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Gastric acid medications like Zantac linked to vitamin B12 deficiency

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Long term use of acid-suppressing medication may lead to malabsorption of vitamin B12.

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Vitamin B12 is necessary for the production of red blood cells and plays an important role in maintaining the health of nerve cells and in the formation of genetic material. Deficiency of vitamin B12 affects both men and women in equal numbers, initially causing symptoms like dizziness and fatigue. Untreated deficiency can result in anemia and damage to the nervous system.

Proton pump inhibitors (PPIs) such as Prilosec and histamine 2 receptor antagonists (H2RAs) which includes Pepcid 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.

Scientists from Kaiser Permanente Division of Research studied the link between the use of PPIs and H2RAs and vitamin B12.

For the study, researchers examined electronic health records (pharmacy, laboratory, and diagnostic databases) within the Kaiser Permanente Northern California population of 25,956 patients with a diagnosis of vitamin B12 deficiency between January 1997 and June 2011 and also included 184,199 patients without vitamin B12 deficiency.

Among the patients with vitamin B12 deficiency, 3120 (12.0%) used PPIs and 1087 (4.2%) used H2RAs (without any PPI use) for two years and 21 749 (83.8%) who had not used either PPIs or H2RAs.

The results showed those who received a two years or more supply of PPIs and H2RAs were linked with risk for vitamin B12 deficiency. Doses over 1.5 PPI pills/day were more strongly associated with vitamin B12 deficiency than were doses less than 0.75 pills/day.

The results also showed that the link was strong among women and younger age groups with more potent acid suppression (PPIs vs. H2RAs), however, the link between the PPls and H2RAs had decreased after discontinuing the medication.

PPIs and H2RAs are usually prescribed by physicians; some are widely available over the counter without a prescription.

In their conclusion the team writes “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.”

The researchers conclude "We cannot completely exclude residual confounding [factors besides the drugs] as an explanation for these findings, but, at minimum, the use of these medications identifies a population at higher risk of B12 deficiency, independent of additional risk factors. 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. These findings should inform discussions contrasting the known benefits with the possible risks of using these medications.”

Dr. Douglas A. Corley, MD, PhD, MPH, a gastroenterologist and research scientist with the Kaiser Permanente Division of Research, commented "This research raises the question of whether people who are taking acid-depressing medications long term should be screened for vitamin B12 deficiency.” "It's a relatively simple blood test, and vitamin supplements are an effective way of managing the vitamin deficiency, if it is found."

This study is published in the Journal of the American Medical Association.

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