Antioxidant supplementation for lung disease in cystic fibrosis.

Systematic review of 20 studies involving 924 children and adults with cystic fibrosis, with 16 oral antioxidant studies (n = 639) and 4 inhaled antioxidant studies (n = 285). The included trials compared active antioxidant regimens with placebo or usual vitamin treatment and assessed lung function, oxidative stress, nutritional outcomes, quality of life, exacerbations, and safety.

This review evaluated oral and inhaled antioxidant supplementation in cystic fibrosis, including oral N-acetylcysteine, reduced glutathione, vitamin E, beta-carotene, selenium, and mixed antioxidant multivitamins, plus inhaled nebulized glutathione or NAC. Regimens ranged from short courses such as 2 months to longer treatment up to 12 months, with doses including NAC 600 to 2800 mg/day, oral glutathione 65 mg/kg/day in 3 divided doses, and inhaled glutathione or NAC delivered by nebulizer or inhalation multiple times daily.

Overall, antioxidant micronutrients did not appear to improve clinical endpoints in cystic fibrosis. Oral N-acetylcysteine showed a small, uncertain effect on FEV1 at 3 months (MD 2.83%, 95% CI -2.16 to 7.83) and a modest benefit at 6 months (MD 4.38%, 95% CI 0.89 to 7.87), while inhaled glutathione improved FEV1 at 3 months (MD 3.50%, 95% CI 1.38 to 5.62) but not clearly at 6 months (MD 2.30%, 95% CI -0.12 to 4.71). Oral glutathione showed larger improvements in FEV1 (MD 17.40%, 95% CI 13.97 to 20.83) and nutritional outcomes, and one mixed antioxidant trial reduced time to first pulmonary exacerbation (HR 0.5, 95% CI 0.25 to 0.98). The authors concluded that any benefit is difficult to separate from concurrent CF therapies and that larger, longer trials are needed.

The evidence base was small, heterogeneous, and mostly short term, with different antioxidants, routes, doses, and outcome measures across studies. Many participants were receiving intensive concurrent CF treatments, which makes the independent effect of supplementation difficult to determine. Several outcomes were based on single studies or low-quality evidence, limiting confidence in the overall conclusions.