Citrulline

Last Updated: November 2, 2023

L-Citrulline, or simply just citrulline, is a nonessential amino acid. It is efficiently turned into L-arginine in the kidneys after supplementation, which makes it a good choice for increasing nitric oxide synthesis in the body.

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Citrulline is most often used for

What is citrulline?

Citrulline is one of the three dietary amino acids in the urea cycle (the other two are L-arginine and L-ornithine). Taking citrulline increases plasma levels of arginine and improves the ammonia recycling process and nitric oxide metabolism. Consequently, citrulline may be useful in situations in which nitric oxide is relevant, such as athletic performance, vascular health, and erectile dysfunction. There are very few foods that have useful amounts of citrulline, but watermelon is a notable exception. The two most common forms of citrulline are L-citrulline and citrulline malate.

What’s the difference between L-citrulline and citrulline malate?

Which foods are rich in citrulline?

What are citrulline’s main benefits?

There is limited evidence that citrulline supplementation can reduce ratings of perceived exertion, decrease muscle soreness, and increase power output and total repetitions performed in resistance training.[1][2][3] More research is needed to determine whether different supplement dosages, different formulations, or longer periods of ingestion can further improve exercise performance.

A considerable amount of research suggests that supplementation with citrulline mildly reduces blood pressure.[4] More research is needed on citrulline’s potential effects for erectile dysfunction, but a small amount of research suggests a beneficial effect.[5]

Does citrulline improve exercise performance?

Does citrulline reduce blood pressure?

Can citrulline help improve symptoms of erectile dysfunction?

What are citrulline’s main drawbacks?

Although the safety of long-term supplementation with high doses of citrulline warrants further investigation, research to date suggests that it is well tolerated in most individuals. Unlike arginine and ornithine, high doses of citrulline don't seem to result in gastrointestinal distress.[2]

Are there any side effects of taking high doses of citrulline?

How does citrulline work?

Citrulline supplementation increases the body’s arginine levels. Because arginine is the main substrate for the synthesis of nitric oxide, citrulline ingestion can indirectly increase nitric oxide production. In turn, given the role of nitric oxide in vasodilation, mitochondrial respiration, calcium handling, and glucose uptake, greater amounts of nitric oxide can theoretically improve circulatory health and muscle function and reduce fatigue.

How is citrulline created in the body?

Where is citrulline metabolized in the body after consumption?

Does citrulline impact muscle protein synthesis?

Does citrulline interact with other nutrients, supplements, or medications?

What are other names for Citrulline?
Note that Citrulline is also known as:
  • L-Citrulline
  • Stimol (Brand Name)
  • citrulline malate
Dosage information

To supplement L-citrulline for circulatory health or to alleviate erectile dysfunction, take 2,000 mg of citrulline, three times a day with meals, for a total daily dose of 6,000 mg. L-citrulline does not need to be taken with meals, however.

To supplement for circulatory health with a citrulline malate supplement, take 1.76 g of citrulline malate for every 1 gram of citrulline you would normally take.

To supplement L-citrulline to enhance sports performance, take 6,000 – 8,000 mg of citrulline malate about an hour before exercise. On days that you don't exercise, it can be broken up into smaller doses.

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Update History
2023-11-02 00:30:05

One new meta analysis added

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We added one additional meta-analysis to the database.

