title: Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study.
abstract: OBJECTIVE
  Amino acid (AA) availability is critical to maintain protein homeostasis and reduced protein intake causes a decline in protein synthesis. Citrulline, an amino acid metabolite, has been reported to stimulate muscle protein synthesis in malnourished rats.
  
  
  METHODS
  To determine whether citrulline stimulates muscle protein synthesis in healthy adults while on a low-protein diet, we studied 8 healthy participants twice in a cross-over study design. Following a 3-days of low-protein intake, either citrulline or a non-essential AA mixture (NEAA) was given orally as small boluses over the course of 8 h. [ring-(13)C6] phenylalanine and [(15)N] tyrosine were administered as tracers to assess protein metabolism. Fractional synthesis rates (FSR) of muscle proteins were measured using phenylalanine enrichment in muscle tissue fluid as the precursor pool.
  
  
  RESULTS
  FSR of mixed muscle protein was higher during the administration of citrulline than during NEAA (NEAA: 0.049 ± 0.005; citrulline: 0.060 ± 0.006; P = 0.03), while muscle mitochondrial protein FSR and whole-body protein turnover were not different between the studies. Citrulline administration increased arginine and ornithine plasma concentrations without any effect on glucose, insulin, C-peptide, and IGF-1 levels. Citrulline administration did not promote mitochondria protein synthesis, transcripts, or citrate synthesis.
  
  
  CONCLUSIONS
  Citrulline ingestion enhances mixed muscle protein synthesis in healthy participants on 3-day low-protein intake. This anabolic action of citrulline appears to be independent of insulin action and may offer potential clinical application in conditions involving low amino acid intake.
authors: Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA; Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France.
authors: Marion
authors: M
authors: Jourdan
authors: Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA. Electronic address: nair.sree@mayo.edu.
authors: K Sreekumaran
authors: KS
authors: Nair
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Rickey E
authors: RE
authors: Carter
authors: Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors: Jill
authors: J
authors: Schimke
authors: Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors: G Charles
authors: GC
authors: Ford
authors: Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France.
authors: Julie
authors: J
authors: Marc
authors: Nutrition Unit, PUI, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris, Créteil, France; Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France.
authors: Christian
authors: C
authors: Aussel
authors: Clinical Chemistry, Cochin and Hotel-Dieu Hospitals, Assistance Publique - Hôpitaux de Paris, Paris, France; Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France.
authors: Luc
authors: L
authors: Cynober
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002956:Citrulline / Q000008:administration & dosage*; D018592:Cross-Over Studies; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins / Q000096:biosynthesis*; D009952:Ornithine / Q000097:blood; D010649:Phenylalanine / Q000008:administration & dosage; D010865:Pilot Projects; D014176:Protein Biosynthesis / Q000187:drug effects; D014443:Tyrosine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004044:Dietary Proteins; D007328:Insulin; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D002956:Citrulline; D014443:Tyrosine; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D001120:Arginine; D009952:Ornithine
keywords: Citrulline; Muscle; Phenylalanine; Protein synthesis