Does Aspirin Inhibit Iron Absorption? Unpacking the Mechanisms of Iron Imbalance

October 13, 2025 •

3 min read

Recent clinical studies have shown that older adults taking a daily low-dose aspirin were approximately 20% more likely to develop anemia compared to those on a placebo, even when accounting for major bleeding events. This suggests the impact of aspirin on iron levels extends beyond the well-known risk of gastrointestinal bleeding, addressing the deeper question of how and why does aspirin inhibit iron absorption.

Quick Summary

Long-term aspirin use can lead to iron deficiency and anemia, not primarily by inhibiting iron absorption but through subtle gastrointestinal bleeding and the iron-chelating action of its metabolites. Clinical evidence indicates a significant association between chronic aspirin use and decreased iron stores.

Key Points

Iron Depletion Mechanisms: Long-term aspirin use impacts iron balance through both chronic gastrointestinal bleeding and the iron-chelating effects of its metabolites.
Not Direct Absorption Inhibition: Aspirin does not primarily inhibit iron absorption in the gut; instead, it causes iron loss through other means.
Chelating Metabolites: Aspirin metabolites, like salicylic acid, bind to and mobilize iron from the body's stores, leading to increased iron excretion.
Clinical Evidence: The ASPREE trial demonstrated that low-dose aspirin increases the risk of anemia and lowers ferritin levels, even when major bleeding is excluded, confirming the role of non-bleeding mechanisms.
Occult Blood Loss: Subtle, unseen bleeding from the GI tract due to aspirin's effects on the stomach lining is a major cause of gradual iron depletion.
Monitoring is Key: Older adults and long-term aspirin users should consider periodic monitoring of hemoglobin and ferritin levels to manage iron status.

While the question, "Does aspirin inhibit iron absorption?" is a common concern, the reality is more complex. Aspirin does not significantly block iron absorption in the intestines. Instead, its long-term use can lead to an overall negative iron balance through two primary mechanisms: subtle, chronic blood loss from the gastrointestinal (GI) tract and the iron-chelating properties of its metabolites. For individuals on long-term, low-dose aspirin therapy, understanding these indirect pathways is crucial for maintaining proper iron status.

The Indirect Pathway: Gastrointestinal Bleeding

As a nonsteroidal anti-inflammatory drug (NSAID), aspirin works by inhibiting cyclooxygenase (COX) enzymes. This has two key effects that contribute to iron deficiency over time:

Reduced Gastric Mucosal Protection: Aspirin inhibits COX-1, an enzyme that produces prostaglandins which protect the stomach and intestinal lining. This inhibition leaves the GI tract more vulnerable to damage from stomach acid, which can cause irritation, tiny ulcers, and chronic, low-grade bleeding.
Occult Blood Loss: This bleeding is often 'occult,' meaning it is not visible and goes unnoticed by the patient. While the blood loss is small on a day-to-day basis, over months or years of continuous aspirin use, it can cause a significant depletion of the body's iron stores and lead to iron-deficiency anemia. This mechanism is particularly relevant for older adults, who are more susceptible to this side effect.

The Chelation Factor: Aspirin Metabolites

In addition to occult bleeding, recent research has identified a second, independent mechanism by which aspirin impacts iron levels: chelation.

Metabolism of Aspirin: When ingested, aspirin is rapidly metabolized into a series of compounds, including salicylic acid and salicyluric acid.
Formation of Chelating Metabolites (ACMs): Many of these metabolites are potent iron-chelating agents. This means they can bind to iron molecules throughout the body, mobilizing iron from cellular stores.
Increased Iron Excretion: Once bound by these chelating metabolites, the iron is more readily excreted from the body, primarily through urine. This process, especially with long-term use, contributes to a gradual and ongoing loss of iron, independent of blood loss.

