To study in clinically stable Chronic Obstructive Pulmonary Disease (COPD) patients with muscle atrophy:

1. The short-term effects of 4 months exercise training including nutritional supplementation versus exercise training alone on physical functioning (skeletal muscle strength and exercise capacity) and body composition.
2. The long-term effects of 4 months of exercise training and nutritional supplementation followed by 8 months of nutritional counseling (with supplementation on advice) and feedback on physical activity level versus 4 months of exercise training and 8 months with feedback on physical activity level alone on physical functioning, body composition and cardiometabolic risk profile;
3. The cost-effectiveness of exercise rehabilitation and nutritional intervention versus exercise rehabilitation alone.

Rationale. Recent guidelines state that pulmonary rehabilitation should be part of integrated care of patients with COPD and not limited to end stage disease. The investigators hypothesize that clinically stable COPD patients muscle atrophy, irrespective of the severity of airflow obstruction, show more pronounced long-term improvement in physical functioning and cardiometabolic risk profile after a rehabilitation programme including nutritional intervention (supplementation and counseling) than after a pulmonary rehabilitation programme without nutritional intervention, at acceptable costs. Nutritional supplementation focuses on enhancing the efficacy of the exercise training. Nutritional counseling aims at maintaining energy balance and modulating cardiovascular disease risk.

Study design. The research aims will be addressed in a multi-centre, randomized, clinical trial.

Phase A, Rehabilitation (4 months):

• Group 1: Supervised exercise training and 3 placebo nutritional supplements daily
• Group 2: Supervised exercise training and 3 nutritional supplements daily

Phase B, Maintenance (8 months):

• Group 1: Exercise counseling (2x)
• Group 2: Exercise counseling (2x), nutritional counseling (5x) (and 1 nutritional supplement a day on indication)

Phase C, Follow-up (3 months):

• Group 1: no intervention
• Group 2: 1 nutritional supplement a day on request

Nature and extent of the burden and risks associated with participation and benefits. This study aims to tailor pulmonary rehabilitation. Participants of group 1 are visiting their rehabilitation centre 3 times for study related measurements within 15 months (2 times feedback on physical activity, 1 measurement visit). Participants of group 2 will be asked to visit their rehabilitation centre for 6 times (1 measurement visit, 3 times nutritional counseling, 1 time for feedback on physical activity, 1 time for nutritional counseling and feedback on physical activity combined) within 15 months. For both groups baseline measurements and outcome measurements after rehabilitation are already included in the CIRO rehabilitation programme.

Inclusion Criteria:

• Chronic Obstructive Pulmonary Disease
• Muscle atrophy (a FFMI under the sex- and age-specific 25th percentile FFMI values, assessed by DEXA)
• Eligible for pulmonary rehabilitation

Exclusion Criteria:

• COPD patients under the age of 18;
• Allergy or intolerance to fish, milk or other components of the study product;
• Investigator's uncertainty about the willingness or ability of the patient to comply with the protocol requirements;
• Not able to stop current supplement use or if total use will be above safe upper limits;
• Participation in any other study involving investigational or marketed products concomitantly or within two weeks prior to entry into the study;
• Pregnancy;
• Life threatening diseases like tuberculosis, carcinoma, AIDS (including HIV+), acute leukaemia etc.