Nutritional Consequences of Long-term Acid Suppression; Are They Clinically Important?

David A. Johnson


Curr Opin Gastroenterol. 2016;32(2):136-140. 

In This Article


Gastric acid plays an essential role in the absorption of dietary iron. The majority of dietary iron is consumed as nonheme iron (ferric, Fe3+), which must be reduced to the ferrous (Fe2+) form to be absorbed by the divalent metal transporter-1 in the duodenum.[8] This process is mediated by not only gastric acid, but also vitamin C, which additionally serves as a reducing and chelating agent to prevent the formation of insoluble compounds.[9] As such, long-term therapy with PPIs may theoretically lead to impaired iron absorption through hypochlorhydric states or alterations in vitamin C activity. This has been evidenced by a small study showing marked reductions in the concentration of vitamin C following 4 weeks of omeprazole therapy in healthy volunteers.[10]

Recognizably, there are reports of increased anemia in patients taking long-term PPIs.[11,12] Long-term follow-up of patients taking PPIs daily for up to 7 years, however, has not shown a clinically significant impairment in iron absorption.[4] The most recent longitudinal follow-up comes from the previously cited 5-year comparative prospective trial of surgery versus PPI therapy for GERD.[7] In this study, there was no evidence of any diminished iron or ferritin levels – both of which were part of the routine extended monitoring (Figs. 2 and 3 Figs 2 and 3).

Figure 2.

Serial serum iron levels: gastroesophageal reflux disease treatment (SOPRAN/LOTUS studies) [7].

Figure 3.

Serial serum ferritin levels: gastroesophageal reflux disease treatment (SOPRAN/LOTUS studies) [7].

Most recently, the use of PPIs has been reported to decrease the need for phlebotomies in patients with hereditary hemochromatosis.[13] In addition to the related pH effect of soluble iron absorption in the intestine, the authors suggested that PPIs also cause a higher pH in the endoscome that means that iron remains bound to transferrin and would not be released into the cytoplasm, thereby having less usable iron stored in the otherwise labile iron pool.

Evidence Summary

The absorption of dietary iron is dependent on gastric acid and also vitamin C. As such, chronic PPI use may impair iron absorption and lead to the development of iron-deficiency anemia. Although there are some retrospective studies that support an association, these studies are not able to appropriately coadjust for significant potential confounding variables. To date, no prospective trials have been conducted to establish a causal effect. In addition, in patients with iron deficiency, available literature suggests that PPIs do not interfere with the absorption of iron supplements that act independent of gastric acid and vitamin C. It seems prudent, however, to periodically monitor patients who have more subject risk for ongoing blood/iron loss who require long-term use of PPIs.