What are normal vitamin B12 (cobalamin) levels?

Normal Vitamin B12 Levels

Normal vitamin B12 levels are generally defined as ≥300 pg/mL (≥221 pmol/L), with deficiency diagnosed at <180 pg/mL (<133 pmol/L) and borderline levels between 180-350 pg/mL (133-258 pmol/L). 1, 2

Standard Reference Ranges

• Deficiency: <180 pg/mL (<133 pmol/L) 1
• Borderline/Indeterminate: 180-350 pg/mL (133-258 pmol/L) 1, 3
• Normal: ≥300 pg/mL (≥221 pmol/L) 2
• UK NDNS defines deficiency: <150 pmol/L (approximately <203 pg/mL) 4

The American Family Physician guidelines establish <180 pg/mL as diagnostic for deficiency, while borderline levels (180-350 pg/mL) warrant further testing with methylmalonic acid (MMA) to confirm functional B12 status. 1

Important Caveats About "Normal" Levels

Standard total B12 tests may not accurately reflect functional B12 status—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid. 4

Limitations of Total Serum B12

• Total B12 measures both active and inactive forms, not just the biologically available vitamin 4
• Active B12 (holotranscobalamin) is more sensitive but not routinely tested 5, 4
• Normal reference ranges vary between laboratories and may not be appropriate for all individuals 4

When to Suspect Functional Deficiency Despite "Normal" Levels

For patients with B12 levels in the borderline range (180-350 pg/mL) or with persistent symptoms despite normal levels, measure: 1, 4

• Methylmalonic acid (MMA): Elevated MMA confirms functional B12 deficiency even with normal serum B12 1, 4
• Homocysteine: Elevated levels suggest functional deficiency 5, 4
• Holotranscobalamin (active B12): More sensitive marker of biologically available B12 5, 4

Geographic and Guideline Variations

European guidelines recommend higher intake levels than UK/US standards, suggesting optimal levels may be higher than traditional reference ranges. 5

• UK RNI: 1.5 µg/day (lowest in Europe) 5
• German Nutrition Society: 3 µg/day 5
• EFSA guideline: 4 µg/day, based on intakes of 4.3-8.6 µg/day associated with normal functional markers 5

Recent Danish studies found that 6 µg/day intake was required to normalize all B12 parameters (serum cobalamin, MMA, holotranscobalamin, and homocysteine) in individuals with normal absorptive capacity. 5

Elevated B12 Levels

Vitamin B12 levels persistently >1,000 pg/mL (>738 pmol/L) on two measurements warrant investigation for underlying pathology, including hematologic malignancy, liver disease, or myeloproliferative disorders. 1, 3

• Elevated B12 (>350 ng/258 pmol per liter) is not indicative of deficiency and requires different diagnostic approach 3
• Associated with increased mortality and cancer risk (risk ratios 1.88-5.9) 3
• Common causes include liver disease, hematologic malignancies (particularly myeloid neoplasms with PDGFRA fusion genes), and active B12 supplementation 3

Clinical Context for Interpretation

Metabolic B12 deficiency is very common in high-risk populations despite "normal" serum levels. 5

High-Risk Populations Requiring Lower Threshold for Testing

• Age ≥60 years: 18.1% have metabolic deficiency; 25% of those ≥85 years have B12 <170 pmol/L 5, 4
• Post-stroke patients: 17.3% have biochemical or metabolic deficiency 5
• Vegetarians/vegans: Limited dietary B12 intake 4
• Metformin users >4 months: Significantly higher deficiency rates 4, 2
• Patients on proton pump inhibitors, H2 blockers, or other medications affecting absorption 4

In stroke patients specifically, a serum B12 <258 pmol/L with elevated homocysteine or MMA defines metabolic deficiency, which was present in 10.6% of patients overall and 18.1% of those >80 years. 5