Lam JR, Schneider JL, Zhao W, Corley DA,
JAMA. 2013; 310(22):2435-2442.
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.
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.
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.
Vitamin B12 deficiency is relatively common, especially among older adults; it has potentially serious medical complications if undiagnosed. Left untreated, vitamin B12 deficiency can lead to dementia, neurologic damage, anemia, and other complications, which may be irreversible. According to data from the National Health and Nutrition Examination Survey, 3.2% of adults older than 50 years are estimated to have low serum vitamin B12 levels.1 Other studies have reported prevalence rates of 5% to 15%, although these may be underestimates of the true prevalence in some population subgroups.2,3 Thus, identifying modifiable risk factors for vitamin B12 deficiency is of significant public health importance.
Acid inhibitors are among the most commonly used pharmaceuticals in the United States. In 2012, 14.9 million patients received 157 million prescriptions for proton pump inhibitors (PPIs); thus, use of PPIs could theoretically increase the population’s risk of vitamin B12 deficiency.4 Gastric acid is required to cleave vitamin B12 from ingested dietary proteins for the essential vitamins to be absorbed, and it is produced by the same cells that produce intrinsic factor, a compound required for vitamin B12 absorption.5 Thus, PPIs and histamine 2 receptor antagonists (H2RAs), which suppress the production of gastric acid, may lead to malabsorption of vitamin B12.
Studies examining the relationship of PPI use and vitamin B12 deficiency have focused primarily on small groups of elderly individuals and yielded inconsistent results. Although some studies suggested that acid suppressive medications are associated with lower vitamin B12 levels in older populations,6-9 others found no association.10-15 To our knowledge, no large population-based studies exist. Therefore, we performed a case-control study to evaluate the relationship between the use of acid-suppressing prescription medications and the risk of vitamin B12 deficiency within a large, community-based population.
Link to abstract on PubMed: Lam JR, et al; JAMA. 2013;310(22):2435-2442.