title: Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double-Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates.
abstract: 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.
  
  
  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 [(13)C2] 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Division of Neonatology and Developmental Biology, Neonatal Research Center, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Calkins
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Sanchez
authors.affiliation: Department of Medicine, Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Chi-Hong
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Yoon
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ryan
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Thuc
authors.initials: T
authors.lastname: Le
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, and Mattel Children's Hospital at UCLA, Los Angeles, California SShew@mednet.ucla.edu.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Shew
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D002908:Chronic Disease; D016638:Critical Illness / Q000628:therapy*; D003545:Cysteine / Q000008:administration & dosage*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004912:Erythrocytes / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000737:chemistry*; D005998:Glycine / Q000008:administration & dosage; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008171:Lung Diseases / Q000188:drug therapy; D008297:Male; D010288:Parenteral Nutrition; D010865:Pilot Projects; D012121:Respiration, Artificial
chemical_list: D000596:Amino Acids; D015850:Interleukin-6; D005978:Glutathione; D003545:Cysteine; D005998:Glycine
keywords: antioxidant; chronic lung disease; inflammation; neonates; parenteral nutrition; prematurity; red blood cell