What is Citrulline?

What is Citrulline?

Citrulline is a non-essential amino acid, meaning your body can build it without relying on food, though you also take it in from fruits and vegetables in the cucurbit family. Biochemists classify it as non-proteinogenic: unlike leucine or lysine, it isn't written into the genetic code and is never assembled directly into muscle tissue. Instead, it works as a metabolic intermediate, shuttling nitrogen through the urea cycle and feeding the arginine-nitric oxide pathway.

The name traces back to Citrullus, the Latin genus for watermelon, where French chemists first isolated the compound in 1930. Naturally occurring citrulline, in the body and in food, is almost entirely the L-enantiomer, so "citrulline" and "L-citrulline" describe the same molecule in nearly every practical context; the D-form has no known biological role and is never sold.

The supplement industry packages this same amino acid in two commercial forms: plain L-citrulline powder, and citrulline malate, where the amino acid is bound to malic acid. Both deliver the same underlying nutrient; they differ in citrulline purity by weight and in which research protocol each has been tested under, covered in full on the dedicated L-citrulline and citrulline malate pages rather than duplicated here.

How it works

Citrulline works through two connected systems: the urea cycle that clears nitrogen, and the arginine-nitric oxide pathway that widens blood vessels. In the liver's urea cycle, the enzyme ornithine transcarbamylase joins ornithine to a carbamoyl phosphate group to form citrulline; citrulline then combines with aspartate through argininosuccinate synthetase to build argininosuccinate, which splits into arginine and fumarate.

That arginine either continues through the urea cycle to be broken down into urea for excretion, or gets pulled aside by nitric oxide synthase and converted into nitric oxide, the molecule that relaxes vascular smooth muscle and increases blood flow to working tissue. A second, separate supply line runs between the gut and kidneys. Enterocytes lining the small intestine convert roughly 13% of the glutamine they absorb into citrulline, which passes straight into the bloodstream because the liver, unlike most amino acids, does not extract citrulline on first pass.

Blood carries that citrulline to the kidneys, where argininosuccinate synthetase and argininosuccinate lyase convert about 80% of it into new arginine, which is why oral citrulline raises blood arginine more reliably than oral arginine itself does. Because intestinal citrulline release tracks how much healthy gut tissue a person has, clinicians also use plasma citrulline as a lab marker of enterocyte mass in conditions like short bowel syndrome, celiac disease, and critical illness.

The formula

Ornithine + carbamoyl phosphate → citrulline → (+ aspartate) → argininosuccinate → arginine + fumarate

This is the third step of the hepatic urea cycle and the same intestinal-renal citrulline-to-arginine axis that also drives nitric oxide production for blood flow.

Types

Worked example

How much actual citrulline you get varies enormously by source. Here is the same nutrient across a food source, a supplement scoop, and the bound form, so you can see why gram-for-gram doses aren't interchangeable.

Notice that an 8 g scoop of citrulline malate and a 3 g scoop of L-citrulline deliver a similar amount of the active amino acid. Dosing by the citrulline malate label gram count, not a citrulline-equivalent claim, is how the research protocols were actually built.

Citrulline vs its two supplement forms

Both forms supply the same active amino acid; the difference is the carrier and the gram dose needed to reach an equivalent citrulline amount. See the dedicated L-citrulline and citrulline malate glossary pages for full dosing protocols and study data.

By goal

• General health and blood flow: A modest 3 g/day dose of L-citrulline is the range studied for blood-flow and blood-pressure outcomes, taken daily rather than as a single pre-workout dose, and continued for several weeks before judging the effect.
• Strength and hypertrophy training: Match the acute pre-workout protocol: 3-6 g of L-citrulline or 6-8 g of citrulline malate about 60 minutes before training, dosed on lifting days to support rep totals across multi-set work.
• Endurance athletes: Evidence for aerobic performance is more mixed than for resistance training. If you use citrulline for endurance work, the same 6-8 g pre-exercise dose is the tested range, but treat any gain as smaller and less consistent.

