Citrulline

amino acid

What is it

Citrulline is a non-essential amino acid produced as part of the urea cycle and converted to L-arginine in the kidneys. Supplements use the L-citrulline form, often as citrulline malate (combined with malic acid). It was first isolated from watermelon, the source of its name.

How it works

Citrulline's headline benefit is that it raises plasma arginine more effectively than oral arginine itself. Oral arginine is degraded by gut and liver arginase before reaching the bloodstream, but citrulline bypasses these enzymes and is converted to arginine in the kidneys. Higher plasma arginine drives nitric oxide synthase to produce more NO, which dilates blood vessels, lowers blood pressure, and increases tissue blood flow. This NO-mediated vasodilation underlies citrulline's three best-evidenced applications: pre-workout pumps and performance, mild erectile dysfunction, and modest blood pressure reduction. Citrulline is also an intermediate in the urea cycle, helping the body dispose of nitrogen waste, and contributes to lactate clearance during exercise. The malate component of citrulline malate is a Krebs cycle intermediate that may contribute small additional energy effects, but L-citrulline does the bulk of the work.

Evidence for 5 uses

AI-assisted evidence assessment — talk to your doctor before relying on any single supplement.

Resistance training performance

Grade B

Good evidence

Multiple randomized trials and meta-analyses show 6 to 8 g citrulline malate pre-workout improves training volume (more reps to failure), reduces muscle soreness 24 to 72 hours post-exercise, and modestly improves anaerobic performance. The pre-workout pump effect is real and reproducible.

Erectile dysfunction

Grade C

Moderate evidence

A 2011 single-blind trial in 24 men with mild ED found 1.5 g/day L-citrulline for 1 month improved erection hardness in 50 percent of men versus 8.3 percent on placebo. Effects are modest compared to PDE5 inhibitors but useful for mild cases or as adjunctive support.

Blood pressure

Grade C

Moderate evidence

Trials of 3 to 6 g/day L-citrulline have shown modest reductions in systolic and diastolic blood pressure in normal and pre-hypertensive adults. Effect sizes are similar to those reported for L-arginine but with better GI tolerability.

Aerobic endurance

Grade C

Moderate evidence

Some trials show modest improvements in cycling time-trial performance and VO2 kinetics with citrulline. Results are less consistent than the strength training data.

Recovery from intense exercise

Grade C

Moderate evidence

Reductions in delayed-onset muscle soreness have been reported after citrulline supplementation pre- and post-exercise. Lactate clearance may also be modestly improved.

2 commercial forms

Citrulline malate (2:1 ratio)

Standard sports format; well absorbed, slightly tart taste from malic acid.

The format used in most positive performance trials. 6 to 8 g delivers 4 to 5 g L-citrulline plus 2 to 3 g malic acid.

Pure L-citrulline

More L-citrulline per gram than the malate; no malic acid contribution.

Cleaner option if you want pure citrulline effects. 3 to 5 g per dose.

Dosage

There is no RDA. Typical doses are 6 to 8 grams of citrulline malate (which contains about 4 to 5 grams of L-citrulline) taken 30 to 60 minutes pre-workout. For pure L-citrulline, doses range from 3 to 6 grams. Blood pressure trials have used 3 to 6 grams per day in divided doses for 4 to 8 weeks. Erectile function studies have used 1.5 to 3 grams per day for several weeks to months.

When and how to take it

Take 6 to 8 grams of citrulline malate (or 3 to 5 grams of pure L-citrulline) 30 to 60 minutes before training on an empty stomach for the strongest pre-workout effect. Effects on blood flow and performance last about 2 to 4 hours. For blood pressure or erectile support, split into morning and evening doses. Citrulline does not stack uncomfortably with caffeine and is a common ingredient in pre-workout blends. Avoid late evening dosing only if you find it disrupts sleep, which is uncommon.

Food sources

Food	Amount	%DV
Watermelon (1 cup)	~250 mg	—
Watermelon rind	much higher than flesh	—
Cucumber (1 cup)	small amounts	—
Cantaloupe (1 cup)	small amounts	—
Pumpkin (1 cup)	modest amounts	—

Safety

Citrulline is well tolerated with fewer GI side effects than arginine at comparable doses. Mild stomach upset or headache can occur, especially with citrulline malate due to malic acid's mild acidity. No formal Tolerable Upper Intake Level has been established. Doses up to 15 grams per day have been used safely in short-term research. Like arginine, citrulline can lower blood pressure and may compound the effects of antihypertensives, PDE5 inhibitors, and nitrates. There is no equivalent of the post-MI safety signal that was raised about high-dose arginine, but cardiology guidance is still wise after a heart attack. People with severe kidney disease should consult a clinician because renal conversion to arginine is the key step.

Who should be cautious

Use cautiously with low blood pressure or on antihypertensive medications. Coordinate with prescribers if you take PDE5 inhibitors. Avoid combining with nitrates. People with severe kidney disease should consult a clinician. Pregnant and breastfeeding women have limited safety data. Coordinate with cardiology after a heart attack.

Interactions

Citrulline can compound blood-pressure-lowering effects of antihypertensives (ACE inhibitors, ARBs, beta-blockers, diuretics, calcium channel blockers) and PDE5 inhibitors (sildenafil, tadalafil, vardenafil). Combining with nitrates can cause dangerous hypotension. May enhance the effects of other vasodilators. No known significant interactions with most cardiovascular, metabolic, or psychiatric medications at typical doses.

Frequently asked questions

Why take citrulline instead of arginine?⌄

Oral arginine is degraded by gut and liver enzymes before reaching circulation, so the actual rise in blood arginine is modest. Citrulline bypasses these enzymes and converts to arginine in the kidneys, ending up at higher plasma arginine levels. For nitric oxide effects, citrulline is generally the more efficient choice.

How much citrulline malate should I take pre-workout?⌄

6 to 8 grams 30 to 60 minutes pre-workout is the dose used in most positive trials. Lower doses (under 4 g) may not produce a noticeable effect.

Can I take citrulline daily?⌄

Yes. Daily use at 3 to 8 g for weeks to months has been well tolerated in trials. Many people use it pre-workout on training days only.

Will citrulline cause a 'flush' like niacin?⌄

No. Citrulline lowers blood pressure mildly via vasodilation but doesn't cause the characteristic histamine-related flush of niacin.

Is citrulline safe with my blood pressure medication?⌄

It may compound the blood-pressure-lowering effect. Monitor your readings and coordinate with your prescriber if you start daily citrulline.

References

Wikidata: Citrulline — Wikidata link

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Disclaimer: These statements have not been evaluated by the FDA. This page is educational, not a substitute for personalized medical advice. Evidence grades are AI-assisted assessments — talk to your doctor before starting any new supplement, especially if you're pregnant, breastfeeding, on medications, or managing a chronic condition.