Citrulline is an amino acid, but not one of the 20 that proteins are built from. EFSA (the EU’s food safety agency) calls it non-proteinogenic in its 2012 protein opinion. That means it is made for other jobs in the body. A 2024 review calls it a non-essential amino acid.
The body makes it, so you do not need to get it from food. We found no health body that sets a daily amount for it. The “L-” in L-citrulline names the form sold as a supplement and used in the trials below.
Your gut cells make citrulline from glutamine and release it into the blood. The kidneys turn it into arginine. Arginine is the raw material for nitric oxide, a gas that relaxes artery walls. Citrulline is also a step in the urea cycle, the liver’s route for clearing ammonia.
It is named for the watermelon, Citrullus, from which it was first isolated in 1914. Watermelon is still the one food with solid measurements, at about 2 to 3 g per kilogram of flesh.
One thing most readers do not know: doctors use the blood level of citrulline to gauge how well the gut lining is working. In people who had lost much of their small bowel, it averaged 20 µmol/L (micromoles per liter of blood) against 40 in healthy controls.
The supplement trials are less clear-cut. One meta-analysis (a study that pools the results of earlier studies) shows a small drop in blood pressure, and another shows none. Exercise performance shows a small, uncertain gain.
Citrulline malate, a different product from L-citrulline, gets its own section below. The arginine page covers the amino acid that citrulline turns into.
Health benefits of citrulline
Almost all human trials of citrulline test supplements, not food. Most used L-citrulline or citrulline malate at 0.8 to 10 g a day. A few used watermelon juice, which gives about 1 g of citrulline in 780 g of juice. The best-studied questions are blood pressure and exercise.
For systolic blood pressure (the top number), one meta-analysis finds a drop of about 4 mmHg (millimeters of mercury, the blood pressure unit). Another finds no effect. For exercise, other meta-analyses find small gains in single-session strength and endurance, with weak or null results for strength and long-term performance.
A trial in preeclampsia (a dangerous rise in blood pressure in pregnancy) found no benefit. Small trials in erectile dysfunction and in older adults are promising but not conclusive. We found no authorized EU health claim for citrulline, and no finding reaches strong evidence. Here is what 17 studies and reviews found, strongest evidence first, including the trials that found nothing.
In 8 trials, L-citrulline lowered systolic pressure by 4.1 mmHg
It pooled randomized trials (people assigned to groups by chance) of oral L-citrulline in adults, searched up to November 2017. Trials had 12 to 34 people each, took 3 to 9 g a day and lasted 1 to 17 weeks. The systolic drop was 4.10 mmHg, while the diastolic (bottom number) drop of 2.08 mmHg could be chance. Only in the trials with 6 g a day or more was the diastolic drop clear (2.75 mmHg). The trials were small and short, and blood pressure was the only outcome.
A second analysis of 5 trials found no change in blood pressure
It pooled clinical trials that measured pressure in the upper arm (brachial) and in the aorta, searched up to May 2018. Upper-arm systolic pressure changed by 0.28 mmHg and diastolic by -1.56 mmHg, both within the range of chance. Aortic pressure did not change either. Body weight explained some of the differences between trials, and the authors conclude that L-citrulline had no beneficial effect on blood pressure.
Citrulline or watermelon cut systolic pressure 4.0 mmHg in older adults
This meta-analysis of 15 trials in middle-aged and older adults tested L-citrulline supplements and watermelon together. So the result cannot be credited to one form. Its 24 datasets had 415 participants, and the systolic drop was 4.02 mmHg and the diastolic drop 2.54 mmHg. People who took L-citrulline together with L-arginine, a blend, had larger drops (10.44 and 4.86 mmHg). The authors report no conflict of interest.
Citrulline malate gave a small exercise gain, with low certainty
Citrulline malate is citrulline bound to malic acid, sold as a different product from plain L-citrulline. The 30 randomized trials had 644 participants and 138 effect sizes. The gain was small (Hedges g 0.16), of low to very low certainty, with a wide range of likely results. The effect on perceived exertion was not clear, and the authors say dose, timing and target group are not established. They call for trials with verified supplement content.
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Citrulline gave a small strength and power gain in a single session
This meta-analysis of 12 studies had 13 samples with 198 healthy people. They took at least 3 g of citrulline at least 30 minutes before resistance sets or sprints of 30 seconds or less. Blends with creatine, caffeine or nitrate were excluded. The pooled effect size was 0.20, and no single study showed a clear result on its own. The authors say the effect is small and may matter only for high-level athletes.
6 to 8 g of citrulline malate added about 3 repetitions (6.4%)
This meta-analysis of 8 studies had 137 participants, mostly strength-trained people. They took citrulline malate 40 to 60 minutes before a session at about 70% of their one-repetition maximum (the most they can lift once). The gain of 3 ± 5 repetitions before muscle failure (standardized difference 0.196) was small. For the lower body it was only a trend (8.1%), and for the upper body it could be chance (5.7%).
