Effect of Long-Term Gastric Acid Suppressive Therapy on Serum Vitamin B12 Levels in Patients with Zollinger-Ellison Syndrome

Abstract Background and aims: Long-term treatment with H + -K + -adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B 12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B 12 levels in patients with Zollinger-Ellison syndrome. Methods: In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H 2 -receptor antagonists (n = 20), serum vitamin B 12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B 12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. Results: The mean duration of omeprazole treatment was 4.5 years, and for H 2 -receptor antagonists 10 years. Vitamin B 12 levels, but not serum folate levels or any hematological parameter, were significantly ( P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion ( P = 0.0014) or complete achlorhydria ( P 12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B 12 levels ( P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B 12 levels during follow-up. Conclusions: Long-term omeprazole treatment leads to significant decreases in serum vitamin B 12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H + -K + -ATPase inhibitors should have serum vitamin B 12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H + -K + -ATPase inhibitors may develop B 12 deficiency.