Parenteral Cysteine Supplementation in Preterm Infants: One Size Does Not Fit All

Due to their gastrointestinal immaturity or the severity of their pathology, many neonates require parenteral nutrition (PN). An amino acid (AA) solution is an important part of PN. Cysteine is a key AA for protein and taurine synthesis, as well as for glutathione synthesis, which is a cornerstone of antioxidant defenses. As cysteine could be synthesized from methionine, it is considered a nonessential AA. However, many studies suggest that cysteine is a conditionally essential AA in preterm infants due to limitations in their capacity for cysteine synthesis from methionine and the immaturity of their cellular cysteine uptake. This critical review discusses the endogenous synthesis of cysteine, its main biological functions and whether cysteine is a conditionally essential AA. The clinical evidence evaluating the effectiveness of the current methods of cysteine supplementation, between 1967 and 2023, is then reviewed. The current understanding of cysteine metabolism is applied to explain why these methods were not proven effective. To respond to the urgent need for changing the current methods of parenteral cysteine supplementation, glutathione addition to PN is presented as an innovative alternative with promising results in an animal model. At the end of this review, future directions for research in this field are proposed.