(OR14-01-26) Citrulline Supplementation Increases Arginine Availability but Not Protein Anabolism in a Preterm Piglet Model

Sunday, July 26, 2026

4:30 PM - 4:42 PM ET

Location: Maryland Ballroom C

Emerging Leaders in Nutrition Science Poster Competition

Presenting Author(s)

RY

Ravi Yadav, PhD

Postdoctoral Research Associate
Texas A&M AgriLife Institute for Advancing Health Through Agriculture (IHA)
College Station, Texas, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

Antonio C Ramos dos Santos, PhD (he/him/his)

Postdoctoral Research Associate
Institute for Advancing Health Through Agriculture, Texas A&M AgriLife Research
College Station, Texas, United States
KJ

Ki Beom Jang

Seoul National University, Research Institute of Agriculture and Life Science
Seoul, Republic of Korea
AS

Agus L. Suryawan, PhD

Baylor College of Medicine
Houston, Texas, United States
RP

Rosemarie D. Parada

Institute for Advancing Health Through Agriculture, Texas A&M AgriLife Research, United States
MM

Mahmoud A. Mohammad, PhD

Baylor College of Medicine
Houston, Texas, United States
CV

Caitlin Vonderohe, DVM; PhD

Baylor College of Medicine
Houston, Texas, United States
BS

Barbara Stoll, PhD

Baylor College of Medicine
Houston, Texas, United States
DB

Douglas G. Burrin, PhD

USDA/ARS Children's Nutrition Research Center, United States
Houston, Texas, United States
MF

Marta L. Fiorotto

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
Teresa A. Davis, PhD, DFASN, FASAS (she/her/hers)

Director
Texas A&M AgriLife Institute for Advancing Health Through Agriculture
College Station, Texas, United States

Disclosure(s):

Ravi Yadav, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Antonio C Ramos dos Santos, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Teresa A. Davis, PhD, DFASN, FASAS: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Lean mass gain is often impaired following preterm birth due to a blunted anabolic response to feeding. Arginine is a conditionally indispensable amino acid in the neonate due, in part, to extensive first-pass metabolism when administered orally. Oral citrulline supplementation, however, may provide an alternative source of arginine. We hypothesized that citrulline supplementation would increase arginine bioavailability and promote lean gain by stimulating muscle protein synthesis.

Methods: Piglets were delivered preterm (107 d gestation; 8 d preterm) by cesarean section. They were maintained on total parenteral nutrition for 1 d and then transitioned to a complete milk-replacement formula via orogastric tube. On d 2, they were randomized to receive the formula supplemented with either alanine (ALA; n = 20) or citrulline (CIT; n = 20) for 12 d. Body composition was assessed by DXA on d 12. On d 13, serial blood samples were collected postprandially over 4 h. Piglets then remained fasted or were fed. A flooding dose of L-[ring- ²H₅] phenylalanine was given either immediately (fasted) or 75 minutes later (fed) to measure fractional protein synthesis rate (Ks). Animals were euthanized 30 minutes later and tissues were collected.

Results: Postprandial plasma citrulline, arginine and ornithine were higher in CIT than ALA pigs, while asparagine, glutamine, serine, glycine, tyrosine, proline, leucine, isoleucine, and valine were reduced (P < 0.05). In longissimus dorsi (LD) muscle, CIT supplementation increased citrulline, arginine, ornithine, 3-guanidinoacetic acid (GAA), and creatine compared with ALA, but branched-chain and the glucogenic amino acids asparagine, glutamine and serine were reduced (P < 0.05). Body weight and lean mass gain were lower (P < 0.05) in CIT- vs. ALA-fed pigs (49 vs 51 g BW/(kg∙d) and 1534 vs 1725 g lean). Feeding increased Ks in skeletal muscles and jejunum (P < 0.05) irrespective of intervention.

Conclusions: Citrulline supplementation increased systemic and intramuscular arginine availability but did not enhance muscle protein synthesis. Increased levels of 3-GAA and creatine suggest increased creatine pathway activity. Our data indicate that increasing arginine availability alone is insufficient to overcome impaired anabolic growth resistance in preterm neonates.

Funding Sources: USDA and NIH