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Vitamin B12 (Cobalamin, Cyanocobalamin)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Essential Water-Soluble Vitamin - Required for DNA Synthesis, Neurological Function & Red Blood Cell Formation)

Synonyms

  • Vitamin B12
  • Cobalamin
  • Cyanocobalamin
  • Hydroxocobalamin
  • Methylcobalamin
  • Adenosylcobalamin
  • Anti-pernicious anemia factor

Units of Measurement

  • pmol/L
  • pg/mL
  • pg/dL
  • pg/100 mL
  • pg%
  • pg/L
  • ng/L

Unit Conversions

Molecular Weight of Vitamin B12 ≈ 1355 g/mol (varies by form)

pmol/L ↔ pg/mL

1 pmol/L=1.355 pg/mL1\ \text{pmol/L} = 1.355\ \text{pg/mL}1 pmol/L=1.355 pg/mL 1 pg/mL=0.738 pmol/L1\ \text{pg/mL} = 0.738\ \text{pmol/L}1 pg/mL=0.738 pmol/L

pg/dL → pg/mL

1 pg/dL=0.01 pg/mL1\ \text{pg/dL} = 0.01\ \text{pg/mL}1 pg/dL=0.01 pg/mL

pg/mL ↔ pg/L / ng/L

1 pg/mL=1000 pg/L=1 ng/L1\ \text{pg/mL} = 1000\ \text{pg/L} = 1\ \text{ng/L}1 pg/mL=1000 pg/L=1 ng/L

pg/100 mL = pg% = pg/dL

Description

Vitamin B12 is a water-soluble cobalt-containing vitamin essential for:

  • DNA synthesis (via methionine synthase)
  • Myelin formation (neurological function)
  • Erythropoiesis (RBC production)
  • Fatty acid & amino-acid metabolism

Humans acquire B12 only from animal-derived foods.
Absorption requires:

  1. Intrinsic Factor (IF) from gastric parietal cells
  2. Terminal ileum for uptake
  3. Normal pancreatic enzymes
  4. Transcobalamin II for transport

B12 stores last 2–5 years, so deficiency develops slowly-except in malabsorption.

Physiological Role

1. DNA Synthesis

Cobalamin is required to convert homocysteine → methionine.
Deficiency → impaired thymidine synthesis → megaloblastic anemia.

2. Neurological Function

B12 is essential for:

  • Myelin synthesis
  • Neurotransmitter balance
  • Spinal cord integrity

Deficiency may cause irreversible neuropathy.

3. Hematologic Function

Deficiency → ineffective erythropoiesis → macrocytosis.

4. Metabolism

Coenzyme for:

  • Methylmalonyl-CoA mutase
  • Methionine synthase

Clinical Significance

LOW VITAMIN B12

Most important clinical aspect.

Hematologic

  • Macrocytic anemia
  • High MCV
  • Pancytopenia (late)
  • Hypersegmented neutrophils

Neurological

  • Peripheral neuropathy
  • Ataxia
  • Paresthesias
  • Loss of vibration/position sense
  • Subacute combined degeneration of spinal cord
  • Cognitive decline / dementia
    Neurological deficits can be irreversible.

GI Symptoms

  • Glossitis (“beefy red tongue”)
  • Anorexia
  • Weight loss

Causes of Deficiency

1. Pernicious Anemia

Most common in adults.
Autoantibodies destroy parietal cells → ↓ Intrinsic Factor.

2. Malabsorption

  • Ileal resection / Crohn’s disease
  • Celiac disease
  • Pancreatic insufficiency
  • Bacterial overgrowth (SIBO)
  • Tapeworm (Diphyllobothrium latum)

3. Dietary Deficiency

  • Strict vegans
  • Elderly
  • Malnutrition

4. Drug-Induced

  • Metformin
  • PPIs / H2 blockers
  • Nitrous oxide (N₂O anesthesia) → inactivation of B12

5. Increased Requirement

  • Pregnancy
  • Hyperthyroidism

Biochemical Markers

  • ↑ Methylmalonic acid (MMA)
  • ↑ Homocysteine

HIGH VITAMIN B12

Less common.

Causes:

  • Liver disease (leakage)
  • Myeloproliferative disorders
  • Leukemia
  • Renal failure
  • High-dose supplementation
  • Transcobalamin II deficiency (paradoxical high level)

High B12 is not harmful by itself-usually indicates underlying disease.

Reference Intervals

(Tietz 8E + Mayo + ARUP + BSH hematology guidelines)

Serum Vitamin B12

  • 200 – 900 pg/mL
    (= 148 – 665 pmol/L)

Borderline

  • 150 – 300 pg/mL
    → check MMA and homocysteine

Deficiency

  • <150 pg/mL (<110 pmol/L)

Neurological symptoms can occur even at “low-normal” levels

Diagnostic Uses

1. Evaluation of Macrocytic Anemia

Tied with folate testing.

2. Neurological Disorders

Rule out reversible causes of neuropathy/dementia.

3. Pernicious Anemia Diagnosis

Combine B12 with:

  • Anti-intrinsic factor antibodies
  • Anti-parietal cell antibodies

4. Monitoring After Bariatric Surgery

Risk of severe malabsorption.

5. Elderly Population Screening

Common subclinical deficiency.

6. Pregnancy & Lactation

Increased demand.

7. Assessing Malabsorption Syndromes

Crohn’s, celiac, pancreatic disease.

Analytical Notes

  • Serum B12 fluctuates; borderline values need MMA.
  • Hemolysis has minimal effect; bilirubin may interfere depending on platform.
  • LC-MS/MS or immunoassays are standard.
  • Methylmalonic acid is more sensitive for early deficiency.

Clinical Pearls

  • Neuropathy may occur without anemia.
  • B12 deficiency + high folate intake → worsened neurological damage.
  • Always treat suspected deficiency immediately-do not wait for confirmatory testing in symptomatic patients.
  • Metformin causes B12 depletion → annual monitoring recommended.
  • In elderly, low B12 is associated with falls, depression, and cognitive decline.

Interesting Fact

Vitamin B12 is the largest and most structurally complex vitamin known, containing a rare cobalt atom at its core.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Vitamins
  2. British Society for Haematology (BSH) - B12/Folate Guidelines
  3. NIH Office of Dietary Supplements - Cobalamin
  4. Mayo Clinic Laboratories - Vitamin B12
  5. ARUP Consult - Vitamin & Anemia Evaluation
  6. WHO Micronutrient Guidelines

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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