What Should Not Be Taken with L-Citrulline?

December 3, 2025 •

4 min read

According to research, L-citrulline is generally considered safe, but its role in increasing nitric oxide production means it can cause potentially dangerous interactions with certain medications. Therefore, understanding what should not be taken with L-citrulline is critical for anyone considering this popular supplement.

Quick Summary

This article explains the most important medication and supplement interactions to avoid when taking L-citrulline, focusing on drugs that affect blood pressure and nitric oxide levels, such as those for hypertension, heart disease, and erectile dysfunction. It also covers important precautions for specific health conditions.

Key Points

Blood Pressure Medications: Avoid combining L-citrulline with antihypertensive drugs, as this can cause a dangerously low drop in blood pressure (hypotension).
Nitrate Medications: Do not take L-citrulline with nitrates for heart conditions like nitroglycerin, due to the high risk of severe hypotension.
Erectile Dysfunction Drugs: L-citrulline should not be mixed with PDE-5 inhibitors like Viagra or Cialis, as both lower blood pressure through vasodilation.
Low Blood Pressure: Individuals with naturally low blood pressure should use L-citrulline with caution due to its potential to further lower blood pressure.
Pre-Surgery Precautions: Stop taking L-citrulline at least two weeks before any scheduled surgery, as it can affect blood pressure control during the procedure.
Pregnancy and Breastfeeding: There is insufficient research on the safety of L-citrulline for pregnant or nursing individuals, so it is best to avoid use.
High Doses and Side Effects: Excessively high doses (over 10 grams) can lead to gastrointestinal issues like nausea, bloating, and discomfort.
Consult a Doctor: Always consult a healthcare professional before starting L-citrulline, especially if you are on any medication or have underlying health issues.

Critical L-Citrulline Interactions with Medications

Blood Pressure Medications (Antihypertensives)

One of the most significant interactions with L-citrulline is with medications designed to lower blood pressure. L-citrulline increases the body's production of nitric oxide, a chemical that causes blood vessels to widen and relax, leading to improved blood flow and reduced blood pressure. When combined with antihypertensive drugs, this effect can be compounded, potentially causing blood pressure to drop to dangerously low levels, a condition known as hypotension. Examples of blood pressure medications include captopril, enalapril, losartan, and furosemide, among many others. Taking L-citrulline alongside these can result in symptoms like dizziness, lightheadedness, and fainting.

Nitrate Medications for Heart Conditions

Patients taking nitrate medications for heart-related chest pain (angina) must avoid L-citrulline. Like L-citrulline, nitrates also work by promoting vasodilation to increase blood flow and oxygen to the heart muscle. Combining the two can lead to a severe drop in blood pressure and an increased risk of dizziness and lightheadedness. Medications in this category include nitroglycerin and isosorbide. The interaction is considered major, and this combination should not be taken.

Erectile Dysfunction (ED) Medications

Phosphodiesterase-5 (PDE-5) inhibitors, a class of medications used to treat erectile dysfunction, should not be combined with L-citrulline. Drugs such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) also function by increasing nitric oxide and relaxing blood vessels to improve blood flow. The combined effect of L-citrulline and PDE-5 inhibitors can cause a dangerously low drop in blood pressure, leading to hypotension. This is a major interaction that requires strict avoidance.

Other Precautions and Considerations

Beyond specific drug interactions, certain groups should exercise caution or avoid L-citrulline altogether:

Pregnancy and Breastfeeding: There is insufficient evidence to determine the safety of L-citrulline during pregnancy or while breastfeeding. It is best to avoid use in these circumstances.
Surgery: Because L-citrulline affects blood pressure, it can interfere with blood pressure control during and after surgical procedures. It is recommended to stop taking L-citrulline at least two weeks before any scheduled surgery.
Low Blood Pressure: Individuals who naturally have low blood pressure (hypotension) should be cautious. The blood pressure-lowering effect of L-citrulline could potentially worsen their condition.

Comparison Table: L-Citrulline and Related Medications


Medication/Supplement Category	Interaction with L-Citrulline	Reason for Interaction	Recommended Action
Antihypertensives	Major interaction; compounded blood pressure lowering effect.	Both lower blood pressure through vasodilation, increasing the risk of hypotension.	Avoid combining; consult a doctor to monitor blood pressure.
Nitrates (for heart disease)	Major interaction; severe hypotension risk.	Both increase blood flow to the heart, leading to a dangerous additive effect.	Do not take this combination.
PDE-5 Inhibitors (ED meds)	Major interaction; significant risk of severe hypotension.	Both increase nitric oxide and blood flow, posing a risk of dangerously low blood pressure.	Do not take this combination.
L-Arginine	No known interaction; potentially synergistic.	L-citrulline converts to L-arginine, boosting its levels. Combined use can increase nitric oxide more effectively.	Consult a doctor but generally considered safe to combine.
Beetroot Juice (Dietary Nitrates)	Potentially synergistic.	Beetroot juice contains nitrates which, like L-citrulline, increase nitric oxide. Combination could enhance effects.	Can be combined with caution, especially if monitoring blood pressure.

Potential Mild Side Effects of L-Citrulline

While interactions are the primary concern, L-citrulline can also cause mild side effects on its own, especially at high doses.

Gastrointestinal Distress: Some individuals may experience stomach discomfort or heartburn, particularly with larger doses. Studies suggest that doses exceeding 10 grams in a single serving increase the risk of digestive issues due to nitric oxide oversaturation in the small intestine.
Asthma or Allergy Issues: In some cases, arginine oversaturation from very high doses can trigger increased asthma or allergy symptoms.
Headaches: High doses or sensitivity can also lead to headaches.

Managing Supplement Combinations

When planning to take L-citrulline, consider these best practices:

Consult a Healthcare Provider: Always discuss any new supplement, including L-citrulline, with your doctor, especially if you have pre-existing health conditions or are on other medications. This is the most crucial step to ensure safety.
Understand Your Health Profile: Be aware of any conditions that affect blood pressure or involve heart health. This knowledge is vital for assessing potential risks.
Start with a Lower Dose: Begin with the minimum effective dose of L-citrulline and observe your body's response. Increase the dosage gradually and only if necessary, staying within safe limits.
Read Labels Carefully: If using a supplement that combines L-citrulline with other ingredients, scrutinize the label to understand the total composition. Some pre-workout formulas may combine L-citrulline with other vasodilators, increasing interaction risks.

Conclusion

While L-citrulline is valued for its ability to boost nitric oxide and improve athletic performance and mild erectile dysfunction, its potent effect on blood vessels means it should never be taken with certain medications. Combining it with drugs for high blood pressure, heart disease nitrates, or erectile dysfunction can lead to a dangerous and severe drop in blood pressure. Always consult with a healthcare provider before adding L-citrulline to your regimen, especially if you are on any other medications, have a history of heart issues, or have low blood pressure. Proper guidance ensures you can benefit from L-citrulline's effects without compromising your safety.

Frequently Asked Questions

No, you should not take L-citrulline with blood pressure medication (antihypertensives). The supplement can further lower blood pressure, which, when combined with medication, can cause a dangerous drop in blood pressure leading to hypotension.

No, it is highly unsafe to combine L-citrulline with nitrates for heart conditions. Both substances cause significant vasodilation, and the combined effect can lead to a severe and dangerous drop in blood pressure.

Erectile dysfunction drugs known as PDE-5 inhibitors, such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), should not be taken with L-citrulline. This combination can cause excessively low blood pressure.

Individuals with naturally low blood pressure should be extremely cautious and consult a healthcare provider before taking L-citrulline, as its blood pressure-lowering effects could worsen their condition.

Yes, it is recommended to stop taking L-citrulline at least two weeks before any scheduled surgery. This is because the supplement can affect blood pressure, which needs to be carefully controlled during and after surgery.

While L-citrulline and L-arginine are often discussed together, they are generally not contraindicated. L-citrulline is a precursor to L-arginine, and combining them can synergistically increase nitric oxide levels. However, it's still best to consult a doctor, especially when mixing supplements.

There is insufficient reliable research on the safety of L-citrulline during pregnancy or breastfeeding, so it is best to avoid its use.

High doses, particularly exceeding 10 grams, can lead to side effects like stomach discomfort, nausea, bloating, headaches, and in rare cases, increased allergy or asthma issues.