Can pantoprazole (proton pump inhibitor) cause a vitamin B12 deficiency?

Pantoprazole and Vitamin B12 Deficiency

Pantoprazole can cause vitamin B12 deficiency with long-term use (more than 3 years), and the FDA drug label includes warnings about this potential adverse effect. 1

Risk of B12 Deficiency with Pantoprazole

• The FDA drug label for pantoprazole specifically warns that low vitamin B12 levels can occur in people who have taken pantoprazole for a long time (more than 3 years) 1
• The FDA recommends healthcare providers monitor for symptoms of B12 deficiency including shortness of breath, lightheadedness, irregular heartbeat, muscle weakness, pale skin, fatigue, mood changes, and tingling or numbness in extremities 1
• The American Gastroenterological Association acknowledges this risk, as FDA drug labels include precautionary notices regarding vitamin B12 deficiencies with proton pump inhibitor (PPI) use 2

Evidence Quality and Conflicting Findings

• Observational studies show mixed results regarding PPI use and B12 deficiency:

  • A large nested case-control study found that higher doses of PPIs (>1.5 pills daily) had a stronger association with B12 deficiency (OR: 1.95; 95% CI: 1.77,2.15) compared to lower doses in individuals using PPIs for ≥2 years 2
  • Duration of PPI use has been inversely correlated with vitamin B12 levels, even among individuals taking multivitamins 2

• However, randomized controlled trials show different results:

  • Analysis of 5-year data from two randomized multicenter studies found no significant differences in serum vitamin B12 levels between PPI users and controls 2
  • These trials had limitations: they were not structured to detect clinically relevant changes, relied solely on serum B12 levels, and did not consistently assess dietary intake or supplement use 2

Recent Research on Pantoprazole Specifically

• A 2023 study found that long-term pantoprazole users (>12 months) did not show significant differences in blood vitamin B12 levels compared to controls 3
• However, a 2022 cohort study found that vitamin B12 levels were significantly lower in patients taking omeprazole compared to those taking pantoprazole, suggesting pantoprazole might have less impact on B12 status 4
• A 2021 study found that approximately 50% of elderly patients on prolonged acid suppression therapy (including pantoprazole) had either deficient (<200 pg/ml) or insufficient (200-300 pg/ml) serum vitamin B12 levels 5

Clinical Monitoring Recommendations

• Despite the potential risk, the American Gastroenterological Association does not currently recommend routine screening for vitamin B12 status or providing supplementation to all individuals taking PPIs 2
• This recommendation is based on the lack of conclusive causal evidence and heterogeneous findings across studies 2
• However, monitoring should be considered for:
  • Patients on pantoprazole for more than 3 years 1
  • Elderly patients, who may be at higher risk 6
  • Patients presenting with symptoms of B12 deficiency 1

Risk Factors and Special Populations

• Patients taking both metformin and PPIs may have compounded risk, as both medications can independently affect B12 absorption 7
• Elderly patients appear to be at higher risk for developing B12 deficiency with PPI use 5
• A 2022 study found that men between ages 18-40 had a higher likelihood of developing B12 deficiency with long-term PPI use 4

Practical Management

• For patients requiring long-term pantoprazole therapy, consider:
  • Periodic assessment of vitamin B12 status after 3 years of continuous use 1
  • Monitoring for clinical symptoms of B12 deficiency 1
  • Using the lowest effective dose of pantoprazole to minimize potential nutritional impacts 2
  • Reassessing the need for continued PPI therapy regularly to ensure judicious long-term use 6