Vitamin B12 Normal Values
Normal vitamin B12 levels are generally defined as >300 pg/mL (>221 pmol/L), with deficiency clearly present at <180 pg/mL (<150 pmol/L) and borderline levels requiring further evaluation between 180-350 pg/mL. 1, 2
Standard Reference Ranges
- Deficient: <180 pg/mL (<150 pmol/L) - requires immediate treatment 1, 2
- Borderline/Indeterminate: 180-350 pg/mL (150-258 pmol/L) - warrants methylmalonic acid (MMA) testing to confirm functional deficiency 1, 2
- Normal: >350 pg/mL (>258 pmol/L) - deficiency unlikely 1
Optimal Target Ranges
- Optimal health: >300 pmol/L (approximately >400 pg/mL) for cardiovascular and musculoskeletal benefits 1
- Stroke prevention: >258 pmol/L - levels below this with elevated homocysteine or MMA define metabolic deficiency 3, 1
- Hemoglobin synthesis in athletes: 400-700 pg/mL - this range optimizes red blood cell parameters 4
Critical Interpretation Pitfalls
Standard serum B12 testing misses functional deficiency in up to 50% of cases, particularly in elderly patients where metabolic deficiency is common despite "normal" serum levels. 1, 5
- In the Framingham Study, 12% had low serum B12, but an additional 50% had elevated MMA indicating metabolic deficiency despite normal B12 levels 1
- Among stroke patients >80 years, 18.1% have metabolic B12 deficiency even with B12 in the "normal" range 3, 1
- Neurological symptoms often present before hematological changes, with approximately one-third of deficiency cases showing no macrocytic anemia 5
When to Measure Additional Markers
For borderline B12 levels (180-350 pg/mL), measure MMA to identify functional deficiency: 1, 2
- MMA has 98.4% sensitivity for B12 deficiency and is more specific than homocysteine 1
- MMA detects an additional 5-10% of patients with B12 deficiency who have low-normal B12 levels 1
- In polyneuropathy patients, 44% had B12 deficiency based solely on abnormal metabolites when serum B12 was normal 1
Active B12 (holotranscobalamin) thresholds: 1
- <25 pmol/L confirms deficiency
- 25-70 pmol/L is indeterminate (requires MMA)
70 pmol/L makes deficiency unlikely
High-Risk Populations Requiring Lower Thresholds
Age ≥60 years: 10.6% have metabolic deficiency overall; 25% of those ≥85 years have B12 <170 pmol/L 3, 1
Post-stroke patients: 17.3% have biochemical or metabolic deficiency; use <258 pmol/L as the threshold for concern 3
Patients on metformin >4 months: significantly higher deficiency rates, especially with doses >1 gm/day 1, 6
Vegetarians/vegans: higher risk due to limited dietary B12 intake 1
Elevated B12 Levels
Persistently elevated B12 (>1,000 pg/mL on two measurements) requires investigation for underlying pathology including hematologic malignancy, liver disease, or critical illness. 7, 2
- Elevated B12 is associated with increased mortality (risk ratios 1.88-5.9) and cancer risk 7
- In critically ill patients, mean B12 of 1719 pg/mL was found in non-survivors versus 1003 pg/mL in survivors 8