Watermelon, Citrulline, and Blood Flow

Table of Contents

1. What Citrulline Is, and Why Watermelon Owns It
2. The Citrulline to Arginine to Nitric Oxide Pathway
3. Why Swallowing Citrulline Beats Swallowing Arginine
4. How Much Citrulline Is Actually in a Slice
5. The Rind: More Per Dry Gram, Less Per Bite
6. Blood Pressure: What the Trials Actually Show
7. Exercise Performance and Muscle Soreness
8. Endothelial Function and the Erection Question
9. Who Is Most Likely to Notice Anything
10. Practical: How Much, Which Melon, What Form
11. Honest Cautions
12. Key Research Papers
13. Connections
14. Featured Videos

What Citrulline Is, and Why Watermelon Owns It

Citrulline is a non-protein amino acid — meaning your body does not build it into muscle or enzymes the way it builds leucine or lysine. It circulates instead as a kind of intermediate, a carrier molecule shuttling nitrogen between the gut, the liver and the kidney. It was first isolated from watermelon in the 1930s, and it is named after the fruit: the genus is Citrullus, and citrulline is the amino acid the plant is famous for stockpiling.

That naming is not a coincidence of history — watermelon really does accumulate the stuff. In a 2005 US Department of Agriculture survey using gas chromatography–mass spectrometry to separate citrulline cleanly from glutamic acid (they co-elute on HPLC, which had muddied earlier numbers), citrulline in watermelon tissue ranged from 3.9 to 28.5 mg per gram of dry weight depending on variety, type, flesh colour and which part of the fruit was tested. Seeded and seedless types were close (16.6 and 20.3 mg/g dry weight). Flesh colour mattered more than most people expect: in that survey, red-fleshed melons held less citrulline than yellow or orange ones (7.4, 28.5 and 14.2 mg/g dry weight respectively).

Very few other foods come close. Other cucurbits — bitter melon, some gourds, cucumber — contain some, and the body makes its own citrulline in the gut from glutamine, but if you are looking for a food that delivers a meaningful dose in a portion a person would actually eat, watermelon stands more or less alone. The site keeps the full amino-acid profile on the Citrulline page; this article is about what happens when the citrulline arrives inside a piece of fruit.

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The Citrulline to Arginine to Nitric Oxide Pathway

The chain has three links, and each one is worth understanding because the interesting behaviour happens at the joints.

1. Citrulline is absorbed and reaches the kidney. Unlike most amino acids, citrulline is not stripped out by the liver on its first pass. It travels through the portal circulation largely untouched and is taken up mainly by the proximal tubule cells of the kidney.
2. The kidney converts citrulline into arginine. Two enzymes do it — argininosuccinate synthase and argininosuccinate lyase — in what is effectively the back half of the urea cycle running as a synthesis pathway rather than a disposal one. The arginine is then released into the bloodstream.
3. Arginine is the substrate for nitric oxide synthase. In the endothelium — the single-cell lining of every blood vessel — the enzyme endothelial nitric oxide synthase (eNOS) takes arginine and oxygen and produces nitric oxide plus citrulline again. Nitric oxide diffuses into the smooth muscle of the vessel wall, activates guanylate cyclase, raises cyclic GMP, and the muscle relaxes. The vessel widens; resistance falls; blood moves more easily.

Notice the loop: making nitric oxide from arginine regenerates citrulline, and the kidney can recycle that citrulline back into arginine. Physiologists call it the citrulline–nitric-oxide cycle, and it means the two amino acids are less like a fuel and its ash and more like two positions of the same molecule.

One more player belongs in the picture because it explains several trial results: ADMA, asymmetric dimethylarginine. ADMA looks enough like arginine to sit in the eNOS active site without being usable, so it competitively blocks nitric oxide production. ADMA rises with age, kidney disease, insulin resistance and high cholesterol. This is why researchers so often report the arginine/ADMA ratio rather than arginine alone: what matters is not how much substrate you have but how much substrate you have relative to the blocker sitting in the same seat.

