L-Citrulline and medications.
L-Citrulline is in the Distil supplement database, evidence Grade B. The page below lists every medication we have explicitly assessed it against.
L-citrulline is an amino acid that the body converts into L-arginine, and it does this more efficiently than taking arginine directly because it has better oral bioavailability. That conversion raises nitric oxide, which widens blood vessels. The evidence is Grade B for cardiovascular effects and Grade B for athletic performance, where randomised trials by Figueroa, Bailey and Pérez-Guisado suggest it may modestly lower blood pressure and improve exercise performance and muscle soreness at 3 to 6g. Erectile function is Grade C and rests on a single small study by Cormio at around 1.5g a day, which was not randomised: the same 24 men took placebo for one month and citrulline the next, and the authors describe it as a pilot needing further research. The pooled analyses often quoted for erectile dysfunction tested L-arginine rather than citrulline, so they do not support this use. The effects are modest rather than dramatic. Two interactions follow directly from the vasodilation mechanism: it adds to the effect of PDE5 inhibitors like sildenafil and tadalafil, and it stacks with blood-pressure-lowering medication, so both are worth flagging to a GP and monitoring. The nitric oxide it raises may also have a mild theoretical blood-thinning action through the same pathway, so if you take an anticoagulant or antiplatelet medicine it is worth a mention to your GP, though there is no good evidence it meaningfully adds to bleeding at supplement doses. It is otherwise very well tolerated, with only mild stomach effects at higher doses. A practical point: match the dose to the goal, since ED and performance protocols differ.
Below are the 11 documented pairs we have explicitly assessed for L-Citrulline: 11 amber. The pairs cluster around 2 mechanisms: Additive blood-pressure lowering and Additive vasodilation. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not listed here is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by medication, and the missing-item form at the bottom of the page routes any uncatalogued medication into our next curation pass.
Documented interactions
Last reviewed 15 June 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Additive blood-pressure lowering
Amber Does interact with Amlodipine?
L-citrulline lowers blood pressure modestly through the nitric oxide pathway, and amlodipine lowers blood pressure by relaxing blood vessels through calcium-channel blockade. Used together, the combined blood-pressure effect is mild but real. Watch for dizziness on standing, especially in the first two weeks. If symptoms appear, tell your GP.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Clonidine?
L-citrulline mildly lowers blood pressure by raising nitric oxide, and clonidine lowers it by reducing the nerve signals that drive blood pressure up. Taken together the effects may stack, so watch for dizziness on standing, especially in the first couple of weeks. The added effect tends to be modest. If symptoms appear, tell your GP.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Guanfacine?
L-citrulline mildly lowers blood pressure by raising nitric oxide, and guanfacine lowers it by reducing the nerve signals that drive blood pressure up. Taken together the effects may stack, so watch for dizziness on standing, especially in the first couple of weeks. The added effect tends to be modest. If symptoms appear, tell your GP.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Lisinopril?
L-citrulline lowers blood pressure modestly through the nitric oxide pathway, and lisinopril lowers blood pressure by blocking the renin-angiotensin system. Used together, the combined blood-pressure effect is mild but real. Watch for dizziness on standing, especially in the first two weeks. If symptoms appear, tell your GP.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Losartan?
L-citrulline lowers blood pressure modestly through the nitric oxide pathway, and losartan lowers blood pressure by blocking angiotensin receptors. Used together, the combined blood-pressure effect is mild but real. Watch for dizziness on standing, especially in the first two weeks. If symptoms appear, tell your GP.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Ramipril?
L-citrulline lowers blood pressure modestly through the nitric oxide pathway, and ramipril lowers blood pressure by blocking the renin-angiotensin system. Used together, the combined blood-pressure effect is mild but real. Watch for dizziness on standing, especially in the first two weeks. If symptoms appear, tell your GP.
Evidence: Limited human data, from small studies or case reports, alongside a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Additive vasodilation
Amber Does interact with Glyceryl trinitrate?
Taking L-citrulline with glyceryl trinitrate (GTN) can add up their blood-pressure-lowering effects, so you may notice more dizziness, lightheadedness or a headache, particularly while a GTN spray or patch is working, because both raise nitric oxide (GTN as an organic nitrate, citrulline by feeding the arginine pathway). This is additive rather than the dangerous amplified drop seen when nitrates are combined with erection medicines such as sildenafil. Keep your citrulline dose steady and tell your GP or cardiologist you take it.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Isosorbide mononitrate?
Taking L-citrulline with isosorbide mononitrate can add up their blood-pressure-lowering effects, so you may notice more dizziness, lightheadedness or a headache, because both raise nitric oxide (the nitrate directly, citrulline by feeding the arginine pathway). This is additive rather than the dangerous amplified drop seen when nitrates are combined with erection medicines such as sildenafil. Keep your citrulline dose steady and tell your GP or cardiologist you take it.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Nicorandil?
Taking L-citrulline with nicorandil can add up their blood-pressure-lowering effects, so you may notice more dizziness, lightheadedness or a headache, because both raise nitric oxide (nicorandil partly as a nitrate, citrulline by feeding the arginine pathway). The combined effect tends to be mild, but tell your GP or cardiologist you take citrulline and keep your dose steady.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Sildenafil (Erectile Dysfunction)?
L-citrulline raises nitric oxide, which widens blood vessels, and sildenafil works on the same nitric oxide pathway. Combining them could add up to a larger drop in blood pressure, so watch for dizziness, flushing, or faintness, particularly in the few hours after a sildenafil dose. Tell your GP if you take both.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Tadalafil?
L-citrulline raises nitric oxide, which widens blood vessels, and tadalafil works on the same nitric oxide pathway. Combining them could add up to a larger drop in blood pressure, so watch for dizziness, flushing, or faintness. Tadalafil lasts much longer than sildenafil, so the window where this matters is wider. Tell your GP if you take both.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope. Use the checker below to surface any medication, and submit a missing item if you take something we have not catalogued.
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