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

• Published in: British journal of nutrition Vol. 99; no. 4; pp. 855 - 862
• Main Authors: Moinard, C., Nicolis, I., Neveux, N., Darquy, S., Bénazeth, S., Cynober, L.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.04.2008
• Subjects: Adult; adverse effects; Amino acids; Amino Acids - blood; Amino Acids - urine; Analysis of Variance; Area Under Curve; Arginine; Arginine - blood; biochemical pathways; Biological and medical sciences; blood chemistry; Blood Glucose - analysis; Calcium - blood; Celiac disease; Chronic illnesses; citrulline; Citrulline - administration & dosage; Citrulline - pharmacokinetics; Clinical medicine; Creatinine - blood; dosage; dose response; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Growth hormone; Growth Hormone - blood; Growth hormones; hormone secretion; Hormones; Humans; Insulin; Insulin - blood; Kidney - metabolism; Load; Male; men; Metabolic Clearance Rate; Metabolism; Nitrogen - urine; Nutrition; Nutrition research; Ornithine; Ornithine - blood; Pharmacokinetics; Physical examinations; Plasma; Side effects; Small intestine; somatotropin; temporal variation; Urine; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Arginine; Pharmacokinetics; Ornithine; Growth hormone; Insulin; Pancreatic hormone; Healthy subject; Citrulline; Blood plasma; Somatotropin; Vertebrata; Mammalia; Adenohypophyseal hormone; Aminoacid; Pharmacokinetics: Arginine: Ornithine: Insulin: Growth hormone; Dose
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114507841110

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.