Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging1. Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.
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The gene expression data are deposited at the European Genome-phenome Archive under accession code EGAS00001003638 and can be accessed subject to signing a data access agreement.
The authors declare the following competing interests: A.S., P.A.A., W.B. and C.R. are employees; P.A. and C.R. are board members; and J.A. and P.A. are members of the Scientific Advisory Board of Amazentis SA, the sponsor of this clinical study. The other authors declare no competing interests.
Journal peer review information: Primary Handling Editor: Christoph Schmitt.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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We would like to thank the volunteers for their participation in the study and Eurofins Optimed study staff for subject recruitment, data collection and processing, and S. Houten for his insight on the acylcarnitine data. Grant support by the Fondation Suisse de Recherche sur les Maladies Musculaires and the Fondation Marcel Levaillant is acknowledged.