Urolithin A is a compound generated by gut microflora from ellagitannins. The compounds are hydrolyzed in the stomach into ellagic acid, which is subsequently converted by the gut microflora into urolithin A. However, not everyone has the right microflora to be able to make the metabolite.
As reported last year by NutraIngredients-USA, start-up life sciences company Amazentis has developed a method to deliver finely calibrated doses of urolithin A. Preliminary data published in Nature Medicine indicated that urolithin A may improve mitochondrial function by stimulating mitophagy, a process by which damaged mitochondria are recycled to permit a renewal with healthy mitochondria. These potent beneficial effects were observed in C. elegans, mammalian cells and rodents.
Scientists from Exponent, Inc. and Amazentis have now reported that the compound does not, “indicate any target organ toxicities at the histopathological level, nor any specific toxic mechanisms,” when tested in repeated dose 28- and 90-day studies. The data also showed there was no genotoxicity after oral consumption.
The scientists concluded that, based on their data the no observable adverse effect level (NOAEL) was the highest dose tested, equivalent to 3451 mg per kilogram of body weight per day in males and 3826 mg per kg of body weight per day in females.
“This study describes for the first time the safety profile of direct oral exposure to [urolithin A] in preclinical models using an extensive battery of tests,” they wrote in Food and Chemical Toxicology.
Safety, bioavailability, and biological activity
In addition to the toxicological studies, data from a Phase 1 trial in healthy elderly individuals presented at the recent International Conference on Frailty and Sarcopenia Research (ICFSR) in Barcelona, Spain supported the safety, bioavailability, and biological activity of the compound.
The trial found that oral supplementation with urolithin A did not result in any serious or any product-related non-serious adverse events. The data also supported that urolithin A was bioavailable to blood and skeletal muscle, and that it upregulated mitochondrial gene expression in elderly skeletal muscle tissue.
For more information, please read our earlier article HERE.
Source: Food and Chemical Toxicology
Published online ahead of print, doi: 10.1016/j.fct.2017.07.050
“Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid”
Authors: J. Heilman et al.