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

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.