What is urolithin A and does it work?
Urolithin A shows cautiously positive signals for muscular endurance in two small randomised studies in older and middle-aged adults, but the primary endpoints were not met and the studies come almost entirely from the manufacturer. It is interesting enough to follow, but too early to say with confidence that the supplement produces measurable health benefits.
Urolithin A is a substance produced by your gut bacteria from plant polyphenols found in pomegranate, berries and nuts. It is therefore not a vitamin or nutrient you take in directly, but a conversion product of your gut microbiome. That makes it unusual: not everyone produces it equally well. Researchers recognise three types of people based on their gut microbiome, with a proportion producing virtually no urolithin A, even when they eat pomegranate. A supplement bypasses that step.
The main mechanism for which urolithin A receives attention is mitophagy: the process by which cells clear out and renew damaged energy factories (mitochondria). That this process is biologically activated in humans was shown by several clinical studies measuring blood markers and gene expression in muscle cells. These are indirect measures, not direct measurements of strength or fitness.
Two randomised, placebo-controlled studies in humans present a mixed picture. In 66 older adults with an average age of 71, muscular endurance in the hand and leg muscles improved significantly versus placebo after just two months. However, that same study did not meet its two primary endpoints: the six-minute walk test and maximum energy production in muscles did not improve demonstrably. A second study in middle-aged adults found an improvement in muscle strength of approximately 12% and better scores on fitness measurements after four months, but here too the primary endpoint (peak muscle function) remained out of reach. Both studies did observe a reduction in an inflammatory marker in the blood. Safety was good across all clinical tests: no noteworthy adverse effects were reported.
In animal models of the muscle disease Duchenne muscular dystrophy, promising results have been seen, but no clinical trials in patients with that condition have yet been conducted.
A serious caveat: most clinical studies were sponsored by or conducted in collaboration with Amazentis, the company behind the commercial urolithin A supplement. Independent confirmation by other research groups is largely absent. In addition, reviewers caution that many laboratory studies in cells used concentrations that the body would never actually reach, which means that certain reported effects from that type of research should be viewed with scepticism.
Two RCTs in humans (PMID 35050355, 35584623), one clinical safety study (PMID 32694802), four reviews (PMID 34030963, 35118817, 35142569, 37892516), and one non-indexed study in animal models/cells (PMID 33827972). No meta-analyses available. Commercial conflict of interest in the clinical studies is a genuine risk for interpretation.