Melatonin supplementation enhances pulmonary rehabilitation outcomes in COPD: a randomized, double-blind, placebo-controlled study.

Melatonin (MLT), the main product of the pineal gland, is involved in muscle tissue repair and regeneration, besides several other important physiologic functions. In COPD, MLT administration can improve lung oxidative stress and sleep quality, but its potential effects on the outcomes of pulmonary rehabilitation (PR) have not been previously investigated. A randomized controlled trial was undertaken to test the hypothesis that a combined approach of rehabilitative exercise training and MLT supplementation could maximize functional performance, health status and quality of life in patients with COPD. Thirty-nine individuals with COPD referred to a supervised PR program at the Federal University of Ceara, Brazil, were randomized to receive MLT (3 mg/day; n = 18) or placebo (n = 21). Exercise capacity (6-min walk test - 6MWT), health status (COPD assessment test), and quality of life (airways questionnaire 20) were investigated as primary outcomes. No differences were observed at baseline in demographic, anthropometric and clinical characteristics between MLT and placebo groups. At the end of PR, superiority of the MLT group was demonstrated in improvement in the distance covered in the 6MWT (71 ± 26 vs. 25 ± 36 m; p < 0.01), health status (-11 ± 6 vs. -3 ± 5; p < 0.01), and quality of life (-6.9 ± 3.0 vs. -1.9 ± 2.4; p < 0.01), compared to the placebo group. In conclusion, MLT supplementation during the course of 12 weeks of PR can improve functional capacity, health status and quality of life in patients with COPD. These findings may have significant implications for the management of this condition.