Normal Range for Vitamin B12 (Cobalamin) Levels
The normal range for vitamin B12 is considered to be above 258 pmol/L (350 ng/L), with levels below 133 pmol/L (180 ng/L) confirming deficiency, and levels between 133-258 pmol/L (180-350 ng/L) considered indeterminate and requiring further testing. 1
Reference Ranges and Interpretation
- Total serum B12 levels below 180 ng/L (133 pmol/L) confirm vitamin B12 deficiency 1
- Levels between 180-350 ng/L (133-258 pmol/L) are considered indeterminate or borderline and may require additional testing 1, 2
- Levels above 350 ng/L (258 pmol/L) suggest vitamin B12 deficiency is unlikely 1
- Some research suggests that optimal B12 status requires levels ≥300 pmol/L, as suboptimal status (below this threshold) occurs in 30-60% of the population 3
Testing Considerations
- Either total B12 (serum cobalamin) or active B12 (holotranscobalamin) can be used as the initial test for suspected B12 deficiency 1
- For indeterminate results (180-350 ng/L), methylmalonic acid (MMA) testing is recommended as a confirmatory test 1, 2
- Elevated MMA levels in patients with borderline B12 levels are diagnostic for vitamin B12 deficiency 2, 4
- Homocysteine levels >20 μmol/L may also suggest B12 deficiency in folate-replete patients 4
Special Considerations for Different Populations
- The prevalence of B12 deficiency increases with age and is significantly higher in those aged ≥60 years 5
- Patients with type 2 diabetes, especially those taking metformin, have higher rates of B12 deficiency 5
- Patients with renal failure may have falsely elevated B12 levels 6
- Chronically ill psychiatric patients have higher rates of B12 deficiency, with 20% showing low levels (<200 pg/ml) and 10% showing deficient levels (<160 pg/ml) 7
Limitations of B12 Testing
- No single laboratory marker is suitable for assessment of B12 status in all patients 4
- Serum B12 assays measure both haptocorrin-bound and transcobalamin-bound B12, but only holotranscobalamin (active B12) is taken up by cells 4
- Functional markers (MMA and homocysteine) may better reflect cellular B12 utilization than abundance markers (serum B12) 4
- Persistently elevated B12 levels (>1,000 pg/mL on two measurements) have been associated with solid tumors, hematologic malignancy, and increased risk of cardiovascular death 2
Clinical Implications
- Neurological symptoms of B12 deficiency may present before hematological abnormalities 1
- Approximately one-third of B12 deficiency cases present without macrocytic anemia 1
- Untreated B12 deficiency can lead to irreversible neurological damage, making early detection crucial 2, 3
- The brain is particularly vulnerable to B12 deficiency; in children, inadequate B12 stunts brain and intellectual development 3
Understanding these reference ranges and their limitations is essential for proper diagnosis and management of vitamin B12 deficiency, which affects approximately 2-3% of adults in the United States 2.