A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults

J Clin Epidemiol. 2004 Apr;57(4):422-8. doi: 10.1016/j.jclinepi.2003.08.015.


Objective: Acid-suppressant drugs are commonly prescribed for elderly patients, a population in which vitamin B(12) deficiency is a common disorder. The purpose of this study was to examine the possible association between use of prescription histamine H-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) and vitamin B(12) deficiency in older adults.

Study design and setting: This was a case-control study in a University-based geriatric primary care setting. Among patients aged 65 years or older with documented serum vitamin B(12) studies between 1990 and 1997, 53 vitamin B(12)-deficient cases were compared with 212 controls for past or current use of prescription H2RA/PPI according to information in subjects' medical records.

Results: Controlling for age, gender, multivitamin use, and Helicobacter pylori infection, chronic (#10878;12 months) current use of H2RA/PPI was associated with a significantly increased risk of vitamin B(12) deficiency (OR 4.45; 95% CI 1.47-13.34). No association was found between past or short-term current use of H2RA/PPI and vitamin B(12) deficiency.

Conclusion: These findings support an association between chronic use of H2RA/PPI by older adults and development of vitamin B(12) deficiency. Additional studies are needed to confirm these findings.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / adverse effects*
  • Case-Control Studies
  • Drug Administration Schedule
  • Female
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / adverse effects*
  • Humans
  • Male
  • Odds Ratio
  • Proton Pump Inhibitors*
  • Vitamin B 12 Deficiency / chemically induced*


  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors