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Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Singh A, D'Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, Aebischer P, Auwerx J, Rinsch C
Cell Reports Medicine 2022 3(5):100633

Bibliography

PubMed
PMID 35584623
PubMed Central
PMC9133463
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
Authors Singh, D'Amico, Andreux, Fouassier, Blanco-Bose, and Rinsch are employees of Amazentis SA, the commercial developer of urolithin A.

Study snapshot

DesignRandomised, double-blind, placebo-controlled trial (NCT03464500)
ModelHuman — sedentary middle-aged adults
Sample88
InterventionOral urolithin A (Mitopure), 500 mg or 1,000 mg daily, vs placebo, for 4 months
Duration4 months
EndpointsPrimary: peak power output (leg press); Secondary: leg muscle strength; Secondary: aerobic endurance (peak VO2); Secondary: 6-minute walk test; Secondary: plasma acylcarnitines and C-reactive protein; Secondary: skeletal muscle mitophagy/mitochondrial protein expression

What the study showed, in plain terms

This trial tested urolithin A for muscle function in middle-aged adults. Its own stated primary goal — peak power output — did not improve significantly. Several secondary measures did: muscle strength rose by about 12%, and aerobic endurance and walking distance also improved, alongside markers of better mitochondrial efficiency and lower inflammation.

Key findings

Urolithin A did not significantly improve the trial's stated primary endpoint, peak power output. It did significantly improve several secondary endpoints: leg muscle strength (approximately 12%), peak VO2 (aerobic endurance), and 6-minute walk distance, alongside reductions in plasma acylcarnitines and C-reactive protein and increased mitophagy-related muscle protein expression.

What this study can and cannot tell us

The trial's own designated primary endpoint (peak power output) was not met. The positive results reported are secondary and exploratory endpoints, which carry a higher risk of false positives and should be read as hypothesis-generating rather than confirmatory. Industry-sponsored, with the majority of authors employed by the company commercialising urolithin A.

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