Can Omeprazole Cause Anemia?: Understanding the Connection Between PPIs and Nutrient Deficiency

October 12, 2025 •

2 min read

While proton pump inhibitors (PPIs) like omeprazole are highly effective, long-term use has been linked to a reduction in iron and vitamin B12 absorption. This prolonged use can lead to nutritional deficiencies, raising the question: can omeprazole cause anemia?

Quick Summary

Long-term use of omeprazole can lead to anemia, particularly iron-deficiency and vitamin B12-deficiency anemia, by impairing nutrient absorption. Risk increases with duration and dosage.

Key Points

Long-term use is the primary risk: The risk of anemia from omeprazole increases significantly with extended use, typically over one to two years.
Iron deficiency is common: Reduced stomach acid impairs the absorption of non-heme iron from food, leading to iron-deficiency anemia.
Vitamin B12 deficiency is also possible: By suppressing gastric acid, omeprazole can also hinder the release of vitamin B12 from dietary proteins, leading to deficiency.
Higher doses increase risk: Taking higher daily doses of omeprazole is associated with a greater risk of developing nutrient deficiencies.
High-risk groups need monitoring: Elderly patients, those with existing deficiencies, and women of childbearing age should be monitored for anemia while on long-term therapy.
Consult a doctor for management: If anemia is suspected, a doctor can adjust medication, recommend alternative iron supplementation (e.g., IV iron), or manage B12 deficiency.
Omeprazole can trigger rare hemolytic anemia: In rare cases, omeprazole has been linked to drug-induced autoimmune hemolytic anemia.

The Mechanism Behind Omeprazole-Induced Anemia

Omeprazole, a proton pump inhibitor (PPI), suppresses gastric acid production to treat conditions like GERD and peptic ulcers. However, this can interfere with nutrient absorption, potentially leading to anemia.

Omeprazole and Iron Deficiency Anemia

Long-term omeprazole use can cause iron deficiency anemia. Stomach acid is vital for absorbing non-heme iron by converting it to a more absorbable form. Reduced stomach acid due to omeprazole hinders this process. Additionally, omeprazole can directly affect iron metabolism by increasing hepcidin, a hormone that reduces iron absorption.

Documented Cases and Evidence

Case reports show a link between long-term omeprazole and iron deficiency anemia, with improvements seen after stopping the medication. Studies also indicate a dose-dependent increased risk of iron deficiency with continuous PPI use for at least a year.

Omeprazole and Vitamin B12 Deficiency Anemia

Omeprazole can also lead to vitamin B12 deficiency anemia. Gastric acid and pepsin are needed to release vitamin B12 from food proteins, and reduced acid impairs this release, leading to malabsorption over time.

Clinical Findings and Risk Factors

A study in The Journal of the American Medical Association found an association between long-term PPI use and vitamin B12 deficiency. Risk factors include long-term therapy, higher doses, existing deficiencies, older age, and women of childbearing age.

Comparing Omeprazole-Induced Anemias

Omeprazole can cause both iron and vitamin B12 deficiency anemias, as well as, rarely, hemolytic anemia.


Feature	Iron Deficiency Anemia (IDA)	Vitamin B12 Deficiency Anemia	Hemolytic Anemia (Rare)
Mechanism	Impaired non-heme iron absorption and altered iron regulation.	Impaired release of vitamin B12 from food.	Autoimmune destruction of red blood cells.
Blood Cell Size	Microcytic	Macrocytic	Can vary
Common Symptoms	Fatigue, weakness, pale skin, shortness of breath, pica.	Fatigue, weakness, neurological and cognitive issues.	Rapid fatigue, dark urine, jaundice, headache.
Onset	Gradual, over months to years.	Gradual, over several years.	Acute, within days or weeks.
Primary Cause	Impaired iron absorption.	Impaired vitamin B12 absorption.	Drug-induced autoimmune reaction.

Managing the Risk of Anemia While on Omeprazole

Managing anemia risk on long-term omeprazole involves monitoring and proactive strategies.

Periodic Monitoring: High-risk patients should have blood tests to check iron and vitamin B12 levels.
Supplementation Strategies: Oral iron may be less effective; intravenous iron or non-oral B12 supplements may be needed. Vitamin C can aid iron absorption.
Re-evaluating Therapy: Discuss with a doctor if long-term PPI use is still necessary. Options include dose reduction, switching to an H2 blocker, or intermittent use.
Dietary Considerations: Increasing heme iron intake (from animal products) may help, as its absorption is less acid-dependent. B12 supplements may be needed if deficiency is confirmed.
Specialist Evaluation: Referral to a specialist may be necessary for complex cases.

Conclusion

Long-term omeprazole use can cause iron and vitamin B12 deficiency anemia by reducing stomach acid needed for nutrient absorption. The risk is higher with long duration, high doses, and in certain populations. Rarely, it can also cause hemolytic anemia. Monitoring, supplementation, and re-evaluating the need for ongoing omeprazole are crucial for managing this risk.

Frequently Asked Questions

Significant nutritional deficiencies typically develop after long-term use, often after more than one or two years of continuous therapy. Short-term use is not generally associated with anemia.

Omeprazole primarily affects iron by hindering its conversion into a more absorbable form and by altering regulatory hormone levels. It affects vitamin B12 by preventing its release from food proteins in the stomach.

Supplementation can be a management strategy, but absorption can still be suboptimal with oral supplements. For diagnosed deficiencies, doctors may recommend higher doses, alternative formulations, or even intravenous iron.

Individuals on high doses or prolonged therapy, older adults, those with a history of nutritional deficiencies, and menstruating women are at a higher risk.

Symptoms of iron deficiency include fatigue, paleness, and shortness of breath. Vitamin B12 deficiency symptoms can include fatigue, neurological issues like numbness, and cognitive changes.

You should not stop taking omeprazole without consulting a doctor. In some cases, discontinuing the medication has resolved the deficiency, but a doctor needs to oversee this process to manage the underlying condition and determine the best course of action.

Yes, in extremely rare cases, omeprazole has been reported to cause autoimmune hemolytic anemia, where the immune system attacks red blood cells.