- Red or tiger top tube
- 5 mL of venous blood
Additional information
- Fasting overnight
- Protect the sample from light by wrapping the tube in foil or other material
- Handle sample gently to prevent hemolysis
- Send the sample immediately to the lab
- Centrifuge and freeze serum if delivery is delayed
- The Folic acid assay measures the concentration of folate in the blood
- Folate is a water-soluble B vitamin (B9)
- Dietary folate is found in sources such as eggs, milk, leafy vegetables, yeast, liver, citrus fruits, and grain products
- Folate is absorbed by the intestinal mucosa, with limited storage occurring in the liver
- Folate is also synthesized by bacteria in the intestines
- Functions of folate include:
- Hematopoiesis
- DNA and RNA synthesis
- Tissue growth
- Cell function
- Protein metabolism
- The principal form of folate found in serum is methyltetrahydrofolate
- The clinical utility of the serum folate level includes:
- Evaluation of macrocytic (megaloblastic) anemia resulting from folic acid or vitamin B12 deficiency
- To assess folate stores during pregnancy
- To monitor the effects of long term parenteral nutrition
- To monitor the response to disorders that may lead to folate deficiency or decreased absorption and storage
- Folate is essential for the normal development of a developing fetus’s neural tube that encloses the spinal cord. Thus, deficiency of folate before and during pregnancy may lead to birth defects. Folate supplements reduce the risk of developing
- Neural tube defects such as spina bifida and anencephaly by 50%
- Cleft lip and palate by 25-50%
- Transposition of great vessels and tetralogy of Fallot by 43%
- Folic acid deficiency may clinically present as:
- Diarrhea
- Depression
- Glossitis (Sore inflamed tongue)
- Signs of anemia (pale skin, tachycardia, weakness, fatigue)
- Weight loss
- Patients with folate deficiency may have elevated serum homocysteine, which is an independent risk factor for heart disease and stroke. Treatment with folic acid reduces the homocysteine levels, but is yet to be shown to reduce risk of atherosclerosis and coronary artery disease (CAD)
- Dietary folic acid probably prevent changes to DNA and appear to reduce the risk in certain cancers such as colon, breast, and esophagus
Additional information
- Highest levels are seen in winter and lower levels are seen during summer
- Excessive folate in the diet may mask the signs of vitamin B12 deficiency, which is common in older adults. In this case an anemia may not be present, but the other features of vitamin B12 deficiency (e.g. neurologic abnormalities) may be present
- Vitamin B12 assay is often done along with folate levels for the evaluation of megaloblastic anemia
- In pure vitamin B12 deficiency state, serum folate levels are normal, but RBC folate levels are decreased, which is due to impairment of the methionine synthetase pathway leading to accumulation of methyltetrahydrofolate
- Vitamin B12 is essential for the conversion of 5-methyltetrahydrofolate to THFA (active form of folate necessary for cellular mechanisms). In this case, 5-methyl THFA is trapped and accumulates in the serum, with resulting low RBC folate and normal serum folate levels. In this situation, treating the underlying vitamin B12 deficiency is the solution
- The serum folate assay, in comparison to RBC folate assay, has low sensitivity and specificity. The advantages with the RBC folate assay include:
- Detects folic acid levels when the cells are made (2 months earlier than serum folate assays)
- It is not affected by the amount of folic acid in the diet
- Interfering factors for folate levels include:
- Recent radioactive scans or radiation within 1 week
- Methotrexate or other folic acid antagonists
- Related laboratory tests include:
- Complete blood count
- Homocysteine
- Vitamin B12
Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.
