What is a normal level of vitamin B12 (cobalamin)?

Normal Levels of Vitamin B12

According to the most recent NICE guidelines, a normal total B12 (serum cobalamin) level is greater than 350 ng/L (258 pmol/L), while a normal active B12 (serum holotranscobalamin) level is greater than 70 pmol/L. 1

Understanding Vitamin B12 Testing

There are two main tests used to measure vitamin B12 status:

1. Total B12 (serum cobalamin):

   • Normal: >350 ng/L (258 pmol/L)
   • Indeterminate range: 180-350 ng/L (133-258 pmol/L)
   • Deficient: <180 ng/L (133 pmol/L)

2. Active B12 (serum holotranscobalamin):

   • Normal: >70 pmol/L
   • Indeterminate range: 25-70 pmol/L
   • Deficient: <25 pmol/L

Interpretation of B12 Test Results

The interpretation of B12 test results can be summarized as follows 1:

Total B12 concentrations	Active B12 concentrations	Interpretation
<180 ng/L (133 pmol/L)	<25 pmol/L	Confirmed vitamin B12 deficiency
180-350 ng/L (133-258 pmol/L)	25-70 pmol/L	Indeterminate result - possible vitamin B12 deficiency
>350 ng/L (258 pmol/L)	>70 pmol/L	Vitamin B12 deficiency unlikely

Confirmatory Testing

When B12 test results fall in the indeterminate range, additional testing may be warranted:

• Methylmalonic acid (MMA) is recommended as a confirmatory test for patients with indeterminate B12 levels who show symptoms or signs of B12 deficiency 1
• MMA provides a more reliable functional assessment of B12 status but is more expensive and less readily available than standard B12 testing

Clinical Implications

Understanding normal B12 levels is important because:

• B12 deficiency can lead to serious health consequences including neurological damage, cognitive impairment, anemia, and increased cardiovascular risk 1
• Both biochemical B12 deficiency (below reference range) and metabolic B12 deficiency (B12 <258 pmol/L with elevated homocysteine or MMA) are common, especially in older adults 1
• Metabolic B12 deficiency is frequently missed when only serum B12 is measured and falls within the "normal" reference range 1

Special Considerations

• B12 deficiency is particularly common in certain populations:

  • Older adults (18.1% of patients >80 years may have metabolic B12 deficiency) 1
  • Vegetarians and vegans 1, 2
  • Patients with certain medical conditions (atrophic gastritis, celiac disease, autoimmune conditions) 1
  • Patients taking medications such as metformin, colchicine, H2 receptor antagonists 1

• When evaluating B12 status in these high-risk groups, clinicians should maintain a high index of suspicion even when B12 levels are in the low-normal range

Remember that early identification and treatment of B12 deficiency is essential to prevent potentially irreversible neurological damage and other complications.