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

Rosanne Jhcg Beijers, Lieke E J van Iersel, Lisanne T Schuurman, Robert J J Hageman, Sami O Simons, Ardy van Helvoort, Harry R Gosker, Annemie Mwj Schols, Rosanne Jhcg Beijers, Lieke E J van Iersel, Lisanne T Schuurman, Robert J J Hageman, Sami O Simons, Ardy van Helvoort, Harry R Gosker, Annemie Mwj Schols

Abstract

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.

Keywords: chronic airways disease; nutrition & dietetics; respiratory medicine (see thoracic medicine).

Conflict of interest statement

Competing interests: AvH is employed by Danone Nutricia Research. RJJH is retired from Danone Nutricia Research. AvH and RJJH report that a patent might derive from the research described in this paper. SOS reports grants and personal fees from GlaxoSmithKline, personal fees from Chiesi, grants from Boehringer Ingelheim, grants from AstraZeneca, all outside the submitted work. HG and AS were granted PPP Allowance made available by Health Holland, Top Sector Life Sciences & Health to Lung Foundation Netherlands and matching by UM, UU, Nutricia Reasearch. All other authors report no competing interests.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design. Measurements at baseline, after 3 months and at the end of the study are indicated as M1, M2 and M3, respectively. After a hospitalisation for a chronic obstructive pulmonary disease exacerbation (H) the recovery phase of 4 weeks will be monitored (T1 and T2). In case patients will be recruited during a hospitalisation for a COPD exacerbation, M1 will take place 4 weeks after discharge. In case the hospitalisation will be within 3 months after baseline, M2 will not take place.
Figure 2
Figure 2
Timeline of measurement day. This outline provides a timeline of a measurement day at M1 and M3. During M2, T1 and T2 a selection of these measurements will be performed as described in table 3. Measurements will be performed in this order unless logistically not possible. 6MWT, 6 min walking test; CANTAB, Cambridge Neuropsychological Test Automated Battery; DEXA, dual-energy X-ray absorptiometry; SECPT, Socially Evaluated Cold-Pressor Test; SPPB, short physical performance battery.

References

    1. Vogelmeier CF, Agusti A, Anzueto A, et al. . Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease (2021 report), 2021. Available:
    1. Lainscak M, Gosker HR, Schols AMWJ. Chronic obstructive pulmonary disease patient journey: hospitalizations as window of opportunity for extra-pulmonary intervention. Curr Opin Clin Nutr Metab Care 2013;16:278–83. 10.1097/MCO.0b013e328360285d
    1. Demeyer H, Costilla-Frias M, Louvaris Z, et al. . Both moderate and severe exacerbations accelerate physical activity decline in COPD patients. Eur Respir J 2018;51. 10.1183/13993003.02110-2017. [Epub ahead of print: 25 01 2018].
    1. Donaldson GC, Seemungal TAR, Bhowmik A, et al. . Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847–52. 10.1136/thorax.57.10.847
    1. Miravitlles M, Ferrer M, Pont A, et al. . Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study. Thorax 2004;59:387–95. 10.1136/thx.2003.008730
    1. Gosker HR, Langen RC, Simons SO. Role of acute exacerbations in skeletal muscle impairment in COPD. Expert Rev Respir Med 2021;15:1–13. 10.1080/17476348.2021.1843429
    1. Falck RS, Davis JC, Liu-Ambrose T. What is the association between sedentary behaviour and cognitive function? A systematic review. Br J Sports Med 2017;51:800–11. 10.1136/bjsports-2015-095551
    1. Teychenne M, Costigan SA, Parker K. The association between sedentary behaviour and risk of anxiety: a systematic review. BMC Public Health 2015;15:513. 10.1186/s12889-015-1843-x
    1. Zhai L, Zhang Y, Zhang D. Sedentary behaviour and the risk of depression: a meta-analysis. Br J Sports Med 2015;49:705–9. 10.1136/bjsports-2014-093613
    1. Gea J, Pascual S, Casadevall C, et al. . Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings. J Thorac Dis 2015;7:E418–38. 10.3978/j.issn.2072-1439.2015.08.04
    1. Rutten EPA, Lenaerts K, Buurman WA, et al. . Disturbed intestinal integrity in patients with COPD: effects of activities of daily living. Chest 2014;145:245–52. 10.1378/chest.13-0584
    1. Matte DL, Pizzichini MMM, Hoepers ATC, et al. . Prevalence of depression in COPD: a systematic review and meta-analysis of controlled studies. Respir Med 2016;117:154–61. 10.1016/j.rmed.2016.06.006
    1. Hung WW, Wisnivesky JP, Siu AL, et al. . Cognitive decline among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:134–7. 10.1164/rccm.200902-0276OC
    1. Yohannes AM, Chen W, Moga AM, et al. . Cognitive impairment in chronic obstructive pulmonary disease and chronic heart failure: a systematic review and meta-analysis of observational studies. J Am Med Dir Assoc 2017;18:451 e1–e11. 10.1016/j.jamda.2017.01.014
    1. van Beers M, Janssen DJA, Gosker HR, et al. . Cognitive impairment in chronic obstructive pulmonary disease: disease burden, determinants and possible future interventions. Expert Rev Respir Med 2018;12:1061–74. 10.1080/17476348.2018.1533405
    1. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33:1165–85. 10.1183/09031936.00128008
    1. Poot B, Travers J, Weatherall M, et al. . Cognitive function during exacerbations of chronic obstructive pulmonary disease. Intern Med J 2019;49:1307–12. 10.1111/imj.14259
    1. Schneider C, Jick SS, Bothner U, et al. . Copd and the risk of depression. Chest 2010;137:341–7. 10.1378/chest.09-0614
    1. Maltais F, Decramer M, Casaburi R, et al. . An official American thoracic Society/European respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2014;189:e15–62. 10.1164/rccm.201402-0373ST
    1. Remels AHV, Gosker HR, Langen RCJ, et al. . The mechanisms of cachexia underlying muscle dysfunction in COPD. J Appl Physiol 2013;114:1253–62. 10.1152/japplphysiol.00790.2012
    1. Langen RCJ, Haegens A, Vernooy JHJ, et al. . NF-κB activation is required for the transition of pulmonary inflammation to muscle atrophy. Am J Respir Cell Mol Biol 2012;47:288–97. 10.1165/rcmb.2011-0119OC
    1. Remels AHV, Gosker HR, Schrauwen P, et al. . Tnf-Alpha impairs regulation of muscle oxidative phenotype: implications for cachexia? Faseb J 2010;24:5052–62. 10.1096/fj.09-150714
    1. Sprooten RTM, Lenaerts K, Braeken DCW, et al. . Increased small intestinal permeability during severe acute exacerbations of COPD. Respiration 2018;95:334–42. 10.1159/000485935
    1. Vaughan A, Frazer ZA, Hansbro PM, et al. . Copd and the gut-lung axis: the therapeutic potential of fibre. J Thorac Dis 2019;11:S2173–80. 10.21037/jtd.2019.10.40
    1. Foster JA, Rinaman L, Cryan JF, Stress CJF. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress 2017;7:124–36. 10.1016/j.ynstr.2017.03.001
    1. Zinellu A, Fois AG, Zinellu E, et al. . Increased kynurenine plasma concentrations and kynurenine-tryptophan ratio in mild-to-moderate chronic obstructive pulmonary disease patients. Biomark Med 2018;12:229–37. 10.2217/bmm-2017-0280
    1. Gosker HR, Clarke G, de Theije CC, et al. . Impaired skeletal muscle kynurenine metabolism in patients with chronic obstructive pulmonary disease. J Clin Med 2019;8. 10.3390/jcm8070915. [Epub ahead of print: 26 06 2019].
