What are the signs of vitamin B12 deficiency?

Signs and Symptoms of Vitamin B12 Deficiency

Vitamin B12 deficiency presents with a constellation of hematologic, neurologic, and psychiatric manifestations that can cause permanent degenerative lesions of the spinal cord if left untreated for longer than 3-3 months. 1, 2

Clinical Manifestations

Hematologic Signs

• Megaloblastic anemia
• Fatigue
• Pallor
• Elevated MCV (macrocytosis)
• Thrombocytopenia

Neurological Manifestations

• Peripheral neuropathy (numbness, tingling in hands and feet)
• Ataxia (difficulty with balance and coordination)
• Abnormal movements (may appear before or after treatment initiation) 3
• Subacute combined degeneration of the spinal cord (if untreated)
• Muscle weakness and hypotonia

Cognitive and Psychiatric Symptoms

• Memory problems and cognitive dysfunction (especially in elderly) 1
• Depression and anxiety 1
• Brain fog 4
• Disorientation 5

Other Symptoms

• Failure to thrive (particularly in infants) 3
• Glossitis (smooth, red, sore tongue)
• Developmental delay or regression in infants 3
• Severe fatigue 5
• Neuropathic pain 5

High-Risk Populations

B12 deficiency is particularly common in:

• Elderly (10-40% prevalence) 1
• Vegetarians and vegans 2, 3
• Patients with malabsorptive conditions 4
• Patients who have undergone gastric or intestinal surgery 5
• Patients taking certain medications:
  • Metformin 1, 4
  • Proton pump inhibitors 4
  • Most antibiotics (can interfere with B12 testing) 2
• Patients with atrophic gastritis 6
• Pregnant and lactating women following vegetarian diets 2, 3
• Infants exclusively breastfed by mothers with B12 deficiency 2, 3

Diagnostic Approach

Initial testing should use either:

• Total serum B12 (cobalamin) or
• Active B12 (serum holotranscobalamin)

Interpretation thresholds 1:

• Total B12 <180 ng/L or active B12 <25 pmol/L: Confirmed deficiency
• Total B12 180-350 ng/L or active B12 25-70 pmol/L: Indeterminate (requires further testing)
• Total B12 >350 ng/L or active B12 >70 pmol/L: Unlikely deficiency

For borderline results (180-350 pg/mL), methylmalonic acid measurement is warranted, with elevation confirming B12 deficiency 4.

Important Clinical Considerations

1. Early detection is crucial: Vitamin B12 deficiency allowed to progress beyond 3 months may produce permanent degenerative lesions of the spinal cord 2.

2. Folic acid warning: Doses of folic acid >0.1 mg/day may mask B12 deficiency by correcting the anemia while allowing neurological damage to progress 2. Never administer folic acid before treating B12 deficiency 1.

3. Atypical presentation in elderly: Older patients may lack classic signs like megaloblastic anemia and instead present primarily with neuropsychiatric symptoms that might be mistakenly attributed to aging 5, 6.

4. Medication interactions: Several medications can affect B12 absorption or testing, including metformin, proton pump inhibitors, and antibiotics 1, 2, 4.

5. Normal B12 levels don't rule out deficiency: Some patients may have normal serum B12 levels but still have functional deficiency, requiring measurement of methylmalonic acid and homocysteine 5.

6. Protein-bound vs. crystalline B12: Elderly patients often have reduced absorption of protein-bound B12 due to atrophic gastritis but maintain ability to absorb crystalline B12 from supplements 6.

By recognizing these signs and symptoms early, particularly in high-risk populations, clinicians can prevent the potentially irreversible neurological complications of vitamin B12 deficiency.