The Effect of Urolithin A (Mitopure®) Supplementation on Muscle Strength in Healthy Middle-Aged Adults (ATLAS 2)

A Confirmatory, Randomised, Double-Blind, Placebo-Controlled, Parallel Study to Assess the Effects of a Dietary Supplement Containing Urolithin A (Mitopure®) on Muscle Strength and Performance in Healthy Middle-Aged Adults

This is a randomised, double-blind, placebo-controlled, parallel study to assess the effects of Urolithin A (Mitopure®) supplementation on muscle strength and performance in healthy middle-aged adults. Participants will be randomized to consume Mitopure® (500 mg), Mitopure® (1000 mg), or placebo once daily for 6 months.

Study Overview

• Status: Recruiting
• Conditions: Healthy Aging; Muscle Function
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Mitopure® 500mg; Dietary supplement: Mitopure® 1000mg

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anurag Singh, MD, PhD
• Study Contact Backup: Name: Brad Currier, PhD; Phone Number: +41 215521272; Email: bcurrier@timeline.com

Study Locations

• Ireland
  • Cork, Ireland, T23 R50R
    • Recruiting
    • Atlantia Clinical Trials
    • Contact: Nontokozo Yusuff, MD; Phone Number: +353 (0) 21-430-7442; Email: nyusuff@atlantiatrials.com
    • Principal Investigator: Nontokozo Yusuff, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Activity Questionnaire (IPAQ).
• 5. Participants with low VO2 peak (defined as <35 mL/kg/min via the ergometer prior to baseline).
• 6. Willing to avoid exercising 48-h prior to study visits and maintain low physical activity status for the duration of the study.
• 7. Willing to avoid caffeine and other stimulants (e.g., energy drinks) 12-h before exercise 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 who are lactating and/or currently breastfeeding.

• 2. Participants currently of biological childbearing potential, but not using a continuous effective method of contraception, as outlined below:

  • a. Complete abstinence from intercourse two weeks prior to administration of the Study Product, throughout the clinical study, until the completion of follow-up procedures or for two weeks following discontinuation of the Study Product in cases where Participant discontinues the study prematurely. (Participants utilising this method must agree to use an alternate method of contraception if they should become sexually active and will be queried on whether they have been abstinent in the preceding two weeks when they present to the clinic for the final visit).
  • b. Has a male sexual partner who is surgically sterilised prior to the Screening 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, mechanical barrier (e.g., male condom, female diaphragm), tubal ligation, or contraceptive pill. The Participant must be using this method for at least one week prior to and one week following the end of the study.
  • e. Use of any intrauterine device (IUD) or contraceptive implant. The Participant must have the device inserted at least two weeks prior to the first screening visit, throughout the study, and two weeks following the end of the study.
• 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; >17 units for men); alcohol/substance abuse disorder).
• 4. Participants consuming large quantities of pomegranate juice or walnuts or frequent 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 the Study 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 would prevent them from fulfilling the study requirements, put the Participant at risk or would confound the interpretation of the study results as judged by the investigator on the basis of medical history and routine laboratory test results. Excluded health conditions include:

  • a. Major illness/surgery in the 12-weeks prior to screening
  • b. Diagnosed cardiovascular disease (NHYA Class III or IV congestive heart failure, atrial fibrillation, uncontrolled arrhythmia, uncontrolled hypertension)
  • c. Diagnosed liver disease (cirrhosis, end stage liver disease)
  • d. Diagnosed kidney disease (stage 3b or 4 chronic kidney disease, or kidney failure)
  • 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 would interfere with the objectives of the study or pose a safety risk or confound the interpretation 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 to visit 1)
  • c. Antipsychotics, monoamine Oxidase Inhibitors (in the 8 weeks prior to visit 1)
  • d. Oral anti- infective (antibiotics, antivirals, antifungals) for acute infections (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 prohibited nutritional or non-nutritional supplements that the investigator believes would interfere with the objectives of the study or pose a safety risk or confound the interpretation of the study results. Prohibited supplements include:

