Chronic obstructive pulmonary disease (COPD) is a very common and chronic lung condition and is a leading cause of morbidity and death. These patients have persistent breathlessness and exercise intolerance, affecting their ability to carry out routine daily tasks. Standard COPD treatments include medicines/puffers as well as participation in a Pulmonary Rehabilitation (PR) program. PR programs are delivered by a diverse team of healthcare experts in exercise and nutrition. It is possible that an emerging nutritional oral supplement could target the muscular dysfunction seen in patients with COPD in part by promoting better working mitochondria, the energy 'engine' of muscle. A series of recently published studies in sedentary adults and in older adults have demonstrated the safety, tolerability, and potential clinical effectiveness of this supplement.

In this regard, the investigators plan to lead a large randomized controlled trial (RCT) to test whether oral supplementation in patients with COPD who are also participating in a standard PR program will improve overall exercise performance. The investigators will also test muscle strength, cognition, body composition, and other clinically important outcomes such as quality of life. Lastly, the investigators will use muscle tissue from a subgroup of volunteers to investigate the effect on muscle/mitochondrial structure/function.

The focus is actually the critical 'first step' before the larger RCT: a pilot and feasibility study on a smaller number of participants with COPD, as an important proof-of-concept that the larger study can, and should, be conducted.

The main objectives for this pilot feasibility study are to document recruitment rates, collect information on participant acceptability of tests, establish the capacity to run the RCT at our site, to demonstrate successful molecular testing of specimens, and to generate pilot data for the outcomes being tested in the larger subsequent RCT.

The overarching goal for the 'larger', future project will be to determine the effect of the oral supplement on exercise capacity, muscle strength, mitochondrial function, health-related quality of life, cognition, symptom burden, and safety/adherence in patients with COPD who are participating in a Pulmonary Rehabilitation program. The goal of the present research project is to complete a pilot and feasibility study testing the same clinical outcomes on a smaller sample of eligible study participants during which participants receive the intervention for 8 weeks.

The primary objective is to determine whether administration of the oral supplement during participation in a standard multi-week in-person Pulmonary Rehabilitation (PR) program is associated with an improvement in exercise endurance capacity in patients with COPD, compared with PR participation and placebo supplementation.

The secondary objectives are to determine the effect of the oral supplement on i) global conditioning and exercise capacity; ii) muscle strength; iii) mitochondrial function; iv) body composition; v) quality of life and burden of disease; vi) cognition; vii) adverse events/complications and adherence, and viii) blood levels of Urolithin A.

We hypothesize that patients with COPD receiving oral supplementation during PR participation will demonstrate an improvement in Constant Work Rate Exercise Test (CRWET) time after 8 weeks when compared to patients with COPD who receive placebo and PR participation.

Inclusion Criteria:

1. Males and females, aged >40, former smokers with ≥10 pack-year smoking history
2. Post-bronchodilator forced expiratory volume at one second (FEV1) / forced vital capacity (FVC) ratio < 0.7, with FEV1 < 80% (moderate, Global Initiative for Chronic Obstructive Lung Disease '(GOLD) 2') FEV1 < 50% (severe, 'GOLD 3') or FEV1 < 30% (very severe, 'GOLD 4') COPD
3. Baseline 6MWD of ≥50m
4. Prior receipt of at least 2 doses of the Coronavirus Disease of 2019 (COVID-19) vaccine

Exclusion Criteria:

1. Inability to participate in a standard PR program
2. Severe/unstable cardiac disease, neurological or orthopedic conditions which could hinder exercise performance
3. Inability to provide consent due to language or cognitive barrier
4. Previous PR participation in the last 12 months, or in a study involving an exercise program in the last 6 months
5. Experienced an exacerbation of COPD (ECOPD) within the prior 4 weeks
6. Long-term oxygen therapy use, or maintenance oral corticosteroid use
7. Presence of pacemaker or implantable cardioverter defibrillator (ICD) (unless participant opts out of bioelectrical impedance assay)
8. Unwilling to agree to refrain from using, or are found to be using, the following supplementary antioxidant vitamins from 7 days prior to dosing and throughout the treatment period: Coenzyme Q10, resveratrol, and L-carnitine
9. Unwilling to agree to refrain from using, or are found to be using, the following dietary restrictions from 7 days prior to dosing and throughout the treatment period: pomegranate juice, walnuts, pecans, strawberries, raspberries, and blackberries
10. Allergy to lecithin, to soy or to sunflower
11. Pregnant, breastfeeding or planning to become pregnant
12. Use of anticoagulant or presence of a clotting disorder (if participating in muscle biopsy subgroup)
13. Allergy to anesthetics such as xylocaine and lidocaine (if participating in muscle biopsy subgroup)
14. Chronic myalgia, fibromyalgia or conditions characterized by regular muscle pain (if participating in muscle biopsy subgroup)
15. Metal fixation plates or screws in the legs from a previous surgery (if participating in muscle biopsy subgroup)