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

Abstract

IntroductionExercise 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.Methods and analysisTwo 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.Ethics and disseminationBoth trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19).Trial registration numberNTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC).

Inositol possesses antifibrotic activity and mitigates pulmonary fibrosis

“…Among these top 25 pathways, 9 metabolic pathways have been well-documented in previous metabolomics studies in IPF, including glutamine metabolism, arginine metabolism and sphingolipid metabolism [ 11 ]. Additionally, 8 out of the 25 pathways were amino acid-associated metabolic pathways, of which the beta-alanine, taurine and hypotaurine, and inositol phosphate metabolism pathways have been reported to participate in the pathogenesis of lung diseases [ 28 – 30 ]. Despite these findings, the roles these metabolites play in lung fibrosis remain enigmatic.…”

The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice

“…Studies have shown that β-alanine supplementation may improve athletic performance and muscle strength in the elderly population ( Furst et al., 2018 ), as well as increase carnosine and improve body fat composition in athletes ( Carvalho et al., 2018 ). Moreover, oral administration of β-alanine increases the concentration of muscle carnosine and enhances exercise endurance in patients with chronic obstructive pulmonary disease ( Meys et al., 2020 ; De Brandt et al., 2022 ). β-Alanine metabolism is strongly correlated with chronic fatigue and physical performance in adolescents ( Zhao et al., 2022 ).…”

Efficacy of 12 weeks oral beta‐alanine supplementation in patients with chronic obstructive pulmonary disease: a double‐blind, randomized, placebo‐controlled trial

“… 42 As literature is contradictory, scarce, and the ‘untrained’ model used in both studies is different, it remains interesting to investigate whether BA supplementation is a promising exercise training aid in patients with COPD. 43 If so, patients might be able to train at higher intensities leading to greater improvement in exercise capacity and ultimately quality of life.…”

“…A recent study by Nemezio et al ., however, showed that muscle carnosine loading was equal in the active (deltoid) and inactive (quadriceps) limbs of paraplegic athletes after BA supplementation 42 . As literature is contradictory, scarce, and the ‘untrained’ model used in both studies is different, it remains interesting to investigate whether BA supplementation is a promising exercise training aid in patients with COPD 43 . If so, patients might be able to train at higher intensities leading to greater improvement in exercise capacity and ultimately quality of life.…”