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Reduced serum vitamin B12 (cobalamin) levels have been documented occasionally during long-term treatment with a proton pump inhibitor (PPI) in selected groups of patients. This has largely been confined to patients being treated for Zollinger-Ellison syndrome who have sustained drug-induced achlorhydria, which does not ordinarily occur during treatment with a PPI. An appreciation of normal cobalamin metabolism and the pharmacological action of the PPIs adequately explain the mechanism for this reduction. PPIs do not promote the development of pernicious anemia.