Clinical Evidence and the ASPREE Trial

Large studies have examined the link between aspirin and iron levels, including the ASPREE trial. The trial found that healthy older adults taking low-dose aspirin daily had a higher rate of anemia compared to those on a placebo. The study reported a 23.5% risk of anemia in the aspirin group over five years versus 20.3% in the placebo group. Aspirin users also showed a greater drop in ferritin levels, indicating reduced iron stores. These findings were observed even when major bleeding events were excluded.

Comparing the Mechanisms: Bleeding vs. Chelation

To better understand how these two mechanisms work together to impact iron status, here is a comparison:


Feature	Chronic Gastrointestinal Bleeding	Iron Chelation by Metabolites
Initiating Factor	Direct damage to the GI lining by aspirin.	Metabolism of aspirin into chelating agents.
Mechanism	Occult (hidden) blood loss from the stomach and intestines depletes iron stores.	Metabolites bind to iron, causing its mobilization and subsequent excretion.
Impact on Iron	Continuous loss of iron-containing red blood cells and heme iron.	Increased excretion of free iron from cellular stores.
Symptom Onset	Gradual and cumulative, leading to progressive iron deficiency over time.	Gradual and cumulative, contributing to an ongoing negative iron balance.
Prevalence	A well-established side effect of NSAIDs, particularly with long-term use.	A more recently identified mechanism, demonstrated to be a significant contributor in long-term users.

Strategies for Managing Iron Levels with Chronic Aspirin Use

For those on long-term aspirin therapy, especially older adults, monitoring iron levels is important. Discuss regular blood tests for hemoglobin and ferritin with your doctor, particularly if you have other anemia risk factors. Be aware of iron deficiency symptoms like fatigue or weakness, which can be mistaken for aging signs. Maintain an iron-rich diet. Consult your doctor about iron supplements, as interactions with aspirin need consideration. Reduce GI bleeding risk by avoiding excess alcohol or other NSAIDs.

Conclusion

In conclusion, while aspirin does not directly inhibit iron absorption significantly, it impacts iron balance through subtle GI blood loss and iron-chelating metabolites. Long-term, low-dose aspirin use increases anemia risk and lowers ferritin, even without major bleeding. Regular monitoring and proactive iron management are crucial for chronic aspirin users, especially older adults. These insights show how regular aspirin alters iron metabolism over time.

NIH news release on the ASPREE study

Frequently Asked Questions

You should not take iron supplements and aspirin at the same time without consulting your doctor. Aspirin is a blood thinner, and iron supplements, especially in high doses, can have their own side effects. Your doctor can help determine the best timing and dosage for any iron supplementation to prevent negative interactions.

Chronic or occult GI bleeding is a slow, subtle, and often undetectable blood loss over a long period, which can cause gradual iron depletion. In contrast, major bleeding is a more severe and sudden event, which is less common but more immediately dangerous.

Aspirin is metabolized into several compounds, including salicylic acid, salicyluric acid, and 2,3-dihydroxybenzoic acid. These metabolites have iron-binding properties that can mobilize iron from the body's internal stores, leading to its excretion.

The symptoms of iron deficiency and anemia can be subtle and develop gradually. They include fatigue, weakness, dizziness, shortness of breath, and sometimes palpitations or pale skin. In older adults, these symptoms may be mistaken for normal aging.

While older adults are at a higher risk due to a combination of factors, including longer duration of use and often lower iron intake, long-term aspirin use can affect iron levels in other populations as well. Individuals with pre-existing chronic conditions, like diabetes or kidney disease, are also more susceptible.

If you are on long-term aspirin therapy, especially if you are an older adult, it's wise to discuss regular monitoring with your healthcare provider. A simple blood test can measure your hemoglobin and ferritin levels to assess your iron status.

The ASPREE trial's key finding was that long-term, low-dose aspirin use significantly increased the risk of anemia and lowered ferritin levels in older adults, even after controlling for major bleeding. This confirms that factors beyond major bleeding contribute to iron deficiency with aspirin use.