Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial

Abstract

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 (β-carotene, coenzyme Q10, γ-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).

Keywords: antioxidant; cystic fibrosis; inflammation; oxidative stress; pulmonary exacerbation.

Figure 1.

Flow diagram of the study participants.

Figure 2.

Mean change in sputum myeloperoxidase (MPO) over 16 weeks by treatment group. The change in sputum MPO over the 16-week treatment period was not significantly different between groups. The adjusted mean difference (Adj. Diff) between groups was −0.17 log₁₀(ng/ml) (95% confidence interval [CI], −0.51 to 0.17; P = 0.32). Error bars show 95% CIs. MVI = multivitamin.

Figure 3.

Time to first pulmonary exacerbation by treatment group. The antioxidant-treated group had a significantly lower risk of first pulmonary exacerbation requiring antibiotics than the control group (covariate-adjusted hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.25–0.98; P = 0.04).

Figure 4.

Mean absolute change in FEV₁% predicted from baseline by treatment group. The 16-week absolute change in mean FEV₁% predicted in the treated group was −0.76%, compared with −2.20% in the control group (difference, 1.43%; 95% confidence interval [CI], −2.30 to 5.16; P = 0.44). Error bars show 95% CIs.

Figure 5.

Difference in 16-week change in mean circulating antioxidant levels between the antioxidant and control groups with corresponding 95% confidence intervals. At Week 16, β-carotene, coenzyme Q10 (CoQ10), γ-tocopherol, and lutein were significantly higher in the antioxidant-treated group compared with the control group (adjusted mean difference; *P < 0.001 for each). Pre–post changes in lycopene and glutathione peroxidase activity did not differ between groups. Error bars show 95% confidence intervals.