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Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial

Liu S, D'Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, Rinsch C, Singh A, Marcinek DJ
JAMA Network Open 2022 5(1):e2144279

Bibliography

PubMed
PMID 35050355
PubMed Central
PMC8777576
DOI
10.1001/jamanetworkopen.2021.44279
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
Sponsored by Amazentis SA, the company that developed and commercialises urolithin A (marketed as Mitopure). Several authors are Amazentis employees.
Competing interests
Co-authors D'Amico, Rinsch, and Singh are employees of Amazentis SA, the commercial developer of urolithin A.

Study snapshot

DesignRandomised, double-blind, placebo-controlled trial (NCT03283462)
ModelHuman — adults aged 65-90
Sample66
InterventionOral urolithin A, 1,000 mg daily, vs placebo, for 4 months
Duration4 months (assessments at baseline, 2 months, 4 months)
EndpointsPrimary: change in 6-minute walk distance; Primary: change in maximal ATP production (hand muscle, MRS); Secondary: muscle endurance/contraction counts (FDI and TA muscles); Secondary: plasma acylcarnitines, ceramides, C-reactive protein

What the study showed, in plain terms

This trial tested urolithin A in older adults for walking distance and mitochondrial energy production — its two primary goals. Neither improved significantly compared with placebo. A secondary measure, muscle endurance, did improve at the 2-month mark, and some blood biomarkers moved in a favourable direction, but the trial's own stated main goals were not met.

Key findings

Urolithin A supplementation did not significantly improve either pre-specified primary endpoint — 6-minute walk distance or maximal ATP production in hand skeletal muscle — compared with placebo. A secondary endpoint, muscle endurance (contraction counts) in the first dorsal interosseus and tibialis anterior muscles, was significantly improved with urolithin A at the 2-month assessment. Plasma acylcarnitines, ceramides, and C-reactive protein were also reduced.

What this study can and cannot tell us

Both pre-specified primary endpoints were null. The positive finding is limited to a secondary endpoint at an interim (2-month) timepoint rather than the full 4-month primary analysis, and the authors state future work is needed to confirm it. Industry-sponsored, with several authors employed by the company commercialising urolithin A.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability