What are the vitamin B12 (B12) deficiency ranges in nanograms per milliliter (ng/mL)?

Vitamin B12 Deficiency Ranges in ng/mL

Vitamin B12 deficiency is defined as a serum level less than 180 pg/mL (or ng/L), with borderline levels between 180-350 pg/mL requiring additional metabolic testing to confirm functional deficiency. 1

Diagnostic Ranges

Vitamin B12 levels are typically categorized as follows:

• Deficient: <180 pg/mL (<180 ng/L)
• Borderline: 180-350 pg/mL (180-350 ng/L)
• Normal: >350 pg/mL (>350 ng/L)

Some studies use slightly different cutoffs:

• <150 pg/mL: Definite deficiency 2, 3
• 150-200 pg/mL: Borderline deficiency 2

• 200 pg/mL: Normal 4

Confirming Functional Deficiency

When B12 levels fall in the borderline range (180-350 pg/mL), additional testing is necessary to confirm functional deficiency:

• Methylmalonic acid (MMA):

  • Normal: <350 nmol/L
  • Elevated (indicating B12 deficiency): >350 nmol/L 5
  • MMA is highly sensitive (98.4%) and specific for B12 deficiency 5

• Homocysteine:

  • Normal: <15 μmol/L
  • Elevated (may indicate B12 deficiency): >15 μmol/L 5, 2
  • Sensitive (95.9%) but less specific than MMA 5

• Holotranscobalamin (active B12):

  • <25 pmol/L: Confirmed deficiency
  • 25-70 pmol/L: Possible deficiency

  • 70 pmol/L: Deficiency unlikely 5

Important Clinical Considerations

1. Metabolic deficiency despite normal serum B12: Studies show that 15-50% of patients with normal serum B12 may have metabolic deficiency 5

2. Age-related considerations: Older adults (especially those ≥75 years) have a higher prevalence of B12 deficiency (approximately 20%) 2

3. Medication effects: Metformin and proton pump inhibitors can cause B12 deficiency with elevated MMA and homocysteine despite potentially normal B12 levels 5, 1

4. Renal impairment: Can cause elevated MMA and homocysteine regardless of B12 status, requiring careful interpretation 5

5. Diagnostic pitfalls: Using different reference ranges can significantly impact diagnostic classification - in one study, using manufacturers' recommended ranges would have changed the diagnostic classifications for 22 of 38 samples 6

Treatment Thresholds

Treatment is recommended when:

• Serum B12 <180 pg/mL
• Borderline B12 (180-350 pg/mL) with elevated MMA (>350 nmol/L) or homocysteine (>15 μmol/L)
• Presence of clinical symptoms consistent with B12 deficiency regardless of borderline levels

The standard treatment is 1000 μg of vitamin B12 daily orally or 1000 μg intramuscularly weekly for 4 weeks followed by monthly maintenance therapy 5.

Remember that early detection and treatment of vitamin B12 deficiency is crucial to prevent potentially irreversible neurological damage, even when hematologic manifestations are absent.