Normal Vitamin B12 Range
The normal range for vitamin B12 varies by laboratory and guideline, but deficiency is generally defined as <150-180 pmol/L (<200-244 pg/mL), borderline as 180-350 pmol/L (244-474 pg/mL), and normal as >300-350 pmol/L (>406-474 pg/mL). 1, 2, 3
Standard Reference Ranges
Deficiency Thresholds
- Serum B12 <150 pmol/L (approximately <203 pg/mL) is considered deficient by UK NDNS standards 1
- <180 pg/mL is diagnostic for deficiency according to American Family Physician guidelines 2
- <200 pg/mL is compatible with deficiency in population studies 3
Borderline Range
- 180-350 pmol/L (244-474 pg/mL) represents an indeterminate range requiring further testing 2, 4
- 200-299 pg/mL is considered borderline in clinical practice 3
Normal Range
- >300-350 pmol/L (>406-474 pg/mL) is generally considered normal 2, 3
- Some laboratories use >258 pmol/L (>350 pg/mL) as the lower limit of normal 1, 5
Critical Limitations of Standard Testing
Standard serum B12 testing misses functional deficiency in up to 50% of cases, as demonstrated in the Framingham Study where 12% had low serum B12 but an additional 50% had elevated methylmalonic acid indicating metabolic deficiency 6, 1
When Standard B12 is Insufficient
- **Serum B12 <258 pmol/L with elevated homocysteine or methylmalonic acid** defines metabolic B12 deficiency, which affects 10.6% of stroke patients overall and 18.1% of those >80 years 6, 1
- Active B12 (holotranscobalamin) measures biologically available B12 and is more sensitive than total B12, though not routinely tested 1, 4
- Methylmalonic acid >280 nmol/L suggests suboptimal B12 status in young patients with normal renal function 4
- Homocysteine >20 µmol/L may suggest B12 deficiency in folate-replete patients 4
Age-Specific Considerations
Elderly populations have significantly higher rates of metabolic deficiency despite "normal" serum B12:
- 25% of patients ≥85 years have B12 <170 pmol/L 1
- 18.1% of patients >80 years have metabolic B12 deficiency 1
- The lowest quartile in the Newcastle 85+ study was <170 pmol/L with elevated homocysteine 6
Geographic and Laboratory Variation
Cut-off points vary widely across studies and laboratories:
- Vitamin B12 ranges from 100-350 pmol/L across different guidelines 7
- Holotranscobalamin ranges from 20-50 pmol/L 7
- Methylmalonic acid ranges from 0.210-0.470 µmol/L 7
- Most studies fail to account for age, analytical methods, gender, and fortified food consumption when establishing cut-offs 7
Common Clinical Pitfalls
Do not rely solely on serum B12 to rule out deficiency, especially in:
- Patients >60 years, where metabolic deficiency is common despite normal serum levels 6, 1
- Patients on metformin, proton pump inhibitors, or other interfering medications 1, 2
- Patients with neurological symptoms, which often precede hematological changes and occur in one-third of cases without macrocytic anemia 1, 8
- Post-bariatric surgery patients, who have high malabsorption risk 1
When B12 is borderline (180-350 pmol/L), always measure methylmalonic acid to identify functional deficiency 2, 4