The Effect of Urolithin A (Mitopure®) Supplementation on Muscle Strength in Healthy Middle-Aged Adults

Inclusion Criteria:

• 1. Be able to give written informed consent.
• 2. Be between 40 to 65 years of age, inclusive.
• 3. Has a BMI between 25.0 and 34.9 kg/m2.
• 4. Low physical activity levels as assessed by the International Physical ActivityQuestionnaire (IPAQ).
• 5. Participants with low VO2 peak (defined as <35 mL/kg/min via the ergometer priorto baseline).
• 6. Willing to avoid exercising 48-h prior to study visits and maintain low physicalactivity status for the duration of the study.
• 7. Willing to avoid caffeine and other stimulants (e.g., energy drinks) 12-h beforeexercise as per study guidelines.
• 8. Willing to consume the Study Product daily for the duration of the study.

Exclusion Criteria:

• 1. Participants who are pregnant or wish to become pregnant during the study or whoare lactating and/or currently breastfeeding.
• 2. Participants currently of biological childbearing potential, but not using acontinuous effective method of contraception, as outlined below:

• a. Complete abstinence from intercourse two weeks prior to administration ofthe Study Product, throughout the clinical study, until the completion offollow-up procedures or for two weeks following discontinuation of the StudyProduct in cases where Participant discontinues the study prematurely. (Participants utilising this method must agree to use an alternate method ofcontraception if they should become sexually active and will be queried onwhether they have been abstinent in the preceding two weeks when they presentto the clinic for the final visit).

• b. Has a male sexual partner who is surgically sterilised prior to theScreening Visit and is the only male sexual partner for that Participant.

• c. Sexual partner(s) is/are exclusively female.

• d. Use of acceptable method of contraception, such as a spermicide, mechanicalbarrier (e.g., male condom, female diaphragm), tubal ligation, or contraceptivepill. The Participant must be using this method for at least one week prior toand one week following the end of the study.

• e. Use of any intrauterine device (IUD) or contraceptive implant. TheParticipant must have the device inserted at least two weeks prior to the firstscreening visit, throughout the study, and two weeks following the end of thestudy.

• 3. Participants with history of drug and/or alcohol abuse at the time of enrolment. (Drinks more than nationally recommended units per week (>11 units for women; >17units for men); alcohol/substance abuse disorder).
• 4. Participants consuming large quantities of pomegranate juice or walnuts orfrequent consumers of raspberries, strawberries or cloudberries (2-week washout).
• 5. Chronic nicotine use.
• 6. Participants who are unable to swallow capsules.
• 7. Is hypersensitive to or has dietary restrictions for any of the components of theStudy Product e.g., gelatine
• 8. Unstable body weight or recent participation in a weight loss program (within 12-weeks prior to screening).
• 9. Has any significant acute or chronic coexisting health conditions that wouldprevent them from fulfilling the study requirements, put the Participant at risk orwould confound the interpretation of the study results as judged by the investigatoron the basis of medical history and routine laboratory test results. Excluded healthconditions include:

• a. Major illness/surgery in the 12-weeks prior to screening

• b. Diagnosed cardiovascular disease (NHYA Class III or IV congestive heartfailure, atrial fibrillation, uncontrolled arrhythmia, uncontrolledhypertension)

• c. Diagnosed liver disease (cirrhosis, end stage liver disease)

• d. Diagnosed kidney disease (stage 3b or 4 chronic kidney disease, or kidneyfailure)

• e. Diagnosed gastrointestinal disease (IBS/IBD, diarrhoea, Acid Reflux)

• f. Uncontrolled thyroid conditions

• g. Uncontrolled diabetes

• h. Metallic implants

• i. Conditions requiring chemotherapy or immunotherapy.

• 10. Current or recent use of a medication that the investigator believes wouldinterfere with the objectives of the study or pose a safety risk or confound theinterpretation of the study results. Prohibited medications include:

• a. Statins or other medications known to impair mitochondrial function.

• b. Anxiolytics, antidepressants, sedative hypnotics (in the 8 weeks prior tovisit 1)

• c. Antipsychotics, monoamine Oxidase Inhibitors (in the 8 weeks prior to visit

• d. Oral anti- infective (antibiotics, antivirals, antifungals) for acuteinfections (in the 12-weeks prior to visit 1)

• e. Proton pump inhibitors (PPIs) (in the 4 weeks prior to visit 1)

• f. Corticosteroids (> 5mg per day in the past 4 weeks prior to visit 1)

• g. GLP-1 agonists (in the 8 weeks prior to visit 1)

• 11. Current or recent (in the past 6-weeks prior to Visit 1) use of prohibitednutritional or non-nutritional supplements that the investigator believes wouldinterfere with the objectives of the study or pose a safety risk or confound theinterpretation of the study results. Prohibited supplements include:

• a. Mitopure® containing supplements

• b. Supplements for muscle strengthening/building or mitochondrial boostingsupplements (e.g. high protein, Vitamin B3 [and precursors], L-carnitine,CoQ10, NAD+, resveratrol)

• 12. Blood donation in the 8-weeks prior to screening.
• 13. Individuals who, in the opinion of the investigator, are considered to be poorattendees or unlikely for any reason to be able to comply with the study.
• 14. Participants may not be participating in other clinical studies. If theparticipant has previously taken part in an experimental study (physical or muscleperformance), the Investigator must ensure sufficient time has elapsed before entryto this study to ensure the integrity of the results.