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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
Sponsored by Amazentis SA, the company that developed and commercialises urolithin A (marketed as Mitopure). Several authors are Amazentis employees or founders.
Competing interests
Authors Andreux, Blanco-Bose, Singh, and Rinsch are employees of Amazentis SA, the commercial developer of urolithin A. This is an industry-sponsored, industry-authored trial.

Study snapshot

DesignRandomised, double-blind, placebo-controlled, dose-ranging trial (single-dose cohort and 4-week repeated-dose cohort)
ModelHuman — healthy, sedentary older adults
Sample60
InterventionOral urolithin A at 250 mg, 500 mg, or 1,000 mg (single dose or repeated daily over 4 weeks) vs placebo
Duration4 weeks (repeated-dose arm)
EndpointsPrimary: safety and tolerability; Secondary: plasma acylcarnitines; Secondary: skeletal muscle mitochondrial gene expression

What the study showed, in plain terms

The first human trial of urolithin A found it safe and well tolerated at doses up to 1,000 mg daily. At the higher doses it also shifted blood and muscle biomarkers in a direction consistent with improved mitochondrial function, though no functional muscle outcome was measured in this trial.

Key findings

Urolithin A met its primary safety and tolerability endpoint across all doses tested. Secondary analyses showed that 500 mg and 1,000 mg doses over 4 weeks modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in a pattern consistent with mitophagy induction. No functional or clinical muscle-performance outcome was assessed in this trial.

What this study can and cannot tell us

Small trial (n=60), short 4-week duration, and biomarker/mechanistic endpoints only — no functional muscle or clinical outcome was tested. 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