THE IMPACT OF CITRULLINE SUPPLEMENTATION ON CARDIOVASCULAR AND EXERCISE PHYSIOLOGY: A NARRATIVE REVIEW
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6401Keywords:
Citrulline, Nitric Oxide, Exercise Physiology, Cardiovascular Function, Sports SupplementationAbstract
Background: L-citrulline is an endogenous non-proteinogenic amino acid involved in nitric oxide (NO) metabolism by increasing L-arginine bioavailability. Its use in sports and cardiovascular disease prevention has gained considerable interest, although its efficacy remains debatable.
Aim of the study: The aim of the study is to evaluate current evidence on the effects of L-citrulline supplementation on physical performance and cardiovascular function.
Materials and methods: A narrative review of the literature was conducted using PubMed/MEDLINE and Google Scholar. 148 publications were analysed, mainly from 2017–2025, including meta-analyses, systematic reviews, randomised controlled trials, and international guidelines.
Results: L-citrulline supplementation increases L-arginine and NO metabolite concentrations, supporting vasodilation and endothelial function. Beneficial effects were reported more often with chronic than acute supplementation. Some studies showed improvements in blood pressure, vascular stiffness, and blood flow, although results remain inconsistent. In exercise settings, supplementation was associated with improved selected resistance-training outcomes and reduced perceived fatigue and post-exercise muscle soreness. Evidence regarding effects on strength, power, and aerobic capacity remains inconclusive.
Conclusions: L-citrulline is a safe and well-tolerated supplement with potential benefits for endothelial function, selected cardiovascular parameters, and some aspects of exercise performance. However, the heterogeneity of available studies prevents firm conclusions, highlighting the need for further long-term randomised clinical trials.
References
Baltazar-Martins, G., Brito de Souza, D., Aguilar-Navarro, M., Muñoz-Guerra, J., Plata, M. D. M., & Del Coso, J. (2019). Prevalence and patterns of dietary supplement use in elite Spanish athletes. J Int Soc Sports Nutr, 16(1), 30. https://doi.org/10.1186/s12970-019-0296-5
Maughan, R. J., Burke, L. M., Dvorak, J., Larson-Meyer, D. E., Peeling, P., Phillips, S. M., et al. (2018). IOC consensus statement: Dietary supplements and the high-performance athlete. Br J Sports Med, 52(7), 439–455. https://doi.org/10.1136/bjsports-2018-099027
Viribay, A., Fernández-Landa, J., Castañeda-Babarro, A., Collado, P. S., Fernández-Lázaro, D., & Mielgo-Ayuso, J. (2022). Effects of citrulline supplementation on different aerobic exercise performance outcomes: A systematic review and meta-analysis. Nutrients, 14(17), 3479. https://doi.org/10.3390/nu14173479
Maric, S., Restin, T., Muff, J. L., Camargo, S. M., Guglielmetti, L. C., Holland-Cunz, S. G., et al. (2021). Citrulline, biomarker of enterocyte functional mass and dietary supplement. Metabolism, transport, and current evidence for clinical use. Nutrients, 13(8), 2794. https://doi.org/10.3390/nu13082794
Papadia, C., Osowska, S., Cynober, L., & Forbes, A. (2018). Citrulline in health and disease. Review on human studies. Clin Nutr, 37(6 Pt A), 1823–1828. https://doi.org/10.1016/j.clnu.2017.10.009
Urschel, K. L., Shoveller, A. K., Uwiera, R. R., Pencharz, P. B., & Ball, R. O. (2006). Citrulline is an effective arginine precursor in enterally fed neonatal piglets. J Nutr, 136(7), 1806–1813. https://doi.org/10.1093/jn/136.7.1806
Kerksick, C. M., Wilborn, C. D., Roberts, M. D., Smith-Ryan, A., Kleiner, S. M., Jäger, R., et al. (2018). ISSN exercise & sports nutrition review update: Research & recommendations. J Int Soc Sports Nutr, 15(1), 38. https://doi.org/10.1186/s12970-018-0242-y
Allerton, T. D., Proctor, D. N., Stephens, J. M., Dugas, T. R., Spielmann, G., & Irving, B. A. (2018). L-citrulline supplementation: Impact on cardiometabolic health. Nutrients, 10(7), 921. https://doi.org/10.3390/nu10070921
Stuehr, D. J. (2004). Enzymes of the L-arginine to nitric oxide pathway. J Nutr, 134(10 Suppl), 2748S–2751S. https://doi.org/10.1093/jn/134.10.2748S
