Weight loss commonly occurs in patients with COPD, negatively influencing their quality of life, treatment response and survival. Loss of muscle protein is generally a central component of this weight loss and independently increases mortality. This study will provide relevant clinical information in regards to the anabolic properties of specific dietary substrates and their co-active anabolic effects. Hypotheses: 1) That supplementation of a hydrolyzed casein-based protein meal with the addition of carbohydrates is more anabolic than a hydrolyzed casein-based protein meal without carbohydrates in COPD patients and healthy older adults; 2) That leucine addition to a hydrolyzed casein-based protein meal only enhances the protein anabolic response in COPD patients and healthy older adults when carbohydrates are not added to the protein meal; 3) That COPD patients have a more efficient protein anabolic response to a hydrolyzed casein-based protein meal than healthy older adults.

A fifth study day was added to measure protein requirements of included individuals to be able to interpret their response to the other interventions on the other study days, and to test the hypothesis that subjects with lower protein requirements respond less to intervention with leucine and/or carbohydrates. For the 5th additional test day we will first approach the 10 COPD and 10 healthy subjects who already completed the first 4 study days (and signed the re-contact form) to come back for this extra test day. We will (pre-)screen these subjects by phone for eligibility and check for changes in their recent medical history (with help of the (pre-)screening questionnaires in CRF). If all inclusion criteria are still met, these subjects will be asked to provide a written re-consent. If necessary, we will recruit new subjects who will complete only one of the four test days (i.e. the test day on which the hydrolyzed casein-based protein meal with carbohydrates is provided) and the additional 5th study day.

The study involves 5 study days. The duration of the first 4 study days is approximately 6.5 hours per day and the duration of the 5th study day is approximately 8 hours. On each of the first 4 study days the effect a casein protein meal with or without leucine and carbohydrates will be examined. On the fifth study day the effect of 4 different levels of casein protein and carbohydrate intake by sip feeding (every 20 minutes) is examined.

Also, subjects will receive a mixture of amino acids (little parts of protein) which are a little bit heavier than normal, called stable isotopes. This is the so-called stable isotope method to investigate protein behavior in the body (protein kinetics). Altogether about 75 ml of blood will be drawn per study day to assess outcome measures.

Inclusion criteria COPD subjects:

• Ability to walk, sit down and stand up independently

• Age 45 years or older

• Ability to lie in supine or elevated position for 5.5 hours

• Diagnosis of moderate to very severe chronic airflow limitation and compliant to the following criteria: Forced Expiratory Volume(FEV1)/Forced Vital Capacity (FVC) < 0.70 and FEV1 < 70% of reference FEV1

• Clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the first test day

• Shortness of breath on exertion

• Willingness and ability to comply with the protocol, including:

  • Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Inclusion criteria healthy control subjects:

• Healthy male or female according to the investigator's or appointed staff's judgment

• Ability to walk, sit down and stand up independently

• Age 45 years or older

• Ability to lay in supine or elevated position for 5.5 hours

• No diagnosis of chronic airflow limitation and compliant to the following criteria: FEV1/FVC > 0.70 and FEV1 ≥ 80% of reference FEV1

• Willingness and ability to comply with the protocol, including:

  • Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Exclusion Criteria all subjects:

• Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)

• Established diagnosis of malignancy

• Established diagnosis of Insulin Dependent Diabetes Mellitus

• History of untreated metabolic diseases including hepatic or renal disorder

• Presence of acute illness or metabolically unstable chronic illness

• Recent myocardial infarction (less than 1 year)

• Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient

• BMI of < 18.5 or ≥ 35 kg/m2

• Dietary or lifestyle characteristics:

  • Use of protein or amino acid containing nutritional supplements within 5 days of first test day
  • Current alcohol or drug abuse

• Indications related to interaction with study products:

  • Known allergy to milk or milk products

• Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day

• Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements

• (Possible) pregnancy