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References
  1. ^Eric T Trexler, Adam M Persky, Eric D Ryan, Todd A Schwartz, Lee Stoner, Abbie E Smith-RyanAcute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-AnalysisSports Med.(2019 May)
  2. ^Rhim HC, Kim SJ, Park J, Jang KMEffect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis.J Sport Health Sci.(2020-Dec)
  3. ^Fredrik Tonstad Vårvik, Thomas Bjørnsen, Adam M GonzalezAcute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-AnalysisInt J Sport Nutr Exerc Metab.(2021 May 19)
  4. ^Barkhidarian B, Khorshidi M, Shab-Bidar S, Hashemi BEffects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis.Avicenna J Phytomed.(2019)
  5. ^Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction
  6. ^Bescós R, Sureda A, Tur JA, Pons AThe effect of nitric-oxide-related supplements on human performanceSports Med.(2012 Feb 1)
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  14. ^Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, Cynober LAlmost all about citrulline in mammalsAmino Acids.(2005 Nov)
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  16. ^Tomlinson C, Rafii M, Ball RO, Pencharz PArginine synthesis from enteral glutamine in healthy adults in the fed state.Am J Physiol Endocrinol Metab.(2011-Aug)
  17. ^van de Poll MC, Ligthart-Melis GC, Boelens PG, Deutz NE, van Leeuwen PA, Dejong CHIntestinal and hepatic metabolism of glutamine and citrulline in humans.J Physiol.(2007-Jun-01)
  18. ^van de Poll MC, Siroen MP, van Leeuwen PA, Soeters PB, Melis GC, Boelens PG, Deutz NE, Dejong CHInterorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism.Am J Clin Nutr.(2007-Jan)
  19. ^Rougé C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetière MF, Darmaun DManipulation of citrulline availability in humansAm J Physiol Gastrointest Liver Physiol.(2007 Nov)
  20. ^Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism
  21. ^Intestinal and hepatic metabolism of glutamine and citrulline in humans
  22. ^Source and fate of circulating citrulline
  23. ^Levillain O, Parvy P, Hassler CAmino acid handling in uremic rats: citrulline, a reliable marker of renal insufficiency and proximal tubular dysfunction.Metabolism.(1997-Jun)
  24. ^Castillo L, Beaumier L, Ajami AM, Young VRWhole body nitric oxide synthesis in healthy men determined from 15N arginine-to-15Ncitrulline labeling.Proc Natl Acad Sci U S A.(1996-Oct-15)
  25. ^Le Plénier S, Walrand S, Noirt R, Cynober L, Moinard CEffects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway?Amino Acids.(2012-Sep)
  26. ^Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, Moinard CCitrulline modulates muscle protein metabolism in old malnourished rats.Am J Physiol Endocrinol Metab.(2006-Sep)
  27. ^Faure C, Raynaud-Simon A, Ferry A, Daugé V, Cynober L, Aussel C, Moinard CLeucine and citrulline modulate muscle function in malnourished aged rats.Amino Acids.(2012-Apr)
  28. ^Direct action of citrulline on muscle protein synthesis: role of the mTORC1 pathway
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  30. ^Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun DOral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over studyClin Nutr.(2011 Dec)
  31. ^C Moinard, I Nicolis, N Neveux, S Darquy, S Bénazeth, L CynoberDose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic studyBr J Nutr.(2008 Apr)
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  39. ^McKinley-Barnard S, Andre T, Morita M, Willoughby DSCombined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesisJ Int Soc Sports Nutr.(2015 Jun 10)
  40. ^Sureda A, Córdova A, Ferrer MD, Pérez G, Tur JA, Pons AL-citrulline-malate influence over branched chain amino acid utilization during exerciseEur J Appl Physiol.(2010 Sep)
  41. ^Callis A, Magnan de Bornier B, Serrano JJ, Bellet H, Saumade RActivity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in manArzneimittelforschung.(1991 Jun)
  42. ^A Callis, B Magnan de Bornier, J J Serrano, H Bellet, R SaumadeActivity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in manArzneimittelforschung.(1991 Jun)
  43. ^Berthe MC, Bernard M, Rasmusen C, Darquy S, Cynober L, Couderc RArginine or citrulline associated with a statin stimulates nitric oxide production in bovine aortic endothelial cells.Eur J Pharmacol.(2011-Nov-30)
  44. ^Ye Y, Martinez JD, Perez-Polo RJ, Lin Y, Uretsky BF, Birnbaum YThe role of eNOS, iNOS, and NF-kappaB in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin.Am J Physiol Heart Circ Physiol.(2008-Jul)
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Examine Database References
  1. Blood Lactate (Exercise) - Benjamin Wax, Andreas N Kavazis, Kevin Weldon, Joseph SperlakEffects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightliftersJ Strength Cond Res.(2015 Mar)
  2. Blood Lactate (Exercise) - Fatih Kiyici, Hüseyin Eroğlu, N Fazil Kishali, Guleda BurmaogluThe Effect of Citrulline/Malate on Blood Lactate Levels in Intensive ExerciseBiochem Genet.(2017 Dec)
  3. Blood Lactate (Exercise) - Andrew J Chappell, Daniel M Allwood, Trevor N SimperCitrulline Malate Fails to Improve German Volume Training Performance in Healthy Young Men and WomenJ Diet Suppl.(2020)
  4. Blood Lactate (Exercise) - Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon ML-citrulline reduces time to exhaustion and insulin response to a graded exercise testMed Sci Sports Exerc.(2006 Apr)
  5. Blood Lactate (Exercise) - Benjamin Wax, Andreas N Kavazis, William LuckettEffects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained MalesJ Diet Suppl.(2016)
  6. Blood Lactate (Exercise) - Eric T Trexler, Dale S Keith, Todd A Schwartz, Eric D Ryan, Lee Stoner, Adam M Persky, Abbie E Smith-RyanEffects of Citrulline Malate and Beetroot Juice Supplementation on Blood Flow, Energy Metabolism, and Performance During Maximum Effort Leg Extension ExerciseJ Strength Cond Res.(2019 Sep)
  7. Weight - Paul Hwang, Flor E Morales Marroquín, Josh Gann, Tom Andre, Sarah McKinley-Barnard, Caelin Kim, Masahiko Morita, Darryn S WilloughbyEight weeks of resistance training in conjunction with glutathione and L-Citrulline supplementation increases lean mass and has no adverse effects on blood clinical safety markers in resistance-trained malesJ Int Soc Sports Nutr.(2018 Jun 27)
  8. Fatigue Symptoms - Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone PJCitrulline/malate promotes aerobic energy production in human exercising muscleBr J Sports Med.(2002 Aug)
  9. Fatigue Symptoms - Pérez-Guisado J, Jakeman PMCitrulline malate enhances athletic anaerobic performance and relieves muscle sorenessJ Strength Cond Res.(2010 May)
  10. Aerobic Exercise Metrics - Stephen J Bailey, Jamie R Blackwell, Terrence Lord, Anni Vanhatalo, Paul G Winyard, Andrew M Jonesl-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humansJ Appl Physiol (1985).(2015 Aug 15)
  11. Muscular Endurance - Adam M Gonzalez, Robert W Spitz, Jamie J Ghigiarelli, Katie M Sell, Gerald T MangineAcute Effect of Citrulline Malate Supplementation on Upper-Body Resistance Exercise Performance in Recreationally Resistance-Trained MenJ Strength Cond Res.(2018 Nov)
  12. Muscular Endurance - Glenn JM, Gray M, Wethington LN, Stone MS, Stewart RW Jr, Moyen NEAcute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained femalesEur J Nutr.(2017 Mar)
  13. Power Output - Eric T Trexler, Adam M Persky, Eric D Ryan, Todd A Schwartz, Lee Stoner, Abbie E Smith-RyanAcute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-AnalysisSports Med.(2019 May)
