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Pharmacokinetic and pharmacodynamic properties of oral L‐citrulline and L‐arginine: impact on nitric oxide metabolism
Open accessAbstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • L‐Arginine is a semiessential amino acid that is converted to nitric oxide (NO) by NO synthase (NOS). • NO improves endothelial function by elevating cyclic guanosine monophosphate. • However, oral L‐arginine treatment in humans is hampered by extensive metabolism. WHAT THIS STUDY ADDS • Oral L‐citrulline supplementation raises plasma L‐arginine concentration and augments NO‐dependent signalling in a dose‐dependent manner. • L‐Citrulline may thus be an alternative to L‐arginine in patients with impaired NOS activity. AIMS: Oral L‐arginine supplementation has been used in several studies to improve endothelium‐dependent, nitric oxide (NO)‐mediated vasodilation. L‐Arginine treatment is hampered by extensive presystemic elimination due to intestinal arginase activity. In contrast, L‐citrulline is readily absorbed and at least in part converted to L‐arginine. The aim of our study was to assess this metabolic conversion and its subsequent pharmacodynamic effects. METHODS: In a double‐blind, randomized, placebo‐controlled cross‐over study, 20 healthy volunteers received six different dosing regimes of placebo, citrulline, and arginine. Pharmacokinetic parameters ( C max , T max , C min , AUC) were calculated after 1 week of oral supplementation. The ratio of plasma L‐arginine over asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase (arginine/ADMA ratio), urinary cyclic guanosine monophosphate (cGMP) and nitrate excretion rates, and flow‐mediated vasodilation (FMD) was measured to assess pharmacodynamic effects. RESULTS: L‐Citrulline dose‐dependently increased AUC and C max of plasma L‐arginine concentration more effectively than L‐arginine ( P < 0.01). The highest dose of citrulline (3 g bid) increased the C min of plasma L‐arginine and improved the L‐arginine/ADMA ratio from 186 ± 8 (baseline) to 278 ± 14 [ P < 0.01, 95% confidence interval (CI) 66, 121]. Moreover, urinary nitrate and cGMP were increased from 92 ± 10 to 125 ± 15 µmol mmol −1 creatinine ( P = 0.01, 95% CI 8, 58) and from 38 ± 3.3 to 50 ± 6.7 nmol mmol −1 creatinine ( P = 0.04, 95% CI 0.4, 24), respectively. No treatment improved FMD over baseline. However, pooled analysis of all FMD data revealed a correlation between the increase of arginine/ADMA ratio and improvement of FMD. CONCLUSION: Our data show for the first time that oral L‐citrulline supplementation raises plasma L‐arginine concentration and augments NO‐dependent signalling in a dose‐dependent manner.
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“Due to this and its non-competitive uptake for cell transport [542], oral citrulline supplementation has been shown to be more effective in increasing arginine [543, 544] and activation of nitric oxide synthase (NOS) [544] as well as various biomarkers of nitric oxide [545].”
From ISSN exercise & sports nutrition review update: research & recommendations (2018) · cites this paper as [543]
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“Citrulline, the end product of arginine-mediated nitric oxide production, has shown the potential to increase plasma nitrate and NO availability (Schwedhelm et al. 2007; Morita et al. 2014).”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Schwedhelm et al. 2007
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“supplementation of older adults with citrulline elevated plasma arginine concentrations for up to 6 h (Moinard et al. 2015; Schwedhelm et al. 2007)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Schwedhelm et al. 2007
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“and increased nitric oxide production in vivo (Churchward-Venne et al. 2014; Schwedhelm et al. 2007).”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Schwedhelm et al. 2007
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“increases both plasma arginine and cGMP (Schwedhelm et al. 2007) and is free of side effects.”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Schwedhelm et al. 2007
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Corretti, M. C., Anderson, T. J., Benjamin, E. J., Celermajer, D. S., Charbonneau, F., Creager, M. A., Deanfield, J. E., Drexler, H., Gerhard‐Herman, M. D., Herrington, D. M., et al. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01746-6 · Cited by 4,606
Böger, R. H., Bode-Böger, S. M., Szuba, A., Tsao, P. S., Chan, J. R., Tangphao, O., Blaschke, T. F., & Cooke, J. P. (1998) · Circulation · doi:10.1161/01.cir.98.18.1842 · Cited by 1,181
Self-citationPollock, J. S., Förstermann, U., Mitchell, J. A., Warner, T. D., Schmidt, H. H. H. W., Nakane, M., & Murad, F. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10480 · Cited by 979
Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns
Chace, D. H., Kalas, T. A., & Naylor, E. W. (2003) · Clinical Chemistry · doi:10.1373/clinchem.2003.022178 · Cited by 621
Almost all about citrulline in mammals
Curis, E., Nicolis, I., Moinard, C., Osowska, S., Zerrouk, N., Bénazeth, S., & Cynober, L. (2005) · Amino Acids · doi:10.1007/s00726-005-0235-4 · Cited by 571
The role of nitric oxide in cardiovascular diseases
NASEEM, K. (2005) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.09.003 · Cited by 557
Asymmetrical Dimethylarginine: The Über Marker?