Schwedhelm, E., Maas, R., Freese, R., Jung, D., Lukacs, Z., Jambrecina, A., et al. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: Impact on nitric oxide metabolism. Br J Clin Pharmacol, 65(1), 51–59. https://doi.org/10.1111/j.1365-2125.2007.02990.x
Bailey, S. J., Blackwell, J. R., Lord, T., Vanhatalo, A., Winyard, P. G., & Jones, A. M. (2015). L-citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol (1985), 119(4), 385–395. https://doi.org/10.1152/japplphysiol.00192.2014
Suzuki, T., Morita, M., Kobayashi, Y., & Kamimura, A. (2016). 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, 13, 6. https://doi.org/10.1186/s12970-016-0117-z
Bahri, S., Zerrouk, N., Aussel, C., Moinard, C., Crenn, P., Curis, E., et al. (2013). Citrulline: From metabolism to therapeutic use. Nutrition, 29(3), 479–484. https://doi.org/10.1016/j.nut.2012.07.002
Thompson, C., Jones, A. M., & Bailey, S. J. (2019). Dietary supplementation in sport and exercise: Evidence, safety and ergogenic benefits (J. R. Hoffman, Ed.). https://doi.org/10.4324/9780429465567
Moncada, S., & Higgs, A. (1993). The L-arginine-nitric oxide pathway. N Engl J Med, 329(27), 2002–2012. https://doi.org/10.1056/NEJM199312303292706
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov, 7(2), 156–167. https://doi.org/10.1038/nrd2466
Figueroa, A., Jaime, S. J., Morita, M., Gonzales, J. U., & Moinard, C. (2020). L-citrulline supports vascular and muscular benefits of exercise training in older adults. Exerc Sport Sci Rev, 48(3), 133–139. https://doi.org/10.1249/JES.0000000000000223
Cholewa, J., Trexler, E., Lima-Soares, F., de Araújo Pessôa, K., Sousa-Silva, R., Santos, A. M., et al. (2019). Effects of dietary sports supplements on metabolite accumulation, vasodilation and cellular swelling in relation to muscle hypertrophy: A focus on "secondary" physiological determinants. Nutrition, 60, 241–251. https://doi.org/10.1016/j.nut.2018.10.011
Vårvik, F. T., Bjørnsen, T., & Gonzalez, A. M. (2021). Acute effect of citrulline malate on repetition performance during strength training: A systematic review and meta-analysis. Int J Sport Nutr Exerc Metab, 31(4), 350–358. https://doi.org/10.1123/ijsnem.2020-0295
Breuillard, C., Cynober, L., & Moinard, C. (2015). Citrulline and nitrogen homeostasis: An overview. Amino Acids, 47(4), 685–691. https://doi.org/10.1007/s00726-015-1932-2
Rimando, A. M., & Perkins-Veazie, P. M. (2005). Determination of citrulline in watermelon rind. J Chromatogr A, 1078(1–2), 196–200. https://doi.org/10.1016/j.chroma.2005.05.009
Moinard, C., Maccario, J., Walrand, S., Lasserre, V., Marc, J., Boirie, Y., & Cynober, L. (2016). Arginine behaviour after arginine or citrulline administration in older subjects. Br J Nutr, 115(3), 399–404. https://doi.org/10.1017/S0007114515004638
Ochiai, M., Hayashi, T., Morita, M., Ina, K., Maeda, M., Watanabe, F., & Morishita, K. (2012). Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Int J Cardiol, 155(2), 257–261. https://doi.org/10.1016/j.ijcard.2010.10.004
Besco, R., Sureda, A., Tur, J. A., & Pons, A. (2012). The effect of nitric-oxide-related supplements on human performance. Sports Med, 42(2), 99–117. https://doi.org/10.2165/11596860-000000000-00000
Wax, B., Kavazis, A. N., & Luckett, W. (2016). Effects of supplemental citrulline-malate ingestion on blood lactate, cardiovascular dynamics, and resistance exercise performance in trained males. J Diet Suppl, 13(3), 269–282. https://doi.org/10.3109/19390211.2015.1008615
Al Jasmi, F., Al Zaabi, N., Al-Thihli, K., Al Teneiji, A. M., Hertecant, J., & El-Hattab, A. W. (2020). Endothelial dysfunction and the effect of arginine and citrulline supplementation in children and adolescents with mitochondrial diseases. J Cent Nerv Syst Dis, 12, 1179573520909377. https://doi.org/10.1177/1179573520909377
Wu, G. (1995). Urea synthesis in enterocytes of developing pigs. Biochem J, 312(3), 717–723. https://doi.org/10.1042/bj3120717
Windmueller, H. G., & Spaeth, A. E. (1981). Source and fate of circulating citrulline. Am J Physiol Endocrinol Metab, 241(6), E473–E480. https://doi.org/10.1152/ajpendo.1981.241.6.E473
World Health Organization. (2023). Global report on hypertension: The race against a silent killer (pp. 1–276).
