Normal Range of Vitamin B12 in Adults
The normal range of vitamin B12 in adults is generally defined as ≥300 pg/mL (≥221 pmol/L), with deficiency confirmed at levels <180 pg/mL (<133 pmol/L) and borderline levels between 180-350 pg/mL (133-258 pmol/L). 1, 2, 3
Standard Reference Ranges
- Deficiency: <180 pg/mL (<133 pmol/L) 1, 3
- Borderline/Indeterminate: 180-350 pg/mL (133-258 pmol/L) 2, 3, 4
- Normal: ≥300 pg/mL (≥221 pmol/L) 1, 4
The UK National Diet and Nutrition Survey (NDNS) uses a slightly lower cutoff, defining deficiency as <150 pmol/L (approximately <203 pg/mL). 2
Important Caveats About Standard Testing
Standard total serum B12 measurements may not accurately reflect functional B12 status, as up to 50% of patients with "normal" serum B12 levels can have metabolic deficiency when assessed by more sensitive markers. 2
When to Use Additional Testing
For borderline levels (180-350 pg/mL), measurement of methylmalonic acid (MMA) is recommended, as elevated MMA confirms functional B12 deficiency even when serum B12 appears normal. 2, 3
Active B12 (holotranscobalamin) measures the biologically active form available for cellular use and is more sensitive than total B12, though not routinely tested. Deficiency is confirmed when active B12 is <25 pmol/L. 1, 2, 5
Population-Specific Considerations
Elderly Adults (≥60 years)
In older adults, metabolic B12 deficiency is substantially more common:
- 18.1% of adults >80 years have metabolic deficiency 2
- 25% of adults ≥85 years have B12 <170 pmol/L 2
- The prevalence of deficiency increases significantly with age 4
High-Risk Populations
Certain groups warrant testing even with levels in the "normal" range if clinical suspicion exists:
- Post-stroke patients (17.3% have biochemical or metabolic deficiency) 2
- Patients on metformin, especially >4 months or doses >1 gm/day 2, 4
- Patients on proton pump inhibitors or H2 receptor antagonists 2
- Vegetarians/vegans (limited dietary B12 intake) 2
- Post-bariatric surgery patients 2
Clinical Implications
Neurological symptoms often present before hematological changes and can become irreversible if untreated, with cognitive difficulties, memory problems, and peripheral neuropathy being common manifestations. 2
Approximately one-third of B12 deficiency cases show no macrocytic anemia, making reliance on complete blood count alone inadequate for diagnosis. 2, 5
For patients with clinical symptoms suggestive of B12 deficiency (fatigue, cognitive difficulties, neuropathy, glossitis) and borderline or low-normal B12 levels, functional testing with MMA and/or homocysteine should be strongly considered rather than accepting the serum B12 as reassuring. 2, 3