Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors

Aliment Pharmacol Ther. 2008 Jun 1;27(11):1110-21. doi: 10.1111/j.1365-2036.2008.03658.x. Epub 2008 Feb 27.


Background: Proton pump inhibitors (PPIs) may cause cyanocobalamin (vitamin B12) malabsorption, but measuring serum B12 alone may underestimate the prevalence. However, B12 deficiency elevates methylmalonic acid and homocysteine, both additional markers of B12 deficiency.

Aim: To determine the true prevalence of B12 deficiency and whether acid suppression by PPI caused it.

Methods: Sixty-one acid hypersecretors (basal acid output >15 mmol/h), 46 with gastrinoma [Zollinger-Ellison (ZE) syndrome] and 15 without [acid hypersecretor without gastrinoma (pseudo-ZE)], were treated with lansoprazole to determine its long-term (up to 18 years) pharmacological and clinical efficacy and safety, particularly as regards malabsorption of B12.

Results: Of 61 patients, six (10%) had low serum B12. Additional tests uncovered B12 deficiency in 13 (31%) of 41 still-available patients, despite normal serum B12. B12 replacement reduced elevated homocysteine and methylmalonic acid, supporting the diagnosis. Also, measuring both basal and stimulated gastric secretion, we found that acid suppression was neither prolonged nor profound enough to explain the B12 deficiency.

Conclusions: In long-term recipients of PPIs, B12 deficiency was more frequent (29%) than detected by measuring only serum B12, and there was not enough acid suppression to explain this deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / adverse effects*
  • Female
  • Gastric Acid / metabolism*
  • Gastric Acidity Determination
  • Humans
  • Hydrogen-Ion Concentration
  • Lansoprazole
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / adverse effects*
  • Statistics as Topic
  • Time Factors
  • Vitamin B 12 / blood
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / chemically induced*
  • Zollinger-Ellison Syndrome / drug therapy*


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Proton Pump Inhibitors
  • Lansoprazole
  • Vitamin B 12