| Conv. Units (ng/mL) | SI Units (nmol/L) | |
|---|---|---|
| Serum Folate Adult |  3 | 7 |
| Serum Folate Child | 5 | 11 |
| RBC Folate | 145 | 315 |
Conditions associated with an increase in folic acid levels include:
- Blind loop syndrome
- Vegetarian diet
- Pernicious anemia
- Excessive dietary intake of folic acid or folic acid supplements
- Vitamin B12 deficiency
- Distal small bowel disease
False elevated levels are found in:
- Hemolyzed specimens
- Iron deficiency anemia
Conditions associated with decreased folic acid levels include:
- Inadequate intake
- Alcoholism
- Anorexia
- Chronic disease
- Malnutrition
- Diet devoid of fresh vegetables or enriched grains
- Total parenteral nutrition
- Malabsorption of folic acid
- Alcoholism
- Bacterial overgrowth in the stomach and intestines
- Celiac disease
- Crohn's disease
- Intestinal resection
- Jejunal bypass procedure
- Short-Bowel Syndrome
- Small bowel disease
- Tropical sprue
- Ulcerative colitis
- Whipple's disease
- Zinc deficiency
- Drugs:
- Anticonvulsants
- Methotrexate
- Triamterene
- Trimethoprim
- Increased requirement
- Infancy
- Pregnancy
- Lactation
- Malignancies
- Metastatic carcinomas
- Acute leukemia
- Myelofibrosis
- Concurrent infection
- Chronic hemolytic anemia
- Sickle cell disease
- Phenocytosis
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Impaired metabolism as in hypothyroidism
- Increased excretion or loss
- Vitamin B12 deficiency
- Hemodialysis
- Increased destruction as in smoking
- Liver disease associated with
- Cirrhosi
- Hepatoma
- Alcoholism (inadequate intake, malabsorption, and increased loss)
- Vitamin B6 deficiency
- Infantile hyperthyroidism
- Exfoliative dermatitis
- Scurvy
- Depression
- Alzheimer disease
- Osteoporosis
- Drugs
- Aminopterin
- Aminosalicylic acid
- Ampicillin
- Antacids
- Anticonvulsants
- Antimalarials
- Aspirin
- Barbiturates
- Chloramphenicol
- Chloroguanide
- Cholestyramine
- Colchicine
- Cycloserine
- Diethylstilbestrol
- Erythromycin
- Estropipate
- Ethanol
- Iron
- Isoniazid
- Levodopa
- Lincomycin
- Metformin
- Methotrexate
- Nitrofurantoin
- Oral contraceptives
- Penicillin
- Pentamidine
- Phenobarbital
- Phenytoin
- Primidone
- Pyrimethamine
- Rifampin
- Sulfasalazine
- Sulfisoxazole
- Tetracycline
- Triamterene
- Trimethoprim
- Cattaneo M. Hyperhomocysteinemia and venous thromboembolism. Semin Thromb Hemost. 2006 Oct;32(7):716-23.
- eMedicine from WebMD®. Folic acid deficiency. [Homepage on the Internet] ©1996-2006. Last updated on May 22, 2006. Last accessed on December 12, 2006. Available at URL: http://www.emedicine.com/MED/topic802.htm
- Galloway M et al. Red cell or serum folate? Results from the National Pathology Alliance benchmarking review. Journal of Clinical Pathology 2003;56:924-926
- Goh YI et al. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can. 2006 Aug;28(8):680-9.
- Laboratory Corporation of America®. Folate (Folic Acid). [Homepage on the internet]©2003. Last udated on May 10, 2006. Last accessed on October 10, 2006. Available at URL:
- http://www.labcorp.com/datasets/labcorp/html/chapter/mono/ri004400.htm
- Medlineplus Medical Encyclopedia®. Folic acid (Folate). [Homepage on the internet]©2005 Last updated on October 27, 2004. Last accessed on October 10, 2006. Available at URL: http://www.nlm.nih.gov/medlineplus/ency/article/002408.htm
- Schnyder G et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA. 2002 Aug 28;288(8):973-9.
- UTMB Laboratory Survival Guide®. Folate, serum. [Homepage on the Internet]© 2006. Last reviewed in February 2006. Last accessed on December 12, 2006. Available at URL: http://www.utmb.edu/lsg/LabSurvivalGuide/CHEM/FOLATE1.html
- Van Guelpen B et al. Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake. Stroke. 2005 Jul;36(7):1426-31. Epub 2005 Jun 2.