Common misconceptions

• "Citrulline and L-citrulline are two different ingredients." They are the same molecule. Nearly all naturally occurring and commercially sold citrulline is the L-enantiomer; the D-form has no established role in human metabolism and isn't sold as a supplement, so "citrulline" and "L-citrulline" are used interchangeably in practice.
• "A gram of citrulline malate gives you a gram of citrulline." Citrulline malate is only about 55-60% citrulline by weight because roughly 40-45% of the powder is the attached malic acid. An 8 g scoop delivers close to 4.5 g of actual citrulline, not the full 8 g.
• "Watermelon gives you a real performance dose." A 300 g serving of watermelon flesh supplies roughly 750 mg to 1 g of citrulline. Performance studies use 3-8 g doses, so you would need several kilograms of watermelon in one sitting to approach a tested amount.
• "Citrulline has no real function besides pre-workout pumps." Citrulline is a genuine urea-cycle intermediate the body relies on to clear nitrogen and build arginine. An inherited deficiency in processing it, citrullinemia, lets ammonia build up dangerously in newborns, which shows how essential the pathway is outside the gym.
• "Citrulline supplementation reliably lowers blood pressure." Trial results are inconsistent. Some meta-analyses report a small drop in blood pressure with daily dosing, others find no effect, so treat blood-pressure benefits as plausible but unproven rather than guaranteed.

Related terms

Citrulline FAQ

What is citrulline good for?

Citrulline is an amino acid taken mainly to raise nitric oxide and blood flow before training, which is linked to completing more reps per set and less next-day muscle soreness. It's also studied on its own for blood pressure, vascular health, and as a clinical marker of gut function.

What foods are highest in citrulline?

Watermelon is the richest natural source of citrulline, with the flesh supplying roughly 250-350 mg per 100 grams and the rind carrying an even higher concentration by dry weight. Smaller amounts occur in other cucurbits like cantaloupe and cucumber, plus trace amounts in legumes, nuts, and chocolate.

Is citrulline the same thing as L-citrulline?

Yes, in practical terms. Citrulline occurs in the body and in food almost exclusively as the L-enantiomer, so "citrulline" and "L-citrulline" refer to the same molecule. The D-form exists chemically but has no known biological role and is never sold as a supplement.

What's the difference between citrulline and citrulline malate?

Citrulline is the amino acid itself. Citrulline malate binds that same amino acid to malic acid, so it's only about 55-60% citrulline by weight versus roughly 97-99% for free-form L-citrulline. You need a larger gram dose of citrulline malate to deliver an equivalent citrulline amount.

How much citrulline is in watermelon?

Fresh watermelon flesh contains about 250-350 mg of citrulline per 100 grams, so a 300 g serving, about two cups cubed, provides roughly 750 mg to 1 gram. The rind holds an even higher concentration by dry weight, though it's rarely eaten on its own.

What does citrulline do in the urea cycle?

Citrulline forms when ornithine transcarbamylase joins ornithine to a carbamoyl phosphate group in liver mitochondria. It then combines with aspartate to build argininosuccinate, which splits into arginine and fumarate. This step carries nitrogen toward excretion as urea while also generating new arginine for the body to use.

Is citrulline better than arginine for nitric oxide?

Usually, yes. Oral arginine is broken down heavily by the arginase enzyme in the gut and liver before it reaches circulation, while citrulline is absorbed intact and converted to arginine in the kidneys. A given dose of citrulline typically raises blood arginine more than an equal dose of arginine itself.

What are the side effects of taking citrulline?

Citrulline is well tolerated across the studied 3-8 gram range. The most common complaints are mild bloating, stomach discomfort, or loose stool, usually at the higher end of dosing. Because it can modestly lower blood pressure, people on blood-pressure medication should check with a doctor before adding it.

Can you take citrulline every day, or only before workouts?

Both approaches are studied, for different goals. A single 6-8 gram dose about an hour before training is the protocol tied to performance benefits, while daily 3 gram dosing over several weeks is the approach used in blood-pressure and vascular-health research, independent of exercise timing.

What is citrullinemia?

Citrullinemia is a rare inherited urea cycle disorder caused by a deficiency in the enzyme argininosuccinate synthetase, which normally converts citrulline into argininosuccinate. Without enough of that enzyme, citrulline and ammonia build up in the blood, which can be life-threatening in newborns and requires lifelong dietary and medical management.

References

1. Citrulline. Wikipedia
2. Physiology, Urea Cycle. StatPearls, NCBI Bookshelf
3. Citrullinemia. MedlinePlus Genetics, NIH
4. Citrulline in the management of patients with urea cycle disorders. PMC, 2023. PMC10362745
5. L-Citrulline Supplement Benefits and Side Effects. Cleveland Clinic
6. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research, 2010. PubMed 20386132
7. Maric S, et al. Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use. Nutrients, 2021. PMC8398474
8. Development of Isocratic RP-HPLC Method for Separation and Quantification of L-Citrulline and L-Arginine in Watermelons. PMC, 2018. PMC5954852