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Why Swallowing Citrulline Beats Swallowing Arginine

Here is the genuinely surprising part, and it is well documented rather than folklore. If your goal is to raise the arginine concentration in your blood, taking citrulline by mouth works better than taking arginine by mouth.

The reason is an enzyme called arginase, which sits in abundance in the wall of the small intestine and in the liver. Arginase breaks arginine down to ornithine and urea. Swallowed arginine runs straight into that wall of enzyme and much of it never reaches the general circulation — a first-pass loss that also explains why oral arginine gives people gastrointestinal upset at the doses that would be needed to overcome it. Citrulline is invisible to arginase. It slips past the gut and the liver, reaches the kidney, and is converted to arginine downstream of the enzyme that would have destroyed it.

A double-blind, randomised, placebo-controlled crossover study in 20 healthy volunteers compared six dosing regimens of placebo, citrulline and arginine after a week on each. Citrulline raised the peak concentration and the total exposure (area under the curve) of plasma arginine more effectively than arginine itself did, and it did so in a dose-dependent way. At the highest dose tested — 3 g of citrulline twice a day — the arginine/ADMA ratio rose from 186 to 278, urinary nitrate excretion rose from about 92 to 125 µmol per mmol of creatinine, and urinary cyclic GMP rose too. Those last two are downstream fingerprints: more nitrate and more cyclic GMP in the urine mean more nitric oxide was actually made and more signalling actually happened.

The same study is worth quoting for its restraint. No treatment improved flow-mediated dilation — the standard ultrasound test of how well an artery widens — compared with baseline. Only when the authors pooled all the flow-mediated dilation data did a correlation appear between the rise in the arginine/ADMA ratio and improvement in the measurement. So: the biochemical machinery moved, convincingly and dose-dependently; the clinical readout in healthy young vessels did not. Healthy endothelium is already doing its job, and there is not much room to improve it.

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How Much Citrulline Is Actually in a Slice

This is the number that decides whether the rest of the page is about food or about supplements, and it deserves to be stated plainly.

In the USDA measurements, watermelon flesh carried about 1.9 mg of citrulline per gram of fresh weight. Run that forward:

• A one-cup serving of diced watermelon is about 150 g — roughly 0.3 g of citrulline.
• A generous two-cup serving, about 280–300 g, is roughly 0.5–0.6 g.
• A whole 3 kg melon, flesh only, is somewhere near 5–6 g — which nobody eats at a sitting, though people have tried.

Now compare that with the doses used in the trials that actually moved blood pressure: 6 g per day of concentrated watermelon extract, or 3 g of pure citrulline twice daily. A large serving of fruit delivers something like a tenth of that. This is not a reason to dismiss watermelon — it is the reason to be honest about which claims belong to the fruit and which belong to the extract. Watermelon supplies a real, measurable, food-level dose of a compound most diets contain almost none of. It does not supply a pharmacological dose, and pages that quietly transfer the extract trials' results onto a bowl of fruit salad are misleading you.

Two smaller variables are worth knowing. Citrulline concentration rises as the fruit ripens, so a properly ripe melon carries more than an underripe one. And, as noted above, yellow and orange-fleshed varieties measured higher than red in the USDA survey — the opposite of what you would guess, since red flesh is what signals lycopene. If you have a choice at a farm stand and citrulline is what you are after, the pale gold melons are not a novelty; they are the stronger source.

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The Rind: More Per Dry Gram, Less Per Bite

"The rind has more citrulline than the flesh" is one of the most repeated watermelon facts on the internet, and it is half true in a way that matters. Here is the whole measurement from the study everyone is quoting:

• Per gram of dry weight: rind 24.7 mg, flesh 16.7 mg. The rind wins clearly.
• Per gram of fresh weight — the food as you would eat it: rind 1.3 mg, flesh 1.9 mg. The flesh wins.

The reversal is not a contradiction, it is a water-content effect. Watermelon flesh is over 91% water, and rind holds proportionally more solid matter, so drying the two samples concentrates the rind's advantage and eating them wet erases it. Gram for gram on your plate, red flesh is the better citrulline source, not worse.

So why does anyone care about the rind? Because it is agricultural waste in enormous quantity. Roughly a third of every melon harvested is discarded rind, and a byproduct stream with 24.7 mg of citrulline per dry gram is an attractive feedstock for food-industry extraction — which is exactly how the authors framed their conclusion, and why watermelon-rind extraction chemistry has become its own small research literature. The rind is also a genuine source of pectin, a soluble fibre used as a gelling agent.

For a home cook, the practical version is simpler: the pale green-white inner rind is edible, mildly cucumber-like, and traditionally pickled across the American South, the Balkans, the Middle East and China, or stir-fried in southern Chinese cooking. Eating it adds fibre the flesh does not have (watermelon flesh is nearly fibre-free at 0.4 g per 100 g) and stops you throwing away a third of what you paid for. Just do not eat it because you were told it is a citrulline shortcut — per bite, it is not.

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Blood Pressure: What the Trials Actually Show

There are two literatures here and they point in slightly different directions, which is exactly why they should be read side by side rather than cherry-picked.

The concentrated-extract trials, mostly from one Florida State University group, are positive and consistent. A crossover study in 14 obese middle-aged adults with prehypertension or stage 1 hypertension gave 6 g daily of a watermelon extract supplying L-citrulline and L-arginine for six weeks against placebo. Brachial systolic pressure fell by about 15 mmHg, ankle systolic by about 11.5 mmHg, diastolic by roughly 7–8 mmHg, and carotid augmentation index — a measure of how hard the reflected pressure wave slams back at the heart — fell by about 9 percentage points. Companion studies from the same group reported reduced aortic pressure and wave reflection in prehypertensive adults, and improved arterial stiffness in postmenopausal women.

Those are real effects and the size is not trivial. But read the design honestly: fourteen people, one research group, a supplement rather than a food, and surrogate vascular endpoints rather than heart attacks. That is hypothesis-generating evidence, not settled fact.

The whole-fruit trial is the sobering one. A randomised, placebo-controlled parallel study published in 2025 gave 39 adults with elevated blood pressure either no watermelon, one cup a day (152 g), or two cups a day (304 g) for four weeks, and measured 24-hour ambulatory blood pressure — a better endpoint than a single clinic reading. The result: no statistically significant difference between the groups. Mean 24-hour pressures were 130.2, 130.0 and 124.9 mmHg for control, one cup and two cups; the two-cup number looks lower but did not reach significance in a study of that size. Fasting glucose, insulin, lipids and nitric oxide did not shift either.

And yet the same trial found something encouraging: plasma L-arginine and the arginine/ADMA ratio rose significantly in the watermelon groups compared with control. In other words, ordinary portions of ordinary fruit did move the biochemistry in the intended direction — the substrate for nitric oxide went up — but four weeks at that dose was not enough to bend the blood-pressure curve.

The honest synthesis is this. The mechanism is real and food-level watermelon engages it. Concentrated extracts at roughly ten times a food dose have lowered blood pressure in small trials of people who already had elevated pressure. Whole fruit at realistic intake has not yet been shown to do so. If you want watermelon in your diet, that is a good idea for many reasons; if you want a blood-pressure treatment, watermelon is not it, and the evidence says so plainly.

One more thing readers deserve to know: a frequently cited 2019 meta-analysis of citrulline supplementation and blood pressure was subsequently retracted by its journal. It still circulates in reference lists and in supplement marketing. We have listed it below marked as retracted so you can recognise it if you meet it, and we have not used it as evidence anywhere on this page.

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Exercise Performance and Muscle Soreness

The sports-nutrition claims split cleanly into the ones with support and the ones without.

Pure citrulline (and citrulline malate) has decent evidence for high-intensity work. A controlled study found that L-citrulline supplementation improved oxygen-uptake kinetics — how fast the aerobic system spins up at the start of hard exercise — and improved high-intensity exercise performance. A comprehensive review of the human literature concluded that citrulline can benefit performance, with the caveats that effects are modest, more consistent for repeated high-intensity efforts and resistance training volume than for steady-state endurance, and heavily dependent on dose and timing.

Watermelon juice itself has weaker evidence, and one clean negative result. Eight recreationally active men took 300 mL a day of watermelon juice concentrate — about 3.4 g of citrulline daily, several times what a large serving of fruit provides — for 16 days in a crossover design against apple juice. Nitric oxide bioavailability improved. Endurance exercise performance did not. The authors said so in the title of the paper, which is more candour than the supplement aisle usually manages.

Muscle soreness is the more interesting signal. A study of natural watermelon juice and citrulline-enriched watermelon juice in athletes found reduced muscle-soreness recovery heart rate and lower perceived soreness at 24 hours after exercise. A later trial with a functional citrulline-enriched watermelon juice in half-marathon runners looked at biochemical, physiological and performance responses in a real race rather than a laboratory. The soreness findings are plausible — better perfusion of working muscle plausibly clears metabolites faster — but these are small studies and the outcome (how sore you feel) is subjective.

Practical reading for an athlete: watermelon juice after a hard session is a pleasant, well-tolerated recovery drink with sugar, fluid, potassium and a modest citrulline dose, and it may take a little of the edge off next-day soreness. It is not an ergogenic aid. If you want the performance effect that the citrulline literature supports, that comes from grams of citrulline or citrulline malate, not from fruit.

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Endothelial Function and the Erection Question

Every few summers a story goes around that watermelon is "nature's Viagra." The comparison is not pure invention — it is just badly scaled.

Sildenafil and the drugs like it work on the same pathway watermelon touches, but at a different point. Nitric oxide raises cyclic GMP; those drugs block the enzyme (phosphodiesterase-5) that destroys cyclic GMP, so the signal that is already there lasts longer and hits harder. Citrulline feeds the front of that pathway by supplying arginine for nitric oxide synthesis. Feeding the front of a pathway and blocking the drain at the back are not the same intervention, and the magnitudes are not remotely comparable.

There is a small pilot literature on oral L-citrulline in mild erectile dysfunction reporting improvement in some men, and the underlying logic — erectile function is fundamentally an endothelial, nitric-oxide-dependent event, and erectile dysfunction is often an early warning sign of generalised endothelial disease — is sound. But the studies are small, the doses are supplement doses, and a bowl of watermelon is not one of them.

The useful takeaway is less exciting and more valuable: the same endothelium that governs erections governs coronary and cerebral blood flow. Anything that genuinely supports endothelial health — not smoking, moving daily, sleeping, keeping blood sugar and blood pressure in range, eating plants including nitrate-rich ones like beets and arugula — is working on the same system. Watermelon is a pleasant contributor to that list, not a substitute for any of it.

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Who Is Most Likely to Notice Anything

Nitric-oxide interventions follow a consistent pattern across the literature: the worse your endothelial function is to start with, the more room there is to improve. That predicts who responds.

• Older adults. Nitric oxide production falls with age and ADMA rises, so the arginine/ADMA ratio drifts the wrong way. Almost all the positive watermelon-extract trials were run in middle-aged and older participants.
• People with elevated or stage 1 blood pressure. Every positive trial above recruited from this group. Healthy young volunteers repeatedly show biochemical changes with no measurable vascular improvement, because there was nothing to fix.
• People with metabolic risk. Insulin resistance impairs eNOS signalling and raises ADMA. Animal work in a diabetic-rat model found watermelon pomace juice improved arginine availability and metabolic markers — suggestive, not transferable to humans on its own.
• Postmenopausal women, in whom arterial stiffness rises after oestrogen declines, were a specific target of two of the Florida State studies.

Conversely: if you are 25, fit and normotensive, the honest expectation from a bowl of watermelon is hydration, potassium, lycopene, and a nice afternoon. That is a perfectly good reason to eat it.

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Practical: How Much, Which Melon, What Form

• A realistic serving is one to two cups (150–300 g), giving roughly 0.3–0.6 g of citrulline, about 45–90 calories, and 170–340 mg of potassium.
• Ripe beats underripe. Citrulline accumulates during ripening, as does lycopene. A melon picked early never catches up — watermelon is non-climacteric and does not sweeten after harvest. Look for a large, deep-yellow ground spot where it sat on the soil, a dull rather than glossy skin, and a heavy feel for its size.
• Yellow and orange varieties measured higher in citrulline than red in the USDA survey. Red varieties carry the lycopene. There is no single "best" melon; they are strong in different things.
• Eat it raw. Citrulline is water-soluble and heat-labile; there is no cooking step that helps here.
• Juice concentrates the dose because you are drinking the liquid from far more fruit than you would chew — which is precisely why juice was used in the trials. It also concentrates the sugar and strips what little fibre there is, so treat watermelon juice as a training drink or a treat, not a daily beverage.
• The inner rind is edible — pickled, stir-fried, or blended into a smoothie. Scrub the outside of the melon before you cut it in any case; see the food-safety article for why that step matters more than most people realise.
• If you want the trial dose, you want a supplement, and you should know that. Watermelon-derived and synthetic L-citrulline are chemically the same molecule; there is no evidence that the fruit-derived version behaves differently. What the fruit adds is water, potassium, lycopene and vitamin C.

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Honest Cautions

Watermelon is one of the safest foods there is, and citrulline is well tolerated at the doses studied. Three things still deserve a mention.

Blood-pressure medication and nitrates. If you take antihypertensive drugs, and especially if you take nitrates for angina or a PDE-5 inhibitor, you are already acting on the nitric-oxide pathway. Ordinary servings of fruit are not a realistic problem. Gram-dose citrulline supplements alongside those drugs are a different question and one worth raising with whoever prescribes them, because the effects are additive by design.

Kidney disease. Citrulline is converted to arginine in the kidney and both are handled renally. In advanced kidney disease, amino acid supplementation is not a casual decision. The fruit itself also carries potassium — modest per 100 g, but watermelon is eaten in large portions, and people on potassium restriction should count it rather than assume that something 91% water is free.

Sugar in large portions. Watermelon is about 6.2 g of sugar per 100 g, which is low, but a 700 g wedge is 43 g of sugar with almost no fibre to slow it. The glycaemic index and glycaemic load question is genuinely misunderstood and is covered properly in the Food Safety and Digestion article.

