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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.

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