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

Rosanne J. H. C. G. Beijers; Harry R. Gosker; Karin J. C. Sanders; Chiel de Theije; Marco Kelders; Gerard Clarke; John F. Cryan; Bram van den Borst; Annemie M. W. J. Schols

doi:10.1016/j.clnu.2020.01.002

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

Rosanne J. H. C. G. Beijers^*, Harry R. Gosker, Karin J. C. Sanders, Chiel de Theije, Marco Kelders, Gerard Clarke, John F. Cryan, Bram van den Borst, Annemie M. W. J. Schols

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) 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-1 alpha 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. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Original language	English
Pages (from-to)	2989-2997
Number of pages	9
Journal	Clinical Nutrition
Volume	39
Issue number	10
DOIs	https://doi.org/10.1016/j.clnu.2020.01.002
Publication status	Published - Oct 2020

Keywords

COPD
Resveratrol
Skeletal muscle
Adipose tissue
Body composition
OBSTRUCTIVE PULMONARY-DISEASE
SKELETAL-MUSCLE
MITOCHONDRIAL DYSFUNCTION
SUPPLEMENTATION
ATROPHY
EXPRESSION
MANAGEMENT
DIAGNOSIS
ENDURANCE
CAPACITY

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@article{cff2c0cc30f544a3b005bc82e27ea7b3,

title = "Resveratrol and metabolic health in COPD: A proof-of-concept randomized controlled trial",

abstract = "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 (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) 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-1 alpha 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. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.",

keywords = "COPD, Resveratrol, Skeletal muscle, Adipose tissue, Body composition, OBSTRUCTIVE PULMONARY-DISEASE, SKELETAL-MUSCLE, MITOCHONDRIAL DYSFUNCTION, SUPPLEMENTATION, ATROPHY, EXPRESSION, MANAGEMENT, DIAGNOSIS, ENDURANCE, CAPACITY",

author = "Beijers, {Rosanne J. H. C. G.} and Gosker, {Harry R.} and Sanders, {Karin J. C.} and {de Theije}, Chiel and Marco Kelders and Gerard Clarke and Cryan, {John F.} and {van den Borst}, Bram and Schols, {Annemie M. W. J.}",

note = "Funding Information: This study was financially supported by Lung Foundation Netherlands (grant: 3.4.12.023) and by the JPI HDHL project ?Ambriosiac? by ZonMW (project number: 529051006). ResVida and placebo capsules were provided by DSM Nutritional Products Ltd. Funding Information: This study was financially supported by Lung Foundation Netherlands (grant: 3.4.12.023 ) and by the JPI HDHL project “Ambriosiac” by ZonMW (project number: 529051006 ). ResVida and placebo capsules were provided by DSM Nutritional Products Ltd. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism",

year = "2020",

month = oct,

doi = "10.1016/j.clnu.2020.01.002",

language = "English",

volume = "39",

pages = "2989--2997",

journal = "Clinical Nutrition",

issn = "0261-5614",

publisher = "Churchill Livingstone",

number = "10",

}

TY - JOUR

T1 - Resveratrol and metabolic health in COPD

T2 - A proof-of-concept randomized controlled trial

AU - Beijers, Rosanne J. H. C. G.

AU - Gosker, Harry R.

AU - Sanders, Karin J. C.

AU - de Theije, Chiel

AU - Kelders, Marco

AU - Clarke, Gerard

AU - Cryan, John F.

AU - van den Borst, Bram

AU - Schols, Annemie M. W. J.

N1 - Funding Information: This study was financially supported by Lung Foundation Netherlands (grant: 3.4.12.023) and by the JPI HDHL project ?Ambriosiac? by ZonMW (project number: 529051006). ResVida and placebo capsules were provided by DSM Nutritional Products Ltd. Funding Information: This study was financially supported by Lung Foundation Netherlands (grant: 3.4.12.023 ) and by the JPI HDHL project “Ambriosiac” by ZonMW (project number: 529051006 ). ResVida and placebo capsules were provided by DSM Nutritional Products Ltd. Publisher Copyright: © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

PY - 2020/10

Y1 - 2020/10

N2 - 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 (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) 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-1 alpha 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. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

AB - 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 (FEVi: 53 +/- 15% predicted; age: 67 +/- 9 years and BMI: 24.5 +/- 3.3 kg/m(2)) 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-1 alpha 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. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

KW - COPD

KW - Resveratrol

KW - Skeletal muscle

KW - Adipose tissue

KW - Body composition

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - SKELETAL-MUSCLE

KW - MITOCHONDRIAL DYSFUNCTION

KW - SUPPLEMENTATION

KW - ATROPHY

KW - EXPRESSION

KW - MANAGEMENT

KW - DIAGNOSIS

KW - ENDURANCE

KW - CAPACITY

U2 - 10.1016/j.clnu.2020.01.002

DO - 10.1016/j.clnu.2020.01.002

M3 - Article

C2 - 31996311

SN - 0261-5614

VL - 39

SP - 2989

EP - 2997

JO - Clinical Nutrition

JF - Clinical Nutrition

IS - 10

ER -