L-Citrulline, watermelon extract, Citrulline

Citrulline is a non-essential amino acid that participates in the urea cycle and increases the plasma levels of ornithine and arginine in the body, improving the ammonia recycling process and nitric oxide metabolism. Consequently, citrulline acts where nitric oxide is used, such as cardiovascular health, athletic performance and erectile dysfunction.

  • Origin: Plant Based, Animal Product, Nonessential
  • Source: Milk, Eggs, Meat, Fish, Nonessential, Watermelon, Melon, Pumpkin, Cucumber
  • Type: Amino Acids
  • Age Range: Adults, Seniors
  • Toxicity: May be toxic in high doses
  • Outcomes: Muscle Health, Fatigue Prevention

What are Citrulline benefits?

Citrulline, also known as L-citrulline, is one of three dietary amino acids in the urea cycle, alongside L-arginine and L-ornithine. Intake of L-citrulline increases plasma levels of ornithine and arginine, improving the process of ammonia recycling and nitric oxide metabolism. It is worth noting that citrulline can be found in watermelon. In addition, according to scientific evidence, several benefits of citrulline supplementation have been found in research, suggesting that it can: reduce blood pressure and improve blood flow, especially for people with hypertension and other cardiovascular problems; improve strength production; reduce fatigue; and provide greater endurance for aerobic and anaerobic exercise.

Table of relations

Outcome
Sub-Outcome
Consistent effects
Strength of effects
Scientific articles
Muscle Health Muscle Health
Fatigue Prevention
See All 3 studies

Muscle Health Citrulline and Muscle Health

The muscles are responsible for body movement, stabilization, regulation of organs, substance transportation and production of heat in addition to being strongly associated with the circulatory and nervous systems. Muscle quality is essential for well being. Supplements that help keep muscles healthy are related to different factors, such as glucose and insulin regulation, protein synthesis, energy metabolism, and others.

  • Fatigue Prevention

    Fatigue is characterized by a reduction in mental energy. It can also appear as acute and/or chronic fatigue. Acute fatigue is due to excessive mentally demanding work. Chronic fatigue is multifactorial, influenced by insomnia, stress, anxiety, depression, causing tiredness and constant lack of motivation. The substances indicated for fatigue help to improve sleep and mood problems as they are neuroprotective, affecting neurological function.

Table of negative interactions

Foods
Watermelon

Related videos about Citrulline

Other Amino Acids

5-HTP

Energy and Mood Weight Management

5-HTP is a substance used to increase levels of Serotonin on the brain. It is synthesized in the body through the amino acid tryptophan. The consum...

Ver mais

Agmatine

Energy and Mood

Agmatine is a compound synthesized from the amino acid arginine by the enzyme arginine decarboxylase.The supplementation occurs in agmatine sulfate...

Ver mais

Arginine

Muscle Health

Arginine is a basic protein, which is the main nitrogen carrier in the blood. The human body uses arginine to synthesize nitric oxide, which helps ...

Ver mais

BCAA

Muscle Health

BCAA is a group of three essential amino acids: Leucine, Isoleucine and Valine. Supplementation promotes muscle gain, protein synthesis and decreas...

