Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels-a pilot randomized trial

J Perinatol. 2024 May;44(5):702-708. doi: 10.1038/s41372-023-01761-x. Epub 2023 Aug 28.

Abstract

Objective: Deficiencies of citrulline and arginine have been associated with adverse outcomes in preterm-infants and data regarding enteral supplementation in preterm infants is limited.

Study design: This randomized -trial [NCT03649932] included 42 preterm infants (gestational age ≤33 weeks) randomized to receive enteral L-citrulline in low (100 mg/kg/day), medium (200 mg/kg/day) and high-dose (300 mg/kg/day) groups for 7 days. Plasma citrulline and arginine levels were obtained pre-and-post supplementation and efficacy was determined by a significant increase in levels after supplementation. A p < 0.05 was considered significant. Safety monitoring included blood-pressure-monitoring as well as complications and death during hospitalization.

Results: A total of 40/42 (95%) of the recruits completed the 7-day supplementation with no adverse events. Plasma-citrulline levels increased significantly in all three groups while plasma-arginine levels increased significantly in the high-dose group.

Conclusion: Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma citrulline and arginine levels.

Clinical trial registration: NCT03649932 https://clinicaltrials.gov/ct2/show/NCT03649932 .

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Arginine* / administration & dosage
  • Arginine* / blood
  • Citrulline* / administration & dosage
  • Citrulline* / blood
  • Dietary Supplements*
  • Enteral Nutrition*
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature* / blood
  • Male
  • Pilot Projects

Substances

  • Citrulline
  • Arginine

Associated data

  • ClinicalTrials.gov/NCT03649932