The overall objective is to investigate the efficacy of targeted nutrient supplementation on daily physical activity level as well as generic health status in patients with COPD. Additionally the investigators aim to investigate the relative effect of targeted nutrient supplementation on the recovery after hospitalization for a COPD exacerbation. The secondary objective is to investigate the effect of targeted nutrient supplementation on mental health, physical performance, blood markers, patient related outcomes and gut health. Additionally, a secondary objective is to compare the gut microbiome composition of patients with COPD compared to healthy controls.

Rationale: Impaired physical and mental health are common features in COPD adversely affecting disease course and quality of life. Furthermore, nutritional status is often impaired due to dietary and plasma nutrient deficiencies, decreased muscle oxidative metabolism and impaired intestinal permeability. The investigators hypothesize that targeted nutrient supplementation can lead to gut-muscle-brain axis-mediated amelioration of physical, cognitive and mental health domains, resulting in a healthier lifestyle, in patients with COPD.

Study design: Randomized, placebo-controlled, double-blind trial.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The nutrient supplement is hypothesized to have beneficial effects on general health because it applies physical and mental health domains. The healthy lifestyle counselling aims to improve medical adherence, to address a healthier lifestyle and to manage weight loss which would contribute to improved general health. Risks and inconveniences are limited to the time investment associated with taking the supplements and measuring days. During the test-days various non-invasive measurements as well as minor invasive blood sampling will be performed. The investigators expect no risk of the nutrient supplementation. Healthy controls will only attend a subgroup of baseline measurements which are limited to non-invasive measurements and one minor invasive blood sampling. Healthy controls will not receive the nutritional supplement.

Inclusion Criteria COPD Patients:

• COPD patients with moderate to very severe disease stage according to GOLD criteria (i.e. GOLD stage II-IV);
• Medically stable.

Exclusion Criteria COPD Patients:

• Age <18 years;
• Allergy or intolerance to components of the study product;
• Not willing or not able to quit vitamin D or fatty acid supplement intake;
• Investigator's uncertainty about the willingness or ability of the patient to comply with the protocol requirements (e.g. leg amputation) or patients suffering from other acute or unstable chronic diseases that will compromise the study outcome (e.g. active cancer requiring treatment);
• Participation in any other study involving investigational or marketed products concomitantly or within four weeks prior to entry into the study;
• Patients with terminal illness;
• Recent hospital admission (<4 weeks prior to the start of the study);
• Temporary oral steroid or antibiotics use due to a COPD exacerbation in the last 4 weeks;
• Lung malignancy in the previous 5 years;
• Diagnosis of dementia or neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, Huntington's chorea, frontotemporal dementia) in the medical records;
• Recent diagnosis of cerebral conditions (<1 year e.g. cerebral infarction, hemorrhage, brain tumors, transient ischemic attack) in the medical records;
• Any medical condition that significantly interferes with digestion and/or gastrointestinal function (e.g. short bowel syndrome, inflammatory bowel disease, gastric ulcers, gastritis, (gastro)-enteritis, GI-cancer) as judged by the investigator.

Inclusion Criteria Healthy Controls

• Forced expiratory volume in 1 second/Forced vital capacity > 0.7;
• Medically stable.

Exclusion Criteria Healthy Controls

• Age <18 years;
• Investigator's uncertainty about the willingness or ability of the patient to comply with the protocol requirements (e.g. leg amputation) or patients suffering from other acute or unstable chronic diseases that will compromise the study outcome (e.g. active cancer requiring treatment);
• Participation in any other study involving investigational or marketed products concomitantly or within four weeks prior to entry into the study;
• Patients with terminal illness;
• Recent hospital admission (<4 weeks prior to the start of the study);
• Temporary antibiotics use in the last 4 weeks;
• Lung malignancy in the previous 5 years;
• Diagnosis of dementia or neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, Huntington's chorea, frontotemporal dementia) in the medical records;
• Recent diagnosis of cerebral conditions (<1 year e.g. cerebral infarction, hemorrhage, brain tumors, transient ischemic attack) in the medical records;
• Any medical condition that significantly interferes with digestion and/or gastrointestinal function (e.g. short bowel syndrome, inflammatory bowel disease, gastric ulcers, gastritis, (gastro)-enteritis, GI-cancer) as judged by the investigator.
• Diagnosis of any chronic lung disease.

Deidentified data will only be shared based on a reasonable request.