Citrulline malate did not improve muscle strength in resistance-trained adults
This meta-analysis of 4 randomized trials had 138 assessments, 69 on citrulline malate and 69 on placebo (a dummy treatment). The pooled effect size was 0.13, with similar results for the upper and lower limbs. The authors conclude that citrulline malate does not improve strength in healthy, resistance-trained people. Few studies were available.
In 10 studies, citrulline gave no benefit for aerobic exercise
All 10 studies compared citrulline alone with placebo. The pooled effect size for aerobic performance was 0.15, a result that could be chance. The effects on perceived exertion (-0.03), oxygen uptake kinetics (0.01) and lactate (0.25) were not clear either. Protocols that gave citrulline over several days seemed to show a positive tendency, which the authors say needs more studies. The authors report no conflict of interest.
Citrulline eased perceived effort and next-day soreness, not blood lactate
This meta-analysis of 13 articles had 206 healthy participants, who took citrulline within 2 hours before exercise. The most common dose was 8 g of citrulline malate. Perceived exertion (how hard the effort felt, 7 studies) fell clearly, and so did soreness 24 hours later. Soreness at 72 hours and blood lactate did not change. Both L-citrulline and citrulline malate were pooled.
In 115 women with preeclampsia, L-citrulline did not prolong pregnancy
This multicenter, double-blind trial (nobody knew who got what) enrolled women before 36 weeks: 58 on L-citrulline and 57 on placebo. The time from inclusion to delivery did not change (hazard ratio 0.90, close to no difference), and newborn outcomes did not differ. At delivery, systolic pressure was clearly higher on citrulline, and so were liver enzymes: ALT 65.1 against 33.2 IU, and AST 70.4 against 33.7 IU. The authors do not see citrulline as a promising treatment for preeclampsia.
8 g of citrulline malate once added reps and cut soreness 40%
In this randomized, double-blind crossover trial, 41 men tried both citrulline malate and placebo. In the last of 8 bench press sets, they did 52.92% more repetitions on citrulline malate. Muscle soreness at 24 and 48 hours was 40% lower. Stomach discomfort was the only side effect, in 14.63% of the men. It was a single dose in one trial, and the pooled analyses above found smaller gains.
1.5 g daily improved erection hardness in half of 24 mild cases
The men did not know what they took (single-blind), but placebo always came first, for 1 month, then L-citrulline for another month. Erection hardness rose from 3 to 4 (normal) in 12 men (50%) on citrulline and in 2 (8.3%) on placebo, a clear gap. Intercourse went from 1.53 times a month on placebo to 2.3 on citrulline, and no adverse events occurred. The authors call it less effective than phosphodiesterase type 5 inhibitor drugs and call for more research.
Citrulline-resveratrol pill raised erection scores when PDE5 drugs fell short
Each pill held 800 mg of L-citrulline and 300 mg of trans-resveratrol. This randomized, double-blind crossover pilot study gave a placebo month and a month on the pill, on top of on-demand drugs. Of 20 men enrolled, 13 finished, and their SHIM erection score was 10.96 on the pill against 8.31 on placebo. The erection hardness score did not clearly change. It is a blend of two ingredients, so the result cannot be credited to citrulline alone.
Watermelon juice for 4 weeks changed no blood vessel measure after menopause
In this randomized, double-blind crossover trial, 21 postmenopausal women drank two 360 mL servings of watermelon juice a day or a same-calorie placebo drink. A 2-week break separated the phases. Blood lycopene rose, and fasting glucose rose slightly. But arginine, citrulline, pulse wave velocity, 24-hour blood pressure and flow-mediated dilation (how well an artery widens) did not change. The authors note that earlier studies in younger adults and in people with hypertension found effects, and watermelon juice holds more than citrulline.
Protein synthesis unchanged on 10 g citrulline; women alone gained lean mass
This randomized trial at several centers included 24 malnourished patients aged 80 to 92. For 3 weeks they took citrulline or an equimolar mix (the same number of molecules) of six non-essential amino acids. Whole-body and liver protein synthesis did not differ. In the subgroup of women, lean mass rose by 1.7 kg and fat mass fell by 1.3 kg. Those changes ran from day 1 to day 20, compared with their own start. The whole group showed no clear differences between treatments.
After child heart surgery, citrulline did not clearly cut pulmonary hypertension
The 40 children had heart surgery with a heart-lung machine and were at risk of pulmonary hypertension (high pressure in the lung arteries) afterward. They took 5 doses of 1.9 g per m² (of body surface) of oral citrulline or placebo around the operation. It developed in 3 of 20 (15%) on citrulline and 6 of 20 (30%) on placebo, a gap that could be chance. No child developed it with plasma citrulline above 37 µmol/L, and citrulline and arginine blood levels were higher on citrulline. Blood pressure did not differ.