Cooke, J. P. (2004) · Circulation · doi:10.1161/01.cir.0000126823.07732.d5 · Cited by 396
Endothelial function and nitric oxide: clinical relevance
Vallance, P. J., & Chan, N. N. (2001) · Heart · doi:10.1136/heart.85.3.342 · Cited by 389
Böger, R. H. (2004) · The Journal of Nutrition · doi:10.1093/jn/134.10.2842s · Cited by 363
Self-citationEnzymes of Arginine Metabolism
Morris, S. M. (2004) · Journal of Nutrition · doi:10.1093/jn/134.10.2743s · Cited by 361
Research works printed but not linked: 1
- Kuhn KP, 2002, Oral citrulline effectively elevates plasma arginine levels for 24 hours in normal volunteers, Circulation, 106, II1
Cited by
Sorted by citations
ISSN exercise & sports nutrition review update: research & recommendations
Kerksick, C. M., Wilborn, C. D., Roberts, M. D., Smith-Ryan, A., Kleiner, S. M., Jäger, R., Collins, R., Cooke, M., Davis, J. N., Galvan, E., et al. (2018) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-018-0242-y · Cited by 945
Arginase: an emerging key player in the mammalian immune system
Munder, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00291.x · Cited by 725
Strategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans
Wu, G., Meininger, C. J., McNeal, C. J., Bazer, F. W., & Rhoads, J. M. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-74180-8_10 · Cited by 344
Arginine and Endothelial Function
Gambardella, J., Khondkar, W., Morelli, M. B., Wang, X., Santulli, G., & Trimarco, V. (2020) · Biomedicines · doi:10.3390/biomedicines8080277 · Cited by 266
l-Citrulline Supplementation: Impact on Cardiometabolic Health
Allerton, T. D., Proctor, D. N., Stephens, J. M., Dugas, T. R., Spielmann, G., & Irving, B. A. (2018) · Nutrients · doi:10.3390/nu10070921 · Cited by 251
Arginine and Citrulline and the Immune Response in Sepsis
Wijnands, K. A. P., Castermans, T. M. R., Hommen, M., Meesters, D. M., & Poeze, M. (2015) · Nutrients · doi:10.3390/nu7031426 · Cited by 217
Luiking, Y. C., Poeze, M., Ramsay, G., & Deutz, N. E. P. (2008) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2007.25765 · Cited by 208
Obesity, Inflammation, and the Potential Application of Pharmaconutrition
Cave, M. C., Hurt, R. T., Frazier, T. H., Matheson, P. J., Garrison, R. N., McClain, C. J., & McClave, S. A. (2008) · Nutrition in Clinical Practice · doi:10.1177/011542650802300116 · Cited by 192
Citrulline: From metabolism to therapeutic use
Bahri, S., Zerrouk, N., Aussel, C., Moinard, C., Crenn, P., Curis, E., Chaumeil, J., Cynober, L., & Sfar, S. (2012) · Nutrition · doi:10.1016/j.nut.2012.07.002 · Cited by 186
Arginine—Dual roles as an onconutrient and immunonutrient
Albaugh, V. L., Pinzon‐Guzman, C., & Barbul, A. (2016) · Journal of Surgical Oncology · doi:10.1002/jso.24490 · Cited by 173
Holguín, F., COMHAIR, S. A. A., Hazen, S. L., Powers, R. W., Khatri, S. S., Bleecker, E. R., Busse, W. W., Calhoun, W. J., Castro, M., Fitzpatrick, A. M., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201207-1270oc · Cited by 169
Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine
Morris, C. R., Hamilton‐Reeves, J. M., Martindale, R. G., Sarav, M., & Ochoa, J. B. (2017) · Nutrition in Clinical Practice · doi:10.1177/0884533617691250 · Cited by 162
Citrulline and nitrogen homeostasis: an overview
Breuillard, C., Cynober, L., & Moinard, C. (2015) · Amino Acids · doi:10.1007/s00726-015-1932-2 · Cited by 159
Oxidative Stress in Airway Diseases
Holguín, F. (2013) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201305-116aw · Cited by 150
The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure
Khalaf, D., Krüger, M., Wehland, M., Infanger, M., & Grimm, D. G. (2019) · Nutrients · doi:10.3390/nu11071679 · Cited by 145
Figueroa, A., Wong, A., Jaime, S. J., & Gonzales, J. U. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000340 · Cited by 147
Citrulline in health and disease. Review on human studies
Papadia, C., Osowska, S., Cynober, L., & Forbes, A. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2017.10.009 · Cited by 143
Morita, M., Hayashi, T., Ochiai, M., Maeda, M., Yamaguchi, T., Ina, K., & Kuzuya, M. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.10.029 · Cited by 140
L-Arginine as a Potential Ergogenic Aid in Healthy Subjects
Álvares, T. S., Meirelles, C. M., Bhambhani, Y. N., Paschoalin, V. M. F., & Gomes, P. S. C. (2011) · Sports Medicine · doi:10.2165/11538590-000000000-00000 · Cited by 138
Bailey, S. J., Blackwell, J. R., Lord, T., Vanhatalo, A., Winyard, P. G., & Jones, A. M. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00192.2014 · Cited by 136
Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men
Ochiai, M., Hayashi, T., Morita, M., Ina, K., Maeda, M., Watanabe, F., & Morishita, K. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2010.10.004 · Cited by 127
l-Arginine and its metabolites in kidney and cardiovascular disease
Popolo, A., Adesso, S., Pinto, A., Autore, G., & Marzocco, S. (2014) · Amino Acids · doi:10.1007/s00726-014-1825-9 · Cited by 129
Cynober, L., Moinard, C., & Bandt, J. P. D. (2010) · Clinical Nutrition · doi:10.1016/j.clnu.2010.07.006 · Cited by 128
Arginine and nitric oxide synthase: Regulatory mechanisms and cardiovascular aspects
Lorin, J., Zeller, M., Guilland, J.-C., Cottin, Y., Vergely, C., & Rochette, L. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300033 · Cited by 126
Suzuki, T., Morita, M., Kobayashi, Y., & Kamimura, A. (2016) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-016-0117-z · Cited by 120
Oxidative stress in surgery in an ageing population: Pathophysiology and therapy
Rosenfeldt, F., Wilson, M. D., Lee, G., Kure, C., Ou, R., Braun, L. A., & de Haan, J. B. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.03.010 · Cited by 126
Tain, Y., Hsieh, C., Lin, I.-C., Chen, C., Sheen, J., & Huang, L. (2010) · Nitric Oxide · doi:10.1016/j.niox.2010.03.005 · Cited by 109
Retinopathy of prematurity: A review of pathophysiology and signaling pathways
Fevereiro‐Martins, M., Marques‐Neves, C., Guimarães, H., & Bicho, M. (2022) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2022.11.007 · Cited by 115
Citrulline and arginine utility in treating nitric oxide deficiency in mitochondrial disorders
El‐Hattab, A. W., Emrick, L., Craigen, W. J., & Scaglia, F. (2012) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2012.06.018 · Cited by 106
Figueroa, A., Sanchez‐Gonzalez, M. A., Perkins-Veazie, P. M., & Arjmandi, B. H. (2010) · American Journal of Hypertension · doi:10.1038/ajh.2010.142 · Cited by 101
Gonzalez, A. M., & Trexler, E. T. (2020) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003426 · Cited by 108
Werner, A., Koschke, M., Leuchtner, N., Luckner‐Minden, C., Habermeier, A., Rupp, J., Heinrich, C., Conradi, R., Closs, E. I., & Munder, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00864 · Cited by 98
Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction
Cormio, L., Siati, M. D., Lorusso, F., Selvaggio, O., Mirabella, L., Sanguedolce, F., & Carrieri, G. (2011) · Urology · doi:10.1016/j.urology.2010.08.028 · Cited by 100
Citrulline: pharmacological perspectives and its role as an emerging biomarker in future
Kaore, S. N., Amane, H. S., & Kaore, N. M. (2012) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2012.01059.x · Cited by 101
The Link Between Erectile and Cardiovascular Health: The Canary in the Coal Mine
Meldrum, D. R., Gambone, J. C., Morris, M. A., Meldrum, D. A. N., Esposito, K., & Ignarro, L. J. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.03.093 · Cited by 96
Bailey, S. J., Blackwell, J. R., Williams, E. R., Vanhatalo, A., Wylie, L. J., Winyard, P. G., & JONES, A. M. (2016) · Nitric Oxide · doi:10.1016/j.niox.2016.06.008 · Cited by 99
Szlas, A., Kurek, J. M., & Krejpcio, Z. (2022) · Nutrients · doi:10.3390/nu14050961 · Cited by 100
Safety and Effectiveness of Arginine in Adults
McNeal, C. J., Meininger, C. J., Reddy, D., Wilborn, C., & Wu, G. (2016) · Journal of Nutrition · doi:10.3945/jn.116.234740 · Cited by 93
Therapeutic Potential of Citrulline as an Arginine Supplement: A Clinical Pharmacology Review
Rashid, J., Kumar, S. S., Job, K. M., Liu, X., Fike, C. D., & Sherwin, C. M. T. (2020) · Pediatric Drugs · doi:10.1007/s40272-020-00384-5 · Cited by 93
Park, S., Son, W., & Kwon, O. (2015) · Journal of Exercise Rehabilitation · doi:10.12965/jer.150254 · Cited by 90
L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health
Aguayo, E., Martínez‐Sánchez, A., Fernández-Lobato, B., & Alacid, F. (2021) · Applied Sciences · doi:10.3390/app11073293 · Cited by 96
Sureda, A., Córdova, A., Ferrer, M. D., Tauler, P., Pérez, G., Tur, J. A., & Pons, A. (2009) · Free Radical Research · doi:10.1080/10715760903071664 · Cited by 86
Lüneburg, N., Xanthakis, V., Schwedhelm, E., SULLIVAN, L. M., Maas, R., Anderssohn, M., Riederer, U., Glazer, N. L., Vasan, R. S., & Böger, R. H. (2011) · Journal of Nutrition · doi:10.3945/jn.111.148197 · Cited by 86
Self-citationAsymmetric Dimethylarginine, Endothelial Dysfunction and Renal Disease
Aldamiz-Echevarria, L. J., & Andrade, F. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911288 · Cited by 84
El‐Hattab, A. W., Emrick, L., Hsu, J. W.-C., Chanprasert, S., Almannai, M., Craigen, W. J., Jahoor, F., & Scaglia, F. (2016) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2016.01.010 · Cited by 87
Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension
Tain, Y., Sheen, J., Chen, C., Yu, H., Tiao, M., Kuo, H.-C., & Huang, L. (2014) · Free Radical Research · doi:10.3109/10715762.2014.895341 · Cited by 84
Agarwal, U., Didelija, I. C., Yuan, Y., Wang, X., & Marini, J. C. (2017) · Journal of Nutrition · doi:10.3945/jn.116.240382 · Cited by 81
Figueroa, A., Trivino, J. A., Sanchez-Gonzalez, M. A., & Vicil, F. (2010) · American Journal of Hypertension · doi:10.1038/ajh.2009.195 · Cited by 79
Cutrufello, P. T., Gadomski, S. J., & Zavorsky, G. S. (2015) · Journal of Sports Sciences · doi:10.1080/02640414.2014.990495 · Cited by 79
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Zago, M., Capodaglio, P., Ferrario, C., Tarabini, M., & Galli, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0202866 · Cited by 79
McCarty, M. F., & DiNicolantonio, J. J. (2015) · AGE · doi:10.1007/s11357-015-9823-8 · Cited by 79
Gonzalez, A. M., Townsend, J. R., Pinzone, A. G., & Hoffman, J. R. (2023) · Nutrients · doi:10.3390/nu15030660 · Cited by 94
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Figueroa, A., Wong, A., Hooshmand, S., & Sanchez‐Gonzalez, M. A. (2012) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3182733794 · Cited by 76
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Holguín, F., Grasemann, H., Sharma, S., Winnica, D., Wasil, K., Smith, V. L., Cruse, M. H., Perez, N., Coleman, E., Scialla, T. J., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.131733 · Cited by 77
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Weckman, A. M., McDonald, C. R., Baxter, J. B., Fawzi, W. W., Conroy, A. L., & Kain, K. C. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz015 · Cited by 74
Trexler, E. T., Persky, A. M., Ryan, E. D., Schwartz, T. A., Stoner, L. R., & Smith‐Ryan, A. E. (2019) · Sports Medicine · doi:10.1007/s40279-019-01091-z · Cited by 78
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Hsu, C., & Tain, Y. (2020) · Antioxidants · doi:10.3390/antiox10010033 · Cited by 71
Maric, S., Restin, T., Muff, J. L., Camargo, S. M. R., Guglielmetti, L. C., Holland-Cunz, S. G., Crenn, P., & Vuille-dit-Bille, R. N. (2021) · Nutrients · doi:10.3390/nu13082794 · Cited by 73
