December 18, 2013
Long-Term Use of Acid-Reducing Drugs Can Effect B12 Levels

Oakland, CA—A new, large study raises fresh concerns about long-term use of proton pump inhibitors (PPIs) and histamine 2 receptor antagonists.

Kaiser Permanente researchers found that use of the drugs to treat heartburn and ulcers for 2 years or more was linked to vitamin B12 deficiency. The study was published recently in the Journal of the American Medical Association.

Untreated vitamin B12 deficiency can increase the risk of dementia, nerve damage, anemia, and other medical complications, some of which may be irreversible, according to the article’s background. It suggests that the drugs’ suppression of stomach acid can reduce absorption of vitamins.

Last year, about 15 million patients received 157 million prescriptions for PPIs, which reduce the production of acid by blocking certain enzymes in the stomach wall. In addition to prescriptions, PPIs and histamine-2-receptor agonists (H2RAs) are readily available OTC without a prescription.

For the study, researchers examined diagnoses, pharmacy orders, and laboratory results for 25,956 adult Kaiser Permanente patients diagnosed with vitamin B12 deficiency in Northern California between January 1997 and June 2011. That group was compared to 184,199 patients without B12 deficiency during the same time period.

Researchers found 12% of the study group with B12 deficiency used PPIs for at least 2 years, compared with 7.2% of the control patients. The effect of H2RA medication was not as strong but still significant with 4.2% of users developing B12 deficiency compared to 3.2% of the control group.

“Patients who took PPI medications for more than two years had a 65% increase in their risk of B12 deficiency,” said co-author Douglas A. Corley, MD, PhD. “Higher doses also were associated with an increased risk, compared with lower doses.”

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

Results also indicated that doses greater than 1.5 PPI pills/day were more strongly associated with vitamin B12 deficiency than were doses less than 0.75 pills/day. Magnitude of the association was stronger in women and younger age groups with more potent acid suppression (PPIs vs. H2RAs), but the association decreased after discontinuation of use, according to the researchers, who added that there was no significant trend with increasing duration of use past the study period.

“These findings do not recommend against acid suppression for persons with clear indications for treatment, but clinicians should exercise appropriate vigilance when prescribing these medications and use the lowest possible effective dose,” the authors write. “These findings should inform discussions contrasting the known benefits with the possible risks of using these medications.”

U.S. Pharmacist Social Connect