doi: 10.1111/j.1472-8206.2009.00716.x ORIGINAL ARTICLE The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers Sylvie Blazejewski a,b , Agne `s Georges c , Karelle Forest a,b , Jean-Benoı ˆt Corcuff c , Abdelilah Abouelfath a,b , Pierre-Olivier Girodet a,b , Mamadou Kamagate a,b , Alain Jacquet a,b , Odile Pillet d , Laurence Bordenave c , Nicholas Moore a,b * a De ´partement de Pharmacologie, Universite ´ Victor Segalen, 33076, Bordeaux, France b Unite ´ de pharmacologie clinique, CHU de Bordeaux, 33076 Bordeaux, France c Service de Me ´decine Nucle ´aire, Ho ˆpital Haut-Le ´ve ˆque, CHU de Bordeaux, 33604 Pessac, France d Service de Re ´animation Me ´dicale, Ho ˆpital Pellegrin, CHU de Bordeaux, 33076 Bordeaux, France INTRODUCTION Arginine is a natural amino acid that physiologically stimulates secretion of the growth hormone (GH) by i.v. administration in human, which is routinely used to diagnose GH deficiency [1]. In France, arginine is also used for the treatment of children with growth retardation linked to a partial deficit in GH secretion [2,3]. In this case, arginine aspartate is administered to children as a single oral intake at the dose of 700 mg/kg/day, the total daily dose being always below 15 g. The recommended treatment duration is 3 months. Growth hormone receptors desensitization has been shown in sheep and rats [4,5]. In addition, GH secretion is regulated by the negative feedback of GH and insulin- like growth factor-1 (IGF-1) [6,7]. These mechanisms could alter the effect of arginine on GH secretion, which is supported by the fact that, in rats, a chronic treatment with arginine aspartate is followed by a progressive decrease in the induction of GH secretion [8]. In humans, no tolerance to GH has been shown. Its continuous administration in deficient subjects has a constant efficacy [9]. However, the GH response to chronic oral arginine, as used in France for the treatment of growth retardation in children, has never Keywords arginine, growth hormone-releasing hormone, human, insulin-like growth factor- binding protein-3, insulin-like growth factor-1 Received 28 June 2007; revised 30 October 2007; accepted 9 February 2009 *Correspondence and reprints: nicholas.moore@pharmaco. u-bordeaux2.fr ABSTRACT To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF- binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions. ª 2009 The Authors Journal compilation ª 2009 Socie ´ te ´ Franc ¸aise de Pharmacologie et de The ´ rapeutique Fundamental & Clinical Pharmacology 23 (2009) 339–344 339