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Long-term use of common heartburn and ulcer medications linked to vitamin B12 deficiency

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 protein 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."

Kaiser Permanente can conduct transformational health research such as this study in part because it has the largest private patient-centered electronic health system in the world. The organization's electronic health record system, Kaiser Permanente HealthConnect®, securely connects 9.1 million patients to 16,000 physicians in almost 600 medical offices and 38 hospitals. It also connects Kaiser Permanente's research scientists to one of the most extensive collections of longitudinal medical data available, facilitating studies and important medical discoveries that shape the future of health and care delivery for patients and the medical community.

In addition to Dr. Corley, co-authors of the study were Jameson R. Lam, MPH, Jennifer L. Schneider, MPH, and Wei Zhao, MPH, all of the Kaiser Permanente Division of Research in Oakland, Calif.

About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR's 550-plus staff is working on more than 250 epidemiological and health services research projects. For more information, visit and follow us @KPDOR.

About Kaiser Permanente

Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America's leading health care providers and not-for-profit health plans. Founded in 1945, our mission is to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve 9.1 million members in eight states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to

Cyrus Hedayati | EurekAlert!
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