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The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans

Andreux PA, Blanco-Bose W, Ryu D, Burdet F, Ibberson M, Aebischer P, Auwerx J, Singh A, Rinsch C
Nature Metabolism 2019 1(6):595-603

Bibliography

PubMed
PMID 32694802
DOI
10.1038/s42255-019-0073-4
Funding
Not disclosed as a separate statement in the sections of the article reviewed for this entry. The study product was supplied by Amazentis SA, whose employees make up the majority of the author list — see the competing-interests note for the relevant disclosure this implies.
Competing interests
Not disclosed as a separate statement in the sections of the article reviewed for this entry. Readers should weigh this alongside a directly relevant fact visible in the author affiliations: the study product, Urolithin A (Mitopure), is manufactured by Amazentis SA, and the majority of the author list — including both lead/corresponding authors — are Amazentis SA employees. This is a company-run and company-authored trial of the company's own product, not an independent academic trial.

Study snapshot

DesignFirst-in-human randomised, controlled trial (single-dose and 4-week multiple-dose phases)
ModelHealthy, sedentary elderly individuals
SampleNot fully specified in the extracted abstract; single-dose and 4-week multiple-dose cohorts across a dose range up to 1,000 mg
InterventionOral urolithin A at multiple doses (single dose, then repeated dosing at 250mg-1,000mg over 4 weeks)
Duration4 weeks (multiple-dose phase)
EndpointsSafety and tolerability (primary); Plasma bioavailability of urolithin A; Plasma acylcarnitine biomarkers; Skeletal muscle mitochondrial gene expression

What the study showed, in plain terms

This 2019 study was the first time urolithin A — a gut-bacteria-derived metabolite of foods like pomegranate — was given to people in a controlled human trial. The main question was simple: is it safe?

The answer was yes, at all doses tested, in healthy but sedentary elderly volunteers. Beyond safety, the researchers found urolithin A was detectable in the blood after dosing, and that 4 weeks of treatment at 500mg or 1,000mg changed blood fat-metabolism markers (acylcarnitines) and gene activity in muscle tissue in a direction consistent with improved mitochondrial function.

This is a safety and biomarker study, not a muscle-strength or clinical-outcome trial — that came in later studies from the same research group. It is also worth being transparent that this is a company-sponsored, company-authored study of the company's own product (urolithin A, marketed as Mitopure, made by Amazentis SA) — a real limitation on how much independent weight to give it, even though the biomarker findings themselves appear methodologically sound.

Key findings

  • Favourable safety profile at all doses tested: urolithin A was well tolerated as both a single dose and over 4 weeks of repeated dosing in elderly volunteers, meeting the study's primary safety outcome.
  • Confirmed oral bioavailability: urolithin A was detectable in plasma at all doses tested, confirming the compound is absorbed after oral administration.
  • Biomarker changes consistent with improved mitochondrial function: 4 weeks of treatment at 500mg and 1,000mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in a direction the authors interpret as a molecular signature of improved cellular health.

What this study can and cannot tell us

Sponsor-run and sponsor-authored. This is a study of Amazentis SA's own product, conducted and written by a majority-Amazentis author list. That does not make the findings wrong, but it is a material fact readers should weigh, and independent replication carries more evidentiary weight.

Biomarker, not functional, endpoints. This trial measured safety, bioavailability, and molecular/biomarker changes — not muscle strength, physical performance, or any hard clinical outcome.

Small, short, and narrowly generalisable. A 4-week trial in a specific elderly, sedentary population does not establish long-term safety or benefit in broader populations.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability