Do Proton Pump Inhibitors (PPIs) decrease iron absorption?

From the Guidelines

Proton pump inhibitors (PPIs) can decrease iron absorption, particularly with long-term use or high doses, as evidenced by a strong association found in a nested case-control study 1.

Key Points to Consider

• The reduction in iron absorption is thought to be due to the decrease in stomach acid production, which is necessary for converting dietary iron into a soluble form that can be absorbed in the small intestine.
• Stomach acid helps transform ferric iron (Fe3+) to the more easily absorbed ferrous iron (Fe2+), and when acid production is suppressed by PPIs, this conversion is less efficient.
• A study found that ≥2 years of PPI use was strongly associated with iron deficiency, especially among individuals who received the higher dose (≥1.5 PPI pills/day) 1.
• Patients on long-term PPI therapy should consider having their iron levels monitored periodically through blood tests to minimize the risk of iron deficiency.
• To enhance iron absorption, iron supplements can be taken with vitamin C (ascorbic acid), and heme iron sources (from animal products) may be better absorbed than plant sources when on PPI therapy.

Clinical Implications

• Healthcare providers should be aware of the potential for PPIs to decrease iron absorption and monitor patients accordingly, especially those at risk for iron deficiency.
• Adjusting PPI dosing or considering alternative acid-reducing medications might be necessary if iron deficiency develops in patients on long-term PPI therapy.

From the FDA Drug Label

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Omeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity Intervention: Mycophenolate mofetil (MMF): Co-administration of omeprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact:Lansoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity

Proton Pump Inhibitors (PPIs), such as omeprazole 2 and lansoprazole 3, can decrease the absorption of iron salts due to their effect on reducing intragastric acidity.

• The reduced absorption of iron salts is a result of the increased gastric pH caused by PPIs.
• This interaction may lead to decreased iron levels, potentially causing or exacerbating iron deficiency.
• Patients taking PPIs and iron supplements should be monitored for signs of iron deficiency, and their treatment regimen should be adjusted as needed to maintain adequate iron levels.

From the Research

Effect of Proton Pump Inhibitors (PPIs) on Iron Absorption

• PPIs have been found to decrease iron absorption, which can lead to iron-deficiency anemia 4, 5, 6, 7.
• A retrospective cohort study found that patients on chronic PPI therapy had significant decreases in mean hemoglobin and hematocrit compared to matched controls 4.
• Case studies have reported iron deficiency anemia in patients taking PPIs for long periods, with no other apparent cause of gastrointestinal blood loss 5, 6.
• Research suggests that PPIs can directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation 7.
• The long-term use of PPIs can also lead to an imbalance in gut microbiota composition, which may contribute to iron deficiency anemia 8.

Mechanism of PPI-Induced Iron Deficiency

• PPIs increase the expression of hepcidin, an important iron regulatory hormone, which can lead to decreased iron absorption 7.
• The aryl hydrocarbon receptor-mediated pathway is involved in the regulation of hepcidin by PPIs 7.
• PPIs can also decrease the protein levels of duodenal and splenic ferroportin, which is essential for iron absorption 7.

Clinical Implications

• Patients on long-term PPI therapy should be monitored for iron deficiency anemia 4, 5, 6.
• Alternative treatments, such as H2 blockers, may be considered for patients at risk of iron deficiency anemia 6, 7.
• Further research is needed to fully understand the mechanisms of PPI-induced iron deficiency and to develop strategies for prevention and treatment 7, 8.