In urea cycle disorders, citrulline alone gave the lowest blood ammonia
This review looked back at 79 patients on a protein-restricted diet, treated at one French center since 1990. Most had ornithine transcarbamylase (57) or carbamoyl phosphate synthetase 1 (15) deficiency, and most also took ammonia-clearing drugs. Mean ammonia was 35.9 µmol/L on citrulline alone, 49.8 on arginine and 53.0 on citrulline plus arginine. Plasma arginine rose from 67.6 to 84.9 on citrulline, and 2 patients had gut side effects. Treatments were not randomized, and one author consulted for a drug maker.
Foods high in citrulline
Watermelon is the food source with measured values, and the amino acid is named after it. A 2019 paper calls watermelon the most important natural plant source of L-citrulline. That study tested 21 cultigens (cultivated plant types).
The highest fresh-weight values were 2.85 g per kilogram in the ‘Crimson Sweet’ watermelon and 2.43 g in ‘Dixielee’. Next came a casaba-type melon (0.86 g), mouse melon (0.64 g) and horned melon rind (0.45 g). The other 16 cultigens had less.
Other studies of watermelon flesh give 2.33 g per kilogram (fresh-cut cultivars) and 1.9 mg per gram (varieties). So a fair summary is 190 to 290 mg per 100 g. Color and plant part matter. In two studies, red and pink flesh held less than yellow or orange flesh.
The rind beat the flesh in two studies: 334 against 233 mg per 100 g, and 61 against about 41 (our arithmetic). In a third, it came out lower (130 against 190).
Juice is more dilute: 780 g of watermelon juice a day gave 1 g of citrulline in one trial. For scale, a 6 g dose like the ones in some trials is about 2.1 to 2.6 kilograms of flesh. That is our arithmetic from the two highest studies.
We found no published measurements for other common foods that we could use, so there is no ranking here. The body makes citrulline from glutamine, so food is not needed to supply it.
| Food | Citrulline per 100 g, fresh weight | Source |
|---|---|---|
| Watermelon flesh, ‘Crimson Sweet’ | about 285 mg (2.85 g/kg) | 1 |
| Watermelon flesh, ‘Dixielee’ | about 243 mg (2.43 g/kg) | 1 |
| Watermelon flesh, fresh-cut cultivars | about 233 mg (2.33 g/kg) | 2 |
| Watermelon flesh, varieties | about 190 mg (1.9 mg/g) | 3 |
| Watermelon rind | 61 to 334 mg, depending on the study and method | 4, 3, 2 |
| Watermelon juice | about 128 mg (1 g in 780 g of juice, our arithmetic) | 5 |
| Casaba-type melon | about 86 mg (0.86 g/kg) | 1 |
| Mouse melon | about 64 mg (0.64 g/kg) | 1 |
| Horned melon rind | about 45 mg (0.45 g/kg) | 1 |
Sources
- Hartman J, Wehner T, Ma G, Perkins-Veazie P. Citrulline and arginine content of taxa of Cucurbitaceae. Horticulturae. 2019.
- Tarazona-Díaz MP, Viegas J, Moldao-Martins M, Aguayo E. Bioactive compounds from flesh and by-product of fresh-cut watermelon cultivars. J Sci Food Agric. 2011.
- Rimando AM, Perkins-Veazie PM. Determination of citrulline in watermelon rind. J Chromatogr A. 2005.
- Du X, Davila M, Ramirez J, Williams C. Free amino acids and volatile aroma compounds in watermelon rind, flesh, and three rind-flesh juices. Molecules. 2022.
- Collins JK, Wu G, Perkins-Veazie P, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition. 2007.
- Cutrufello PT, Gadomski SJ, Zavorsky GS. The effect of l-citrulline and watermelon juice supplementation on anaerobic and aerobic exercise performance. J Sports Sci. 2015.
- Assefa AD, Hur OS, Ro NY, et al. Fruit morphology, citrulline, and arginine levels in diverse watermelon (Citrullus lanatus) germplasm collections. Plants (Basel). 2020.
- Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids. 2005.
How citrulline works
Most of the biochemistry below is well established. But it comes from reviews, blood measurements in small groups of people, and some cell and animal work, not from trials of health outcomes.
Four ideas cover it. The gut makes citrulline and the kidneys turn it into arginine, and cells recycle it when they make nitric oxide. The liver uses it in the urea cycle, and its blood level reflects how well the gut lining works. Here is each one, how much gets through when you take it by mouth, and what has been seen in people.
The gut makes it and the kidneys turn it into arginine
A 2005 review describes three separate routes for citrulline in mammals. In one, the gut makes citrulline from glutamine and releases it into the blood, and the kidneys convert it back into arginine. The review calls circulating citrulline a masked form of arginine that avoids being taken up by the liver.
This is why researchers took an interest in it as a supplement. Oral arginine is partly broken down on the way in, with an absolute bioavailability of about 20% for a 10 g dose in 10 volunteers. Bioavailability is the share that reaches the blood. Citrulline, by contrast, is readily absorbed and at least partly converted to arginine, according to a 2008 study.
The arginine page has the details on arginine.
How citrulline reaches the tissues, from the gut to the kidneys. Simplified. Not to scale.
Cells recycle it when they make nitric oxide
The enzyme that makes nitric oxide (NO) from arginine leaves citrulline behind. In most tissues that make NO, the same review says, citrulline is turned back into arginine by the enzyme argininosuccinate synthetase (ASS). That keeps arginine available.
The Nobel Assembly explained in 1998 how NO works on blood vessels. NO made by their inner layer relaxes the muscle cells beneath, and the vessel widens. That link is why citrulline was tried for blood pressure, exercise and erection. The trials below show that a plausible chain on paper does not always give a result in people.
How citrulline is recycled when cells make nitric oxide. Simplified. Not to scale.
The liver uses it in the urea cycle
In the liver, the same review says, one enzyme (OCT) makes citrulline and ASS uses it on the way to urea. Urea carries ammonia out of the body.
Inherited defects of the cycle, called urea cycle disorders, affect an estimated 1 in 8,000 births, according to 2012 European guidelines. Patients have high blood ammonia, either shortly after birth or later in life.
Blood citrulline helps to tell these disorders apart. It is very high in ASS deficiency (citrullinemia type I) and low in ornithine transcarbamylase deficiency. In most US states, Taiwan and Australia, newborn screening checks citrulline in dried blood spots for ASS deficiency. The guidelines say the benefit of this has not been formally evaluated.
How much gets through
In 20 healthy volunteers, 3 g of citrulline twice a day lifted the ratio of arginine to ADMA from 186 to 278. ADMA is a natural blocker of NO production. Citrulline also raised blood arginine more than arginine itself did.
In 8 men given single doses of 2, 5, 10 and 15 g, none had side effects. Less than 5% of the citrulline was lost in the urine. At the highest doses, citrulline built up in the blood while arginine rose less than expected. The kidneys’ conversion may have become saturated.
In a trial of watermelon juice, 780 and 1,560 g a day for 3 weeks gave 1 and 2 g of citrulline. That raised fasting arginine by 12% and 22%, while blood citrulline stayed stable. The chart puts these doses in perspective.
Grams of citrulline, drawn to scale. Teal: the citrulline in the watermelon juice of two trials. Orange: supplement doses; the 5.3 g is the citrulline in 8 g of citrulline malate, and the 15 g is the largest single dose in a dose-ranging study of 8 men.
Its blood level shows how well the gut lining works
Citrulline is made by the cells lining the small bowel, so when they are lost its blood level falls. In 57 adults with short bowel syndrome, it averaged 20 against 40 µmol/L in 51 controls. It also tracked the length of the remaining small bowel closely (r = 0.86, a strong link).
A level of 20 µmol/L separated permanent from transient intestinal failure. Its sensitivity was 92% and its specificity 90%, so it sorted most patients correctly.
In 52 patients with villous atrophy (a flattened gut lining), which includes celiac disease, the average was 24. That compares with 39 in people with anorexia nervosa and a normal gut lining. The level rose again in those whose gut lining healed on a gluten-free diet. This is a test used by doctors, not a reason to take citrulline.
Average fasting blood citrulline in two studies, drawn to scale. The 40 for healthy adults was the same in both studies.
What has been seen in people
The clearest findings are about blood chemistry and a few medical uses. Citrulline reliably raises blood arginine, and it is a treatment option in some urea cycle disorders. Its blood level tracks the gut lining.
The health outcomes are weaker. Blood pressure fell by about 4 mmHg in two pooled analyses and did not in a third. Exercise gains were small and often null. A trial in preeclampsia found no benefit and some harm signals, and erectile and muscle results come from small trials.
Most of these trials are among the study cards above and in the forms section below.
Sources
- Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids. 2005.
- Bouillanne O, Melchior JC, Faure C, et al. Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: the Ciproage randomized controlled trial. Clin Nutr. 2019.
- 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.
- Tangphao O, Grossmann M, Chalon S, Hoffman BB, Blaschke TF. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol. 1999.
- The Nobel Prize in Physiology or Medicine 1998. Press release. The Nobel Assembly at Karolinska Institutet. 12 October 1998.
- Häberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012.
- Quinonez SC, Lee KN. Citrullinemia type I. GeneReviews. University of Washington, Seattle. Updated 2022.
- Moinard C, Nicolis I, Neveux N, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008.
- Collins JK, Wu G, Perkins-Veazie P, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition. 2007.
- Cutrufello PT, Gadomski SJ, Zavorsky GS. The effect of l-citrulline and watermelon juice supplementation on anaerobic and aerobic exercise performance. J Sports Sci. 2015.
- Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011.
- Martín-Olmedo JJ, Miras-Moreno S, Cuadra-Montes K, et al. Malate or not? Acute effects of L-citrulline versus citrulline malate on neuromuscular performance in young, trained adults: a randomized, double-blind, placebo-controlled crossover trial. Int J Sport Nutr Exerc Metab. 2025.
- Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000.
- Crenn P, Vahedi K, Lavergne-Slove A, et al. Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology. 2003.
How much citrulline do you need?
No amount of citrulline is recommended, because it is not essential. The body makes it, and it is not built into proteins.
The WHO, FAO and UN University (2007) set requirements for the nine essential amino acids, and their report does not mention citrulline. EFSA’s 2012 opinion derived no reference values for amino acids. It found the data insufficient to set an upper level for protein.
The EU Register of nutrition and health claims has no entry for citrulline. We found no Daily Value, requirement or authorized claim for citrulline in these sources.
The body can run short in a few situations. Deficiencies of citrulline and arginine have been linked to adverse outcomes in preterm infants. Blood citrulline falls when the gut lining is damaged, and low citrulline goes with some inherited urea cycle defects. Those cases call for medical care, not a supplement from a shop.
Citrulline deficiency: signs and who is at risk
We found no description of a deficiency caused by eating too little citrulline in healthy people, and no signs to look for. The groups with low levels are medical ones.
Damaged gut lining is the most common reason. In people with villous atrophy (celiac disease and similar conditions), the average blood level was 24 µmol/L against 40 in healthy adults. The lowest levels, under 10, went with diffuse total villous atrophy.
After a year on a gluten-free diet, the level rose in the 6 patients whose gut lining responded. It did not rise in the 3 whose lining did not.
Inherited urea cycle disorders are the other group. Ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase 1 deficiency come with low blood citrulline.
The 2012 European guidelines say arginine must be supplied in these disorders, either as arginine or as its precursor L-citrulline. L-citrulline may be given instead of L-arginine in some of them, with no study comparing the two (a grade C recommendation). In a French review of 79 patients, citrulline alone went with the lowest ammonia and raised arginine.
The opposite happens in citrullinemia type I, where an enzyme defect makes blood citrulline very high, usually above 500 µmol/L. Treatment then includes protein restriction, ammonia-clearing drugs and arginine, not citrulline. These conditions need a specialist.
Low citrulline can also appear around surgery and birth. In 40 children having heart surgery, no child with a plasma citrulline above 37 µmol/L developed pulmonary hypertension afterward. In 42 preterm infants given 100, 200 or 300 mg per kg a day of L-citrulline for 7 days, blood citrulline rose in every group. Blood arginine rose in the highest-dose group, and there were no adverse events.
Sources
- Protein and amino acid requirements in human nutrition: report of a joint WHO/FAO/UNU expert consultation. WHO Technical Report Series 935. World Health Organization. 2007.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for protein. EFSA J. 2012.
- European Commission. EU Register of nutrition and health claims made on foods.
- Qasim A, Mehdi MQ, Bhatia S, Franco-Fuenmayor ME, Jain SK. Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels: a pilot randomized trial. J Perinatol. 2024.
- Crenn P, Vahedi K, Lavergne-Slove A, et al. Plasma citrulline: a marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology. 2003.
- Häberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012.
- Quinonez SC, Lee KN. Citrullinemia type I. GeneReviews. University of Washington, Seattle. Updated 2022.
- Imbard A, Bouchereau J, Arnoux JB, et al. Citrulline in the management of patients with urea cycle disorders. Orphanet J Rare Dis. 2023.
- Smith HA, Canter JA, Christian KG, et al. Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline. J Thorac Cardiovasc Surg. 2006.
- Summar M. Potential therapeutic uses of L-citrulline beyond genetic urea cycle disorders. J Inherit Metab Dis. 2024.
- Qasim A, Mehdi MQ, Bhatia S, Franco-Fuenmayor ME, Jain SK. Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels: a pilot randomized trial. J Perinatol. 2024.
Forms of citrulline: absorption and effects
Two products dominate: L-citrulline, the free amino acid, and citrulline malate, which is citrulline bound to malic acid. They do not hold the same amount of citrulline. In one 2025 trial, 8 g of citrulline malate held 5.3 g of citrulline and 2.7 g of malate. So a label that says 8 g of citrulline malate does not mean 8 g of citrulline.
Compare the grams of citrulline on the label. Watermelon juice and extracts are food-based sources, and some products blend citrulline with arginine or other ingredients.
The only head-to-head test of L-citrulline and citrulline malate that we found compared both with placebo in 43 trained adults. Neither beat placebo. We found no trial comparing the two forms for blood pressure or erection.
Some claim that the malate adds energy, or that time-release or “pump” formulas work better, but we found no trial of any of these claims. The arginine page covers arginine, which citrulline is converted into.
| Form | What it is | What studies show | Source |
|---|---|---|---|
| L-citrulline | The free amino acid. Label grams are grams of citrulline. | Raised blood arginine more than arginine itself in 20 volunteers; 3 g twice a day lifted the arginine to ADMA ratio from 186 to 278. Single doses of 2 to 15 g caused no side effects in 8 men, although at the highest doses blood arginine rose less than expected. 1.5 g a day for a month improved erection hardness in a small single-blind study, and a single 6 g dose did not improve exercise. | 5, 6, 4, 2 |
| Citrulline malate | Citrulline bound to malic acid. In one trial 8 g held 5.3 g of citrulline and 2.7 g of malate. | Trials mostly used 6 to 8 g. A pooled analysis found 3 more repetitions (6.4%) before failure, a larger one of 30 trials found a small gain in performance (g 0.16, low to very low certainty), and a single 8 g dose cut soreness by 40% in 41 men. In 43 trained adults a 2025 trial found no benefit from either form. | 7, 9, 8, 1 |
| Watermelon juice or extract | A food source that also holds other compounds, such as lycopene. | 780 and 1,560 g of juice a day for 3 weeks (1 and 2 g of citrulline) raised fasting arginine by 12% and 22%. 710 mL (about 1 g) before exercise did not help, and two 360 mL servings a day for 4 weeks changed no vascular measure in 21 postmenopausal women. | 3, 2, 13 |
| Citrulline plus arginine | A blend of two amino acids, sold or tested together. | In a pooled analysis in middle-aged and older adults the subgroup on both had a larger systolic drop (10.44 mmHg) than the whole group, and the result cannot be credited to citrulline alone. In 119 children with sickle cell disease, a food supplement with arginine and citrulline did not differ significantly from the basic version on artery dilation (1.00 percentage points, p = 0.18). | 10, 12 |
| Citrulline plus trans-resveratrol | A blend: 800 mg of L-citrulline and 300 mg of trans-resveratrol a day. | Raised erectile function scores in 13 men who still had problems on PDE5 drugs, in a crossover pilot study. The result cannot be credited to citrulline alone. | 11 |
Here are the three form-specific studies, all with limited evidence.
L-citrulline and citrulline malate both failed to beat placebo
This randomized, double-blind, placebo-controlled crossover trial tested 43 trained adults, 21 women and 22 men. They took placebo, L-citrulline (5.3 g of citrulline) or citrulline malate (5.3 g of citrulline plus 2.7 g of malate) 45 minutes before testing. Neither form improved maximal or ballistic performance, repetitions, bar speed or perceived exertion. It is the only head-to-head test of the two forms we found.
A single dose of citrulline or watermelon juice did not improve exercise
In this randomized, double-blind study, 22 people tried every drink. The drinks were 710 mL of watermelon juice (about 1.0 g of citrulline), 6 g of L-citrulline in a 7.5% sucrose drink, or placebo. They took them 1 or 2 hours before testing. Repetitions, time to exhaustion, maximal oxygen use, anaerobic threshold and flow-mediated dilation did not differ, whatever the timing or sex.
Three weeks of watermelon juice raised fasting arginine by 12% and 22%
In this crossover trial with a controlled diet, 12 to 23 people per treatment drank 0, 780 or 1,560 g of watermelon juice a day. They did so for 3 weeks, which gave 1 or 2 g of citrulline a day. Arginine rose by 12% on the lower dose, and arginine and ornithine by 22% and 18% on the higher dose. Blood citrulline stayed stable, and the authors read this as the citrulline in the juice being converted to arginine. Arginine was a blood marker here, not a health outcome.
Sources
- Martín-Olmedo JJ, Miras-Moreno S, Cuadra-Montes K, et al. Malate or not? Acute effects of L-citrulline versus citrulline malate on neuromuscular performance in young, trained adults: a randomized, double-blind, placebo-controlled crossover trial. Int J Sport Nutr Exerc Metab. 2025.
- Cutrufello PT, Gadomski SJ, Zavorsky GS. The effect of l-citrulline and watermelon juice supplementation on anaerobic and aerobic exercise performance. J Sports Sci. 2015.
- Collins JK, Wu G, Perkins-Veazie P, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition. 2007.
- Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011.
- 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.
- Moinard C, Nicolis I, Neveux N, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008.
- Vårvik FT, Bjørnsen T, Gonzalez AM. Acute effect of citrulline malate on repetition performance during strength training: a systematic review and meta-analysis. Int J Sport Nutr Exerc Metab. 2021.
- Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010.
- Wang X, Fan X, Chang J, et al. Effects of citrulline malate supplementation on exercise performance: a systematic review and three-level meta-analysis. Nutrients. 2026.
- Luo P, Chen J, Liu K, Zhang J. Does l-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults? A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN. 2025.
- Shirai M, Hiramatsu I, Aoki Y, et al. Oral L-citrulline and transresveratrol supplementation improves erectile function in men with phosphodiesterase 5 inhibitors: a randomized, double-blind, placebo-controlled crossover pilot study. Sex Med. 2018.
- Cox SE, Ellins EA, Marealle AI, et al. Ready-to-use food supplement, with or without arginine and citrulline, with daily chloroquine in Tanzanian children with sickle-cell disease: a double-blind, random order crossover trial. Lancet Haematol. 2018.
