Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome

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 <0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B-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. (C) 1998 by Excerpta Medica, Inc.