Glutathione May Benefit Lung Function in Cystic Fibrosis

By Marilynn Larkin

October 31, 2019

NEW YORK (Reuters Health) - Inhaled and oral glutathione may benefit lung function in patients with cystic fibrosis (CF), although vitamin and mineral antioxidant supplementation does not appear to have a positive treatment effect, an updated Cochrane Review reveals.

"In this revised version of the review, we chose to extend the list of oral antioxidant micronutrients with glutathione (GSH) and N-acetylcysteine (NAC), as a precursor of GSH, administered orally," Dr. Oana Ciofu of the University of Copenhagen told Reuters Health by email.

"In accordance with a previous review on the topic, oral supplementation with antioxidants does not show a beneficial effect on clinical outcomes, but does show an improvement in the laboratory measurements of the supplements," she noted.

"According to results summarized in this review, the administration of inhaled glutathione seems to stop the deterioration in lung function in people with CF," she said. 'This is in contrast to conclusions of a previous Cochrane Review analyzing the use of nebulized and oral thiol derivatives, including NAC and glutathione, in people with CF."

Dr. Ciofu and colleagues searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and PubMed through January 2019. Twenty studies (924 children and adults with CF, almost equal gender split, ages six months to 59 years) were included. Sixteen studies compared oral supplements to placebo and four compared inhaled supplements to placebo. Only one of the included studies was judged to be bias-free.

As reported online October 3 in the Cochrane Library, study outcomes varied widely. For example, with regard to oral supplements, the change from baseline in forced expiratory volume in one second (FEV1) % predicted at three months and six months was only reported for NAC versus control. Four studies reported at three months; however, the authors were uncertain whether NAC improved FEV1 % predicted because the evidence quality was very low. By contrast, two studies with moderate-quality evidence showed that, at six months, NAC probably increased FEV1 % predicted from baseline.

With regard to inhaled supplements, outcomes also varied, as researchers looked at different endpoints. For example, two studies with moderate-quality evidence showed inhaled glutathione probably improves FEV1 % predicted at three months but not at six months compared to placebo. Another study with moderate-quality evidence reported that inhaled glutathione probably made little or no difference to the change in quality of life from baseline. No study reported on the change from baseline in BMI at six months, but one study reported at two months and another study at 12 months; neither found any difference at either time point.

Summing up, the authors state, "Based on the available evidence, inhaled and oral glutathione appear to improve lung function, while oral administration decreases oxidative stress...Evidence ranged from very low to moderate quality. All but one study had some bias, mostly because data were not fully reported (likely to affect our results). We were also largely unsure if participants knew which treatment they received, both in advance and once the studies started (unsure how this might affect our results)."

Dr. Ciofu added, "A common drawback of these studies is that the participants are intensively treated with inhaled antibiotics and other treatments that led to a significant improvement of their lung function, making further improvements by addition of antioxidants difficult to assess without very large number of participants."

Future studies should consider replacing lung function measurements with computed tomography scans or a lung clearance index to evaluate the effects on lung inflammation and pathology, she advised.

Dr. Robert Giusti, director of the Pediatric Cystic Fibrosis Center at NYU Langone's Hassenfeld Children's Hospital in New York City, commented in an email to Reuters Health, "In general, the findings from this review are not surprising and I do not think that clinical practice will change. The CF Foundation has clinical practice guidelines for CF care, and antioxidant supplementation has never been advocated as an essential treatment. I personally do not recommend the addition of oral or inhaled antioxidants."

"I have heard... that CF patients purchase these products either online or at nutrition and vitamin stores and try them based on the hope that they will prove beneficial," he said. "The lack of clear benefit in the review hopefully will alter this practice."

"I do not think that there is harm in taking oral supplements," he said. "However, I am concerned that patients may not be taking all the medications recommended by their CF physicians because of the time commitment required to administer these treatments daily. If patients rely on oral supplements of antioxidants in place of proven therapies, that is a concern for less than optimal outcomes."

"I do recommend against the use of inhaled N-acetylcysteine and all inhaled antioxidant supplements - e.g., essential oils and peppermint oil - because there is evidence that these drugs can result in the sensation of chest tightness, and bronchospasm," he concluded.


Cochrane Libr 2019.


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