  14. Power Output - Glenn JM, Gray M, Jensen A, Stone MS, Vincenzo JLAcute citrulline-malate supplementation improves maximal strength and anaerobic power in female, masters athletes tennis playersEur J Sport Sci.(2016 Nov)
  15. Body Fat - Arturo Figueroa, Stacey Alvarez-Alvarado, Michael J Ormsbee, Takudzwa A Madzima, Jeremiah C Campbell, Alexei WongImpact of L-citrulline supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressureExp Gerontol.(2015 Mar)
  16. Oxygen Uptake - John Ashley, Youngdeok Kim, Joaquin U GonzalesImpact of l-citrulline supplementation on oxygen uptake kinetics during walkingAppl Physiol Nutr Metab.(2018 Jun)
  17. Immunity - Sureda A, Cordova A, Ferrer MD, Tauler P, Perez G, Tur JA, Pons AEffects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exerciseFree Radic Res.(2009 Sep)
  18. Plasma Arginine - Takashi Suzuki, Masahiko Morita, Yoshinori Kobayashi, Ayako KamimuraOral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover studyJ Int Soc Sports Nutr.(2016 Feb 19)
  19. Power Output - Joshua L Gills, Jordan M Glenn, Michelle Gray, Braden Romer, Hocheng LuAcute citrulline-malate supplementation is ineffective during aerobic cycling and subsequent anaerobic performance in recreationally active malesEur J Sport Sci.(2020 Feb 18)
  20. Rate of Perceived Exertion - Sean T Stanelle, Kelsey L McLaughlin, Stephen F CrouseOne Week of L-Citrulline Supplementation Improves Performance in Trained CyclistsJ Strength Cond Res.(2020 Mar)
  21. Heart Rate - Figueroa A, Trivino JA, Sanchez-Gonzalez MA, Vicil FOral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young menAm J Hypertens.(2010 Jan)
  22. Heart Rate - Marcos Angel Sanchez-Gonzalez, Andrew Paul Koutnik, Katherine Ramirez, Alexei Wong, Arturo FigueroaThe effects of short term L-citrulline supplementation on wave reflection responses to cold exposure with concurrent isometric exerciseAm J Hypertens.(2013 Apr)
  23. Heart Rate - Arturo Figueroa, Stacey Alvarez-Alvarado, Salvador J Jaime, Roy Kalfonl-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight menBr J Nutr.(2016 Jul)
  24. Arterial Stiffness - Joaquin U Gonzales, Andrea Raymond, John Ashley, Youngdeok KimDoes l-citrulline supplementation improve exercise blood flow in older adults?Exp Physiol.(2017 Dec 1)
  25. Blood Pressure - Huan-Huan Yang, Xin-Li Li, Wei-Guo Zhang, Arturo Figueroa, Li-Hua Chen, Li-Qiang QinEffect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trialsNutr Metab (Lond).(2019 Dec 26)
  26. Blood Pressure - Powers R, et al[7-OR]: L-Citrulline administration increases the arginine/ADMA ratio, decreases blood pressure and improves vascular function in obese pregnant womenPregnancy Hypertens.()
  27. Blood Flow - Jeffrey M Rogers, Joshua Gills, Michelle GrayAcute effects of Nitrosigine® and citrulline malate on vasodilation in young adultsJ Int Soc Sports Nutr.(2020 Feb 24)
  28. Heart Rate - Brian Cunniffe, Maria Papageorgiou, Barbara OʼBrien, Nathan A Davies, George K Grimble, Marco CardinaleAcute Citrulline-Malate Supplementation and High-Intensity Cycling PerformanceJ Strength Cond Res.(2016 Sep)
  29. Aerobic Exercise Metrics - Harnden CS, Agu J, Gascoyne TEffects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis.J Int Soc Sports Nutr.(2023-Dec)
  30. Total Antioxidant Capacity (TAC) - S Azizi, M Ebrahimi-Mameghani, M Mobasseri, N Karamzad, R MahdaviOxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trialJ Hum Nutr Diet.(2020 Jul 19)
  31. Blood Pressure - Karla Balderas-Munoz, Lilia Castillo-Martínez, Arturo Orea-Tejeda, Oscar Infante-Vázquez, Marcelo Utrera-Lagunas, Raúl Martínez-Memije, Candace Keirns-Davis, Bryan Becerra-Luna, Gabriela Sánchez-VidalImprovement of ventricular function in systolic heart failure patients with oral L-citrulline supplementationCardiol J.(2012)
