Herb & supplement monograph

L-citrulline Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS ·Updated July 2026

What is this page for?

First and foremost: how L-citrulline interacts with medications. The heart of this page is the interaction list — every drug L-citrulline is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what L-citrulline is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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L-citrulline Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant L-citrulline drug interaction appears low for most people. None of the listed interactions are rated major, and the concerns behind the moderate ratings rest mostly on theory rather than on effects proven in people.

Interactions deserving the most attention

The combinations worth the most awareness involve blood pressure medications and PDE-5 inhibitors such as erectile dysfunction drugs. The concern is that L-citrulline converts to L-arginine, which can relax blood vessels, so in theory adding it to these medicines could drop blood pressure too far. That said, human studies of L-citrulline at typical doses have not shown meaningful blood pressure lowering, which softens this concern considerably.

What the rest of the list means

The long list of interacting medications reflects these two drug categories, which together cover many individual prescriptions. A high count does not mean each combination is harmful; the predicted additive effect on blood pressure is theoretical, and the available human research has not confirmed a clinically meaningful change.

Check your medications against L-citrulline

Based on HelloPharmacist’s L-citrulline interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with L-citrulline

178 medications have a known interaction with L-citrulline, graded by severity. Select any drug for the full evidence-based detail.

Don’t want to scroll the list? Just ask.

Tell us the medications you take and we’ll check each one against L-citrulline using our pharmacist-reviewed interaction data.

AI summaries are generated from our L-citrulline interaction data for education only — always confirm with your pharmacist. How we use AI

2,830 drugs

Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
Each drug listed above links to the full report for that exact L-citrulline combination — clinical detail, likelihood, evidence level, and citations.
Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

The big picture

The kinds of drugs L-citrulline affects

Every type of medication (drug category) L-citrulline is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 2 drug categories L-citrulline interacts with

Antihypertensive DrugsPhosphodiesterase-5 Inhibitors

Antihypertensive Drugs

Theoretically, concomitant use of L-citrulline with antihypertensive drugs might have additive effects and increase the chance of hypotension.
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation. However, a meta-analysis of 5 small clinical studies suggests that taking L-citrulline 3-6 grams daily for 1-8 weeks does not lower blood pressure when compared with control.

Likelihood Possible Evidence B

Phosphodiesterase-5 Inhibitors

Theoretically, concurrent use of phosphodiesterase-5 (PDE-5) inhibitors and L-citrulline might result in additive vasodilation.
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation. Theoretically, taking L-arginine with PDE-5 inhibitors might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported.

Likelihood Possible Evidence D

Monograph

L-citrulline: Uses, Safety & Side Effects

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Reviewed July 2026 ·

The bottom line

L-citrulline is an amino acid that the body turns into L-arginine to help make nitric oxide, which relaxes blood vessels and may improve blood flow. It is popular for exercise performance and circulation, but the evidence is mixed and most benefits are modest. It appears generally well tolerated, but talk to your pharmacist or doctor before starting, especially if you have a health condition or are pregnant.

Part used: Amino acid (made by the body and found in foods; supplements are usually made by fermentation)
Common forms: Powder, capsules, tablets; also sold as citrulline malate

People commonly use it for

Exercise performance
Muscle soreness and fatigue
Blood flow and circulation
Erectile dysfunction
Blood pressure support

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance

OverallUse caution

Generally well tolerated in healthy adults, but long-term safety is not fully studied.

PregnancyInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full pregnancy detail

BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

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Overview

L-citrulline is an amino acid that your body makes on its own and that you also get from foods. Watermelon is one of the best-known natural sources, and the name actually comes from the Latin word for watermelon. Smaller amounts are found in other foods, and your body also makes citrulline as part of normal metabolism.

Supplement forms are usually produced through fermentation. You will often see two products on store shelves: plain L-citrulline and citrulline malate, which is L-citrulline combined with malic acid. People most often take it as a powder or capsule for exercise, circulation, and general cardiovascular support.

How it works

After you take L-citrulline, your body converts it into another amino acid called L-arginine. L-arginine is then used to make nitric oxide, a molecule that helps relax and widen blood vessels. Wider, more relaxed blood vessels can mean better blood flow and a small drop in blood pressure.

Interestingly, taking L-citrulline can raise blood arginine levels more steadily than taking L-arginine directly, because it bypasses some of the body's breakdown processes. L-citrulline also plays a role in the urea cycle, which helps the body clear ammonia, a waste product of metabolism.

Much of this is based on biochemistry and short-term human studies. The way it affects athletic performance and circulation in real life is still being studied.

Effectiveness

Does L-citrulline work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by Dr. Brian Staiger, PharmD.

Evidence overview · 18 uses evaluated

1 Possibly effective 1 Leans ineffective 16 Insufficient evidence

How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.

2Likely EffectiveGood evidence, though not yet conclusive.

3Possibly EffectiveSome evidence suggests a benefit.

4Possibly IneffectiveSome evidence it may not help.

5Likely IneffectiveFairly strong evidence it doesn’t help.

6IneffectiveStrong evidence it doesn’t work.

7Insufficient Reliable Evidence to RateToo little research to say either way.

Possibly Effective Athletic performance