Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.

An increase in GSH may be attained by NAC or Gln supplementation, with NAC acting by increasing cysteine levels and Gln likely acting by replenishing the glycine pool (trial registered at http://www.clinicaltrials.gov, identifier NCT00910442).

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