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Key Research Papers

1. Rimando AM, Perkins-Veazie PM. Determination of citrulline in watermelon rind. Journal of Chromatography A. 2005;1078(1-2):196-200. — doi:10.1016/j.chroma.2005.05.009
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. British Journal of Clinical Pharmacology. 2008;65(1):51-59. — doi:10.1111/j.1365-2125.2007.02990.x
3. Collins JK, Wu G, Perkins-Veazie P, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition. 2007;23(3):261-266. — doi:10.1016/j.nut.2007.01.005
4. Singh K, Liao H, Edirisinghe I, Burton-Freeman B, Sandhu AK. Dose-response effect of watermelon consumption on ambulatory blood pressure in adults with elevated blood pressure: a randomized controlled pilot trial. Nutrients. 2025;17(19):3073. — doi:10.3390/nu17193073
5. Figueroa A, Sanchez-Gonzalez MA, Wong A, Arjmandi BH. Watermelon extract supplementation reduces ankle blood pressure and carotid augmentation index in obese adults with prehypertension or hypertension. American Journal of Hypertension. 2012;25(6):640-643. — doi:10.1038/ajh.2012.20
6. Figueroa A, Sanchez-Gonzalez MA, Perkins-Veazie PM, Arjmandi BH. Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study. American Journal of Hypertension. 2011;24(1):40-44. — doi:10.1038/ajh.2010.142
7. Figueroa A, Wong A, Hooshmand S, Sanchez-Gonzalez MA. Effects of watermelon supplementation on arterial stiffness and wave reflection amplitude in postmenopausal women. Menopause. 2013;20(5):573-577. — doi:10.1097/GME.0b013e3182733794
8. Bailey SJ, Blackwell JR, Williams E, et al. Two weeks of watermelon juice supplementation improves nitric oxide bioavailability but not endurance exercise performance in humans. Nitric Oxide. 2016;59:10-20. — doi:10.1016/j.niox.2016.06.008
9. Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG, Jones AM. L-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. Journal of Applied Physiology. 2015;119(4):385-395. — doi:10.1152/japplphysiol.00192.2014
10. Gonzalez AM, Trexler ET. Effects of citrulline supplementation on exercise performance in humans: a review of the current literature. Journal of Strength and Conditioning Research. 2020;34(5):1480-1495. — doi:10.1519/JSC.0000000000003426
11. Tarazona-Díaz MP, Alacid F, Carrasco M, Martínez I, Aguayo E. Watermelon juice: potential functional drink for sore muscle relief in athletes. Journal of Agricultural and Food Chemistry. 2013;61(31):7522-7528. — doi:10.1021/jf400964r
12. Martínez-Sánchez A, Ramos-Campo DJ, Fernández-Lobato B, Rubio-Arias JA, Alacid F, Aguayo E. Biochemical, physiological, and performance response of a functional watermelon juice enriched in L-citrulline during a half-marathon race. Food & Nutrition Research. 2017;61(1):1330098. — doi:10.1080/16546628.2017.1330098
13. Ochiai M, Hayashi T, Morita M, et al. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. International Journal of Cardiology. 2012;155(2):257-261. — doi:10.1016/j.ijcard.2010.10.004
14. Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. British Journal of Nutrition. 2008;99(4):855-862. — doi:10.1017/S0007114507841110
15. Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids. 2005;29(3):177-205. — doi:10.1007/s00726-005-0235-4
16. Wu G, Morris SM Jr. Arginine metabolism: nitric oxide and beyond. Biochemical Journal. 1998;336(Pt 1):1-17. — doi:10.1042/bj3360001
17. Volino-Souza M, Oliveira GV, Conte-Junior CA, Figueroa A, Alvares TS. Current evidence of watermelon (Citrullus lanatus) ingestion on vascular health: a food science and technology perspective. Nutrients. 2022;14(14):2913. — doi:10.3390/nu14142913
18. Figueroa A, Wong A, Jaime SJ, Gonzales JU. Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance. Current Opinion in Clinical Nutrition and Metabolic Care. 2017;20(1):92-98. — doi:10.1097/MCO.0000000000000340
19. Wong A, Alvarez-Alvarado S, Jaime SJ, et al. Combined whole-body vibration training and L-citrulline supplementation improves pressure wave reflection in obese postmenopausal women. Applied Physiology, Nutrition, and Metabolism. 2016;41(3):292-297. — doi:10.1139/apnm-2015-0465
20. Wu G, Collins JK, Perkins-Veazie P, et al. Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. The Journal of Nutrition. 2007;137(12):2680-2685. — doi:10.1093/jn/137.12.2680
21. RETRACTED — listed so readers can recognise it, not as evidence. Mahboobi S, Tsang C, Rezaei S, Jafarnejad S. Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of clinical trials. Journal of Human Hypertension. 2019;33(1):10-21. — doi:10.1038/s41371-018-0108-4
22. Live search: PubMed: watermelon, citrulline and blood pressure
23. Live search: PubMed: citrulline and erectile dysfunction

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Connections

• Watermelon — main topic page
• Watermelon — Benefits Deep Dive
• Watermelon: History and Origins
• Watermelon Lycopene and Heart Health
• Watermelon for Hydration and Electrolytes
• Watermelon: Food Safety, FODMAPs, and Blood Sugar
• Citrulline
• Arginine
• Beets — dietary nitrate, the other nitric-oxide route
• Lycopene
• Potassium
• Magnesium
• Cardiology — heart and vascular conditions
• Tomatoes
• Pomegranate
• Cucumber

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