  • a. Mitopure® containing supplements
  • b. Supplements for muscle strengthening/building or mitochondrial boosting supplements (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 poor attendees or unlikely for any reason to be able to comply with the study.
• 14. Participants may not be participating in other clinical studies. If the participant has previously taken part in an experimental study (physical or muscle performance), the Investigator must ensure sufficient time has elapsed before entry to this study to ensure the integrity of the results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Placebo softgels
Experimental: 500 mg Mitopure®	Dietary supplement: Mitopure® 500mg; Softgels providing 500 mg of Mitopure®
Experimental: 1000 mg Mitopure®	Dietary supplement: Mitopure® 1000mg; Softgels providing 1000 mg of Mitopure®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum isokinetic knee flexion strength	Change in maximum isokinetic knee flexion strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum isokinetic knee flexion strength	Change in maximum isokinetic knee flexion strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	4 months
Maximum isokinetic knee extension strength	Change in maximum isokinetic knee extension strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	4, 6 months
Maximum isometric knee flexion strength	Change in maximum isometric knee flexion strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	4, 6 months
Maximum isometric knee extension strength	Change in maximum isometric knee extension strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	4, 6 months
Maximum shoulder flexion strength	Change in maximum shoulder flexion strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	4, 6 months
Maximum shoulder extension strength	Change in maximum shoulder extension strength between Mitopure® groups and placebo measured by Biodex dynamometry (unit: Nm)	4, 6 months
Body composition (lean mass)	Change in lean mass between Mitopure® groups and placebo measured by dual-energy X-ray absorptiometry (unit: kg)	4, 6 months
Physical performance (vertical jump)	Change in physical performance between Mitopure® groups and placebo measured by maximum vertical jump height (unit: cm)	4, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular fitness (VO2max)	Change in cardiovascular fitness (VO2max) between Mitopure® groups and placebo measured by a graded exercise test (unit: mL/kg/min)	4, 6 months
Physical capacity (time to exhaustion)	Change in physical capacity between Mitopure® groups and placebo measured by time to exhaustion during the graded exercise test (unit: minutes)	4, 6 months
Physical capacity (maximum cycling distance)	Change in physical capacity between Mitopure® groups and placebo measured by maximum cycling distance during the graded exercise test (unit: meters)	4, 6 months
Physical performance (30-second chair stand)	Change in physical performance between Mitopure® groups and placebo measured by the 30-second chair stand test (unit: repetitions)	4, 6 months
Physical performance (6-minute walk test)	Change in physical performance between Mitopure® groups and placebo measured by the 6-minute walk test (unit: meters)	4, 6 months
Physical performance (timed up-and-go)	Change in physical performance between Mitopure® groups and placebo measured by the timed up-and-go test (unit: seconds)	4, 6 months
Blood acylcarnitine level	Change in blood acylcarnitine level between Mitopure® groups and placebo	6 months
Blood inflammation level	Change in blood inflammatory markers (TNF-alpha, IL-6, hsCRP) between Mitopure® groups and placebo	6 months
Plasma Urolithin A level	Change in plasma Urolithin A level between Mitopure® groups and placebo	6 months
Habitual dietary intake	Change in habitual dietary intake between Mitopure® groups and placebo measured by 3-day diet diary	4, 6 months
Habitual physical activity	Change in habitual physical activity between Mitopure® groups and placebo measured by the International Physical Activity Questionnaire	4, 6 months
Daily fatigue	Change in self-reported daily fatigue between Mitopure® groups and placebo measured by FACIT-Fatigue questionnaire	4, 6 months
Safety (adverse events)	Adverse events monitored throughout trial	6 months

Collaborators and Investigators

• Sponsor: Amazentis SA
• Collaborators: Atlantia Food Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Urolithin A
• Other Study ID Numbers: AFCRO-197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No