  32. Blood Pressure - Juan José Orozco-Gutiérrez, Lilia Castillo-Martínez, Arturo Orea-Tejeda, Oscar Vázquez-Díaz, Adrián Valdespino-Trejo, René Narváez-David, Candace Keirns-Davis, Olín Carrasco-Ortiz, Adolfo Navarro-Navarro, Rocío Sánchez-SantillánEffect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fractionCardiol J.(2010)
  33. Muscle Soreness - da Silva DK, Jacinto JL, de Andrade WB, Roveratti MC, Estoche JM, Balvedi MCW, de Oliveira DB, da Silva RA, Aguiar AFCitrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in Untrained Young Adult MenNutrients.(2017 Oct 18)
  34. Blood Flow - Kim van Wijck, Karolina A P Wijnands, Dennis M Meesters, Bas Boonen, Luc J C van Loon, Wim A Buurman, Cornelis H C Dejong, Kaatje Lenaerts, Martijn PoezeL-citrulline improves splanchnic perfusion and reduces gut injury during exerciseMed Sci Sports Exerc.(2014 Nov)
  35. Heart Rate Variability - Casonatto J, et alCitrulline malate supplementation might potentiate post-exercise hypotension in hypertensives: A 24-hour analysisSci Sport.()
  36. High-density lipoprotein (HDL) - Ochiai M, Hayashi T, Morita M, Ina K, Maeda M, Watanabe F, Morishita KShort-term effects of L-citrulline supplementation on arterial stiffness in middle-aged menInt J Cardiol.(2012 Mar 8)
  37. Blood Pressure - Juliano Casonatto, Daniel Massaharu Enokida, Kamila GrandolfiInter-Individual Responses to Citrulline Malate Oral Supplementation on Post-Exercise Hypotension in Hypertensives: A 24-Hour AnalysisArq Bras Cardiol.(2019 Jul 10)
  38. Blood Pressure - Qiu J, et all-citrulline supplementation reduced peripheral blood pressure in Chinese adults with prehypertensionJ Hypertens.()
  39. Asthma Symptoms - Fernando Holguin, Hartmut Grasemann, Sunita Sharma, Daniel Winnica, Karen Wasil, Vong Smith, Margaret H Cruse, Nancy Perez, Erika Coleman, Timothy J Scialla, Loretta G QueL-Citrulline increases nitric oxide and improves control in obese asthmaticsJCI Insight.(2019 Dec 19)
  40. Heart Rate Variability - Alexei Wong, Oksana Chernykh, Arturo FigueroaChronic l-citrulline supplementation improves cardiac sympathovagal balance in obese postmenopausal women: A preliminary reportAuton Neurosci.(2016 Jul)
  41. Liver Fibrosis - Zahra Darabi, Mina Darand, Zahra Yari, Mehdi Hedayati, Amirhosein Faghihi, Shahram Agah, Azita HekmatdoostInflammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease: a randomized, double blind, placebo-controlled, clinical trialBMC Res Notes.(2019 Feb 15)
  42. Blood Pressure - Babak Sharif Kashani, Paritash Tahmaseb Pour, Majid Malekmohammad, Neda Behzadnia, Faezeh Sheybani-Afshar, Mohammad Fakhri, Samira Chaibakhsh, Farah Naghashzadeh, Salavan AidenlouOral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trialJ Cardiol.(2014 Sep)
  43. Growth Hormone - Sureda A, Córdova A, Ferrer MD, Pérez G, Tur JA, Pons AL-citrulline-malate influence over branched chain amino acid utilization during exerciseEur J Appl Physiol.(2010 Sep)
  44. Growth Hormone - C Moinard, I Nicolis, N Neveux, S Darquy, S Bénazeth, L CynoberDose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic studyBr J Nutr.(2008 Apr)
  45. Insulin - Thibault R, Flet L, Vavasseur F, Lemerle M, Ferchaud-Roucher V, Picot D, Darmaun DOral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over studyClin Nutr.(2011 Dec)
  46. Erections - Luigi Cormio, Mario De Siati, Fabrizio Lorusso, Oscar Selvaggio, Lucia Mirabella, Francesca Sanguedolce, Giuseppe CarrieriOral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunctionUrology.(2011 Jan)
  47. Blood Pressure - Heidi A B Smith, Jeffrey A Canter, Karla G Christian, Davis C Drinkwater, Frank G Scholl, Brian W Christman, Geraldine D Rice, Frederick E Barr, Marshall L SummarNitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrullineJ Thorac Cardiovasc Surg.(2006 Jul)