, Folate Deficiency Anemia Diagnosis & Treatment

Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location

Indicates the location of the laboratory that performs the test



Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification

Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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

Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Information

Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

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

Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.

FOL Folate, S 2284-8

Test Setup Resources

Setup Files

Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports

Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports

International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

(Video) Folate deficiency

SI Normal Reports | SI Abnormal Reports


What is good level of serum folate? ›

Normal Results

The normal range is 2.7 to 17.0 nanograms per milliliter (ng/mL) or 6.12 to 38.52 nanomoles per liter (nmol/L). Normal value ranges may vary slightly among different labs. Talk to your provider about the meaning of your test results.

What does serum folate mean in a blood test? ›

This is a blood test to measure the concentration of folate in the liquid part of your blood, called serum, or in your red blood cells. The concentration in the red blood cells will be higher than in the serum.

What does it mean if serum folate is low? ›

Vitamin B12 or B9 (commonly called folate) deficiency anaemia occurs when a lack of vitamin B12 or folate causes the body to produce abnormally large red blood cells that can't function properly. Red blood cells carry oxygen around the body using a substance called haemoglobin.

What is the level of serum folate in vitamin B12 deficiency? ›

In addition, a PS would show macrocytic red blood cells (RBCs)and/or megaloblasts and hypersegmented neutrophils. Ordering serum vitamin b12 and folate levels can help differentiate between the two. Generally, serum folate levels <2 ng/mL are considered deficient, while levels > 4 ng/ml are considered as normal.

What cancers cause folic acid deficiency? ›

Folic acid deficiency in humans has been linked with megaloblastic anaemia, neural tube defects in the neonate, and heart disease. Folate has also been implicated in the development of cancer, especially cancer of the colorectum.

Is folate and vitamin B12 the same thing? ›

Your body needs vitamin B-12, also called cobalamin, and folate, also called folic acid, to function normally. Both nutrients play important roles in creating red blood cells and making DNA and RNA to help build cells. B-12 also helps your nervous system function as it should.

Can folate cause nerve pain? ›

Causing too much folate (vitamin B9) is associated with increased risk for a nerve-damage disorder in older adults who have a common genetic variant.

Is low folate levels serious? ›

Although it's uncommon, vitamin B12 or folate deficiency (with or without anaemia) can lead to complications, particularly if you have been deficient in vitamin B12 or folate for some time. Potential complications can include: problems with the nervous system. temporary infertility.

What is the most common cause of folate deficiency? ›

Folate deficiency caused by a lack of dietary folate is more common in people who have a generally unbalanced and unhealthy diet, people who regularly misuse alcohol, and people following a fad diet that does not involve eating good sources of folate.

What diseases cause low folate? ›

  • Diseases in which folic acid is not well absorbed in the digestive system (such as celiac disease or Crohn disease)
  • Drinking too much alcohol.
  • Eating overcooked fruits and vegetables. ...
  • Hemolytic anemia.
  • Certain medicines (such as phenytoin, sulfasalazine, or trimethoprim-sulfamethoxazole)
19 Jul 2021

Is serum folate test accurate? ›

High folate levels can also mean a vitamin B12 deficiency. Body cells need vitamin B12 to use folate. So if vitamin B12 levels are very low, folate can't be used by the cells, and high levels of it may build up in the blood. But a folate test is not a reliable way to test for a vitamin B12 deficiency.

How do I know if my folate is low? ›

Common symptoms of folate deficiency can include: Tiredness, fatigue and lethargy. Muscle weakness. Neurological signs, such as a feeling of pins and needles, tingling, or burning, or peripheral neuropathy, i.e. a numbness in the extremities.

What is an abnormal folate level? ›

The reference range of the red blood cell (RBC) folate level also varies by age, as follows : Adults: 140-628 ng/mL or 317-1422 nmol/L. Children: Over 160 ng/mL or over 362 nmol/L.

What causes folic acid levels to drop? ›

You don't eat enough foods that have folic acid. These include green leafy vegetables, fresh fruits, fortified cereals, yeast, and meats (including liver). You drink too much alcohol. You have certain diseases of the lower digestive tract, such as celiac disease.

Does low folate cause weight gain? ›

Furthermore, folate deficiency may lead to body weight gain and adiposity [12]. Several studies has indicated a link between low folate intake or low serum folate concentration and greater body mass, BMI, overall fat accumulation, and higher waist circumference [13,14,15,16].

How long does it take to correct folate deficiency? ›

Folate-deficiency anemia most often responds well to treatment within 3 to 6 months. It will likely get better when the underlying cause of the deficiency is treated.

Do I replace folate or B12 first? ›

Algorithm 1: Serum cobalamin <150 mcg or serum cobalamin 150-250 ng/ml and neurological/neuropsychiatric symptoms with no other identifiable cause or strong clinical suspicion of deficiency (eg SACD) at any B12 level Check folate level but replace B12 first if deficient.

Does folate deficiency cause neuropathy? ›

In conclusion, our results suggest that folate deficiency is a risk factor for neuropathy in patients younger than 40 years. Importantly, the risk of peripheral neuropathy increased as serum folate decreased, and even insufficient serum folate of 6.8 to 13.5 nmol/L appeared to be important.

What part of the body does folate affect? ›

Folate (vitamin B-9) is important in red blood cell formation and for healthy cell growth and function. The nutrient is crucial during early pregnancy to reduce the risk of birth defects of the brain and spine.

Can low folate cause anxiety? ›

“Problems with folate metabolism have been associated with depression and/or anxiety.

How does folate affect the brain? ›

Some of the important functions folate aides in are the creation of DNA and RNA, formation of neurotransmitters, and the formation of the nervous system during pregnancy. Folate is also known to help with depression, mental fatigue, and irritability because it can be quickly broken down and supply the body with energy.

What should I take if my folate is low? ›

What's the Treatment? Folate deficiency anemia is prevented and treated by eating a healthy diet. This includes foods rich in folic acid, such as nuts, leafy green vegetables, enriched breads and cereals, and fruit. Your doctor will also likely prescribe you a daily folic acid supplement.

Can folate deficiency be cured? ›

To treat folate deficiency anaemia, your GP will usually prescribe daily folic acid tablets to build up your folate levels. They may also give you dietary advice so you can increase your folate intake. Good sources of folate include: broccoli.

What does it mean if serum folate is high? ›

High values

High levels of folate in the blood may mean that you eat a diet rich in folate or folic acid, take vitamins, or take folic acid pills. Consuming more folate than the body needs does not cause problems. High folate levels can also mean a vitamin B12 deficiency. Body cells need vitamin B12 to use folate.

What happens if your folate level is high? ›

Excess folic acid intake may speed age-related mental decline, particularly in people with low vitamin B12 levels. One study in people over the age of 60 linked high blood levels of folate or UMFA to mental decline in those with low vitamin B12 levels.

What foods cause high folate levels? ›

15 Healthy Foods That Are High in Folate (Folic Acid)
  • Legumes. Legumes are the fruit or seed of any plant in the Fabaceae family, including: ...
  • Asparagus. Asparagus contains a concentrated amount of many vitamins and minerals, including folate. ...
  • Eggs. ...
  • Leafy greens. ...
  • Beets. ...
  • Citrus fruits. ...
  • Brussels sprouts. ...
  • Broccoli.
26 Feb 2020

Is 20 a good folate level? ›

Optimal Result: 3 - 20 ng/mL, or 6.80 - 45.32 nmol/L.

Can you have high folate and low B12? ›

The combination of high folate and low vitamin B12 in older adults could be the result of vitamin B12 malabsorption or non- resolution of deficiency even with supplementation, and hence the higher risk for negative health outcomes compared to those who have low vitamin B12, but not high folate.


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