Marion Jourdan1, K Sreekumaran Nair2, Rickey E Carter3, Jill Schimke4, G Charles Ford4, Julie Marc5, Christian Aussel6, Luc Cynober7. 1. Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA; Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France. 2. Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA. Electronic address: nair.sree@mayo.edu. 3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. 4. Division of Endocrinology and Metabolism, Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA. 5. Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France. 6. Nutrition Unit, PUI, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris, Créteil, France; Laboratory of Biological Nutrition EA 4466, Paris-Descartes University, Paris, France. 7. 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.
Abstract
BACKGROUND & AIMS: 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.
RCT Entities:
BACKGROUND & AIMS: 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.
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