Strobel, J., Mieth, M., Endreß, B., Auge, D., König, J., Fromm, M. F., & Maas, R. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.06.002 · Cited by 67
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Visser, M., Paulus, W. J., Vermeulen, M. A. R., Richir, M. C., Davids, M., Wisselink, W., de Mol, B. A. J. M., & van Leeuwen, P. A. M. (2010) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfq158 · Cited by 66
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Roberts, B. M., Helms, E. R., Trexler, E. T., & Fitschen, P. J. (2020) · Journal of Human Kinetics · doi:10.2478/hukin-2019-0096 · Cited by 79
Uyanga, V. A., Amevor, F. K., Liu, M., Cui, Z., Zhao, X., & Lin, H. (2021) · Nutrients · doi:10.3390/nu13113782 · Cited by 78
Wong, A., Alvarez‐Alvarado, S., Jaime, S. J., Kinsey, A. W., Spicer, M. T., Madzima, T. A., & Figueroa, A. (2015) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2015-0465 · Cited by 65
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Hsu, C., & Tain, Y. (2019) · Nutrients · doi:10.3390/nu11071452 · Cited by 70
Bourdon, A., Parnet, P., Nowak, C., Tran, N.-T., Winer, N., & Darmaun, D. (2016) · Journal of Nutrition · doi:10.3945/jn.115.221267 · Cited by 66
Rhim, H. C., Kim, S. J., Park, J., & Jang, K.-M. (2020) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.02.003 · Cited by 68
The Role of Amino Acids in Endothelial Biology and Function
Li, M., Wu, Y., & Ye, L. (2022) · Cells · doi:10.3390/cells11081372 · Cited by 65
Lee, Y., Su, Y., Liu, T., Tsai, C., Chang, C., & Yu, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02911 · Cited by 62
Churchward-Venne, T. A., Cotie, L. M., MacDonald, M. J., Mitchell, C. J., Prior, T., Baker, S. K., & Phillips, S. M. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00096.2014 · Cited by 58
Plasma citrulline level as a biomarker for cancer therapy-induced small bowel mucosal damage.
Barzal, J., Szczylik, C. A., Rzepecki, P., Jaworska, M., & Anuszewska, E. (2014) · Acta Biochimica Polonica · doi:10.18388/abp.2014_1823 · Cited by 59
Figueroa, A., Alvarez‐Alvarado, S., Ormsbee, M. J., Madzima, T. A., Campbell, J. C., & Wong, A. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.01.046 · Cited by 58
Rhim, H. C., Kim, M. S., Park, Y.-J., Choi, W. S., Park, H. K., Kim, H. G., Kim, A., & Paick, S. H. (2019) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2018.12.002 · Cited by 57
Tain, Y., & Hsu, C. (2022) · Antioxidants · doi:10.3390/antiox11030511 · Cited by 58
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Metadata
- Authors
- Schwedhelm, E., Maas, R., Freese, R., Jung, D., Lukacs, Z., Jambrecina, A., Spickler, W., Schulze, F., & Böger, R. H.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Schwedhelm, Edzard
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2007-10-22
- Volume
- 65
- Issue
- 1
- Pages
- 51-59
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC2291275
- OpenAlex
- W2162463567
- Cited by
- 494
- References
- 43
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 22 · 2023: 47 · 2022: 42 · 2021: 48 · 2020: 42 · 2019: 30 · 2018: 27 · 2017: 24 · 2016: 32 · 2015: 33 · 2014: 27 · 2013: 16 · 2012: 16
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- citrulline, L-arginine, nitric oxide, nitric oxide synthase, asymmetric dimethylarginine, flow-mediated dilation, endothelial function, cyclic GMP, urinary nitrate, arginase, oral supplementation, pharmacokinetics, pharmacodynamics, dose-response relationship, nitric oxide metabolism, endothelium-dependent vasodilation
- MeSH terms
- Administration, Oral, Arginine, Citrulline, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Nitric Oxide, Placebos, Vasodilation, Cross-Over Studies, Nitric Oxide Synthase
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