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

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Abstract
Objective Deficiencies of citrulline and arginine have been associated with adverse outcomes in preterm-infants (PI) and data regarding enteral supplementation in PI is unknown. Study Design: This randomized-controlled-trial [NCT03649932] included 42 PI (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 3 groups while plasma-arginine levels increased significantly in the medium and high-dose groups. Conclusion Enteral L-citrulline supplementation in PI is safe and effective in increasing plasma citrulline and arginine levels.