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

Abstract

Background: Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD.

Methods: In this double-blind, randomized, placebo (PL)-controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV₁ % predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co-primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed.

Results: Beta-alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49-4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO₂ peak: +0.5 [-0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [-1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [-179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1-quartile 3); 100 (98-100)%) and PL (98 (96-100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes.

Conclusions: Beta-alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed.

Keywords: Carnosine; Chronic obstructive pulmonary disease; Oxidative/carbonyl stress; Physical capacity.

Figure 1

CONSORT flow diagram of the study. AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BA, beta‐alanine; PL, placebo.

Figure 2

Effect of oral BA supplementation on muscle carnosine and related metabolites in muscle and plasma/serum in patients with chronic obstructive pulmonary disease. Muscle carnosine and related metabolites are depicted in Panels (A)–(F) (BA = circles, PL = triangles) by individual data points, and mean is shown in black and dotted line. Flat line = a main effect of time is present (†). Half tick‐down line = effects of time (†) and/or group (*) were explored separately by within (baseline vs. outcome within BA and PL) or between (BA vs. PL on baseline and outcome time point) analysis when a significant interaction group × time effect was present. BA, beta‐alanine; CN1, carnosinase; PL, placebo; WW, wet weight.

Figure 3

Effect of oral BA supplementation on oxidative and carbonyl stress in patients with COPD. Muscle proteins affected by carbonylation (Panels A–C) and 4HNE (B–D) (BA = circles, PL = triangles). Panels (A) and (B) show the quantification of muscle proteins affected by carbonylation and 4HNE relative to loading control GAPDH by individual data points, and mean is shown in black and dotted line. Panels (C) and (D) show a representative western blot (in total, 10 western blots were performed for both carbonylation and 4HNE) for muscle proteins affected by carbonylation and 4HNE, respectively. Baseline (B) and outcome (O) intervention samples of four patients with COPD (two patients in each group: BA/PL) were loaded per blot. Black vertical lines are lines where the blot was cut. 4HNE, 4‐hydroxynonenal; a.u., arbitrary units; BA, beta‐alanine; COPD, chronic obstructive pulmonary disease; GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; kDa, kilodalton; PL, placebo.