- Ellis AC, Mehta T, Nagabooshanam VA, et al. Daily 100% watermelon juice consumption and vascular function among postmenopausal women: a randomized controlled trial. Nutr Metab Cardiovasc Dis. 2021.
Is citrulline safe? Supplements, dose and interactions
Citrulline from food, such as watermelon, is not a concern. We found no requirement, upper limit or authorized health claim for citrulline in the WHO 2007 report, EFSA’s 2012 protein opinion or the EU Register. So we found no official safe limit.
What is known comes from trials. A 2022 review of amino acid supplement side effects covered citrulline. It says the effects of high doses and long-term use need more research.
- Doses and stomach effects. In 8 healthy men, single doses of 2, 5, 10 and 15 g caused no side effects. The authors call short-term use safe and well tolerated. In a trial of 8 g of citrulline malate before a workout, 14.63% of 41 men reported stomach discomfort. A month of 1.5 g a day caused no adverse events in 24 men. Of 42 preterm infants, 40 finished a week of 100 to 300 mg per kg a day with none.
- Pregnancy. In 115 women with preeclampsia, L-citrulline did not prolong pregnancy. Liver enzymes (ALT 65.1 against 33.2 IU) and systolic pressure were higher at delivery than on placebo. A small trial in women with chronic hypertension found 3 g twice a day acceptable for 8 weeks. It was too small to show an effect on blood pressure. Ask a doctor before taking citrulline in pregnancy.
- Blood pressure medicines and erection drugs. Citrulline lowered blood pressure by about 4 mmHg in some pooled analyses. So tell a doctor if you take blood pressure medicine or nitrates. A pilot study added 800 mg of citrulline with trans-resveratrol to on-demand PDE5 drugs, and the 13 men who finished had no adverse events. We found no trial of citrulline with nitrates. The authors of the 2011 erection trial call citrulline less effective than PDE5 inhibitors in the short term.
- Inherited disorders and transplants. People with urea cycle disorders take L-citrulline or L-arginine under a specialist’s plan. People with citrullinemia type I, whose blood citrulline is already very high, do not use it. In a pilot study, 16 people with urea cycle disorders took long-term L-citrulline and arginine after a liver transplant. Their growth and neurocognitive outcomes (thinking and learning) did not differ from 36 who took none.
How to get more citrulline
- Watermelon. The flesh holds about 190 to 290 mg per 100 g in the studies above. A 6 g trial dose would take more than 2 kilograms of flesh, so food and supplement trials are not the same thing.
- Your body already makes it. Gut cells make citrulline from glutamine and the kidneys turn it into arginine, so healthy people do not need a supplement to get citrulline.
- If you try a supplement, read the label in grams of citrulline. Trials used 0.8 to 10 g a day, and 8 g of citrulline malate was 5.3 g of citrulline in one trial. The evidence for blood pressure, exercise and erection is small and mixed. So ask a doctor first if you take blood pressure drugs, are pregnant or have a metabolic disorder.
Sources
- Protein and amino acid requirements in human nutrition: report of a joint WHO/FAO/UNU expert consultation. WHO Technical Report Series 935. World Health Organization. 2007.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for protein. EFSA J. 2012.
- European Commission. EU Register of nutrition and health claims made on foods.
- Moinard C, Nicolis I, Neveux N, et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008.
- Holeček M. Side effects of amino acid supplements. Physiol Res. 2022.
- Winer N, Misbert E, Masson D, et al. Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial. Am J Clin Nutr. 2025.
- Ormesher L, Worton SA, Best A, et al. CHronic hypERtension and L-citRulline studY (CHERRY): an early-phase randomised controlled trial in pregnancy. Reprod Sci. 2024.
- Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011.
- Shirai M, Hiramatsu I, Aoki Y, et al. Oral L-citrulline and transresveratrol supplementation improves erectile function in men with phosphodiesterase 5 inhibitors: a randomized, double-blind, placebo-controlled crossover pilot study. Sex Med. 2018.
- Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010.
- Qasim A, Mehdi MQ, Bhatia S, Franco-Fuenmayor ME, Jain SK. Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels: a pilot randomized trial. J Perinatol. 2024.
- Posset R, Garbade SF, Gleich F, et al. Impact of supplementation with L-citrulline/arginine after liver transplantation in individuals with urea cycle disorders. Mol Genet Metab. 2024.
- Quinonez SC, Lee KN. Citrullinemia type I. GeneReviews. University of Washington, Seattle. Updated 2022.
- Häberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012.
- Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi B. Effects of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis. Avicenna J Phytomed. 2019.
- 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.
- Luo P, Chen J, Liu K, Zhang J. Does l-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults? A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN. 2025.
- Martín-Olmedo JJ, Miras-Moreno S, Cuadra-Montes K, et al. Malate or not? Acute effects of L-citrulline versus citrulline malate on neuromuscular performance in young, trained adults: a randomized, double-blind, placebo-controlled crossover trial. Int J Sport Nutr Exerc Metab. 2025.
- Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids. 2005.
- Hartman J, Wehner T, Ma G, Perkins-Veazie P. Citrulline and arginine content of taxa of Cucurbitaceae. Horticulturae. 2019.
- Tarazona-Díaz MP, Viegas J, Moldao-Martins M, Aguayo E. Bioactive compounds from flesh and by-product of fresh-cut watermelon cultivars. J Sci Food Agric. 2011.
History of citrulline
Before 1930, the word citrulline also named a resin produced by Citrullus colocynthis, a relative of the watermelon. A 2011 historical review asks in its title whether citrulline was first a laxative substance. It says that resin is not the amino acid we mean today.
The same review shows that the amino acid was isolated earlier than usually stated. Koga and Ohtake isolated it in 1914, although their work did not settle its structure.
In 1930 Mitsunori Wada described it as a new amino acid in the pressed juice of the watermelon, then called Citrullus vulgaris. The name comes from the watermelon’s genus. Its role came later: citrulline turned out to be a step in the urea cycle. As the 2005 review explains, it is also a way for the gut to send arginine to the kidneys.
Two findings put it into supplements. In 2000, Crenn and colleagues showed that its blood level marks a working gut lining. In 2008, Schwedhelm and colleagues showed that oral citrulline raised blood arginine more than arginine itself. The trials that followed, on blood pressure, exercise and erection, are mostly small.
Sources
- Citrulline. Wikipedia.
- Fragkos KC, Forbes A. Was citrulline first a laxative substance? The truth about modern citrulline and its isolation. Nihon Ishigaku Zasshi. 2011.
- Wada M. On the occurrence of a new amino acid in watermelon, Citrullus vulgaris, Schrad. Proc Imp Acad. 1930.
- Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids. 2005.
- Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000.
- 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.
Frequently asked questions about citrulline
Is citrulline an essential amino acid?
No. The body makes it in the gut cells from glutamine, and a 2024 review calls it a non-essential amino acid. It is also not one of the amino acids built into proteins. EFSA’s 2012 opinion lists it among the non-proteinogenic ones, and the WHO’s 2007 report sets needs only for the nine essential amino acids. The body can run short in a few medical situations, such as a damaged gut lining or some urea cycle disorders.
Is citrulline better than arginine?
It raised blood arginine more in one study. In 20 healthy volunteers, citrulline raised plasma arginine more than arginine itself. In another study, only about 20% of a 10 g oral dose of arginine reached the blood. We found no trial that shows citrulline gives better health results than arginine. The arginine page covers the arginine trials.
What is the difference between L-citrulline and citrulline malate?
L-citrulline is the amino acid alone, while citrulline malate is citrulline bound to malic acid. In one 2025 trial, 8 g of citrulline malate held 5.3 g of citrulline and 2.7 g of malate. That trial compared both forms with placebo in 43 trained adults, and neither beat placebo. We found no other head-to-head test.
Does citrulline improve workouts?
Maybe a little, once. A meta-analysis of 12 studies found a small gain in strength and power (effect size 0.20). One of 8 studies found about 3 more repetitions with 6 to 8 g of citrulline malate. A meta-analysis of 4 studies found no gain in muscle strength, and one of 10 studies found none for aerobic outcomes. A larger analysis of 30 trials rated the certainty of a small gain as low to very low.
Does citrulline lower blood pressure?
A little in some analyses, not in others. A meta-analysis of 8 trials found a systolic drop of 4.1 mmHg at 3 to 9 g a day. One of 15 trials in older adults, which included watermelon, found 4.0 mmHg. A third meta-analysis of 5 trials found no change. The trials are small and short, and they measured blood pressure, not heart attacks.
Does citrulline help erectile dysfunction?
It may help a little in mild cases, from small trials. In 24 men with mild erectile dysfunction, 1.5 g a day for a month brought normal erection hardness to 50% against 8.3% on placebo. But the placebo month always came first. A pilot trial of citrulline with trans-resveratrol helped men who still had problems on PDE5 drugs. Ask a doctor before combining them.
How much citrulline is in watermelon?
About 190 to 290 mg per 100 g of flesh in the studies above, which is about 2 to 3 g per kilogram. The ‘Crimson Sweet’ cultivar had 2.85 g per kilogram. The rind gave 61 to 334 mg per 100 g, depending on the study. A trial dose of 6 g would take about 2.1 to 2.6 kilograms of flesh, by our arithmetic.
How much citrulline can you take a day?
No official upper limit exists that we found. Trials used 0.8 to 10 g a day, and single doses up to 15 g caused no side effects in 8 healthy men. But 8 g of citrulline malate gave stomach discomfort to 14.63% of 41 men. Ask a doctor first if you are pregnant, take blood pressure medicine or have a kidney, liver or metabolic condition.