Ver mais

References

  1. ^ a b Figueroa A, et al. Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study. Am J Hypertens. (2011)
  2. ^ a b Kaore SN, Amane HS, Kaore NM. Citrulline: pharmacological perspectives and its role as an emerging biomarker in future. Fundam Clin Pharmacol. (2013)
  3. ^ Rimando AM, Perkins-Veazie PM. Determination of citrulline in watermelon rind. J Chromatogr A. (2005)
  4. ^ Mandel H, et al. Elevated plasma citrulline and arginine due to consumption of Citrullus vulgaris (watermelon). J Inherit Metab Dis. (2005)
  5. ^ Tangphao O, et al. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol. (1999)
  6. ^ Collins JK, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition. (2007)
  7. ^ a b Curis E, et al. Almost all about citrulline in mammals. Amino Acids. (2005)
  8. ^ Metabolism of citrulline in man.
  9. ^ Tomlinson C, et al. Arginine synthesis from enteral glutamine in healthy adults in the fed state. Am J Physiol Endocrinol Metab. (2011)
  10. ^ van de Poll MC, et al. Intestinal and hepatic metabolism of glutamine and citrulline in humans. J Physiol. (2007)
  11. ^ van de Poll MC, et al. Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am J Clin Nutr. (2007)
  12. ^ a b c d e f g h Rougé C, et al. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol. (2007)
  13. ^ Bommarius AS, Makryaleas K, Drauz K. An enzymatic route to L-ornithine from L-arginine–activation and stabilization studies on L-arginase. Biomed Biochim Acta. (1991)
  14. ^ Bommarius AS, Drauz K. An enzymatic route to L-ornithine from arginine–activation, selectivity and stabilization of L-arginase. Bioorg Med Chem. (1994)
  15. ^ a b Häberle J, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. (2012)
  16. ^ a b Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes.
  17. ^ Enzymes of Arginine Metabolism.
  18. ^ Lameu C, de Camargo AC, Faria M. L-arginine signalling potential in the brain: the peripheral gets central. Recent Pat CNS Drug Discov. (2009)
  19. ^ Flam BR, Eichler DC, Solomonson LP. Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle. Nitric Oxide. (2007)
  20. ^ a b Dhanakoti SN, et al. Renal arginine synthesis: studies in vitro and in vivo. Am J Physiol. (1990)
  21. ^ a b c d e f g h i j Sureda A, et al. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. (2010)
  22. ^ a b c d e f g h i j k l Thibault R, et al. Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study. Clin Nutr. (2011)
  23. ^ a b c d e Moinard C, 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)
  24. ^ Curis E, Crenn P, Cynober L. Citrulline and the gut. Curr Opin Clin Nutr Metab Care. (2007)
  25. ^ Bahri S, et al. Mechanisms and kinetics of citrulline uptake in a model of human intestinal epithelial cells. Clin Nutr. (2008)
  26. ^ a b Sureda A, et al. Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise. Free Radic Res. (2009)
  27. ^ Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism.
  28. ^ Intestinal and hepatic metabolism of glutamine and citrulline in humans.
  29. ^ Source and fate of circulating citrulline.
  30. ^ Levillain O, Parvy P, Hassler C. Amino acid handling in uremic rats: citrulline, a reliable marker of renal insufficiency and proximal tubular dysfunction. Metabolism. (1997)
  31. ^ Whole body nitric oxide synthesis in healthy men determined from {15N} arginine-to-{15N}citrulline labeling.
  32. ^ Sase A, et al. Changes of hippocampal beta-alanine and citrulline levels are paralleling early and late phase of retrieval in the Morris Water Maze. Behav Brain Res. (2013)
  33. ^ Orozco-Gutiérrez JJ, et al. Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction. Cardiol J. (2010)
  34. ^ Orea-Tejeda A, et al. The effect of L-arginine and citrulline on endothelial function in patients in heart failure with preserved ejection fraction. Cardiol J. (2010)
  35. ^ Kameda N, et al. The effect of L-citrulline ingestion on ECG QT interval and autonomic nervous system activity. J Physiol Anthropol. (2011)
  36. ^ Ochiai M, et al. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Int J Cardiol. (2012)
  37. ^ Changes in central artery blood pressure and wave reflection during a cold pressor test in young adults.
  38. ^ Ahlund C, Pettersson K, Lind L. Pulse wave analysis on fingertip arterial pressure: effects of age, gender and stressors on reflected waves and their relation to brachial and femoral artery blood flow. Clin Physiol Funct Imaging. (2008)
  39. ^ West SG, et al. Oral L-arginine improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men. J Nutr. (2005)