    1. Kennedy PJ, Cryan JF, Dinan TG, et al. . Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology 2017;112:399–412. 10.1016/j.neuropharm.2016.07.002
    1. Dueñas-Espín I, Demeyer H, Gimeno-Santos E, et al. . Depression symptoms reduce physical activity in COPD patients: a prospective multicenter study. Int J Chron Obstruct Pulmon Dis 2016;11:1287–95. 10.2147/COPD.S101459
    1. Coultas DB, Jackson BE, Russo R, et al. . Home-Based physical activity coaching, physical activity, and health care utilization in chronic obstructive pulmonary disease. chronic obstructive pulmonary disease self-management activation research trial secondary outcomes. Ann Am Thorac Soc 2018;15:470–8. 10.1513/AnnalsATS.201704-308OC
    1. Spruit MA, Singh SJ, Garvey C, et al. . An official American thoracic Society/European respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013;188:e13–64. 10.1164/rccm.201309-1634ST
    1. Egan C, Deering BM, Blake C, et al. . Short term and long term effects of pulmonary rehabilitation on physical activity in COPD. Respir Med 2012;106:1671–9. 10.1016/j.rmed.2012.08.016
    1. Mador MJ, Patel AN, Nadler J. Effects of pulmonary rehabilitation on activity levels in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil Prev 2011;31:52–9. 10.1097/HCR.0b013e3181ebf2ef
    1. Steele BG, Belza B, Cain KC, et al. . A randomized clinical trial of an activity and exercise adherence intervention in chronic pulmonary disease. Arch Phys Med Rehabil 2008;89:404–12. 10.1016/j.apmr.2007.11.003
    1. van de Bool C, Rutten EPA, van Helvoort A, et al. . A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD. J Cachexia Sarcopenia Muscle 2017;8:748–58. 10.1002/jcsm.12219
    1. Chan A-W, Tetzlaff JM, Altman DG, et al. . Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Zhu B, Zhu B, Xiao C, et al. . Vitamin D deficiency is associated with the severity of COPD: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis 2015;10:1907–16. 10.2147/COPD.S89763
    1. European Food Safety Authority . Dietary reference values for nutrients. summary report, 2017. Available:
    1. Resnicow K, DiIorio C, Soet JE, et al. . Motivational interviewing in health promotion: it sounds like something is changing. Health Psychol 2002;21:444–51.
    1. Cazzola M, MacNee W, Martinez FJ, et al. . Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 2008;31:416–69. 10.1183/09031936.00099306
    1. Cindy Ng LW, Jenkins S, Hill K. Accuracy and responsiveness of the stepwatch activity monitor and ActivPAL in patients with COPD when walking with and without a rollator. Disabil Rehabil 2012;34:1317–22. 10.3109/09638288.2011.641666
    1. Lyden K, Keadle SK, Staudenmayer J, et al. . The activPALTM accurately classifies activity intensity categories in healthy adults. Med Sci Sports Exerc 2017;49:1022–8. 10.1249/MSS.0000000000001177
    1. Demeyer H, Mohan D, Burtin C, et al. . Objectively measured physical activity in patients with COPD: recommendations from an international Task force on physical activity. Chronic Obstr Pulm Dis 2021;8:528–50. 10.15326/jcopdf.2021.0213
    1. Pickard AS, Wilke C, Jung E, et al. . Use of a preference-based measure of health (EQ-5D) in COPD and asthma. Respir Med 2008;102:519–36. 10.1016/j.rmed.2007.11.016
    1. Lowe C, Rabbitt P. Test\re-test reliability of the CANTAB and ISPOCD neuropsychological batteries: theoretical and practical issues. Neuropsychologia 1998;36:915–23. 10.1016/S0028-3932(98)00036-0
    1. Lovibond PF, Lovibond SH. The structure of negative emotional states: comparison of the depression anxiety stress scales (DASS) with the Beck depression and anxiety inventories. Behav Res Ther 1995;33:335–43. 10.1016/0005-7967(94)00075-u
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. 10.1111/j.1600-0447.1983.tb09716.x
    1. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav 1983;24:385–96.
    1. Schwabe L, Haddad L, Schachinger H. Hpa axis activation by a socially evaluated cold-pressor test. Psychoneuroendocrinology 2008;33:890–5. 10.1016/j.psyneuen.2008.03.001
    1. O'Brien KM, Tronick EZ, Moore CL. Relationship between hair cortisol and perceived chronic stress in a diverse sample. Stress Health 2013;29:337–44. 10.1002/smi.2475
    1. van Ockenburg SL, Schenk HM, van der Veen A, et al. . The relationship between 63days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals. Psychoneuroendocrinology 2016;73:142–7. 10.1016/j.psyneuen.2016.07.220
    1. Guralnik JM, Simonsick EM, Ferrucci L, et al. . A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85–94. 10.1093/geronj/49.2.m85
    1. Patel MS, Mohan D, Andersson YM, et al. . Phenotypic characteristics associated with reduced short physical performance battery score in COPD. Chest 2014;145:1016–24. 10.1378/chest.13-1398
    1. Rantanen T, Guralnik JM, Foley D, et al. . Midlife hand grip strength as a predictor of old age disability. JAMA 1999;281:558–60. 10.1001/jama.281.6.558
    1. Rantanen T, Harris T, Leveille SG, et al. . Muscle strength and body mass index as long-term predictors of mortality in initially healthy men. J Gerontol A Biol Sci Med Sci 2000;55:M168–73. 10.1093/gerona/55.3.M168
    1. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories . Ats statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111–7. 10.1164/ajrccm.166.1.at1102
    1. ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 2002;166:518–624. 10.1164/rccm.166.4.518
    1. Vercoulen JH, Swanink CM, Fennis JF, et al. . Dimensional assessment of chronic fatigue syndrome. J Psychosom Res 1994;38:383–92. 10.1016/0022-3999(94)90099-X
    1. Buysse DJ, Reynolds CF, Monk TH, et al. . The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213. 10.1016/0165-1781(89)90047-4
    1. Pelsers MMAL, Namiot Z, Kisielewski W, et al. . Intestinal-Type and liver-type fatty acid-binding protein in the intestine. tissue distribution and clinical utility. Clin Biochem 2003;36:529–35. 10.1016/S0009-9120(03)00096-1
    1. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32:920–4. 10.3109/00365529709011203
    1. Ramiro-Garcia J, Hermes GDA, Giatsis C, et al. . NG-Tax, a highly accurate and validated pipeline for analysis of 16S rRNA amplicons from complex biomes. F1000Res 2016;5:5. 10.12688/f1000research.9227.2
    1. Jones PW, Harding G, Berry P, et al. . Development and first validation of the COPD assessment test. Eur Respir J 2009;34:648–54. 10.1183/09031936.00102509
    1. van der Molen T, Willemse BWM, Schokker S, et al. . Development, validity and responsiveness of the clinical COPD questionnaire. Health Qual Life Outcomes 2003;1:13. 10.1186/1477-7525-1-13
    1. Bestall JC, Paul EA, Garrod R, et al. . Usefulness of the medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581–6. 10.1136/thx.54.7.581
    1. Markland D. Self-determination moderates the effects of perceived competence on intrinsic motivation in an exercise setting. J Sport Exercise Psy 1999;21:351–61. 10.1123/jsep.21.4.351
    1. Markland D, Ingledew DK. The measurement of exercise motives: factorial validity and invariance across gender of a revised exercise motivations inventory. Br J Health Psychol 1997;2:361–76. 10.1111/j.2044-8287.1997.tb00549.x
    1. Markland D, Tobin V. A modification to the behavioural regulation in exercise questionnaire to include an assessment of Amotivation. Journal of Sport and Exercise Psychology 2004;26:191–6. 10.1123/jsep.26.2.191
    1. Rose EA, Markland D, Parfitt G. The development and initial validation of the exercise causality orientations scale. J Sports Sci 2001;19:445–62. 10.1080/026404101300149393
    1. McAuley E, Duncan T, Tammen VV. Psychometric properties of the intrinsic motivation inventory in a competitive sport setting: a confirmatory factor analysis. Res Q Exerc Sport 1989;60:48–58. 10.1080/02701367.1989.10607413
    1. van Beers M, Rutten-van Mölken MPMH, van de Bool C, et al. . Clinical outcome and cost-effectiveness of a 1-year nutritional intervention programme in COPD patients with low muscle mass: the randomized controlled NUTRAIN trial. Clin Nutr 2020;39:405–13. 10.1016/j.clnu.2019.03.001
    1. Demeyer H, Burtin C, Hornikx M, et al. . The minimal important difference in physical activity in patients with COPD. PLoS One 2016;11:e0154587. 10.1371/journal.pone.0154587
    1. Han B, Enas NH, McEntegart D. Randomization by minimization for unbalanced treatment allocation. Stat Med 2009;28:3329–46. 10.1002/sim.3710
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975;31:103–15. 10.2307/2529712
    1. Nurk E, Drevon CA, Refsum H, et al. . Cognitive performance among the elderly and dietary fish intake: the Hordaland health study. Am J Clin Nutr 2007;86:1470–8. 10.1093/ajcn/86.5.1470
    1. Grosso G, Micek A, Marventano S, et al. . Dietary n-3 PUFA, fish consumption and depression: a systematic review and meta-analysis of observational studies. J Affect Disord 2016;205:269–81. 10.1016/j.jad.2016.08.011
    1. Ma W-J, Li H, Zhang W, Zhai J, et al. . Effect of n-3 polyunsaturated fatty acid supplementation on muscle mass and function with aging: A meta-analysis of randomized controlled trials✰. Prostaglandins Leukot Essent Fatty Acids 2021;165:102249. 10.1016/j.plefa.2021.102249
    1. Remels AHV, Langen RCJ, Schrauwen P, et al. . Regulation of mitochondrial biogenesis during myogenesis. Mol Cell Endocrinol 2010;315:113–20. 10.1016/j.mce.2009.09.029
    1. Yaqoob P, Calder P. Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunol 1995;163:120–8. 10.1006/cimm.1995.1106
    1. Duvall MG, Levy BD. Dha- and EPA-derived resolvins, protectins, and maresins in airway inflammation. Eur J Pharmacol 2016;785:144–55. 10.1016/j.ejphar.2015.11.001
    1. Remels AHV, Langen RCJ, Gosker HR, et al. . Ppargamma inhibits NF-kappaB-dependent transcriptional activation in skeletal muscle. Am J Physiol Endocrinol Metab 2009;297:E174–83. 10.1152/ajpendo.90632.2008
    1. Giudetti AM, Cagnazzo R. Beneficial effects of n-3 PUFA on chronic airway inflammatory diseases. Prostaglandins Other Lipid Mediat 2012;99:57–67. 10.1016/j.prostaglandins.2012.09.006
    1. Chapkin RS, Akoh CC, Miller CC. Influence of dietary n-3 fatty acids on macrophage glycerophospholipid molecular species and peptidoleukotriene synthesis. J Lipid Res 1991;32:1205–13.
