A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD

Abstract

Background: Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited. The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass.

Methods: Eighty-one COPD patients with low muscle mass, admitted to out-patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega-3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training.

Results: The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid. Intention-to-treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048). After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001). Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (-18%,P = 0.005).

Conclusions: High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction. Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo.

Keywords: Emphysema; Muscle function; Nutrient supplementation; Physical activity; Pulmonary rehabilitation.

Figure 1

NUTRAIN flowchart. A total of 1640 patients referred for pulmonary rehabilitation were assessed for trial eligibility. COPD patients (post‐bronchodilator FEV1/FVC <0.7) were eligible when they had low muscle mass (FFMI < sex‐ and age‐specific 25th percentile FFMI values) and referred for outpatient rehabilitation. A total of 1420 patients were excluded and 139 eligible patients declined to participate; 81 patients were enrolled in the trial and randomized to NUTRITION or PLACEBO. Two of the 81 randomized patients did not start the treatment. During the PR, the drop‐out rate was 9.5% (4 patients) in NUTRITION and 5.4% (2 patients) in PLACEBO.

Figure 2

Plasma status of supplemented nutrients. A: Baseline plasma nutrient levels compared with healthy controls. Dark grey bars represent NUTRAIN patients with COPD. White bars represent healthy controls. B: Mean change from baseline in plasma concentrations of supplemented nutrients. Light grey bars represent patients that received PLACEBO. Mid grey bars represent patients that received NUTRITION. * P < 0.05; **P < 0.01; *** P < 0.001.

Figure 3

Mean pre‐ and post‐ values of A: Lower limb muscle strength; B: Exercise performance. Light grey bars represent patients that received PLACEBO. Mid grey bars represent patients that received NUTRITION. * P < 0.05; **P < 0.01; *** P < 0.001.

Figure 4

Mean pre‐ and post‐ values of A: Respiratory muscle strength; B: Physical activity level. Light grey bars represent patients that received PLACEBO. Mid grey bars represent patients that received NUTRITION. * P < 0.05; **P < 0.01.