urolithin

Urolithin refers to a family of phenolic metabolites produced by gut bacteria from ellagitannins and ellagic acid, compounds found in several fruits and nuts such as pomegranates, raspberries, strawberries, and walnuts. The best-studied member is urolithin A, but urolithin B and related compounds, including isourolithin A and urolithin C, are also detected in humans. In the body, urolithins are mainly present as conjugated forms (glucuronides or sulfates) after intestinal processing and absorption.

Formation and variability: Ellagitannins are hydrolyzed in the gut to ellagic acid, which is then converted by intestinal microbes into urolithins. The resulting metabolite profile varies between individuals due to differences in gut microbiota composition, a phenomenon described as urolithin metabotyping. Some people predominantly produce urolithin A, others generate urolithin B and related metabolites, while some produce a mix.

Bioavailability and metabolism: Urolithins are absorbed primarily as conjugates in the systemic circulation and are excreted in urine and feces. The pharmacokinetic profile depends on the specific urolithin and the individual's microbiome and liver metabolism.

Biological relevance: In preclinical studies, urolithins, particularly urolithin A, have shown anti-inflammatory and antioxidant effects and the ability to induce mitophagy, the selective removal of damaged mitochondria. These findings have spurred interest in aging, muscle function, and metabolic health, though most evidence comes from cell or animal models.

Clinical evidence and safety: Human studies are limited and results are variable. Some trials with urolithin A supplementation or ellagitannin-rich diets report modest improvements in mitochondrial function or physical performance in older adults, but findings are not consistent. Urolithins appear generally well tolerated in clinical assessments, with long-term safety not yet established.