Urolithin A

Urolithin A is a gut-derived metabolite produced when colonic bacteria transform ellagitannins and ellagic acid — polyphenols found in pomegranates, walnuts, and berries — via species such as Gordonibacter urolithinfaciens; because the requisite microbiome varies between individuals, dietary ellagitannin intake does not reliably raise urolithin A levels in all people. The compound activates mitophagy through mechanisms including inhibition of prohibitin-2 and indirect PINK1/Parkin pathway engagement, and improves mitochondrial respiration in preclinical models. In human randomized trials, a phase I safety and biomarker study (Andreux et al., 2019) established tolerability in older adults, while the ATLAS trial (Singh et al., 2022) in overweight middle-aged adults showed improvements in skeletal muscle mitophagy markers, aerobic endurance, and muscle strength as secondary endpoints; the primary endpoint (peak power output) was not met, and both trials were conducted by Amazentis, the commercial developer. Regulatory status: sold as a dietary supplement in many countries; not approved as a drug; longer-term safety and efficacy trials are ongoing.