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 .