Oral Reduced L-Glutathione Improves Nutritional Status and Pulmonary Function in Cystic Fibrosis Patients

CT Bishop, A Visca

Objectives: Since reduced L-glutathione (GSH) egresses epithelial cells through the CFTR, we postulate that misdistribution of GSH could play a role in the pathophysiology of CF. Growth failure is one of the early manifestations of CF in pediatric patients and nutritional status correlates with pulmonary function. Furthermore, since oral GSH has been shown to be a safe and effective FDA-approved treatment for cachexia from other conditions, we postulated oral GSH might be effective in ameliorating nutritional status in cystic fibrosis.

Design: We performed an age-stratified, randomized, placebo-controlled, double-blinded, repeated measures clinical trial of oral reduced L-gluathione (GSH) in 44 pediatric cystic fibrosis patients, ages 18 months to 10 years, over six months (dose 65 mg/kg, divided into three doses per day.)

Results: The GSH treatment group gained an average of 22.1 Body Mass Index (BMI) percentile points over the course of six months, with no adverse side effects (versus placebo +4.9, p<.0001). Mean weight percentile in the treatment group rose from 22.8 to 43.2, representing almost a doubling of these children's mean weight percentile at baseline. Other measures, including fecal calprotectin (GSH -52.0 versus placebo +0.5), height percentile (+6.5 versus -2.7), FEV1% (+18.0 versus +0.6) and FVC% (+10.5 versus -4.3), also improved significantly (all p<.0001 except FVC, p<.001) in the GSH treatment group.

Conclusion: We conclude that oral reduced L-glutathione should be considered in pediatric patients to improve nutritional status as well as pulmonary function. The improvement of primary and secondary outcomes suggests an important role for glutathione distribution both in pahtophysiology of cystic fibrosis as well as treatment of this condition. Further study is warranted.