SI UNITS (recommended)

CONVENTIONAL UNITS

(Vitamin B9 – Essential for DNA Synthesis, Cell Division, Pregnancy, and Hematology)

Synonyms

  • Folate
  • Folic acid (synthetic form)
  • Vitamin B9
  • Tetrahydrofolate (THF) derivatives
  • RBC folate
  • Serum folate

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/dL = 0.01 ng/mL
ng/dL = ng% = ng/100 mL
1 ng/mL = 1000 ng/L = 1 µg/L

Description

Folate is a water-soluble B-vitamin (Vitamin B9) required for:

  • DNA synthesis
  • Purine and pyrimidine formation
  • Red blood cell (RBC) production
  • Methylation reactions (with B12)
  • Neural tube development in pregnancy

The body does not store folate extensively, so deficiency can develop rapidly (weeks–months).

Dietary sources include leafy vegetables, legumes, fruits, liver, and fortified grains.

Physiological Role

Folate is essential for:

  • Cell division
  • Bone marrow function
  • Fetal neurodevelopment
  • Homocysteine metabolism (via methylation)
  • S-adenosylmethionine (SAMe) production

Deficiency affects rapidly dividing cells first (e.g., bone marrow, GI mucosa).

Clinical Significance

Low Folate (Folate Deficiency)

Most common and clinically important finding.

Causes

  • Poor dietary intake
  • Alcoholism
  • Malabsorption (celiac disease, IBD)
  • Medications (methotrexate, phenytoin, TMP-SMX)
  • Pregnancy / increased requirements
  • Hemolytic anemia (↑ cell turnover)
  • Bariatric surgery
  • Prematurity in infants

Symptoms

  • Macrocytic anemia (MCV ↑)
  • Fatigue, pallor
  • Glossitis
  • Diarrhea
  • Elevated homocysteine
  • NO neurologic features (unlike B12 deficiency)

Pregnancy Risk

Low folate in pregnancy →
Neural tube defects (NTD), including:

  • Spina bifida
  • Anencephaly

High Folate

Usually benign.

Possible causes:

  • Supplementation
  • Fortified diets
  • Bacterial overgrowth
  • Hemolysis (false elevation)

High folate does not mask B12 deficiency neurologically but may normalize hematologic indices.

Reference Intervals

(Tietz 8E + WHO + AACE + Mayo + ARUP)

Serum 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

Better reflects long-term stores.

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

Pregnancy Targets

  • >4 ng/mL serum folate
  • >150 ng/mL RBC folate

WHO Criteria

  • RBC folate < 305 nmol/L → Increased NTD risk

Diagnostic Uses

1. Evaluation of Macrocytic Anemia

Differentiate folate deficiency from B12 deficiency.

2. Pregnancy Screening

Assess adequate folate to prevent neural tube defects.

3. Malabsorption Disorders

Celiac disease, Crohn’s disease, short bowel syndrome.

4. Alcohol Dependence

Alcohol interferes with folate absorption and metabolism.

5. Hyperhomocysteinemia Evaluation

Folate deficiency → ↑ Homocysteine (CV risk marker).

6. Monitoring Therapy

Assess response to folic acid supplementation.

Analytical Notes

  • Serum folate reflects recent intake; RBC folate reflects long-term status.
  • Hemolysis falsely increases folate (release from RBCs).
  • Fasting sample preferred but not mandatory.
  • Some medications reduce folate levels (antiepileptics, antifolates).

Clinical Pearls

  • Folate deficiency causes macrocytic anemia without neurologic symptoms (unlike B12).
  • Always check B12 along with folate.
  • Pregnancy requires higher folate; supplementation reduces NTD risk by >70%.
  • Borderline folate levels should not be ignored — repeat testing or treat empirically.
  • Alcoholism is one of the most common causes of low folate worldwide.

Interesting Fact

Folate was discovered in spinach (Latin: folium = leaf), hence the name.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Vitamins & Nutrition.
  2. WHO: Serum & RBC Folate Thresholds for NTD Prevention.
  3. AACE/ACE Guidelines - Vitamin Deficiency Testing.
  4. BCSH Hematology Guidelines - Macrocytic Anemia.
  5. Mayo Clinic Laboratories - Folate.
  6. ARUP Consult - Folate & B12 Interpretation.
  7. MedlinePlus / NIH - Folate Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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