    1. Guixà-González R, Javanainen M, Gómez-Soler M, et al. . Membrane omega-3 fatty acids modulate the oligomerisation kinetics of adenosine A2A and dopamine D2 receptors. Sci Rep 2016;6:19839. 10.1038/srep19839
    1. Carabelli B, Delattre AM, Waltrick APF, et al. . Fish-Oil supplementation decreases Indoleamine-2,3-Dioxygenase expression and increases hippocampal serotonin levels in the LPS depression model. Behav Brain Res 2020;390:112675. 10.1016/j.bbr.2020.112675
    1. McGlory C, Calder PC, Nunes EA. The influence of omega-3 fatty acids on skeletal muscle protein turnover in health, disuse, and disease. Front Nutr 2019;6:144. 10.3389/fnut.2019.00144
    1. van de Bool C, Mattijssen-Verdonschot C, van Melick PPMJ, et al. . Quality of dietary intake in relation to body composition in patients with chronic obstructive pulmonary disease eligible for pulmonary rehabilitation. Eur J Clin Nutr 2014;68:159–65. 10.1038/ejcn.2013.257
    1. Varraso R, Fung TT, Barr RG, et al. . Prospective study of dietary patterns and chronic obstructive pulmonary disease among US women. Am J Clin Nutr 2007;86:488-95. 10.1093/ajcn/86.2.488
    1. Varraso R, Fung TT, Hu FB, et al. . Prospective study of dietary patterns and chronic obstructive pulmonary disease among US men. Thorax 2007;62:786–91. 10.1136/thx.2006.074534
    1. Hirayama F, Lee AH, Binns CW, et al. . Dietary intake of isoflavones and polyunsaturated fatty acids associated with lung function, breathlessness and the prevalence of chronic obstructive pulmonary disease: possible protective effect of traditional Japanese diet. Mol Nutr Food Res 2010;54:909–17. 10.1002/mnfr.200900316
    1. Broekhuizen R, Wouters EFM, Creutzberg EC, et al. . Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 2005;60:376–82. 10.1136/thx.2004.030858
    1. Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: tryptophan's metabolites in exercise, inflammation, and mental health. Science 2017;357. 10.1126/science.aaf9794. [Epub ahead of print: 28 Jul 2017].
    1. Richard DM, Dawes MA, Mathias CW, et al. . L-Tryptophan: basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res 2009;2:45–60. 10.4137/ijtr.s2129
    1. Young SN. The effect of raising and lowering tryptophan levels on human mood and social behaviour. Philos Trans R Soc Lond B Biol Sci 2013;368:20110375. 10.1098/rstb.2011.0375
    1. Vardar-Yagli N, Saglam M, Savci S, et al. . Impact of sleep quality on functional capacity, peripheral muscle strength and quality of life in patients with chronic obstructive pulmonary disease. Expert Rev Respir Med 2015;9:233–9. 10.1586/17476348.2015.1009041
    1. Cleutjens FAHM, Pedone C, Janssen DJA, et al. . Sleep quality disturbances and cognitive functioning in elderly patients with COPD. ERJ Open Res 2016;2. 10.1183/23120541.00054-2016. [Epub ahead of print: 28 09 2016].
