Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study

British Journal of Nutrition - Tập 99 Số 4 - Trang 855-862 - 2008
Christophe Moinard1, Ioannis Nicolis2, N. Neveux1,3, Sylviane Darquy1, S. Bénazeth2, Luc Cynober1,3
1Laboratoire de Biologie de la Nutrition, EA 2498, Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l'Observatoire, 75270Paris Cedex 06, France
2Laboratoire de Biomathématiques, EA 2498, Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l'Observatoire, 75270Paris Cedex 06, France
3Service de Biochimie, Hôtel-Dieu, AP-HP, 1, Place du Parvis Notre Dame, 75181Cedex O4 Paris, France

Tóm tắt

Previous experimental studies have highlighted that citrulline (CIT) could be a promising pharmaconutrient. However, its pharmacokinetic characteristics and tolerance to loading have not been studied to date. The objective was to characterise the plasma kinetics of CIT in a multiple-dosing study design and to assess the effect of CIT intake on the concentrations of other plasma amino acids (AA). The effects of CIT loading on anabolic hormones were also determined. Eight fasting healthy males underwent four separate oral loading tests (2, 5, 10 or 15 g CIT) in random order. Blood was drawn ten times over an 8 h period for measurement of plasma AA, insulin and growth hormone (Gh). Urine samples were collected before CIT administration and over the next 24 h. None of the subjects experienced side effects whatever the CIT dose. Concerning AA, only CIT, ornithine (ORN) and arginine (ARG) plasma concentrations were affected (maximum concentration 146 (sem 8) to 303 (sem 11) μmol/l (ARG) and 81 (sem 4) to 179 (sem 10) μmol/l (ORN); time to reach maximum concentration 1·17 (sem 0·26) to 2·29 (sem 0·20) h (ARG) and 1·38 (sem 0·25) to 1·79 (sem 0·11) h (ORN) according to CIT dose). Even at high doses, urinary excretion of CIT remained low ( < 5 %). Plasma insulin and Gh were not affected by CIT administration. Short-term CIT administration is safe and well-tolerated. CIT is a potent precursor of ARG. However, at the highest doses, CIT accumulated in plasma while plasma ARG levels increased less than expected. This may be due to saturation of the renal conversion of CIT into ARG.

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Tài liệu tham khảo

10.1093/ajcn/38.2.264

10.1016/S0026-0495(97)90002-0

10.1093/jn/130.11.2626

10.1016/S0360-3016(03)00781-8

10.1016/S0041-1345(02)02669-6

Castillo, 1995, Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis, Am J Physiol, 268, E360

Neveux, 2004, Metabolic and Therapeutic Aspects of Amino Acids in Clinical Nutrition, 17

10.1136/gut.2004.042317

10.1093/ajcn/39.4.514

10.1097/MCO.0b013e32829fb38d

Farges, 1997, Aging of the small bowel: relationship between morphological and functional changes and protein metabolism, J Nutr Health Aging, 1, 17

10.1016/S0016-5085(03)00170-7

10.1097/00006676-200310000-00001

10.1080/07315724.1990.10720343

Wakabayashi, 2004, Metabolic and Therapeutic Aspects of Amino Acids in Clinical Nutrition, 135

10.1016/j.nut.2007.01.005

10.1093/jn/128.8.1249

Vaubourdolle, 1989, Fate of enterally administered ornithine in healthy animals: interactions with α-ketoglutarate, Nutrition, 5, 183

10.1016/0305-4179(87)90123-9

10.1016/0955-2863(95)00066-9

10.1016/0026-0495(83)90154-3

10.1038/333664a0

Bahri, 2005, Characterization of l-citrulline transport in human intestinal caco-2 cells, Clin Nutr, 24, 630

Sakamoto, 1986, Akaike Information Criterion Statistics

10.1097/00000658-198810000-00013

10.1007/BF00807268

2005, A Language and Environment for Statistical Computing

10.1016/j.ghir.2004.12.004

10.1177/0148607191015006696

10.1177/0148607104028006423

10.1007/s00726-005-0235-4

Windmueller, 1981, Source and fate of circulating citrulline, Am J Physiol, 241, E473

Dhanakoti, 1990, Renal arginine synthesis: studies in vitro and in vivo, Am J Physiol, 259, E437

10.1515/CCLM.2000.067

10.1093/ajcn/83.2.508S

10.1111/j.1527-3466.2006.00275.x

10.1016/0261-5614(88)90033-7

10.1203/00006450-199210000-00019

Barbul, 1995, Amino Acid Metabolism and Therapy in Health and Nutritional Disease, 361

10.1152/ajpendo.00398.2005

Waugh, 2001, Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results, J Natl Med Assoc, 93, 363

10.1093/jn/137.6.1646S

10.1007/s10545-005-0467-1

10.1093/jn/137.6.1621S

10.1046/j.1365-2125.1999.00883.x

10.1016/S0014-5793(01)03123-4

10.1079/BJN19950025

10.1016/j.jss.2005.04.004

10.1016/j.chroma.2005.05.009

10.1042/bj2810045

10.1093/jn/136.7.1806

10.1073/pnas.90.16.7749

10.1016/j.jtcvs.2006.02.012

Wu, 1993, Regulation of l-arginine synthesis from l-citrulline by l-glutamine in endothelial cells, Am J Physiol, 265, H1965

10.1053/gast.2000.20227

10.1093/jn/134.10.2783S

10.1093/jn/137.6.1693S

Drotman, 1972, Citrulline metabolism in the perfused rat liver, Am J Physiol, 222, 973, 10.1152/ajplegacy.1972.222.4.973

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British Journal of Nutrition

Tập 99 Số 4

855-862

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