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

2023-08-28
Journal of perinatology : official journal of the California Perinatal Association 44(5)
- Amna Qasim
- Mohammad Q Mehdi
- Snigdha Bhatia
- Maria E Franco-Fuenmayor
- Sunil K Jain

PubMed: 37640809
DOI: 10.1038/s41372-023-01761-x

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 40
Population: 42 preterm infants (gestational age ≤33 weeks)
Methods: randomized-trial; 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
Duration: 7 days

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 .

Research Insights

L-Citrulline→Increased Arginine Level
plasma-arginine levels increased significantly in the high-dose group
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day, 200 mg/kg/day, 300 mg/kg/day
L-Citrulline→Increased Plasma Citrulline Level
Plasma-citrulline levels increased significantly in all three groups
Effect
Beneficial
Effect size
Small
Dose
100 mg/kg/day, 200 mg/kg/day, 300 mg/kg/day

Adverse Events Reported

L-Citrulline→Overall tolerability
A total of 40/42 (95%) of the recruits completed the 7-day supplementation with no adverse events.
Finding
Reported