    1. Song SB, Park JS, Chung GJ, et al. . Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide. Metabolomics 2019;15:137. 10.1007/s11306-019-1604-4
    1. Gulcev M, Reilly C, Griffin TJ, et al. . Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2016;11:2435–46. 10.2147/COPD.S107844
    1. Dzik KP, Kaczor JJ. Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. Eur J Appl Physiol 2019;119:825–39. 10.1007/s00421-019-04104-x
    1. Ryan ZC, Craig TA, Folmes CD, et al. . 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells. J Biol Chem 2016;291:1514–28. 10.1074/jbc.M115.684399
    1. Spedding S, Vitamin D. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients 2014;6:1501–18. 10.3390/nu6041501
    1. Eyles DW, Smith S, Kinobe R, et al. . Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005;29:21–30. 10.1016/j.jchemneu.2004.08.006
    1. Buell JS, Dawson-Hughes B, Vitamin D. Vitamin D and neurocognitive dysfunction: preventing "D"ecline? Mol Aspects Med 2008;29:415–22. 10.1016/j.mam.2008.05.001
    1. van Etten E, Stoffels K, Gysemans C, et al. . Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 2008;66:S125–34. 10.1111/j.1753-4887.2008.00096.x
    1. Måhlin C, von Sydow H, Osmancevic A, et al. . Vitamin D status and dietary intake in a Swedish COPD population. Clin Respir J 2014;8:24–32. 10.1111/crj.12030
    1. Zhu M, Wang T, Wang C, et al. . The association between vitamin D and COPD risk, severity, and exacerbation: an updated systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis 2016;11:2597–607. 10.2147/COPD.S101382
    1. Romme EAPM, Smeenk FWJM, Rutten EPA, et al. . Osteoporosis in chronic obstructive pulmonary disease. Expert Rev Respir Med 2013;7:397–410. 10.1586/17476348.2013.814402
    1. Persson LJP, Aanerud M, Hiemstra PS, et al. . Chronic obstructive pulmonary disease is associated with low levels of vitamin D. PLoS One 2012;7:e38934. 10.1371/journal.pone.0038934
    1. Kokturk N, Baha A, Oh Y-M, et al. . Vitamin D deficiency: what does it mean for chronic obstructive pulmonary disease (COPD)? A compherensive review for pulmonologists. Clin Respir J 2018;12:382–97. 10.1111/crj.12588
    1. Carson EL, Pourshahidi LK, Madigan SM, et al. . Vitamin D status is associated with muscle strength and quality of life in patients with COPD: a seasonal prospective observation study. Int J Chron Obstruct Pulmon Dis 2018;13:2613–22. 10.2147/COPD.S166919
    1. Hornikx M, Van Remoortel H, Lehouck A, et al. . Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trial. Respir Res 2012;13:84. 10.1186/1465-9921-13-84
    1. Alavi Foumani A, Mehrdad M, Jafarinezhad A, et al. . Impact of vitamin D on spirometry findings and quality of life in patients with chronic obstructive pulmonary disease: a randomized, double-blinded, placebo-controlled clinical trial. Int J Chron Obstruct Pulmon Dis 2019;14:1495–501. 10.2147/COPD.S207400
    1. Jolliffe DA, Greenberg L, Hooper RL, et al. . Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax 2019;74:337–45. 10.1136/thoraxjnl-2018-212092
    1. Martineau AR, Jolliffe DA, Greenberg L, et al. . Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess 2019;23:1–44. 10.3310/hta23020
    1. Pelgrim CE, Peterson JD, Gosker HR, et al. . Psychological co-morbidities in COPD: targeting systemic inflammation, a benefit for both? Eur J Pharmacol 2019;842:99–110. 10.1016/j.ejphar.2018.10.001
    1. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125:1401–12. 10.1093/jn/125.6.1401
    1. den Besten G, van Eunen K, Groen AK, et al. . The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54:2325–40. 10.1194/jlr.R036012
    1. Janbazacyabar H, van Bergenhenegouwen J, Verheijden KAT, et al. . Non-Digestible oligosaccharides partially prevent the development of LPS-induced lung emphysema in mice. PharmaNutrition 2019;10:100163. 10.1016/j.phanu.2019.100163
    1. Hanson C, Lyden E, Rennard S, et al. . The relationship between dietary fiber intake and lung function in the National health and nutrition examination surveys. Ann Am Thorac Soc 2016;13:643–50. 10.1513/AnnalsATS.201509-609OC
    1. Szmidt MK, Kaluza J, Harris HR, et al. . Long-Term dietary fiber intake and risk of chronic obstructive pulmonary disease: a prospective cohort study of women. Eur J Nutr 2020;59:1869–79. 10.1007/s00394-019-02038-w

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