Drug & supplement interaction

L-citrulline + Pregabalin

Pregabalin brand names: Lyrica, Lyrica CR.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between L-citrulline and Pregabalin in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

L-citrulline and Pregabalin

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Pregabalin and L-citrulline in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

L-citrulline safety at a glance

L-citrulline overall Use caution Generally well tolerated in healthy adults, but long-term safety is not fully studied.
Pregnancy Avoid There is not enough safety data, so it is best to avoid supplements during pregnancy.
Breastfeeding Avoid Safety while breastfeeding is unknown, so avoid supplemental use.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Pregabalin and L-citrulline? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Pregabalin

Interactions in our licensed database are recorded against drug classes, not just single drug names. Pregabalin is filed under 3 classifications — including cns depressants, oral drugs. L-citrulline has documented interactions with 2 drug classes — the most serious being antihypertensive drugs (moderate) and phosphodiesterase-5 inhibitors (moderate) — and none of Pregabalin’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

L-citrulline Does Interact With Other Medications

L-citrulline has 178 moderate known drug interactions in our database — Pregabalin isn’t one of them. If you take anything else, check it against the full list below.

Moderate 178 No known interaction 2,652 (incl. Pregabalin)
Taking anything else?

Check Another of Your Medications Against L-citrulline

Covers the 2,830 medications we’ve checked against L-citrulline. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests L-citrulline and Pregabalin May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Raised blood pressure Worth acting on Additional detail

    L-citrulline

    “Orally, 2 of 25 patients with pulmonary hypertension reported cough while taking 1 gram of powdered L-citrulline in water daily.”

    L-citrulline · Natural Medicines adverse-effect record, reported in cough.

    1 source cited
    1. 94963. Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol 2014;64:231-5. PubMed

    “Orally, 2 of 25 patients with pulmonary hypertension reported increased urinary frequency and edema while taking 1 gram of powdered L-citrulline in water daily.”

    L-citrulline · Natural Medicines adverse-effect record, reported in hypertension.

    1 source cited
    1. 94963. Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol 2014;64:231-5. PubMed

    Pregabalin

    Listed in the ADVERSE REACTIONS section of the FDA label for Pregabalin. Read the label on DailyMed ›

  • Stomach upset Additional detail

    L-citrulline

    “Orally, gastrointestinal intolerance, stomach discomfort, and heartburn have been reported with L-citrulline use.”

    L-citrulline · Natural Medicines adverse-effect record, reported in dyspepsia.

    3 sources cited
    1. 94955. Balderas-Munoz K, Castillo-Martínez L, Orea-Tejeda A, et al. Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation. Cardiol J 2012;19:612-7. PubMed
    2. 94963. Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol 2014;64:231-5. PubMed
    3. 94966. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 2010;24:1215-22. PubMed

    Pregabalin

    Listed in the ADVERSE REACTIONS section of the FDA label for Pregabalin. Read the label on DailyMed ›

  • Swelling Additional detail

    L-citrulline

    Recorded for L-citrulline in the same Natural Medicines adverse-effect record shown under Raised blood pressure above.

    Pregabalin

    Listed in the ADVERSE REACTIONS section of the FDA label for Pregabalin. Read the label on DailyMed ›

Reported for L-citrulline but not commonly for Pregabalin: heartburn and cough.

Effects for Pregabalin come from the ADVERSE REACTIONS section of its FDA label; effects for L-citrulline come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Overlapping uses

What Pregabalin Is Prescribed For, and What L-citrulline Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Pregabalin is a prescription medicine with approved uses on its FDA label. L-citrulline is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Pregabalin is prescribed for: Pregabalin is used to manage several types of nerve pain, including neuropathic pain from diabetic peripheral neuropathy (nerve damage caused by diabetes) and postherpetic neuralgia (lingering nerve pain after shingles). It is also used to treat fibromyalgia and neuropathic pain associated with spinal cord injury. Lyrica (capsule and oral solution), pregabalin capsules, and pregabalin oral solution are also approved as add-on therapy for partial-onset seizures — Lyrica for patients 1 month and older, and pregabalin capsules for patients 17 years and older. Lyrica CR and pregabalin extended-release tablets are approved only for diabetic peripheral neuropathy pain and postherpetic neuralgia — their effectiveness for fibromyalgia or as seizure add-on therapy has not been established.

L-citrulline has been studied for:

  • Diabetes studied, not established L-citrulline has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    L-citrulline for diabetes

    It is unclear if oral L-citrulline is beneficial in patients with diabetes.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Pregabalin on your own; if you are taking L-citrulline for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About L-citrulline or Pregabalin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers L-citrulline or Pregabalin, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Pregabalin

This page covers L-citrulline only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Pregabalin page lists 95 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 73 moderate · 15 minor.

From our pharmacist’s overview on the Pregabalin page

“Pregabalin (Lyrica) calms overactive nerves, which is how it eases nerve pain, seizures, and anxiety, and that calming action stacks with almost everything on this list. Of the 95 supplements and herbs, the large majority add their own sedation on top of pregabalin's, and a few can tip that into genuine danger, with deep sedation and s…”

Reviewed by 2 · Jul 18, 2026

Open the Pregabalin interaction page

One more smart check

Taking L-citrulline as Part of a Dietary Supplement Product? Check It for Interactions

We hold 63 real supplement products containing L-citrulline, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-citrulline. Even though L-citrulline itself has no known interaction with Pregabalin, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where L-citrulline and Pregabalin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement L-citrulline
Top half

#611 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Pregabalin
Top 5%

#40 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every L-citrulline reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The L-citrulline and Pregabalin records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About L-citrulline

What is L-citrulline?

L-citrulline
  • Exercise performance
  • Muscle soreness and fatigue
  • Blood flow and circulation
  • Erectile dysfunction
  • Blood pressure support

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.

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

An interaction check asks whether these two react with each other — it does not ask whether L-citrulline is a good idea for someone in your situation. Here is what our L-citrulline record says about it on its own.

L-citrulline: dosing

There is no official standardized dose of L-citrulline, and the right amount can depend on the form (plain L-citrulline versus citrulline malate) and the reason for use. Doses used in studies vary widely.Because of this, the best approach is to follow the directions on the product label and start with the lowest suggested amount.

From our L-citrulline monograph — the full record covers uses, side effects and every documented interaction.

Read the full L-citrulline monograph & all interactions
Medication

About Pregabalin

What Is Pregabalin Used For?

Brand names: Lyrica, Lyrica CR

Pregabalin is used to manage several types of nerve pain, including neuropathic pain from diabetic peripheral neuropathy (nerve damage caused by diabetes) and postherpetic neuralgia (lingering nerve pain after shingles). It is also used to treat fibromyalgia and neuropathic pain associated with spinal cord injury.

Lyrica (capsule and oral solution), pregabalin capsules, and pregabalin oral solution are also approved as add-on therapy for partial-onset seizures — Lyrica for patients 1 month and older, and pregabalin capsules for patients 17 years and older. Lyrica CR and pregabalin extended-release tablets are approved only for diabetic peripheral neuropathy pain and postherpetic neuralgia — their effectiveness for fibromyalgia or as seizure add-on therapy has not been established.

Most-Reported Side Effects for Pregabalin

From FAERS, the FDA’s public side-effect reporting system (270,557 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Fatigue 15,629 reports
Dizziness 14,844 reports
Nausea 14,507 reports
Headache 13,067 reports
Malaise 12,884 reports
See full Pregabalin drug information
Keep checking

Other Drugs & L-citrulline

Browse every other medication we’ve checked against L-citrulline — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
178Moderate
0Minor
2,651No known interaction
178 Moderate 2,651 No interaction
Moderate

178 interactions

Showing 60 of 178 moderate interactions — see all 178 on the L-citrulline page.

No interaction 2,651 drugs checked — show the list

We also checked L-citrulline against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,651 medications checked with no known interaction — see the full L-citrulline list.

See the full L-citrulline interactions page
See every supplement checked against Pregabalin, ranked by severity
Evidence & sources

L-citrulline References

The 8 references that drive our L-citrulline monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Cheng JW, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35:755-64. PubMed
  2. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008;65:51-9. PubMed
  3. Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006;24:275-90. PubMed
  4. Balderas-Munoz K, Castillo-Martínez L, Orea-Tejeda A, et al. Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation. Cardiol J 2012;19:612-7. PubMed
  5. Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol 2014;64:231-5. PubMed
  6. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 2010;24:1215-22. PubMed
  7. Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of clinical trials. Curr Hypertens Rep. 2018;20(11):98. PubMed
  8. Xu Z, Liu C, Liu S, Zhou Z. Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials. Andrologia. 2021:e14007. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking L-citrulline and Pregabalin Together: Common Questions

Is it safe to take L-citrulline with Pregabalin?
We do not list a known interaction between L-citrulline and Pregabalin. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do L-citrulline and Pregabalin have any of the same side effects?
Yes — our sources link each of them separately to 3 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are L-citrulline and Pregabalin used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for L-citrulline in each. That is a conversation for your prescriber, especially if Pregabalin is being adjusted to a target.
How was the L-citrulline and Pregabalin combination checked?
Interactions in our licensed database are recorded against drug classes. Pregabalin is filed under 3 classifications, and L-citrulline has documented interactions with 2 drug classes — none of Pregabalin's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does L-citrulline interact with any other medications?
Yes. L-citrulline has 178 documented drug interactions in our database — Pregabalin is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Pregabalin interact with any supplements?
Yes. Pregabalin has documented interactions with 95 supplements in our database — L-citrulline is not one of them. The Pregabalin interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

L-citrulline monograph Uses, safety profile, and every drug interaction in one place Pregabalin drug information The full plain-English guide to this medication Pregabalin supplement interactions Every supplement checked against Pregabalin, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 8 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Pregabalin and L-citrulline?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.