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Folic acid (Vitamin B9)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Synthetic Form of Folate – Essential for DNA Synthesis, Cell Growth & Pregnancy Health)

Synonyms

  • Folic acid
  • Vitamin B9
  • Pteroylmonoglutamic acid
  • Folacin
  • Folic acid (synthetic)
  • Dietary folate equivalent (DFE)
  • B-complex vitamin

Units of Measurement

  • pmol/L
  • nmol/L
  • ng/mL
  • ng/dL
  • ng/100 mL
  • ng%
  • ng/L
  • µg/L

Key Conversions

1 ng/mL = 2.266 nmol/L (MW ≈ 441 g/mol)
1 ng/mL = 100 ng/dL
1 ng/mL = 1000 ng/L = 1 µg/L
ng/dL = ng% = ng/100 mL

Description

Folic acid is the synthetic, fully oxidized form of Vitamin B9, used in:

  • Supplements
  • Fortified foods (grains, cereals, flour)

Inside the body, it is converted into biologically active folates (e.g., tetrahydrofolate), which play critical roles in:

  • DNA/RNA synthesis
  • Red blood cell formation
  • Neural tube development
  • Homocysteine metabolism

Folic acid is more stable than natural folate, allowing reliable supplementation and food fortification.

Physiological Role

Folic acid (after conversion to THF) supports:

  • Cell division & growth
  • Purine & thymidylate synthesis
  • Formation of methionine from homocysteine
  • Methylation reactions (epigenetics)
  • Hematopoiesis (bone marrow function)

Rapidly dividing tissues (RBCs, fetus, GI mucosa) are most affected by deficiency.

Clinical Significance

Low Folic Acid Levels

Most commonly due to:

1. Poor dietary intake

Common in:

  • Elderly
  • Malnutrition
  • Alcoholism

2. Malabsorption

  • Celiac disease
  • Crohn’s disease
  • Bariatric surgery

3. Increased requirements

  • Pregnancy
  • Hemolytic anemia
  • Malignancy
  • Inflammatory disorders

4. Drugs

  • Methotrexate
  • Trimethoprim
  • Phenytoin
  • Sulfasalazine
  • Anticonvulsants

Clinical features

  • Macrocytic anemia
  • Fatigue, pallor
  • Glossitis
  • Diarrhea
  • Elevated homocysteine

Note: Unlike B12 deficiency → folate deficiency does not cause neuropathy.

High Folic Acid Levels

Usually due to:

  • Supplementation
  • Fortified diet
  • Recent folate intake

High folic acid is usually not harmful but may:

  • Mask hematologic signs of B12 deficiency
  • Allow neurological damage to progress unchecked

Reference Intervals

(Tietz 8E + WHO + Mayo + ARUP)

Serum Folic Acid / Folate

  • >4 ng/mL (≈ >9 nmol/L) = normal
  • 2–4 ng/mL (4.5–9 nmol/L) = borderline
  • <2 ng/mL (≈ <4.5 nmol/L) = deficiency

RBC Folate (Long-term stores)

  • >150 ng/mL (≈ >340 nmol/L) = normal

Pregnancy Requirements

  • WHO recommends daily 400–800 µg folic acid to prevent neural tube defects.

Diagnostic Uses

1. Macrocytic Anemia Workup

Differentiate folate deficiency from B12 deficiency.

2. Pregnancy Screening

Ensures adequate levels for fetal neural tube development.

3. Homocysteine Elevation

Folate deficiency → ↑ homocysteine → cardiovascular risk.

4. Nutrition Assessment in Alcoholism

Alcohol reduces absorption and hepatic storage.

5. Monitoring Supplementation

Evaluate effectiveness of folic acid therapy.

Analytical Notes

  • Serum reflects recent dietary intake.
  • RBC folate reflects long-term folate stores.
  • Hemolysis falsely elevates folate (RBC folate leaks into serum).
  • Fasting sample preferred for serum folate.

Clinical Pearls

  • Folic acid is crucial during the first 28 days of pregnancy - when neural tube closure occurs.
  • Folate deficiency causes macrocytosis without neurologic symptoms (unlike B12).
  • Always check Vitamin B12 together with folate.
  • Alcoholism is one of the most common causes of folate deficiency.
  • Fortified grains have reduced NTD incidence globally by >70%.

Interesting Fact

Folic acid fortification in flour (USA, Canada, Australia) has prevented tens of thousands of neural tube defects since implementation.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Vitamins & Nutrition.
  2. WHO Guidelines - Folic Acid Supplementation & NTD Prevention.
  3. AACE/ACE Vitamin Deficiency Guidelines.
  4. BCSH Hematology Standards - Macrocytosis.
  5. Mayo Clinic Laboratories - Folate/Folic Acid.
  6. ARUP Consult - Folate & B12 Interpretation.
  7. MedlinePlus / NIH - Folic Acid Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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