Adverse Effects of Proton Pump Inhibitor Drugs: Clues and Conclusions

Denis M. McCarthy


Curr Opin Gastroenterol. 2010;26(6):624-631. 

In This Article

Enteric Malabsorption

Inhibition of gastric secretion of acid, pepsin, intrinsic factor, vitamin C and other substances has given rise to concerns about a number of possibly resulting clinical deficiency states.


Both hydrochloric and ascorbic acids secreted by the stomach are involved in converting ferric to ferrous iron and maintaining it in the reduced state. Ascorbic acid, whether of dietary or gastric origin, also chelates nonheme iron and keeps it in solution until absorbed. PPIs inhibit secretion of both substances. In addition, vitamin C is unstable at high pH and is readily converted to dehydro-ascorbic acid in inflamed H. pylori-infected mucosa. Thus, conditions for iron absorption are significantly suboptimal during PPI therapy, particularly in the presence of H. pylori gastritis. Despite use of PPIs to reduce iron absorption in hemochromatosis and observations that omeprazole inhibited the correction of iron deficiency anemia by oral iron until the PPI was stopped, there has been no prospective study of the association of PPI therapy with iron deficiency anemia and no proper trial of the efficacy of oral iron administration during PPI therapy.[23] PPI use has also been linked with the possible development of painful restless legs syndrome, long associated with iron deficiency and low serum ferritin concentrations. In my opinion, iron deficiency is the most important of the uninvestigated potential adverse effects of PPI therapy, especially in the elderly and the poorly nourished, and is in urgent need of prospective studies.