The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans
Open accessAbstract
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 aging 1. 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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Administration of urolithin A in the first-in-human clinical trial is safe and induces a molecular signature of mitochondrial health in the skeletal muscle of healthy sedentary elderly individuals.
“Administration of urolithin A in the first-in-human clinical trial has also been shown to be safe and to induce a molecular signature of mitochondrial health in the skeletal muscle of healthy sedentary elderly individuals [161].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [161]
Oral administration of urolithin A improves mitochondrial function and promotes muscle health in the elderly.
“Moreover, oral administration of urolithin A improves mitochondrial function and promotes muscle health in the elderly [94].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [94]
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- Authors
- Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C.
- Affiliations
- Amazentis (Switzerland) (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Rinsch, Chris
- ORCID
- Venue
- Nature Metabolism
- Published
- 2019-06-14
- Volume
- 1
- Issue
- 6
- Pages
- 595-603
- ISSN
- 2522-5812 (ISSN-L)
- OpenAlex
- W2951032968
- Cited by
- 590
- References
- 30
- Citations by year
- 2026: 118 · 2025: 100 · 2024: 78 · 2023: 72 · 2022: 94 · 2021: 61 · 2020: 54 · 2019: 12
- FWCI
- 42.06
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- urolithin A, mitophagy, mitochondrial health, skeletal muscle, aging, older adults, safety, bioavailability, acylcarnitines, mitochondrial gene expression, gut microbiota metabolites
- MeSH terms
- Aged, Coumarins, Dose-Response Relationship, Drug, Humans, Mitochondria, Sedentary Behavior, Mitophagy
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