Cysteine Supplementation to Parenteral Nutrition Improves Red Blood Cell Glutathione Concentrations of Critically Ill Preterm Neonates

Oscar R Herrera,Michael C Storm,Emma M Tillman,Richard A Helms

doi:10.4236/fns.2018.95047

Oscar R Herrera, Michael C Storm + Show 2 more

Open Access

https://doi.org/10.4236/fns.2018.95047

Copy DOI

Abstract

Premature neonates have immature antioxidant enzyme systems rendering them more susceptible to oxidative injury. One key antioxidant is glutathione (GSH). The rate limiting amino acid (AA) in GSH production is thought to be cysteine. Critically ill premature neonates who are parenterally fed are often supplemented with additional cysteine, yet the need for cysteine and optimal dose is unknown. This was a prospective, un-blinded, three-group, randomized crossover study aimed to evaluate three doses of cysteine by analyzing red blood cell (RBC) GSH, plasma AA, weight, and nitrogen balance. Neonates were randomized to receive 72 hours of each of the following cysteine doses: 10 mg/g AA, 20 mg/g AA, and 40 mg/g AA. GSH, plasma AAs, weight, and nitrogen balance were evaluated at baseline (after 72 hours of 0 mg/g AA), day three, day six, and day nine. Sixteen patients completed all doses of cysteine, which resulted in significantly increased RBC GSH concentrations over baseline. Plasma concentrations of cystine, total and free cysteine/cystine, glycine and serine increased with cysteine dose. All cysteine doses were associated with adequate weight gain, and positive nitrogen balance. These results are contrary to more recent studies of cysteine effect on RBC GSH concentrations in preterm neonates and infants, but may reflect the severity of illness in our study subjects, where cysteine requirements may be increased.

Highlights

Preterm neonates are presumed to be deficient in the antioxidant glutathione (GSH) rendering them more susceptible to diseases associated with reactive oxygen species (ROS) including bronchopulmonary dysplasia (BPD), periventricular leukomalacia, and retinopathy of prematurity (ROP) [1]
Neonates were excluded from the study if they had any of the following major medical problems: inborn errors of metabolism, chromosomal abnormalities, end-stage liver or renal disease, peritoneal dialysis/hemofiltration, intraventricular hemorrhage (Grade IV), postnatal corticosteroid usage, extracorporeal membrane oxygenation (ECMO) support, or greater than 10% of nutritional goal as enteral intake
We sequentially evaluated cysteine dose effect on red blood cell (RBC) GSH concentrations, plasma amino acid (AA) concentrations, growth, and nitrogen balance in critically ill, post-surgical preterm neonates

Summary

Introduction

Preterm neonates are presumed to be deficient in the antioxidant glutathione (GSH) rendering them more susceptible to diseases associated with reactive oxygen species (ROS) including bronchopulmonary dysplasia (BPD), periventricular leukomalacia, and retinopathy of prematurity (ROP) [1]. Neonatal survivors of critical illness, exposed to ROS, often are affected by many health related complications causing long-term morbidity [2]. Lowering oxidative injury risk should be a priority for critically ill preterm neonates. The amino acid (AA) cysteine comprises a third of the tri-peptide GSH and directly influences GSH production (Figure 1). Cysteine has been suggested to be a conditionally-essential AA for neonates, in the preterm neonate. There have been multiple studies actively debating this issue [3] [4] [5]

Methods

Results

Conclusion