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Cochrane Database Syst Rev. 2019 Oct 03;10:CD007020. doi: 10.1002/14651858.CD007020.pub4. Epub 2019 Oct 03.

Antioxidant supplementation for lung disease in cystic fibrosis.

The Cochrane database of systematic reviews

Oana Ciofu, Sherie Smith, Jens Lykkesfeldt

Affiliations

  1. Department of International Health, Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3, Copenhagen, Denmark, 2200.

PMID: 31580490 PMCID: PMC6777741 DOI: 10.1002/14651858.CD007020.pub4

Abstract

BACKGROUND: Airway infection leads to progressive damage of the lungs in cystic fibrosis (CF) and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, beta-carotene and selenium) or N-acetylcysteine (NAC) as a source of glutathione, may therefore potentially help maintain an oxidant-antioxidant balance. Glutathione or NAC can also be inhaled and if administered in this way can also have a mucolytic effect besides the antioxidant effect. Current literature suggests a relationship between oxidative status and lung function. This is an update of a previously published review.

OBJECTIVES: To synthesise existing knowledge on the effect of antioxidants such as vitamin C, vitamin E, beta-carotene, selenium and glutathione (or NAC as precursor of glutathione) on lung function through inflammatory and oxidative stress markers in people with CF.

SEARCH 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. We also searched online trials registries.Last search of Cystic Fibrosis Trials Register: 08 January 2019.

SELECTION CRITERIA: Randomised and quasi-randomised controlled studies comparing antioxidants as listed above (individually or in combination) in more than a single administration to placebo or standard care in people with CF.

DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed the risk of bias in the included studies. We contacted study investigators to obtain missing information. If meta-analysed, studies were subgrouped according to supplement, method of administration and the duration of supplementation. We assessed the quality of the evidence using GRADE.

MAIN RESULTS: One quasi-randomised and 19 randomised controlled studies (924 children and adults) were included; 16 studies (n = 639) analysed oral antioxidant supplementation and four analysed inhaled supplements (n = 285). Only one of the 20 included studies was judged to be free of bias.Oral supplements versus controlThe change from baseline in forced expiratory volume in one second (FEV

AUTHORS' CONCLUSIONS: With regards to micronutrients, there does not appear to be a positive treatment effect of antioxidant micronutrients on clinical end-points; however, oral supplementation with glutathione showed some benefit to lung function and nutritional status. Based on the available evidence, inhaled and oral glutathione appear to improve lung function, while oral administration decreases oxidative stress; however, due to the very intensive antibiotic treatment and other concurrent treatments that people with CF take, the beneficial effect of antioxidants remains difficult to assess in those with chronic infection without a very large population sample and a long-term study period. Further studies, especially in very young children, using outcome measures such as lung clearance index and the bronchiectasis scores derived from chest scans, with improved focus on study design variables (such as dose levels and timing), and elucidating clear biological pathways by which oxidative stress is involved in CF, are necessary before a firm conclusion regarding effects of antioxidants supplementation can be drawn. The benefit of antioxidants in people with CF who receive CFTR modulators therapies should also be assessed in the future.

