What medications can affect vitamin B12 levels?

Medications That Affect Vitamin B12 Levels

Several medications can significantly reduce vitamin B12 levels, most notably metformin and proton pump inhibitors (PPIs), which should be monitored in long-term users to prevent deficiency-related complications. 1

Key Medications That Decrease Vitamin B12 Levels

Proton Pump Inhibitors (PPIs)

• Mechanism: Reduce gastric acid secretion necessary for converting dietary protein-bound B12 to free B12 for absorption 2
• Risk factors:
  • Long-term use (>2 years) 3
  • Higher doses (>1.5 pills/day) have stronger association (OR: 1.95; 95% CI: 1.77-2.15) 3
  • Duration of use inversely correlates with B12 levels 2, 4
• Specific PPIs implicated:
  • Omeprazole 5, 4
  • Pantoprazole 6, 7
  • Lansoprazole 6
  • Esomeprazole 1

Metformin

• Mechanism: Interferes with calcium-dependent absorption of the vitamin B12-intrinsic factor complex 1
• Evidence: The lowering effect increases with time, with significantly higher risk for B12 deficiency after 4-5 years of use 1
• Monitoring: Consider periodic measurement of vitamin B12 levels in metformin-treated individuals, especially those with anemia or peripheral neuropathy 1

H2 Receptor Antagonists

• Risk: Associated with 25% increased risk of vitamin B12 deficiency with ≥2 years of use (OR: 1.25; 95% CI: 1.17-1.34) 3
• Examples: Ranitidine 8

Other Medications

• Colchicine 1
• Phenobarbital 1
• Pregabalin 1
• Primidone 1

Clinical Implications and Monitoring

Signs and Symptoms of B12 Deficiency

• Neurological manifestations:
  • Peripheral neuropathy (pins and needles, numbness)
  • Balance issues and falls
  • Impaired gait 1
• Cognitive symptoms:
  • Difficulty concentrating
  • Short-term memory loss
  • "Brain fog" 1
• Hematologic findings:
  • Anemia
  • Macrocytosis 1
• Other symptoms:
  • Fatigue
  • Glossitis
  • Visual disturbances 1

Monitoring Recommendations

• For metformin users:

  • Monitor B12 levels annually in patients who have been on metformin for more than 4 years 1
  • Pay special attention to those with anemia or peripheral neuropathy 1

• For PPI users:

  • FDA drug labels include precautionary notices regarding risks for vitamin B12 deficiencies 1
  • Consider monitoring in long-term users (>2 years), especially with high doses 2, 3
  • Even patients taking multivitamins may experience B12 decline with long-term PPI use 2

Prevention Strategies

• Use PPIs at the lowest effective dose for the shortest duration necessary 2
• Consider periodic reassessment of the need for continued PPI therapy 2
• For patients requiring long-term acid suppression, consider B12 supplementation if levels are declining

Special Considerations

• Patients with multiple risk factors (e.g., elderly patients on both metformin and PPIs) may be at particularly high risk 9
• Vegans or those with limited animal food intake on these medications have compounded risk 9
• Patients with malabsorption syndromes or history of gastrointestinal surgery require closer monitoring 9

Common Pitfalls

• Relying solely on serum B12 levels without considering methylmalonic acid (MMA) for confirmation in indeterminate cases 1
• Failing to recognize neurological symptoms of B12 deficiency, which can occur even with normal hematologic parameters
• Not considering medication-induced B12 deficiency in patients with unexplained neuropathy or cognitive decline

While the American Gastroenterological Association does not currently recommend routine screening for nutrient deficiencies in PPI users, clinicians should remain vigilant about monitoring high-risk patients and those on long-term therapy 1.