HEALTH NEWS

Study Title:

Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency.

Study Abstract

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.

From press release:

Long-term use of commonly prescribed heartburn and ulcer medications is linked to a higher risk of vitamin B12 deficiency, according to a new study published in the Journal of the American Medical Association.

Left untreated, vitamin B12 deficiency can increase the risk of dementia, nerve damage, anemia, and other medical complications, some of which may be irreversible. Stomach acid aids in vitamin B12 absorption; suppressing the acids can lead to the health-threatening vitamin deficiency.

Researchers examined the electronic health records (including diagnoses, pharmacy orders, and laboratory results) of 25,956 adult Kaiser Permanente patients diagnosed with vitamin B12 deficiency in Northern California between January 1997 and June 2011, and compared them with 184,199 patients without B12 deficiency during the same time period.

This is the first large, population-based study linking vitamin B12 deficiency to acid-suppressing medications, which are among the most commonly used pharmaceuticals in the United States. In 2012, about 15 million people received 157 million prescriptions for a class of anti-acid medications known as proton pump inhibitors (PPIs).

"Patients who took PPI medications for more than two years had a 65 percent increase in their risk of B12 deficiency," said Douglas A. Corley, MD, PhD, a gastroenterologist and research scientist with the Kaiser Permanente Division of Research. "Higher doses also were associated with an increased risk, compared with lower doses. Kaiser Permanente's electronic health records allowed us to look at what happens in the real world for these commonly used medications."

While PPIs and a related class of anti-acid medications called histamine-2-receptor agonists (H2RAs) are usually prescribed by physicians, some are widely available over the counter without a prescription.

Among the 25,956 patients who had vitamin B12 deficiency, 12 percent used PPIs for at least two years, compared with 7.2 percent of the control patients. The impact of taking any daily dosage of H2RA medications was less pronounced but also significant: 4.2 percent of patients with B12 deficiency used these medications versus 3.2 percent of control patients.

"This research raises the question of whether people who are taking acid-depressing medications long term should be screened for vitamin B12 deficiency," Dr. Corley said. "It's a relatively simple blood test, and vitamin supplements are an effective way of managing the vitamin deficiency, if it is found."

Study Information

Lam JR, Schneider JL, Zhao W, Corley DA.
Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency.
JAMA
2013 December
Kaiser Permanente Division of Research