References

  1. J Cyst Fibros. 2007 Jan;6(1):35-40 - PubMed
  2. Am J Clin Nutr. 1997 Feb;65(2):575-7 - PubMed
  3. Arch Dis Child. 1974 Mar;49(3):247 - PubMed
  4. Cochrane Database Syst Rev. 2015 Jan 18;1:CD008482 - PubMed
  5. J Am Diet Assoc. 1996 Jul;96(7):693-702; quiz 703-4 - PubMed
  6. Dig Dis Sci. 2007 Feb;52(2):347-52 - PubMed
  7. Acta Paediatr Suppl. 1994 Apr;83(395):49-57 - PubMed
  8. Acta Paediatr. 2002;91(7):793-8 - PubMed
  9. BMJ. 1989 Apr 22;298(6680):1098 - PubMed
  10. Eur J Med Res. 2009 Aug 12;14(8):352-8 - PubMed
  11. Cochrane Database Syst Rev. 2013 Jul 12;(7):CD007168 - PubMed
  12. Practitioner. 1981 Apr;225(1354):557-60 - PubMed
  13. J Am Coll Nutr. 2001 Apr;20(2 Suppl):157-65 - PubMed
  14. Am J Respir Crit Care Med. 2018 Sep 1;198(5):639-647 - PubMed
  15. Am J Clin Nutr. 1997 Jun;65(6):1858-66 - PubMed
  16. Ann N Y Acad Sci. 1989;570:156-69 - PubMed
  17. J Cyst Fibros. 2015 Mar;14(2):211-8 - PubMed
  18. PLoS Med. 2009 Jul 21;6(7):e1000097 - PubMed
  19. J Clin Invest. 1977 Jul;60(1):233-41 - PubMed
  20. Prog Lipid Res. 2004 May;43(3):200-27 - PubMed
  21. J Appl Physiol (1985). 1993 Dec;75(6):2419-24 - PubMed
  22. Eur Respir J. 1996 Feb;9(2):334-9 - PubMed
  23. Cochrane Database Syst Rev. 2014 May 14;(5):CD007298 - PubMed
  24. Pediatrics. 1961 Apr;27:578-88 - PubMed
  25. Pediatr Res. 1972 Jan;6(1):26-31 - PubMed
  26. J Am Diet Assoc. 1995 Apr;95(4):454-9 - PubMed
  27. Thorax. 2001 Jan;56(1):48-52 - PubMed
  28. Clin Chem. 1993 Jun;39(6):1023-8 - PubMed
  29. Pediatr Pulmonol Suppl. 1991;7:56-63 - PubMed
  30. Eur J Respir Dis Suppl. 1980;111:122-6 - PubMed
  31. Acta Paediatr. 1995 Oct;84(10):1132-6 - PubMed
  32. Biochim Biophys Acta. 2012 May;1822(5):690-713 - PubMed
  33. J Neuropathol Exp Neurol. 1980 Sep;39(5):584-97 - PubMed
  34. Am J Respir Crit Care Med. 2013 Jul 1;188(1):83-9 - PubMed
  35. J Cyst Fibros. 2008 Mar;7(2):116-22 - PubMed
  36. J Am Diet Assoc. 1999 Dec;99(12):1569-72 - PubMed
  37. J Pediatr. 1996 Jul;129(1):181-2 - PubMed
  38. Clin Chim Acta. 1995 Jan 31;234(1-2):137-46 - PubMed
  39. J Pediatr. 1995 Sep;127(3):491-4 - PubMed
  40. Ann Nutr Metab. 2000;44(1):30-7 - PubMed
  41. Eur Respir J. 2005 Nov;26(5):948-68 - PubMed
  42. Aust Paediatr J. 1982 Mar;18(1):40-2 - PubMed
  43. Cochrane Database Syst Rev. 2018 Aug 09;8:CD006751 - PubMed
  44. Int J Vitam Nutr Res. 1998;68(2):83-7 - PubMed
  45. Pediatriia. 1983 Apr;(4):36-7 - PubMed
  46. Free Radic Biol Med. 2017 Dec;113:236-243 - PubMed
  47. Eur Respir J. 1988 Feb;1(2):161-7 - PubMed
  48. Theor Biol Med Model. 2008 Apr 28;5:8 - PubMed
  49. Am J Epidemiol. 1997 Dec 1;146(11):939-48 - PubMed
  50. Cochrane Database Syst Rev. 2017 Mar 06;3:CD009422 - PubMed
  51. J Pediatr Gastroenterol Nutr. 1997 Jul;25(1):120-2 - PubMed
  52. J Nutr. 2003 Mar;133 Suppl 3:933S-940S - PubMed
  53. Ann Nutr Metab. 2000;44(5-6):207-11 - PubMed
  54. Curr Opin Investig Drugs. 2001 Jul;2(7):900-6 - PubMed
  55. Pediatr Res. 1994 Oct;36(4):487-93 - PubMed
  56. J Cyst Fibros. 2015 Mar;14(2):219-27 - PubMed
  57. Med J Aust. 1974 Feb 9;1(6):169-74 - PubMed
  58. J Clin Invest. 2007 Sep;117(9):2592-601 - PubMed
