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Original Investigation |

Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency

Jameson R. Lam, MPH1; Jennifer L. Schneider, MPH1; Wei Zhao, MPH1; Douglas A. Corley, MD, PhD1
[+] Author Affiliations
1Division of Research, Kaiser Permanente, Oakland, California
JAMA. 2013;310(22):2435-2442. doi:10.1001/jama.2013.280490.
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Published online

Importance  Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies.

Objective  To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States.

Design, Setting, and Patients  We evaluated the association between vitamin B12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25 956 patients having incident diagnoses of vitamin B12 deficiency between January 1997 and June 2011 with 184 199 patients without B12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases.

Main Outcomes and Measures  Risk of vitamin B12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression.

Results  Among patients with incident diagnoses of vitamin B12 deficiency, 3120 (12.0%) were dispensed a 2 or more years’ supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years’ supply of H2RAs (without any PPI use), and 21 749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13 210 (7.2%) were dispensed a 2 or more years’ supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years’ supply of H2RAs (without any PPI use), and 165 092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years’ supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) and a 2 or more years’ supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48-1.78]; P = .007 for interaction).

Conclusions and Relevance  Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.

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Figure.
Association Between a 2 or More Years’ Supply of Proton Pump Inhibitors (PPIs) and a Diagnosis of Vitamin B12 Deficiency, Stratified by Time Since Most Recent Prescription

Patients in the current user category received their last PPI prescription in the last year prior to the index date; those in the recent user category received their last PPI prescription 1 to 1.9 years prior to the index date; those in the former user category received their last PPI prescription 2 to 2.9 years prior to the index date; those in the remote former user category received their last PPI prescription 3 or more years prior to the index date.

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