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Clin Nutr. 2015 Jun;34(3):449-56. doi: 10.1016/j.clnu.2014.04.019. Epub 2014 May 4.

Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study.

Author information

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.

KEYWORDS:

Citrulline; Muscle; Phenylalanine; Protein synthesis

PMID:
24972455
PMCID:
PMC4309748
DOI:
10.1016/j.clnu.2014.04.019
[Indexed for MEDLINE]
Free PMC Article

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