Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double-Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates

Background: This study's objective was to determine if parenteral cysteine when compared with isonitrogenous noncysteine supplementation increases erythrocyte reduced glutathione (GSH) in neonates at high risk for inflammatory injury. Material and Methods: Neonates with a score for neonatal acute physiology >10 requiring mechanical ventilation and parenteral nutrition (PN) were randomized in a double-blinded, placebo-controlled study to receive parenteral cysteine-HCl (CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/d for >= 7 days. A 6-hour [C-13(2)] glycine IV infusion was administered at study week 1 to determine the fractional synthetic rate of GSH (FSR-GSH). Results: Baseline characteristics were similar between the CYS (n = 17) and ISO groups (n = 21). Erythrocyte GSH and total glutathione concentrations, GSH: oxidized GSH (GSSG), and FSR-GSH after treatment were not different between groups. However, the CYS group had a larger individual positive change in GSH and total glutathione (infusion day - baseline) compared with the ISO group (P = .02 for each). After adjusting for treatment, a lower enrollment weight and rate of red blood cell transfusion were associated with a decreased change in total glutathione and GSH (P < .05 for each). Conclusion: When compared with isonitrogenous noncysteine supplementation, high-dose cysteine supplementation for at least 1 week in critically ill neonates resulted in a larger and more positive individual change in GSH. Smaller infants and those who received transfused blood demonstrated less effective change in GSH with cysteine supplementation. The benefit of cysteine remains promising and deserves further investigation.