Folic acid

Anemia

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Folic acid, also known as vitamin B9, is a water-soluble B vitamin essential for: DNA synthesis and repair, Red blood cell formation

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Folic Acid Test Information Guide

Why is it done?
- Measures serum or red blood cell (RBC) folic acid levels to assess vitamin B9 status and detect deficiency
- Diagnoses folate deficiency anemia and investigates causes of macrocytic anemia
- Evaluates nutritional status in patients with malabsorption disorders, alcoholism, or poor dietary intake
- Monitors folate levels in patients taking medications that deplete folic acid (methotrexate, phenytoin, sulfasalazine)
- Assesses risk of neural tube defects and complications during pregnancy
- Investigates elevated homocysteine levels and cardiovascular risk factors
- Typically ordered when patients present with symptoms of anemia, neurological symptoms, or during routine health screening
Normal Range
- Serum Folate: 2.7 to 17.0 ng/mL (6.1 to 38.5 nmol/L) or greater than 5.4 ng/mL is typically considered normal
- Red Blood Cell (RBC) Folate: Greater than 140 ng/mL (greater than 317 nmol/L) is considered normal; more specific indicator of tissue folate stores
- Interpretation: Values within normal range indicate adequate folate status and sufficient stores for normal metabolic function
- Low Values (<2.7 ng/mL serum; <140 ng/mL RBC): Indicate folate deficiency with potential for anemia and neurological complications
- High Values: Rarely elevated and usually not clinically significant; may indicate excessive supplementation or certain conditions
- Note: Reference ranges may vary between laboratories; consult specific lab's reference values
Interpretation
- Low Folic Acid (<2.7 ng/mL serum): Suggests folate deficiency from inadequate dietary intake, malabsorption, increased demand (pregnancy, lactation), or medication effects; may cause megaloblastic anemia, glossitis, diarrhea, and neuropsychiatric symptoms
- Borderline Low (2.7-4.0 ng/mL): May indicate early deficiency; RBC folate testing recommended for confirmation; consider supplementation if risk factors present
- Normal Range (>5.4 ng/mL): Indicates adequate folate status; sufficient for normal DNA synthesis, cell division, and neurological function
- High Values (>17.0 ng/mL): Uncommon and rarely pathologic; may result from high-dose supplementation or B12 deficiency; excessive folate supplementation does not provide additional benefit
- RBC Folate vs. Serum Folate: RBC folate reflects long-term tissue stores (120-day lifespan of RBCs); serum folate reflects recent dietary intake and is more sensitive to acute changes
- Factors Affecting Results: Recent dietary intake, B12 deficiency status (may mask folate deficiency), hemolysis, medications (methotrexate, phenytoin, sulfasalazine, trimethoprim), alcohol consumption, renal dialysis, and certain genetic polymorphisms
- Clinical Significance: Folate is essential for DNA synthesis and repair; deficiency increases risk of neural tube defects in pregnancy, cardiovascular disease via elevated homocysteine, cognitive decline, and cancer; combined B12/folate deficiency requires differentiation for appropriate treatment
Associated Organs
- Primary Systems Involved:
  - Gastrointestinal tract (absorption and dietary sources)
  - Hematopoietic system (red blood cell production)
  - Nervous system (DNA synthesis and neurological function)
  - Liver (storage and metabolism of folate)
  - Reproductive system (pregnancy outcomes and fetal development)
- Diseases and Conditions Associated with Abnormal Results:
  - Megaloblastic anemia (abnormal large red blood cells)
  - Celiac disease and inflammatory bowel disease (Crohn's, ulcerative colitis)
  - Small intestinal bacterial overgrowth (SIBO) and tropical sprue
  - Alcoholic liver disease and cirrhosis
  - Chronic kidney disease requiring dialysis
  - Hemolytic anemia and sickle cell disease (increased folate demand)
  - Hyperthyroidism and malignancy (increased cell turnover)
  - Elevated homocysteine and cardiovascular disease risk
- Complications of Deficiency:
  - Neural tube defects (spina bifida, anencephaly) in pregnancy
  - Severe anemia causing fatigue, dyspnea, and heart complications
  - Peripheral neuropathy and subacute combined degeneration (especially if B12 deficient)
  - Cognitive impairment and depression
  - Increased homocysteine and thrombotic risk
Follow-up Tests
- Initial Follow-up Tests for Low Folic Acid:
  - Red Blood Cell (RBC) folate level - confirms serum folate findings and reflects tissue stores
  - Vitamin B12 level - assess for concurrent B12 deficiency requiring different treatment
  - Complete Blood Count (CBC) - evaluate for anemia, macrocytosis, and WBC/platelet abnormalities
  - Homocysteine level - assess cardiovascular risk and determine if combined deficiency present
  - Methylmalonic acid (MMA) - helps differentiate B12 deficiency from folate-only deficiency
- Diagnostic Tests to Identify Cause of Deficiency:
  - Celiac serology (tissue transglutaminase antibody) - if malabsorption suspected
  - Intrinsic factor and parietal cell antibodies - evaluate for pernicious anemia
  - Liver function tests - assess hepatic storage and metabolism
  - Kidney function tests (BUN, creatinine) - evaluate renal status in dialysis patients
  - Upper endoscopy with small bowel biopsy - if small intestinal pathology suspected
- Monitoring and Follow-up After Treatment:
  - Repeat folic acid level 4-8 weeks after supplementation initiation to assess response
  - Repeat CBC 8-12 weeks post-treatment to confirm anemia resolution
  - Annual monitoring in patients taking folate-depleting medications
  - Periconception and first trimester monitoring in pregnant women
  - Homocysteine re-check if cardiovascular risk reduction is therapeutic goal
- Related Complementary Tests:
  - Methylenetetrahydrofolate reductase (MTHFR) genetic testing - for patients with recurrent pregnancy loss
  - Vitamin B6 and riboflavin levels - assess overall B vitamin status
Fasting Required?
- Fasting: NO - Fasting is not required for folic acid testing
- Food and Beverage: Normal diet and fluids are permitted; test can be performed at any time of day
- Medications to Avoid: Do not hold any medications unless specifically instructed; continue routine medications as prescribed (note that some medications like methotrexate may affect results but should not be discontinued)
- Patient Preparation Requirements:
  - Arrive at laboratory appointment well-rested and relaxed to minimize stress-related variations
  - Bring current medication list for review by healthcare provider
  - Notify phlebotomist of any history of hemolysis during blood draw to prevent sample destruction
  - Verify laboratory's specific instructions if RBC folate testing also ordered (may have special processing)
  - Avoid alcohol for 24 hours before testing for most accurate results if possible
  - Be aware that recent folic acid supplementation may elevate serum levels; inform provider if begun recently
  - If multiple tests ordered (B12, folate, CBC), single blood draw can obtain all samples

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