Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B₁₂ Deficiency in Zollinger-Ellison...

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B₁₂ (VB₁₂) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB₁₂ deficiency, determined by assessing serum VB₁₂ levels, measurements of VB₁₂ body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB₁₂ deficiency with significantly lower serum and body VB₁₂ levels (p < 0.0001). The presence of VB₁₂ deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB₁₂ deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB₁₂ levels and decreased VB₁₂-body stores, which can result in VB₁₂ deficiency.