title: High plasma citrulline and arginine levels ensured by sustained-release citrulline supplementation in rats.
abstract: OBJECTIVE
  Dietary-supplemented arginine has been shown to have positive effects on cardiovascular disease, but several drawbacks exist and could potentially be avoided by using L-citrulline, since it is recycled to L-arginine. However, citrulline is very rapidly metabolized. We therefore developed a sustained-release form of citrulline and evaluated its metabolic behavior in rats.
  
  
  METHODS
  Male Sprague Dawley rats were divided into three groups: receiving "empty microcapsule" (control group), 1 g/kg/d immediate-release citrulline (IR citrulline group), or 1 g/kg/d sustained-release citrulline (SR citrulline group). Citrulline was given each day at 9 a.m. after blood samples for 9 d, and on day 10, blood samples were drawn every 4 h to study the decrease in plasma amino acid concentrations.
  
  
  RESULTS
  SR citrulline led to a sustained increase in citrullinemia and argininemia compared to IR citrulline, and on day 6 argininemia was significantly (P < 0.01) higher with SR compared to IR citrulline. Moreover, argininemia was significantly higher in the SR citrulline group than in controls throughout the study and SR citrulline maintained high argininemia and citrullinemia, at least over 12 h.
  
  
  CONCLUSIONS
  This experimental study provides a strong rationale for using this new formulation for atherosclerosis treatment.
authors.affiliation: Laboratoire de Biologie de la Nutrition, EA2498, Université Paris-Descartes, Paris, France. marie-clotilde.berthe@trs.aphp.fr
authors.forename: Marie-Clotilde
authors.initials: MC
authors.lastname: Berthe
authors.forename: Sylviane
authors.initials: S
authors.lastname: Darquy
authors.forename: Charlotte
authors.initials: C
authors.lastname: Breuillard
authors.forename: Lynda
authors.initials: L
authors.lastname: Lamoudi
authors.forename: Julie
authors.initials: J
authors.lastname: Marc
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chaumeil
authors.forename: Rémy
authors.initials: R
authors.lastname: Couderc
mesh_terms: D000818:Animals; D001120:Arginine / Q000097:blood*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000473:pathology; D002956:Citrulline / Q000008:administration & dosage* / Q000097:blood*; D003692:Delayed-Action Preparations / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D020162:Hyperargininemia / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003692:Delayed-Action Preparations; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine