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Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials.

  • Meys, Roy1, 2, 3
  • Stoffels, Anouk A F4, 2, 3, 5
  • de Brandt, Jana6
  • van Hees, Hieronymus W H5
  • Franssen, Frits M E4, 2, 3
  • Sillen, Maurice J H7
  • Wouters, Emiel F M4, 2, 3
  • Burtin, Chris6
  • Klijn, Peter8, 9
  • Bij de Vaate, Eline8
  • van den Borst, Bram5
  • Otker, Jacqueline M10, 11
  • Donkers, Jos11
  • Schleich, Florence N12
  • Hayot, Maurice13
  • Pomiès, Pascal13
  • Everaert, Inge14
  • Derave, Wim14
  • Spruit, Martijn A4, 2, 3, 6
  • 1 Department of Research and Development, CIRO, Horn, The Netherlands [email protected] , (Netherlands)
  • 2 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands. , (Netherlands)
  • 3 Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands. , (Netherlands)
  • 4 Department of Research and Development, CIRO, Horn, The Netherlands. , (Netherlands)
  • 5 Department of Pulmonary Diseases, Radboud UMC Dekkerswald, Nijmegen, The Netherlands. , (Netherlands)
  • 6 Reval Rehabilitation Research, Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, DIepenbeek, Belgium. , (Belgium)
  • 7 Department of Physiotherapy, CIRO, Horn, The Netherlands. , (Netherlands)
  • 8 Department of Pulmonology, Merem Pulmonary Rehabilitation Centre, Hilversum, The Netherlands. , (Netherlands)
  • 9 Department of Pulmonary Medicine, Amsterdam UMC, Amsterdam, The Netherlands. , (Netherlands)
  • 10 Patient Advisory Council, Lung Foundation Netherlands, Amersfoort, The Netherlands. , (Netherlands)
  • 11 Client Council, CIRO, Horn, The Netherlands. , (Netherlands)
  • 12 Department of Respiratory Medicine, CHU Sart-Tilman Liege, GIGA I3, Liege, Belgium. , (Belgium)
  • 13 PhyMedExp, INSERM - CNRS, University of Montpellier - Montpellier CHU, Montpellier, France. , (France)
  • 14 Department of Movement and Sport Sciences, University Ghent, Ghent, Belgium. , (Belgium)
Published Article
BMJ Open
Publication Date
Sep 13, 2020
DOI: 10.1136/bmjopen-2020-038836
PMID: 32928863


Exercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD. Two randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured. Both trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19). NTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC). © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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