Understanding What Organ Does Aleve Affect and its Side Effects

October 6, 2025 •

4 min read

As one of the most widely used classes of drugs globally, nonsteroidal anti-inflammatory drugs (NSAIDs) like Aleve (naproxen) are highly effective but carry known risks, including potential gastrointestinal complications in up to 60% of patients. Understanding what organ does Aleve affect is crucial for safe usage, particularly for long-term users and those with pre-existing health conditions.

Quick Summary

Aleve (naproxen) primarily affects the stomach, kidneys, and cardiovascular system by inhibiting prostaglandin synthesis. Short-term use is generally safe, but prolonged or high-dose use increases the risk of gastrointestinal bleeding, ulcers, kidney damage, heart attack, and stroke. Rare cases of liver injury are also possible.

Key Points

Inhibits COX Enzymes: Aleve works by inhibiting cyclooxygenase (COX) enzymes, particularly COX-1, which is crucial for the protective lining of the stomach and blood flow to the kidneys.
High Risk for Stomach Damage: The gastrointestinal (GI) tract is a primary target, with risks including ulcers, irritation, and serious bleeding, especially with prolonged use or high doses.
Potential for Kidney Injury: Aleve can reduce blood flow to the kidneys, increasing the risk of acute kidney injury (AKI) and chronic kidney disease (CKD), particularly in older adults or those with pre-existing conditions.
Cardiovascular Event Risk: It carries a risk of heart attack and stroke, though studies suggest naproxen has a lower risk profile compared to some other NSAIDs.
Rare Liver Damage: While rare, Aleve can cause drug-induced liver injury, with the risk being higher in those with pre-existing liver disease or heavy alcohol consumption.
Safe Usage Guidelines: To minimize risks, take the lowest effective dose for the shortest time, and always with food.
Talk to a Doctor: Individuals with underlying health issues affecting the GI tract, kidneys, heart, or liver should consult a healthcare provider before using Aleve.

How Aleve Works

Aleve, with the active ingredient naproxen sodium, belongs to a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs). Its primary mechanism is the inhibition of cyclooxygenase (COX) enzymes, specifically both COX-1 and COX-2. COX enzymes are responsible for converting arachidonic acid into prostaglandins, which are compounds that promote inflammation, fever, and pain. By blocking these enzymes, Aleve reduces the production of prostaglandins, thereby alleviating pain and inflammation.

While this mechanism provides therapeutic benefits, it also affects other organs where prostaglandins play a protective role. For example, COX-1 is crucial for maintaining the stomach's protective lining and ensuring proper blood flow to the kidneys. Non-selective inhibition of COX-1 is the basis for many of Aleve's potential side effects.

The Gastrointestinal System: A Primary Target

The gastrointestinal (GI) tract is one of the most directly and commonly affected organ systems. The protective lining of the stomach and intestines relies on prostaglandins. By inhibiting COX-1, Aleve compromises this mucosal barrier, making it more vulnerable to irritation from stomach acid.

This can lead to a range of GI issues, from mild indigestion to severe and potentially fatal complications.

Stomach irritation and ulcers: Common side effects include heartburn, indigestion, and stomach pain. With long-term use, this can progress to peptic ulcers (sores in the stomach or small intestine).
Gastrointestinal bleeding: Ulcers can lead to serious bleeding, which may be asymptomatic. Symptoms of severe bleeding include black, tarry stools; bloody vomit; or persistent, severe stomach pain.
NSAID-induced enteropathy: Damage is not limited to the stomach and can extend to the small and large intestines, leading to inflammation and lesions.

The Kidneys: Impaired Function and Damage

The kidneys rely on prostaglandins to regulate blood flow and maintain proper function. Aleve’s inhibition of COX enzymes can interfere with this process, reducing blood flow to the kidneys and potentially causing damage, especially in high-risk individuals.

Acute Kidney Injury (AKI): In susceptible individuals (e.g., those who are dehydrated, older adults, or people with pre-existing kidney or heart disease), Aleve can trigger a sudden decline in kidney function.
Fluid retention: The medication can cause the body to retain salt and water, leading to elevated blood pressure and swelling in the ankles, feet, or hands. This can strain the kidneys and worsen conditions like heart failure.
Chronic Kidney Disease (CKD): While occasional, low-dose use is typically safe for the kidneys, long-term or high-dose usage significantly increases the risk of progressive and chronic kidney damage.

