Beta-alanine supplementation in patients with COPD receiving non-linear periodized exercise (NLPE) training: randomized placebo-controlled trial.

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) is the rate-limiting precursor to carnosine synthesis and BA supplementation has been shown to consistently elevate muscle carnosine in a variety of populations. Hence, it is very plausible to hypothesize that BA supplementation in COPD patients following a non-linear periodized exercise (NLPE) training program (as part of pulmonary rehabilitation; PR) will increase muscle carnosine levels, which in turn will result in a positive effect on exercise tolerance and lower-limb muscle function.

It is hypothesized that beta-alanine supplementation in patients with COPD following a non-linear periodized exercise (NLPE) training program (as part of pulmonary rehabilitation; PR) will increase muscle carnosine levels, which in turn will result in a positive effect on exercise tolerance and lower-limb muscle function. These adaptations may translate into improved functional capacity during activities of daily living and improved quality of life. The primary targets of both exercise training and BA supplementation are the muscles of ambulation. Nevertheless, it seems reasonable to hypothesize that an enhanced bio-availability of carnosine in the body, by means of beta-alanine supplementation, may have an anti-oxidative effect in both the muscle and the brain.

The regular PR program at CIRO and Dekkerswald consists of a baseline assessment, followed by an in- or outpatient PR program and is ended with a post-rehabilitation assessment. After completion of the baseline assessment and obtaining informed consent, an additional study-related appointment is scheduled with included patients approximately 1-2 week prior to the start of the PR program. This additional testing day will be repeated after the rehabilitation period. Study duration per subject will be approximately 10 to 12 weeks. During the regular (baseline and post) assessments, the following outcomes will be measured: exercise capacity, tolerance and endurance, quadriceps muscle function, body composition, physical activity, dyspnoea, health-related quality of life, anxiety and depression, fatigue, pulmonary function and patient characteristics. The study-related appointments include: fasting venous blood sampling, a vastus lateralis muscle biopsy (optional, not required) and two cognitive function tests (M-WCST and SCWT). During the PR program the patients will receive NLPE as standard care. Patient safety and compliance will be constantly monitored during the PR program.

Oral beta-alanine (sustained-release Carnosyn®; 3.2 g/day) or identical looking placebo supplementation for a duration of 8-10 weeks.