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Therapeutics

Urolithin A

Urolithin A is a compound your gut bacteria make. They produce it by transforming ellagitannins and ellagic acid, polyphenols found in pomegranates, walnuts, and berries, using species like Gordonibacter urolithinfaciens. Here is the catch: not everyone carries the right microbes, so eating those foods does not reliably raise urolithin A in every person. The compound triggers mitophagy, the recycling of worn-out mitochondria, partly by inhibiting prohibitin-2 and nudging the PINK1/Parkin pathway. It also improves mitochondrial breathing in lab models. In human trials, a phase I study (Andreux et al., 2019) showed it is safe in older adults. The ATLAS trial (Singh et al., 2022) in overweight middle-aged adults found gains in muscle mitophagy markers, endurance, and strength, but only as secondary outcomes; the main goal (peak power) was missed. Both trials were run by Amazentis, the company that develops it. As for status: it is sold as a dietary supplement in many countries, not approved as a drug, and longer trials are ongoing.

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Sources

  1. Singh A, D'Amico D, Andreux PA et al. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicinedoi:10.1016/j.xcrm.2022.100633
  2. Andreux PA, Blanco-Bose W, Ryu D et al. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolismdoi:10.1038/s42255-019-0073-4

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