Effect of targeted nutrient supplementation on physical activity and health-related quality of life in COPD: study protocol for the randomised controlled NUTRECOVER trial.

INTRODUCTION: Physical and mental health are often affected in chronic obstructive pulmonary disease (COPD) adversely affecting disease course and quality of life. Abnormalities in whole body and cellular energy metabolism, dietary and plasma nutrient status and intestinal permeability have been well established in these patients as systemic determinants of functional decline and underexplored treatable traits. The aim of this study is to investigate the efficacy of 1 year targeted nutrient supplementation on physical activity level and health-related quality of life in patients with COPD. METHODS AND ANALYSIS: This study is a single-centre randomised, placebo-controlled, double-blind trial in 166 patients with COPD recruited from multiple hospitals in the Netherlands. The intervention group will receive a multinutrient supplement, including vitamin D, tryptophan, long-chain polyunsaturated fatty acids and prebiotic dietary fibres as main components (94 kCal per daily dose). The control group will receive an isocaloric isonitrogenous placebo. Both groups will ingest one portion per day for at least 12 months and will additionally receive counselling on healthy lifestyle and medical adherence over the course of the study. Coprimary outcomes are physical activity assessed by triaxial accelerometry and health-related quality of life measured by the EuroQol-5 dimensions questionnaire. Secondary outcomes are cognitive function, psychological well-being, physical performance, patient-reported outcomes and the metabolic profile assessed by body composition, systemic inflammation, plasma nutrient levels, intestinal integrity and microbiome composition. Outcomes will be measured at baseline and after 12 months of supplementation. In case patients are hospitalised for a COPD exacerbation, a subset outcome panel will be measured during a 4-week recovery period after hospitalisation. ETHICS AND DISSEMINATION: This study was approved by the local Ethics Committee of Maastricht University. Subjects will be included after written informed consent is provided. Study outcomes will be disseminated through presentations at (inter)national conferences and through peer-reviewed journals. TRIAL REGISTRATION: NCT03807310.

Resveratrol and metabolic health in COPD: A proof-of-concept randomized controlled trial.

BACKGROUND: Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD. METHODS: In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEV1: 53 ± 15% predicted; age: 67 ± 9 years and BMI: 24.5 ± 3.3 kg/m2) received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1α as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol -0.95 ± 1.01 kg vs placebo -0.16 ± 0.66 kg, p = 0.049) due to a reduction in lean mass (resveratrol -1.79 ± 1.67 kg vs 0.37 ± 0.86 kg, p = 0.026). CONCLUSION: We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov NCT02245932.

Measuring successful aging: an exploratory factor analysis of the InCHIANTI Study into different health domains.

Advocating continued health into old age, so called successful aging, is a growing public health goal. However, the development of tools to measure aging is limited by the lack of appropriate outcome measures, and operational definitions of successful aging. Using exploratory factor analysis, we attempted to identify distinguishable health domains with representative variables of physical function, cognitive status, social interactions, psychological status, blood biomarkers, disease history, and socioeconomic status from the InCHIANTI study. We then used logistic and mixed effect regression models to determine whether the resulting domains predicted outcomes of successful aging over a nine-year follow-up. A four-domain health model was identified: neuro-sensory function, muscle function, cardio-metabolic function and adiposity. After adjustment for age and gender, all domains contributed to the prediction of walking speed (R2=0.73). Only the muscle function domain predicted dependency (R2=0.50). None of the domains were a strong, significant predictor of self-rated health (R2=0.18) and emotional vitality (R2=0.23). Cross-sectional findings were essentially replicated in the longitudinal analysis extended to nine-year follow-up. Our results suggest a multi-domain health model can predict objective but not subjective measures of successful aging.