The effects of arginine and citrulline supplementation in parenteral nutrition in Yucatan miniature piglets

Clancy, Zack (2024) The effects of arginine and citrulline supplementation in parenteral nutrition in Yucatan miniature piglets. Masters thesis, Memorial University of Newfoundland.

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Abstract

In situations where infants cannot tolerate oral feeding, direct intravenous infusion of nutrients, known as parenteral feeding, can be lifesaving. Prolonged parenteral feeding can induce metabolic and physiological changes ranging from reduced blood flow to the gut and gut atrophy to reduced systemic protein synthesis. Gut atrophy hinders the intestinal synthesis of arginine, an amino acid that plays a crucial role in protein and nitric oxide synthesis, as well as guanidinoacetate and, in turn, creatine synthesis. Supplemental arginine can increase systemic arginine availability, thus enhancing arginine availability for protein, creatine and nitric oxide synthesis, and potentially ameliorating gut atrophy. However, supplemental arginine is rapidly extracted from circulation by the liver; thus, we propose supplementing citrulline, an arginine precursor that bypasses the liver, as a means to increase systemic arginine availability. The study's objective is to improve arginine availability via supplemental citrulline, a novel ingredient for parenteral nutrition (PN) solutions. We hypothesized that citrulline supplementation would enhance arginine availability, thereby increasing whole-body protein, creatine and NO synthesis to a greater extent than arginine alone. The effects of supplemental arginine and citrulline on protein, creatine and NO synthesis were investigated in 7-10 day-old Yucatan piglets. Piglets received one of three nutritional interventions: control PN, arginine-supplemented PN, or citrulline-supplemented PN for six days. On study day 6, a primed and continuous infusion of isotopically labelled phenylalanine, tyrosine, guanidinoacetate, arginine and citrulline was conducted for 6 hours. Isotope enrichment of tracers and their products, fluxes and conversions were measured and used to calculate whole-body synthesis of protein (phenylalanine and tyrosine tracers), guanidinoacetate (arginine and guanidinoacetate tracers) and nitric oxide (arginine and citrulline tracers). Supplemental citrulline increased arginine synthesis and release in the kidney, thus illustrating that citrulline is an effective means of increasing systemic arginine availability. Arginine and citrulline appeared to increase arginine availability for nitric oxide (NO). However, their effects on blood flow were not as pronounced as hypothesized, suggesting alternative metabolic fates for the increased NO produced via NOS. Furthermore, there was no treatment effect on whole-body protein synthesis; tissuespecific protein synthesis in the gut, liver, and kidneys was increased with citrulline supplementation only, thus suggesting that citrulline may improve arginine availability for protein synthesis. Arginine supplementation enhanced liver creatine synthesis, and citrulline showed promise in maintaining gut and kidney function, potentially due to its role in sustaining protein synthesis rates, compared to arginine supplementation. Due to the complex regulation of interorgan protein, creatine and NO synthesis, more research is needed to fully understand the effects arginine and citrulline supplementation have on parenterally fed neonates during a critical period in neonatal development.

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