Vitamin B12 Normal Range and Diagnostic Thresholds
Vitamin B12 levels should be maintained above 300 pmol/L (approximately 400 pg/mL) for optimal health, with deficiency clearly defined as levels below 150 pmol/L (203 pg/mL). 1
Diagnostic Thresholds
The interpretation of B12 levels follows a tiered approach:
Clear Deficiency
- Serum B12 <150 pmol/L (<203 pg/mL or <180 ng/L): This represents clear deficiency requiring immediate treatment 1, 2
- At this level, no additional testing is needed—treatment should begin immediately 1
Borderline/Indeterminate Range
- Serum B12 180-350 pg/mL (133-258 pmol/L or 200-300 pg/mL): This gray zone requires additional functional testing 1, 2
- Measure methylmalonic acid (MMA) to confirm functional deficiency—MMA >271 nmol/L or >0.26 μmol/L confirms true B12 deficiency 1, 3
- MMA testing is critical because up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by MMA 1
Normal/Optimal Range
- Serum B12 >300 pmol/L (>400 pg/mL): This represents adequate levels for most individuals 1
- Target range 30-44 ng/mL (220-325 pmol/L): This provides optimal benefits for musculoskeletal and cardiovascular health 1
- Levels >350 pg/mL make deficiency unlikely 1
Alternative Testing: Active B12 (Holotranscobalamin)
Active B12 is a more sensitive marker than total B12, measuring only the biologically available form: 1
- <25 pmol/L: Confirms deficiency
- 25-70 pmol/L: Indeterminate—requires MMA testing
- >70 pmol/L: Makes deficiency unlikely
Active B12 costs approximately £18 per test versus £2 for total B12, which limits routine use, but it's more accurate for detecting functional deficiency 1
Critical Pitfalls to Avoid
Standard serum B12 testing misses functional deficiency in up to 50% of cases. 1 The Framingham Study demonstrated that 12% had low serum B12, but an additional 50% had elevated MMA indicating metabolic deficiency despite "normal" B12 levels 1
High-Risk Populations Requiring Lower Thresholds
Certain populations develop metabolic deficiency at higher B12 levels than standard cutoffs suggest:
- Age ≥60 years: 18.1% have metabolic deficiency; 25% of those ≥85 years have B12 <170 pmol/L 1
- Post-stroke patients: 17.3% have biochemical or metabolic deficiency 1
- Autoimmune thyroid disease: 28-68% prevalence of B12 deficiency 1
- Post-bariatric surgery: High risk due to reduced intrinsic factor 1
- Metformin use >4 months: Significantly increased deficiency risk 1
For these populations, consider treatment even with borderline levels (B12 <258 pmol/L) if homocysteine or MMA is elevated 1
Functional Markers for Confirmation
When B12 levels fall in the indeterminate range, functional markers provide definitive diagnosis:
Methylmalonic Acid (MMA)
- 98.4% sensitivity for B12 deficiency 1
- More specific than homocysteine (elevated in only 12.2% of folate-deficient patients versus 91% for homocysteine) 1
- Cost: £11-80 per test 1
- Falsely elevated in: hypothyroidism, renal insufficiency, hypovolemia 1
Homocysteine
- Target <10 μmol/L for optimal cardiovascular outcomes 1, 4
- >15 μmol/L suggests functional B12 deficiency 4
- Less specific than MMA—elevated in folate deficiency and other conditions 1
Laboratory Reference Ranges Vary
Normal reference ranges vary between laboratories and may not be appropriate for all individuals. 1 Most U.S. laboratories use 200-900 pg/mL as the reference range 5, but this doesn't account for individual metabolic needs or functional deficiency.
The UK NDNS defines deficiency as <150 pmol/L (approximately <203 pg/mL), but European guidelines suggest optimal levels may be higher than traditional reference ranges 1
Recommended Daily Intake
- Dietary Reference Intake (DRI): 2.4 μg/day for healthy adults 1
- EFSA Adequate Intake: 4 μg/day for healthy adults (based on biomarker combination) 1
- Pregnancy: 5 μg/day 1
- Lactation: 4.5 μg/day 1
The German Nutrition Society recommends 3 μg/day, while EFSA recommends 4 μg/day based on intakes of 4.3-8.6 μg/day associated with normal functional markers 1