Randomized controlled trial of dietary creatine as an adjunct therapy to physical training in chronic obstructive pulmonary disease

Rationale: Skeletal muscle strength and bulk are reduced in patients with chronic obstructive pulmonary disease (COPD) and influence quality of life, survival, and utilization of health care resources. Exercise training during pulmonary rehabilitation (PR) can reverse some of these effects. In athletes and healthy elderly individuals, dietary creatine supplementation (CrS) has been shown to augment high-intensity exercise training, thereby increasing muscle mass. Objectives: This article examines the effect of CrS on functional exercise capacity and muscle performance in people with COPD. Methods: One hundred subjects with COPD (mean [SD] age, 68.2 [8.2] yr; FEV1, 44.0 [19.6] %predicted) were randomized to a double-blind, placebo-controlled, parallel group trial of CrS during 7 weeks of PR encompassing aerobic and resistance exercises. Subjects ingested creatine (22 9/d loading for 5 d; maintenance, 3.76 g/d throughout PR) or placebo. Baseline, postloading, and postrehabilitation measurements included pulmonary function, body composition, peripheral muscle strength, and functional performance (shuttle walking tests). A volunteer subgroup (n = 44) had pre- and postloading quadriceps muscle biopsies. Measurements and Main Results: Eighty subjects completed the trial (38 creatine, 42 placebo). All outcome measures significantly improved after PR. There were no significant differences between groups post-PR (mean [SD] change in incremental shuttle walk distance, 84 [791 m in the creatine group vs. 83.8 [60] m in the placebo group; P = 1.0; knee extensorwork, 19.2 [16] Nm [Newton meters] in the creatine group vs. 19.5 [17] Nm in the placebo group; P = 0.9). Muscle biopsies showed evidence of creatine uptake. Conclusions: This adequately powered, randomized, placebo-controlled trial shows that CrS does not augment the substantial training effect of multidisciplinary PR for patients with COPD. Clinical trial registered with https://portal.nihr.ac.uk/Pages/ NRRArchiveSearch.aspx (NO123138126).