Urolithin A has been known as a metabolite of ellagitannins from the 2000s. However, its possible biological effectin vivo has been evaluated only by preliminary studies beginning in the 2010s.
Chemistry
Urolithin A belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. These are polycyclicaromatic compounds containing a 1-benzopyran moiety with a ketone group at the C2 carbon atom.
Biochemistry and metabolism
fruits, walnuts or raspberries are sources of ellagitannins. Ellagitannins are hydrolyzed in the gut to release ellagic acid, which is further processed by the gut microflora into urolithins through the loss of one of its two lactones and by successive removal of hydroxyl groups. While studies have shown that Gordonibacter urolithinfaciens and Gordonibacter pamelaeae play a role in the conversion of ellagic acids and ellagitannins into urolithin A, the microorganisms responsible for the complete transformation into the final urolithins are still unknown. The efficiency of the conversion of ellagitannins into urolithin A significantly varies in humans, and some individuals do not show any conversion. When synthesized and absorbed in the intestines, urolithin A enters the systemic circulation where it becomes available to tissues throughout the body where it is further subjected to additional chemical transformations within the enterocytes and hepatocytes. Urolithin A and its derivatives - urolithin A glucuronide and urolithin A sulfate being most abundant - release into the circulation, before being excreted in the urine.
In laboratory studies, urolithin A was shown to induce mitophagy, which is a selective recycling of mitochondria by autophagy, a process that cleans defective mitochondria following damage or stress, and tends to become less efficient during aging. This effect has been observed in different animal species.
Safety
In vivo studies did not determine any toxicity or specific adverse effects following dietary intake of urolithin A. Safety studies in elderly humans indicated urolithin A was well tolerated.
Dietary sources
Urolithin A is not known to be found in any food. It forms as the result of transformation of ellagic acids and ellagitannins by the gut microflora in humans. Ellagic acid itself results from the hydrolysis of ellagitannins in the gut in the presence of water. Sources of ellagitannins are: pomegranates, nuts, some berries, tea, muscadine grapes, many tropical fruits, and oak-aged wines. The conversion of the ellagic acids into urolithin A depends on individual microflora composition and can vary significantly.