  40. ^ Figueroa A, et al. Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men. Am J Hypertens. (2010)
  41. ^ Smith HA, et al. Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline. J Thorac Cardiovasc Surg. (2006)
  42. ^ Nakata M, Yada T. Endocrinology: nitric oxide-mediated insulin secretion in response to citrulline in islet beta-cells. Pancreas. (2003)
  43. ^ a b Nakata M, et al. Citrulline-argininosuccinate-arginine cycle coupled to Ca2+-signaling in rat pancreatic beta-cells. Biochem Biophys Res Commun. (1997)
  44. ^ a b c Hickner RC, et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. (2006)
  45. ^ Faure C, et al. Citrulline enhances myofibrillar constituants expression of skeletal muscle and induces a switch in muscle energy metabolism in malnourished aged rats. Proteomics. (2013)
  46. ^ a b c d e f g Giannesini B, et al. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle. Eur J Pharmacol. (2011)
  47. ^ a b Bendahan D, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. (2002)
  48. ^ Bescós R, et al. Acute administration of inorganic nitrate reduces VO(2peak) in endurance athletes. Med Sci Sports Exerc. (2011)
  49. ^ Bailey SJ, et al. Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance. J Appl Physiol. (2010)
  50. ^ Brown GC. Nitric oxide and mitochondrial respiration. Biochim Biophys Acta. (1999)
  51. ^ Briand J, et al. Use of a microbial model for the determination of drug effects on cell metabolism and energetics: study of citrulline-malate. Biopharm Drug Dispos. (1992)
  52. ^ a b c d Callis A, et al. Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Arzneimittelforschung. (1991)
  53. ^ Demura S, et al. The effect of L-ornithine hydrochloride ingestion on performance during incremental exhaustive ergometer bicycle exercise and ammonia metabolism during and after exercise. Eur J Clin Nutr. (2010)
  54. ^ Sugino T, et al. L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. (2008)
  55. ^ Ammonia Production in Muscle and other Tissues: the Purine Nucleotide Cycle.
  56. ^ Regulation of the urea cycle and TCA cycle by ammonia.
  57. ^ Fitts RH, Balog EM. Effect of intracellular and extracellular ion changes on E-C coupling and skeletal muscle fatigue. Acta Physiol Scand. (1996)
  58. ^ a b c Takeda K, et al. Effects of citrulline supplementation on fatigue and exercise performance in mice. J Nutr Sci Vitaminol (Tokyo). (2011)
  59. ^ a b c d e Le Plénier S, et al. Effects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway. Amino Acids. (2012)
  60. ^ a b Osowska S, et al. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab. (2006)
  61. ^ a b Faure C, et al. Leucine and citrulline modulate muscle function in malnourished aged rats. Amino Acids. (2012)
  62. ^ a b Direct action of citrulline on muscle protein synthesis: role of the mTORC1 pathway.
  63. ^ a b Cynober L, de Bandt JP, Moinard C. Leucine and citrulline: two major regulators of protein turnover. World Rev Nutr Diet. (2013)
  64. ^ a b c Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. (2010)
  65. ^ Komori K, et al. Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3′,5′-monophosphate (cGMP) pathway in human corpus cavernosal smooth muscle cells. J Sex Med. (2008)
  66. ^ Xin ZC, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. (2003)
  67. ^ Mulhall JP, et al. Validation of the erection hardness score. J Sex Med. (2007)
  68. ^ Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction.
  69. ^ a b McKinley-Barnard S, et al. Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. J Int Soc Sports Nutr. (2015)
  70. ^ a b Berthe MC, et al. Arginine or citrulline associated with a statin stimulates nitric oxide production in bovine aortic endothelial cells. Eur J Pharmacol. (2011)
  71. ^ a b c Ye Y, et al. The 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)
  72. ^ a b Nakata S, et al. Statin treatment upregulates vascular neuronal nitric oxide synthase through Akt/NF-kappaB pathway. Arterioscler Thromb Vasc Biol. (2007)
  73. ^ a b Kolyada AY, Fedtsov A, Madias NE. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors upregulate inducible NO synthase expression and activity in vascular smooth muscle cells. Hypertension. (2001)
  74. ^ a b Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr. (2007)
  75. ^ Collier SR, Casey DP, Kanaley JA. Growth hormone responses to varying doses of oral arginine. Growth Horm IGF Res. (2005)
  76. Cormio L, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. (2011)
  77. Babak Sharif Kashani, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol. (2014)
  78. Jeffrey M Rogers, Joshua Gills, Michelle Gray. Acute effects of Nitrosigine® and citrulline malate on vasodilation in young adults. J Int Soc Sports Nutr. (2020)
  79. Joaquin U Gonzales, et al. Does l-citrulline supplementation improve exercise blood flow in older adults?. Exp Physiol. (2017)
  80. Alexei Wong, Oksana Chernykh, Arturo Figueroa. Chronic l-citrulline supplementation improves cardiac sympathovagal balance in obese postmenopausal women: A preliminary report. Auton Neurosci. (2016)
  81. Arturo Figueroa, et al. Impact of L-citrulline supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure. Exp Gerontol. (2015)
  82. Arturo Figueroa, et al. l-Citrulline supplementation attenuates blood pressure, wave reflection and arterial stiffness responses to metaboreflex and cold stress in overweight men. Br J Nutr. (2016)
  83. Huan-Huan Yang, et al. Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials. Nutr Metab (Lond). (2019)
  84. S Azizi, et al. Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trial. J Hum Nutr Diet. (2020)
  85. Zahra Darabi, et al. Inflammatory markers response to citrulline supplementation in patients with non-alcoholic fatty liver disease: a randomized, double blind, placebo-controlled, clinical trial. BMC Res Notes. (2019)
  86. Fernando Holguin, et al. L-Citrulline increases nitric oxide and improves control in obese asthmatics. JCI Insight. (2019)
  87. John Ashley, Youngdeok Kim, Joaquin U Gonzales. Impact of l-citrulline supplementation on oxygen uptake kinetics during walking. Appl Physiol Nutr Metab. (2018)
  88. Fatih Kiyici, et al. The Effect of Citrulline/Malate on Blood Lactate Levels in Intensive Exercise. Biochem Genet. (2017)
  89. da Silva DK, et al. Citrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in Untrained Young Adult Men. Nutrients. (2017)
  90. Sean T Stanelle, Kelsey L McLaughlin, Stephen F Crouse. One Week of L-Citrulline Supplementation Improves Performance in Trained Cyclists. J Strength Cond Res. (2020)
  91. Andrew J Chappell, Daniel M Allwood, Trevor N Simper. Citrulline Malate Fails to Improve German Volume Training Performance in Healthy Young Men and Women. J Diet Suppl. (2020)
  92. Eric T Trexler, et al. Effects of Citrulline Malate and Beetroot Juice Supplementation on Blood Flow, Energy Metabolism, and Performance During Maximum Effort Leg Extension Exercise. J Strength Cond Res. (2019)
  93. Juliano Casonatto, Daniel Massaharu Enokida, Kamila Grandolfi. Inter-Individual Responses to Citrulline Malate Oral Supplementation on Post-Exercise Hypotension in Hypertensives: A 24-Hour Analysis. Arq Bras Cardiol. (2019)
  94. Joshua L Gills, et al. Acute citrulline-malate supplementation is ineffective during aerobic cycling and subsequent anaerobic performance in recreationally active males. Eur J Sport Sci. (2020)
  95. Hwang P, et al. Eight 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 males. J Int Soc Sports Nutr. (2018)
  96. Glenn JM, et al. Acute citrulline-malate supplementation improves maximal strength and anaerobic power in female, masters athletes tennis players. Eur J Sport Sci. (2016)
  97. Suzuki T, et al. Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. J Int Soc Sports Nutr. (2016)
  98. Brian Cunniffe, et al. Acute Citrulline-Malate Supplementation and High-Intensity Cycling Performance. J Strength Cond Res. (2016)
  99. Glenn JM, et al. Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. Eur J Nutr. (2017)
  100. Bailey SJ, et al. l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol (1985). (2015)
  101. Wax B, Kavazis AN, Luckett W. Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males. J Diet Suppl. (2016)
  102. Wax B, et al. Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. J Strength Cond Res. (2015)
  103. Kim van Wijck, et al. L-citrulline improves splanchnic perfusion and reduces gut injury during exercise. Med Sci Sports Exerc. (2014)
  104. Marcos Angel Sanchez-Gonzalez, et al. The effects of short term L-citrulline supplementation on wave reflection responses to cold exposure with concurrent isometric exercise. Am J Hypertens. (2013)
  105. Karla Balderas-Munoz, et al. Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation. Cardiol J. (2012)
  106. Adam M Gonzalez, et al. Acute Effect of Citrulline Malate Supplementation on Upper-Body Resistance Exercise Performance in Recreationally Resistance-Trained Men. J Strength Cond Res. (2018)
  107. Eric T Trexler, et al. Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis. Sports Med. (2019)