Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 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

Affiliations
Free PMC article
Randomized Controlled Trial

Citrulline Stimulates Muscle Protein Synthesis in the Post-Absorptive State in Healthy People Fed a Low-Protein Diet - A Pilot Study

Marion Jourdan et al. Clin Nutr. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Effect of small bolus intakes of citrulline (grey line with triangle) or a non-essential amino acid (NEAA) mixture (black line with square) on citrulline, serine, arginine and ornithine plasma concentrations over the course of 8 hours. Data are means ± SE. The differences in the change in levels over the course of treatment are reported in Table 2.
Figure 2
Figure 2
Effect of citrulline on whole body (A) and mixed muscle (B) protein synthesis. No significant differences for phenylalanine (Phe flux) and tyrosine flux (Tyr flux) and phenylalanine incorporation into a protein (Phe protein) was noted between NEAA (AA) and citrulline (CL) days. Phenylalanine conversion to tyrosine (Phe Tyr) was modestly (p=0.05) higher during citrulline and NEAA days. A higher (p=0.03) fractional synthesis rate (FSR) of mixed muscle protein was noted on citrulline day. Data are means ± SE. Cross over analysis (see methods) was used to compare groups. *P<0.05 citrulline vs. NEAA.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback