Effects of an antioxidant-enriched multivitamin in cystic fibrosis

Scott D. Sagel, Umer Khan, Raksha Jain, Gavin Graff, Cori L. Daines, Jordan M Dunitz, Drucy Borowitz, David M. Orenstein, Ibrahim Abdulhamid, Julie Noe, John P. Clancy, Bonnie Slovis, Michael J. Rock, Karen S. McCoy, Steven Strausbaugh, Floyd R. Livingston, Konstantinos A. Papas, Michele L. Shaffer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

treated and control groups. Systemic antioxidant (b-carotene, coenzyme Q10, g-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P, 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

Rationale: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant–antioxidant imbalance and oxidative stress. Objectives: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. Methods: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. Measurements and Main Results: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (b-carotene, coenzyme Q10, g-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P , 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

Original languageEnglish (US)
Pages (from-to)639-647
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume198
Issue number5
DOIs
StatePublished - Sep 1 2018

Fingerprint

Cystic Fibrosis
Antioxidants
Lung
coenzyme Q10
Control Groups
Leukocyte L1 Antigen Complex
Peroxidase
Inflammation
Lutein
Oxidative Stress
Tocopherols
Carotenoids
Clinical Trials
Anti-Bacterial Agents
Growth
Sputum

Keywords

  • Antioxidant
  • Cystic fibrosis
  • Inflammation
  • Oxidative stress
  • Pulmonary exacerbation

Cite this

Effects of an antioxidant-enriched multivitamin in cystic fibrosis. / Sagel, Scott D.; Khan, Umer; Jain, Raksha; Graff, Gavin; Daines, Cori L.; Dunitz, Jordan M; Borowitz, Drucy; Orenstein, David M.; Abdulhamid, Ibrahim; Noe, Julie; Clancy, John P.; Slovis, Bonnie; Rock, Michael J.; McCoy, Karen S.; Strausbaugh, Steven; Livingston, Floyd R.; Papas, Konstantinos A.; Shaffer, Michele L.

In: American journal of respiratory and critical care medicine, Vol. 198, No. 5, 01.09.2018, p. 639-647.

Research output: Contribution to journalArticle

Sagel, SD, Khan, U, Jain, R, Graff, G, Daines, CL, Dunitz, JM, Borowitz, D, Orenstein, DM, Abdulhamid, I, Noe, J, Clancy, JP, Slovis, B, Rock, MJ, McCoy, KS, Strausbaugh, S, Livingston, FR, Papas, KA & Shaffer, ML 2018, 'Effects of an antioxidant-enriched multivitamin in cystic fibrosis', American journal of respiratory and critical care medicine, vol. 198, no. 5, pp. 639-647. https://doi.org/10.1164/rccm.201801-0105OC
Sagel, Scott D. ; Khan, Umer ; Jain, Raksha ; Graff, Gavin ; Daines, Cori L. ; Dunitz, Jordan M ; Borowitz, Drucy ; Orenstein, David M. ; Abdulhamid, Ibrahim ; Noe, Julie ; Clancy, John P. ; Slovis, Bonnie ; Rock, Michael J. ; McCoy, Karen S. ; Strausbaugh, Steven ; Livingston, Floyd R. ; Papas, Konstantinos A. ; Shaffer, Michele L. / Effects of an antioxidant-enriched multivitamin in cystic fibrosis. In: American journal of respiratory and critical care medicine. 2018 ; Vol. 198, No. 5. pp. 639-647.
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T1 - Effects of an antioxidant-enriched multivitamin in cystic fibrosis

AU - Sagel, Scott D.

AU - Khan, Umer

AU - Jain, Raksha

AU - Graff, Gavin

AU - Daines, Cori L.

AU - Dunitz, Jordan M

AU - Borowitz, Drucy

AU - Orenstein, David M.

AU - Abdulhamid, Ibrahim

AU - Noe, Julie

AU - Clancy, John P.

AU - Slovis, Bonnie

AU - Rock, Michael J.

AU - McCoy, Karen S.

AU - Strausbaugh, Steven

AU - Livingston, Floyd R.

AU - Papas, Konstantinos A.

AU - Shaffer, Michele L.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - treated and control groups. Systemic antioxidant (b-carotene, coenzyme Q10, g-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P, 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).Rationale: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant–antioxidant imbalance and oxidative stress. Objectives: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. Methods: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. Measurements and Main Results: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (b-carotene, coenzyme Q10, g-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P , 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

AB - treated and control groups. Systemic antioxidant (b-carotene, coenzyme Q10, g-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P, 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).Rationale: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant–antioxidant imbalance and oxidative stress. Objectives: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. Methods: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. Measurements and Main Results: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (b-carotene, coenzyme Q10, g-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P , 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Conclusions: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

KW - Antioxidant

KW - Cystic fibrosis

KW - Inflammation

KW - Oxidative stress

KW - Pulmonary exacerbation

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