  59. Eur Respir J. 2014 Jul;44(1):122-9 - PubMed
  60. Eur J Pediatr. 1985 Nov;144(4):374-8 - PubMed
  61. Int J Epidemiol. 2002 Feb;31(1):140-9 - PubMed
  62. Am J Clin Nutr. 1996 Jul;64(1):87-93 - PubMed
  63. Pediatr Pulmonol. 2008 Mar;43(3):281-7 - PubMed
  64. Free Radic Biol Med. 1995 Dec;19(6):725-33 - PubMed
  65. Am J Clin Nutr. 1995 Apr;61(4):843-7 - PubMed
  66. J Paediatr Child Health. 2005 Dec;41(12):663-8 - PubMed
  67. J Pediatr. 1993 May;122(5 Pt 1):810-2 - PubMed
  68. Arch Dis Child. 1981 Sep;56(9):708-14 - PubMed
  69. Med Lett Drugs Ther. 1975 Aug 15;17(17):69-70 - PubMed
  70. Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 1):341-57 - PubMed
  71. Clin Chem Lab Med. 1999 May;37(5):511-6 - PubMed
  72. Adv Pharmacol. 1997;38:491-513 - PubMed
  73. Am J Respir Crit Care Med. 2007 Apr 15;175(8):822-8 - PubMed
  74. Qual Life Res. 2003 Feb;12(1):77-85 - PubMed
  75. Int J Vitam Nutr Res. 1987;57(3):253-9 - PubMed
  76. J Pediatr. 2009 Nov;155(5):623-8.e1 - PubMed
  77. Mol Aspects Med. 2003 Dec;24(6):391-402 - PubMed
  78. Cochrane Database Syst Rev. 2010 Dec 08;(12):CD007020 - PubMed
  79. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4628-33 - PubMed
  80. Ann N Y Acad Sci. 1972 Dec 18;203:237-47 - PubMed
  81. J Pediatr Gastroenterol Nutr. 1996 May;22(4):341-5 - PubMed
  82. Arch Dis Child. 1971 Jun;46(247):341-4 - PubMed
  83. Univ Mich Med Cent J. 1966 Mar-Apr;32(2):82-5 - PubMed
  84. Am J Clin Nutr. 2003 Jan;77(1):150-9 - PubMed
  85. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1524-7 - PubMed
  86. J Cyst Fibros. 2010 Sep;9(5):332-8 - PubMed
  87. J Pediatr Gastroenterol Nutr. 2015 Jun;60(6):802-10 - PubMed
  88. J Pediatr. 1980 Mar;96(3 Pt 1):421-2 - PubMed
  89. Am J Clin Nutr. 2002 Apr;75(4):668-75 - PubMed
  90. Int J Vitam Nutr Res. 1978;48(4):324-32 - PubMed
  91. Nutr Rev. 2000 Feb;58(2 Pt 1):39-53 - PubMed
  92. Adv Exp Med Biol. 1990;264:175-8 - PubMed
  93. Metabolism. 2004 Jan;53(1):37-41 - PubMed
  94. Adv Exp Med Biol. 1990;264:555-72 - PubMed
  95. Pharmacol Ther. 2014 Feb;141(2):150-9 - PubMed
  96. Med Klin (Munich). 1995 Jan 15;90 Suppl 1:41-5 - PubMed
  97. J R Soc Med. 1986;79 Suppl 12:32-5 - PubMed
  98. Am J Clin Nutr. 1996 May;63(5):722-8 - PubMed
  99. Respir Care. 2016 Jan;61(1):78-84 - PubMed
  100. Physiology (Bethesda). 2017 Sep;32(5):380-390 - PubMed
  101. Free Radic Biol Med. 1995 May;18(5):849-59 - PubMed
  102. Eur Respir J. 1989 Mar;2(3):234-7 - PubMed
  103. J Cyst Fibros. 2015 Mar;14(2):203-10 - PubMed
  104. Cochrane Database Syst Rev. 2014 Aug 07;(8):CD007020 - PubMed
  105. J Clin Pharm Ther. 2009 Oct;34(5):515-22 - PubMed
  106. Redox Biol. 2015 Dec;6:198-205 - PubMed
  107. Pediatr Res. 1996 Jul;40(1):130-4 - PubMed
  108. Eur J Pediatr. 1996 Apr;155(4):281-5 - PubMed
  109. Chest. 2005 Jan;127(1):308-17 - PubMed
  110. J Cyst Fibros. 2017 May;16(3):342-345 - PubMed
  111. Z Kinderheilkd. 1975;119(4):279-91 - PubMed
  112. Food Chem Toxicol. 1999 Sep-Oct;37(9-10):963-6 - PubMed
  113. BMJ. 2003 Sep 6;327(7414):557-60 - PubMed

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