Popular drugs that are used to control stomach acid may increase the risk of a serious vitamin deficiency, suggests a new study.

Researchers found people who were diagnosed with vitamin B12 deficiency were more likely to be taking proton-pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs), compared to those not diagnosed with the condition.

The drugs are commonly used to treat conditions like acid reflux - also known as GERD - and peptic ulcers.

“This doesn’t mean people should stop their medications,” Dr. Douglas Corley, the study’s senior author, said. “People take these for good reasons. They improve quality of life and prevent disease.”

“It does raise the question that people who are taking these medications should have their B12 levels checked,” he added.

Corley, a gastroenterologist, is a researcher at the Kaiser Permanente Division of Research in Oakland, California.

Humans typically get vitamin B12 from eating animal products. B12 is also added to many processed foods and can also be purchased as a supplement.

Without enough vitamin B12, people become tired, weak, constipated and anemic, according to the U.S. National Institutes of Health. Ultimately, the vitamin deficiency can lead to nerve damage and dementia.

The problem is that the body absorbs B12 with the help of stomach acid. Because PPIs and H2RAs limit the stomach’s production of acid - and the body needs stomach acid to absorb B12 - the drugs could “theoretically increase the population’s risk of vitamin B12 deficiency,” the researchers write in the Journal of the American Medical Association (JAMA).

Commonly used PPIs include omeprazole (also known as Prilosec), esomeprazole (sold as Nexium), and lansoprazole (Prevacid). H2RAs include cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac).

For the new study, the researchers compared the medical records of nearly 26,000 Northern California residents who were diagnosed with a vitamin B12 deficiency between 1997 and 2011, and nearly 185,000 people with healthy B12 levels.

Among those who were vitamin B12 deficient, 12 percent had been on PPIs for at least two years and about 4 percent were on H2RAs for an equally long period.

By comparison, among people without a diagnosis of B12 deficiency, 7 percent had been on PPIs for two or more years and 3 percent were on H2RAs long-term.

Not only were PPIs and H2RAs tied to an increased risk of vitamin B12 deficiency, but higher doses were more strongly associated with deficiency than weaker ones, the researchers found.

Those findings, Corley said, suggests that people should use the drugs for as short a time as possible, and take the lowest dose that’s still effective.

While the study can’t prove that PPIs or H2RAs caused vitamin B12 deficiency, this isn’t the first study to link anti-acid drugs to complications.

Previous research has tied PPIs to the diarrhea-causing bacteria Clostridium difficile.

“I think the study is interesting because we’re becoming more and more aware that these drugs are being too widely prescribed,” Dr. Peter Green said.

Green, who was not involved with the new study, is a professor of medicine and director of the Celiac Disease Center at Columbia University Medical Center in New York.

In 2012, 14.9 million people in the U.S. received 157 million prescriptions for PPIs, according to the researchers.

“I think it’s just another little piece of evidence that physicians should take notice of to get patients off them,” Green said.

He said lifestyle changes may be an alternative treatment along with a switch to H2RAs, which are less potent and were not as strongly linked to vitamin B12 deficiency.

Corley said patients can ask their doctor if they should be on these drugs, whether they need to be on such a strong dose and if they should be screened for vitamin B12 deficiency.

“It is a cause for concern, but it’s not an emergency for the average person,” he said. “People shouldn’t stop their medication based on this study alone.”

SOURCE: JAMA, online December 10, 2013

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

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.

Jameson R. Lam, MPH; Jennifer L. Schneider, MPH; Wei Zhao, MPH; Douglas A. Corley, MD, PhD