The Cardiovascular System: Risks of Heart Attack and Stroke

The U.S. Food and Drug Administration (FDA) has strengthened warnings regarding the cardiovascular risks of NSAIDs, including Aleve. This risk involves a higher chance of experiencing serious thrombotic events like heart attack and stroke, especially with prolonged use or higher doses.

However, studies have suggested that naproxen may carry a lower overall cardiovascular risk compared to some other NSAIDs. Despite this, it remains a concern, particularly for those with pre-existing heart conditions. The risk is heightened in individuals with cardiovascular disease or risk factors, and Aleve should not be used by those undergoing heart bypass surgery.

The Liver: Metabolism and Rare Hepatotoxicity

The liver is the primary organ responsible for metabolizing naproxen. While the incidence is very low, serious liver problems, including drug-induced liver injury (DILI), have been reported in rare cases.

Elevated liver enzymes: Some patients on prolonged courses of naproxen may experience elevated liver enzymes, which usually return to normal after discontinuing the drug.
Risk factors: Individuals with pre-existing liver disease or those who consume alcohol heavily may have an increased risk of liver damage when taking Aleve.

Comparison of Aleve's Primary Effects on Organs


Organ System	Primary Effect	Risk Factors for Adverse Effects	Symptoms of Concern
Gastrointestinal	Mucosal damage leading to ulcers and bleeding	Age > 60, history of ulcers/bleeding, high doses, alcohol use	Stomach pain, black/tarry stools, bloody vomit
Kidneys	Reduced blood flow, fluid retention	Dehydration, pre-existing kidney/heart disease, older age	Decreased urination, swelling, confusion
Cardiovascular	Increased risk of heart attack, stroke, and heart failure	History of heart disease, high blood pressure, prolonged use	Chest pain, shortness of breath, unexplained sweating
Liver	Metabolism; rare, but possible, hepatotoxicity	Pre-existing liver disease, heavy alcohol use	Yellowing skin (jaundice), abdominal pain, dark urine

How to Minimize Risk

To reduce the risk of adverse effects, especially on the stomach and kidneys, consider these strategies:

Use the lowest effective dose: Take the minimum dosage necessary for the shortest duration.
Take with food: Always take Aleve with food or milk to reduce stomach irritation.
Stay hydrated: Adequate hydration is especially important when taking NSAIDs to protect kidney function.
Know your risks: If you have pre-existing conditions like heart or kidney disease, or regularly consume alcohol, discuss alternatives with a healthcare provider.
Consider alternatives: For those with higher risk, alternatives like acetaminophen (Tylenol) may be safer for the kidneys and stomach, though it carries its own liver risks, particularly with overdose.

Conclusion

While Aleve is a safe and effective over-the-counter medication for many, it is not without risks. The primary organs affected by Aleve are the stomach, kidneys, and heart, with potential for rare liver complications. The medication’s mechanism of action, which inhibits prostaglandin production, is responsible for both its therapeutic effects and its potential for harm. The key to safe usage involves careful dosing, taking the medication for the shortest duration necessary, and being aware of personal risk factors. Always consult a healthcare professional to determine if Aleve is the right choice for your needs, especially for chronic pain management or if you have underlying health issues.

Learn more about NSAIDs and their effects from the National Kidney Foundation.

Frequently Asked Questions

Aleve can cause stomach irritation, heartburn, and, with prolonged use, serious issues like ulcers and bleeding by compromising the stomach's protective lining. Taking it with food or milk helps reduce this risk.

Yes, Aleve can cause kidney damage by reducing blood flow to the kidneys, which can lead to acute kidney injury. The risk is higher with long-term, high-dose use and in people with pre-existing kidney disease, heart failure, or high blood pressure.

Yes, all NSAIDs, including Aleve, carry a risk of cardiovascular issues, such as heart attack and stroke. However, some studies suggest Aleve may have a smaller overall risk compared to other NSAIDs.

Aleve is metabolized by the liver and can, in rare cases, cause drug-induced liver injury. The risk is very low for most people but is higher for those with pre-existing liver problems or heavy alcohol use.

For most people, Aleve is safe for short-term, occasional use. Prolonged use increases the risk of serious side effects on the GI tract, kidneys, and cardiovascular system. Consult a doctor for guidance on long-term pain management.

Aleve should be avoided by people with a history of stomach ulcers or GI bleeding, severe kidney or liver disease, uncontrolled high blood pressure, heart failure, and those undergoing heart bypass surgery.

For individuals with concerns about their stomach or kidneys, acetaminophen (Tylenol) is often recommended as it does not affect these organs in the same way. However, it can affect the liver, especially in cases of overdose.