Theodorou, A. A., Chatzinikolaou, P. N., Margaritelis, N. V., Christodoulou, F., Tsatalas, T., & Paschalis, V. (2023). Short-term L-citrulline supplementation does not affect inspiratory muscle oxygenation and respiratory performance in older adults. Nutrients, 15(8), 1951. https://doi.org/10.3390/nu15081951
Maharaj, A., Fischer, S. M., Dillon, K. N., Kang, Y., Martinez, M. A., & Figueroa, A. (2022). Effects of L-citrulline supplementation on endothelial function and blood pressure in hypertensive postmenopausal women. Nutrients, 14(20), 4396. https://doi.org/10.3390/nu14204396
Tryfonos, A., Christodoulou, F., Pamboris, G. M., Christodoulides, S., & Theodorou, A. A. (2023). Short-term L-citrulline supplementation does not affect blood pressure, pulse wave reflection, or arterial stiffness at rest and during isometric exercise in older males. Sports (Basel), 11(9), 177. https://doi.org/10.3390/sports11090177
Figueroa, A., Maharaj, A., Kang, Y., Dillon, K. N., Martinez, M. A., Morita, M., et al. (2023). Combined citrulline and glutathione supplementation improves endothelial function and blood pressure reactivity in postmenopausal women. Nutrients, 15(7), 1557. https://doi.org/10.3390/nu15071557
Luo, P., Chen, J., Liu, K., & Zhang, J. (2025). 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, 69, 653–664. https://doi.org/10.1016/j.clnesp.2025.07.1130
Ozcan, B., Blachot-Minassian, B., Paradis, S., Mazière, L., Chambion-Diaz, M., Bouyon, S., et al. (2022). L-citrulline supplementation reduces blood pressure and myocardial infarct size under chronic intermittent hypoxia, a major feature of sleep apnea syndrome. Antioxidants (Basel), 11(12), 2326. https://doi.org/10.3390/antiox11122326
Jamwal, S., & Sharma, S. (2018). Vascular endothelium dysfunction: A conservative target in metabolic disorders. Inflamm Res, 67(5), 391–405. https://doi.org/10.1007/s00011-018-1129-8
Klawitter, J., Hildreth, K. L., Christians, U., Kohrt, W. M., & Moreau, K. L. (2017). A relative L-arginine deficiency contributes to endothelial dysfunction across the stages of the menopausal transition. Physiol Rep, 5(17). https://doi.org/10.14814/phy2.13409
Shatanawi, A., Momani, M. S., Al-Aqtash, R., Hamdan, M. H., & Gharaibeh, M. N. (2020). L-citrulline supplementation increases plasma nitric oxide levels and reduces arginase activity in patients with type 2 diabetes. Front Pharmacol, 11, 584669. https://doi.org/10.3389/fphar.2020.584669
Morita, M., Hayashi, T., Ochiai, M., Maeda, M., Yamaguchi, T., Ina, K., & Kuzuya, M. (2014). Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability. Biochem Biophys Res Commun, 454(1), 53–57. https://doi.org/10.1016/j.bbrc.2014.10.029
Kang, Y., Dillon, K. N., Levitt, D. E., & Figueroa, A. (2025). Effects of L-citrulline supplementation on endothelial function, arterial stiffness, and blood glucose level in the fasted and acute hyperglycemic states in middle-aged and older adults with type 2 diabetes. Nutrients, 17(23), 3739. https://doi.org/10.3390/nu17233739
Flores-Ramírez, A. G., Tovar-Villegas, V. I., Maharaj, A., Garay-Sevilla, M. E., & Figueroa, A. (2021). Effects of L-citrulline supplementation and aerobic training on vascular function in individuals with obesity across the lifespan. Nutrients, 13(9), 2991. https://doi.org/10.3390/nu13092991
Wax, B., Kavazis, A. N., Weldon, K., & Sperlak, J. (2015). Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. J Strength Cond Res, 29(3), 786–792. https://doi.org/10.1519/JSC.0000000000000670
Glenn, J. M., Gray, M., Wethington, L. N., Stone, M. S., Stewart, R. W., Jr., & Moyen, N. E. (2017). Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. Eur J Nutr, 56(2), 775–784. https://doi.org/10.1007/s00394-015-1124-6
Pérez-Guisado, J., & Jakeman, P. M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res, 24(5), 1215–1222. https://doi.org/10.1519/JSC.0b013e3181cb28e0
Chappell, A. J., Allwood, D. M., Johns, R., Brown, S., Sultana, K., Anand, A., & Simper, T. (2018). Citrulline malate supplementation does not improve German volume training performance or reduce muscle soreness in moderately trained males and females. J Int Soc Sports Nutr, 15(1), 42. https://doi.org/10.1186/s12970-018-0245-8
Farney, T. M., Bliss, M. V., Hearon, C. M., & Salazar, D. A. (2019). The effect of citrulline malate supplementation on muscle fatigue among healthy participants. J Strength Cond Res, 33(9), 2464–2470. https://doi.org/10.1519/JSC.0000000000002356
Gonzalez, A. M., Yang, Y., Mangine, G. T., Pinzone, A. G., Ghigiarelli, J. J., & Sell, K. M. (2023). Acute effect of L-citrulline supplementation on resistance exercise performance and muscle oxygenation in recreationally resistance trained men and women. J Funct Morphol Kinesiol, 8(3), 88. https://doi.org/10.3390/jfmk8030088
Fick, A. N., Kowalsky, R. J., Stone, M. S., Hearon, C. M., & Farney, T. M. (2021). Acute and chronic citrulline malate supplementation on muscle contractile properties and fatigue rate of the quadriceps. Int J Sport Nutr Exerc Metab, 31(6), 490–496. https://doi.org/10.1123/ijsnem.2021-0117
Gonzalez, A. M., Spitz, R. W., Ghigiarelli, J. J., Sell, K. M., & Mangine, G. T. (2018). Acute effect of citrulline malate supplementation on upper-body resistance exercise performance in recreationally resistance-trained men. J Strength Cond Res, 32(11), 3088–3094. https://doi.org/10.1519/JSC.0000000000002373
Gonzalez, A. M., Pinzone, A. G., Lipes, S. E., Mangine, G. T., Townsend, J. R., Allerton, T. D., Sell, K. M., & Ghigiarelli, J. J. (2022). Effect of watermelon supplementation on exercise performance, muscle oxygenation, and vessel diameter in resistance-trained men. Eur J Appl Physiol, 122(7), 1627–1638. https://doi.org/10.1007/s00421-022-04940-4
Rhim, H. C., Kim, S. J., Park, J., & Jang, K. M. (2020). 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, 9(6), 553–561. https://doi.org/10.1016/j.jshs.2020.02.003
da Silva, D. K., Jacinto, J. L., de Andrade, W. B., Roveratti, M. C., Estoche, J. M., Balvedi, M. C. W., de Oliveira, D. B., da Silva, R. A., & Aguiar, A. F. (2017). Citrulline malate does not improve muscle recovery after resistance exercise in untrained young adult men. Nutrients, 9(10), 1132. https://doi.org/10.3390/nu9101132
Caballero-García, A., Pascual-Fernández, J., Noriega-González, D. C., Bello, H. J., Pons-Biescas, A., Roche, E., & Córdova-Martínez, A. (2021). L-citrulline supplementation and exercise in the management of sarcopenia. Nutrients, 13(9), 3133. https://doi.org/10.3390/nu13093133
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Copyright (c) 2026 Jan Szewczyk, Izabela Grzyb, Alicja Smolińska, Maria Bołoz, Patrycja Krawczyk, Zuzanna Wątek, Katarzyna Łysynkiewicz, Sylwia Haba, Ewa Dapkiewicz, Dawid Gąsowski
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