What is considered a low vitamin B12 (cobalamin) level?

Defining Low Vitamin B12 Levels

A vitamin B12 level below 180 ng/L (or 180 pmol/L) is considered deficient, while levels between 180-350 ng/L are considered indeterminate or borderline, requiring additional metabolic testing for confirmation. 1

Diagnostic Thresholds for Vitamin B12 Deficiency

Vitamin B12 deficiency diagnosis relies on specific laboratory thresholds:

Threshold	Interpretation
Total B12 <180 ng/L (or pmol/L)	Confirmed deficiency
Total B12 180-350 ng/L	Indeterminate/borderline (requires additional testing)
Total B12 >350 ng/L	Unlikely deficiency

Metabolic Markers for Confirming B12 Deficiency

When B12 levels fall in the indeterminate range (180-350 ng/L), measuring metabolic markers provides more accurate diagnosis:

• Methylmalonic acid (MMA): More specific marker for B12 deficiency

  • Elevated in 98.4% of B12 deficient patients 2
  • Testing has additional value when vitamin B12 is below 304 pmol/L (412 pg/mL) 3

• Homocysteine: Sensitive but less specific

  • Elevated in 95.9% of B12 deficient patients 2
  • May also be elevated in folate deficiency, pyridoxine deficiency, hypothyroidism, renal insufficiency, and hypovolemia 2

Clinical Significance of Different Thresholds

• Absolute deficiency: <148 pmol/L (200 pg/mL) 4, 3
• Borderline: 200-299 pg/mL 4
• Normal: ≥300 pg/mL 4

Research indicates that metabolic B12 deficiency can occur at higher serum B12 levels than previously thought:

• 90% sensitivity for detecting metabolic deficiency at B12 <264 pmol/L (358 pg/mL)
• 95% sensitivity at B12 <304 pmol/L (412 pg/mL) 3

High-Risk Populations

Vitamin B12 deficiency is particularly common in:

• Elderly (10-15% of people over age 60) 5
• Individuals with atrophic gastritis (reduced protein-bound B12 absorption) 5
• Patients with type 2 diabetes on metformin (especially doses >1g/day) 4
• Patients with distal symmetric polyneuropathy (3.6% prevalence) 2
• Vegetarians and vegans 1
• Patients with malabsorption disorders or ileal resection 1

Clinical Pitfalls

• Serum B12 levels alone may not be reliable due to methodological problems affecting sensitivity and specificity 1
• Patients may have metabolic B12 deficiency despite "normal-low" B12 levels (200-500 pg/dL) 2
• Elderly patients often lack classic signs of B12 deficiency (like megaloblastic anemia) despite having deficiency 5
• Symptoms can be diverse, ranging from neurological to psychiatric, and may be subtle or non-specific 6

Practical Approach to Diagnosis

1. Measure serum B12 level
2. If <180 ng/L: confirmed deficiency, begin treatment
3. If 180-350 ng/L: measure MMA and homocysteine
4. If MMA and/or homocysteine elevated: metabolic B12 deficiency confirmed
5. Consider treatment response as confirmatory when diagnosis is uncertain

This approach ensures that both absolute deficiency and metabolic deficiency (with normal-low B12 levels but elevated metabolites) are properly identified and treated.