Tier 3 — preclinical

Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid

Heilman J, Andreux P, Tran N, Rinsch C, Blanco-Bose W
Food and Chemical Toxicology 2017 108(Pt A):289-297

Bibliography

PubMed
PMID 28757461
DOI
10.1016/j.fct.2017.07.050
Competing interests
Andreux, Rinsch and Blanco-Bose were affiliated with Amazentis SA; the study is part of the commercial Urolithin A development program.

Study snapshot

DesignGenotoxicity battery plus oral toxicokinetic and 28-day/90-day repeated-dose rat safety studies
ModelIn vitro genotoxicity systems and rats
SampleMultiple standard toxicology cohorts
InterventionSynthetic Urolithin A across escalating dietary doses up to 5% by weight
Duration28 and 90 days for repeated-dose studies
EndpointsGenotoxicity; Toxicokinetics; Clinical observations; Blood chemistry and hematology; Target-organ toxicity; NOAEL

What the study showed, in plain terms

This was the foundational formal safety assessment for direct Urolithin A administration. It found no genotoxic signal and no target-organ toxicity in repeated-dose rat studies up to the highest tested dose, while showing that glucuronide and sulfate conjugates dominate systemic metabolism. It supports the early safety package but does not replace human long-term safety data.

Key findings

Urolithin A was not genotoxic in the test battery.

Repeated-dose rat studies found no specific target-organ toxicity at the tested doses.

The highest tested 90-day dose was the NOAEL.

Glucuronidated and sulfated metabolites predominated after exposure.

What this study can and cannot tell us

Animal toxicology cannot establish multi-year human safety.

Doses were far above common supplement doses and should not be directly translated to humans.

Commercial Amazentis affiliations were present.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

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