Overview
The name citrulline comes from Citrullus vulgaris, the Latin term for watermelon. Unlike some amino acids, L-citrulline isn't used to make protein, but it might help increase other chemicals the body needs to make protein. It might also help improve blood flow and reduce blood pressure.
People use L-citrulline for athletic performance, sickle cell disease, erectile dysfunction (ED), high blood pressure in the lungs, heart disease, and many other conditions, but there is no good scientific evidence to support most of these uses.
Uses & Effectiveness ?
Possibly Effective for
- Athletic performance. Taking L-citrulline by mouth might help improve some types of exercise performance such as weight lifting. But its effects on aerobic exercises such as running are unclear.
Side Effects
Special Precautions and Warnings
Children: L-citrulline is possibly safe when taken by mouth.
Surgery: L-citrulline might affect blood pressure. It might interfere with blood pressure control during and after surgery. Stop taking L-citrulline at least 2 weeks before a scheduled surgery.
Interactions ?
Medications for high blood pressure (Antihypertensive drugs) interacts with L-CITRULLINE
L-citrulline might lower blood pressure. Taking L-citrulline along with medications that lower blood pressure might cause blood pressure to go too low. Monitor your blood pressure closely.
Medications for male sexual dysfunction (Phosphodiesterase-5 Inhibitors) interacts with L-CITRULLINE
L-citrulline might lower blood pressure. Some medications for male sexual dysfunction can also lower blood pressure. Taking L-citrulline along with these medications might cause blood pressure to go too low.
Moderate Interaction
Be cautious with this combination
Dosing
Barr FE, Tirona RG, Taylor MB, et al. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg 2007;134:319-26. View abstract.
Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr 2001;138:S56-61. View abstract.
Carpenter TO, Levy HL, Holtrop ME, et al. Lysinuric protein intolerance presenting as childhood osteoporosis. Clinical and skeletal response to citrulline therapy. New Engl J Med 1985;312:290-4. View abstract.
Collins JK, Wu G, Perkins-Veazie P, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition 2007;23:261-6. View abstract.
Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids 2005;29:177-205. View abstract.
Hayashi T, Juliet PAR, Matsui-Hirai H, et al. L-citrulline and L-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits. Proc Natl Acad Sci U S A 2005;102:13681-6. View abstract.
Hickner RC, Tanner CJ, Evans CA, et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc 2006;38:660-6. View abstract.
Mandel H, Levy N, Izkovitch S, Korman SH. Elevated plasma citrulline and arginine due to consumption of Citrullus vulgaris (watermelon). J Inherit Metab Dis 2005;28:467-72. View abstract.
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;99:855-62. View abstract.
Osowska S, Duchemann T, Walrand S, et al. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab 2006;291:E582-6. View abstract.
Osowska S, Moinard C, Neveux N, et al. Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection. Gut 2004;53:1781-6. View abstract.
Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006;24:275-90. View abstract.
Ruiz E, Del Rio M, Somoza B, et al. L-citrulline, the by-product of nitric oxide synthesis, decreases vascular smooth muscle cell proliferation. J Pharmacol Exp Therap 1999;290:310-3. View abstract.
Ruiz E, Tejerina T. Relaxant effects of L-citrulline in rabbit vascular smooth muscle. Br J Pharmacol 1998;125:186-92. View abstract.
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;65:51-9. View abstract.
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;132:58-65. View abstract.
Tremblay GC. Ornithine or citrulline therapy in treatment of Reye's syndrome (letter). New Engl J Med 1975;292:160-1. View abstract.
Waugh WH, Daeschner CW 3rd, Files BA, et al. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. J Natl Med Assoc 2001;93:363-71. View abstract.
Azizi S, Mahdavi R, Mobasseri M, Aliasgharzadeh S, Abbaszadeh F, Ebrahimi-Mameghani M. The impact of L-citrulline supplementation on glucose homeostasis, lipid profile, and some inflammatory factors in overweight and obese patients with type 2 diabetes: A double-blind randomized placebo-controlled trial. Phytother Res. 2021;35(6):3157-3166. View abstract.
Bailey SJ, Blackwell JR, Lord T, et al. l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol (1985) 2015;119:385-95. View abstract.
Balderas-Munoz K, Castillo-Martínez L, Orea-Tejeda A, et al. Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation. Cardiol J 2012;19:612-7. View abstract.
Barr FE, Tirona RG, Taylor MB, et al. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg 2007;134:319-26. View abstract.
Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr 2001;138:S56-61. View abstract.
Carpenter TO, Levy HL, Holtrop ME, et al. Lysinuric protein intolerance presenting as childhood osteoporosis. Clinical and skeletal response to citrulline therapy. New Engl J Med 1985;312:290-4. View abstract.
Cheng JW, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35:755-64. View abstract.
Collins JK, Wu G, Perkins-Veazie P, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition 2007;23:261-6. View abstract.
Cormio L, De Siati M, Lorusso F, et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology 2011;77:119-22. View abstract.
Curis E, Nicolis I, Moinard C, et al. Almost all about citrulline in mammals. Amino Acids 2005;29:177-205. View abstract.
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;33:1459-66. View abstract.
Divito B, McLaughlin M, Jacobs I. The Effects of L-Citrulline on Blood-Lactate Removal Kinetics Following Maximal-Effort Exercise. J Diet Suppl. 2021:1-13. View abstract.
Figueroa A, Trivino JA, Sanchez-Gonzalez MA, Vicil F. Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men. Am J Hypertens 2010;23:12-6. View abstract.
Hafner P, Bonati U, Klein A, et al. Effect of combination L-citrulline and metformin treatment on motor function in patients with Duchenne muscular dystrophy: a randomized clinical trial. JAMA Netw Open. 2019;2(10):e1914171. View abstract.
Hanff E, Hafner P, Bollenbach A, et al. Effects of single and combined metformin and L-citrulline supplementation on L-arginine-related pathways in Becker muscular dystrophy patients: possible biochemical and clinical implications. Amino Acids. 2018;50(10):1391-1406. View abstract.
Hayashi T, Juliet PAR, Matsui-Hirai H, et al. L-citrulline and L-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits. Proc Natl Acad Sci U S A 2005;102:13681-6. View abstract.
Hickner RC, Tanner CJ, Evans CA, et al. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc 2006;38:660-6. View abstract.
Hwang P, Morales Marroquín FE, Gann J, 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;15(1):30. View abstract.
Kameda N, Okigawa T, Kimura T, et al. The effect of L-citrulline ingestion on ECG QT interval and autonomic nervous system activity. J Physiol Anthropol 2011;30:41-5. View abstract.
Mandel H, Levy N, Izkovitch S, Korman SH. Elevated plasma citrulline and arginine due to consumption of Citrullus vulgaris (watermelon). J Inherit Metab Dis 2005;28:467-72. View abstract.
Martínez-Sánchez A, Alacid F, Rubio-Arias JA, Fernández-Lobato B, Ramos-Campo DJ, Aguayo E. Consumption of watermelon juice enriched in l-citrulline and pomegranate ellagitannins enhanced metabolism during physical exercise. J Agric Food Chem 2017;65(22):4395-4404. View abstract.
McKinley-Barnard S, Andre T, Morita M, Willoughby DS. Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. J Int Soc Sports Nutr 2015;12:27. View abstract.
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;20(11):98. View abstract.
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;99:855-62. View abstract.
Nguyen S, Rajfer J, Shaheen M. Safety and efficacy of daily Revactin in men with erectile dysfunction: a 3-month pilot study. Transl Androl Urol. 2018;7(2):266-73. View abstract.
Ochiai M, Hayashi T, Morita M, et al. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Int J Cardiol 2012;155:257-61. View abstract.
Orozco-Gutiérrez JJ, Castillo-Martínez L, Orea-Tejeda A, 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;17:612-8. View abstract.
Osowska S, Duchemann T, Walrand S, et al. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab 2006;291:E582-6. View abstract.
Osowska S, Moinard C, Neveux N, et al. Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection. Gut 2004;53:1781-6. View abstract.
Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 2010;24:1215-22. View abstract.
Rhim HC, Kim SJ, Park J, Jang KM. Effect 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;9(6):553-561. View abstract.
Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006;24:275-90. View abstract.
Ruiz E, Del Rio M, Somoza B, et al. L-citrulline, the by-product of nitric oxide synthesis, decreases vascular smooth muscle cell proliferation. J Pharmacol Exp Therap 1999;290:310-3. View abstract.
Ruiz E, Tejerina T. Relaxant effects of L-citrulline in rabbit vascular smooth muscle. Br J Pharmacol 1998;125:186-92. View abstract.
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;65:51-9. View abstract.
Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol 2014;64:231-5. View abstract.
Shirai M, Miyoshi Y, Ogasa T, et al. Oral Testofen, L-Citrulline, Resveratrol, and Caffeine Supplement Drink Improves Sexual Function in Men with Phosphodiesterase 5 Inhibitors: Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. World J Mens Health. 2021;39(4):733-739. View abstract.
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;132:58-65. View abstract.
Sureda A, Córdova A, Ferrer MD, et al. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol 2010;110:341-51. View abstract.
Suzuki I, Sakuraba K, Horiike T, et al. A combination of oral L-citrulline and L-arginine improved 10-min full-power cycling test performance in male collegiate soccer players: a randomized crossover trial. Eur J Appl Physiol 2019;119(5):1075-84. View abstract.
Suzuki T, Morita M, Kobayashi Y, Kamimura A. 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;13:6. View abstract.
Tremblay GC. Ornithine or citrulline therapy in treatment of Reye's syndrome (letter). New Engl J Med 1975;292:160-1. View abstract.
Valaei K, Mehrabani J, Wong A. Effects of L-citrulline supplementation on nitric oxide and antioxidant markers after high-intensity interval exercise in young men: a randomized controlled trial. Br J Nutr. 2021:1-23. View abstract.
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;31(4):350-358. View abstract.
Vors C, Rancourt-Bouchard M, Couillard C, Gigleux I, Couture P, Lamarche B. Sex May Modulate the Effects of Combined Polyphenol Extract and L-citrulline Supplementation on Ambulatory Blood Pressure in Adults with Prehypertension: A Randomized Controlled Trial. Nutrients. 2021;13(2):399. View abstract.
Waugh WH, Daeschner CW 3rd, Files BA, et al. Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. J Natl Med Assoc 2001;93:363-71. View abstract.
Xu Z, Liu C, Liu S, Zhou Z. Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials. Andrologia. 2021:e14007. View abstract.
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