Urolithin A
/ Gut microbial metabolite of ellagitannins; mitophagy inducer (small molecule)ALIAS · Urolithin A · UA · Mitopure (Amazentis trade)
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Tier 2. Small randomised trials of synthetic urolithin A in older adults: Andreux and colleagues (2019) first-in-human pharmacokinetic and biomarker study; Singh and colleagues (2022) and Liu and colleagues (2022) randomised trials evaluating muscle function and mitophagy biomarkers in middle-aged and older adults. Sold by Amazentis as the dietary supplement Mitopure under the US DSHEA framework; not FDA-approved for any indication.
Urolithin A (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one) is a dibenzopyranone metabolite produced by specific commensal gut bacteria from dietary ellagitannins (pomegranate, walnuts, raspberries, and other polyphenol-rich foods) via sequential hydrolysis to ellagic acid and then progressive dehydroxylation through urolithin M-5, urolithin M-6, urolithin C, and urolithin D intermediates to urolithin A. Production capacity is highly variable across human microbiomes — only roughly one-third to one-half of adults host the requisite consortium, providing the rationale for direct supplementation with synthetic urolithin A rather than relying on dietary precursor conversion.
The principal proposed mechanism is induction of mitophagy — the selective autophagic clearance of damaged mitochondria — at concentrations achievable through oral dosing of synthetic urolithin A. Mechanistic studies in C. elegans and rodent muscle have reported improvements in mitochondrial function and exercise capacity coincident with mitophagy activation; the human translation aims to test whether the same mechanism produces measurable functional benefit in age-related mitochondrial decline.
Tier 2. Andreux and colleagues (2019) reported the first-in-human pharmacokinetic and safety study of synthetic urolithin A (Mitopure) in 60 healthy older adults, demonstrating dose-dependent plasma urolithin A exposure and mitophagy gene expression changes in skeletal muscle biopsies. Singh and colleagues (2022) randomised 88 middle-aged adults to four months of urolithin A versus placebo and reported improvements in muscle endurance and mitochondrial biomarkers. Liu and colleagues (2022) randomised 66 middle-aged to older adults to urolithin A and reported skeletal muscle endurance improvements.
Generally well-tolerated in the published trial doses (250-1000 mg/day for up to four months). Reported adverse events were predominantly mild and gastrointestinal. Long-term safety beyond the durations studied has not been characterised.
Regulatory status
- FDA status:
- Not FDA-approved
The geroscience translation — whether mitophagy induction in skeletal muscle produces meaningful functional benefit at the population scale and over years — remains open. The published trials use surrogate endpoints (muscle endurance tasks, mitochondrial gene expression) rather than hard outcomes; sample sizes are modest and the sponsor (Amazentis) has authored or supported much of the published trial literature, a methodological consideration relevant to interpretation. Dietary precursor approaches (pomegranate, walnut consumption) are confounded by individual microbiome variation in conversion capacity. Vendor positioning frequently extrapolates beyond the controlled trial evidence base to broad anti-aging claims.