title: Antioxidant supplementation for lung disease in cystic fibrosis.
abstract: BACKGROUND
  Airway infection leads to progressive damage of the lungs in cystic fibrosis and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) or glutathione may therefore potentially help maintain an oxidant-antioxidant balance. Current literature suggests a relationship between oxidative status and lung function.
  
  
  OBJECTIVE
  To synthesize existing knowledge of the effect of antioxidants such as vitamin C, vitamin E, ß-carotene, selenium and glutathione in cystic fibrosis lung disease.
  
  
  METHODS
  The Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and PubMed were searched using detailed search strategies. We contacted authors of included studies and checked reference lists of these studies for additional, potentially relevant studies.Last search of Cystic Fibrosis Trials Register: 29 August 2013.
  
  
  METHODS
  Randomized controlled studies and quasi-randomized controlled studies of people with cystic fibrosis comparing antioxidants as listed above (individually or in combination) in more than a single administration to placebo or standard care.
  
  
  METHODS
  Two authors independently selected studies, extracted data and assessed the risk of bias in the included studies. We contacted trial investigators to obtain missing information. Primary outcomes are lung function and quality of life; secondary outcomes are oxidative stress, inflammation, nutritional status, days on antibiotics and adverse events during supplementation. If meta-analysed, studies were subgrouped according to method of administration and the duration of supplementation.
  
  
  RESULTS
  One quasi-randomized and nine randomized controlled studies were included, with a total of 436 participants. Eight studies analyzed oral supplementation with antioxidants and two inhaled supplements.One study (n = 46) of an oral combined supplement demonstrated a significant difference in forced expiratory volume at one second expressed as per cent predicted after two weeks in favour of the control group, mean difference -4.30 (95% confidence interval -5.64 to -2.96); however a further study (n = 41) of oral supplementation with glutathione showed a significant improvement in this outcome and in forced vital capacity after six months from the treatment start, mean difference 17.40 (95% confidence interval 13.69 to 21.11) and 14.80 (95% confidence interval 9.66 to 19.94) respectively. The combined supplement study also indicated a significant improvement in quality of life favouring control, mean difference -0.06 points on the quality of well-being scale (95% confidence interval -0.12 to -0.01). Based on one study (n = 41) of oral glutathione supplementation in children, the supplements had a positive effect on the nutritional status (body mass index %) of the patients, mean difference 17.20 (95% confidence interval 12.17 to 22.23). In two studies (n = 83) that supplemented vitamin E, there was an improvement after two months in the blood levels of vitamin E, mean difference 11.78 μM/L (95% confidence interval 10.14 to 13.42).Based on one of the two studies of inhaled glutathione supplementation, there was an improvement in the forced expiratory volume at one second expressed as per cent predicted after three and six months (n = 153), mean difference 2.57 (95% confidence interval 2.24 to 2.90) and 0.97 (95% confidence interval 0.65 to 1.29) respectively. Only one of the studies reported quality of life data that could be analysed, but data showed no significant differences between treatment and control.None of the 10 included studies was judged to be free of bias.
  
  
  CONCLUSIONS
  There appears to be conflicting evidence regarding the clinical effectiveness of antioxidant supplementation in cystic fibrosis. Based on the available evidence, glutathione (administered either orally or by inhalation) appears to improve lung function in some cases and decrease oxidative stress; however, due to the very intensive antibiotic treatment and other treatments that cystic fibrosis patients receive, the beneficial effect of antioxidants is very difficult to assess in patients with chronic infection without a very large population sample and a long-term (at least six months) study period. Further studies, especially in very young patients, examining clinically relevant outcomes, dose levels, timing and the elucidation of clear biological pathways by which oxidative stress is involved in cystic fibrosis, are necessary before a firm conclusion regarding effects of antioxidants supplementation can be drawn.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark, 2200.
authors.forename: Oana
authors.initials: O
authors.lastname: Ciofu
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy*; D006801:Humans; D018977:Micronutrients / Q000627:therapeutic use*; D018384:Oxidative Stress; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012643:Selenium / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D018977:Micronutrients; D014815:Vitamins; D014810:Vitamin E; D012643:Selenium; D001205:Ascorbic Acid