Urolithin A (Mitopure)
Gut-microbiota-derived ellagitannin metabolite with preliminary RCT signal for muscle endurance and mitophagy markers, first 'mitophagy-inducer' supplement to reach clinical trials.
Why
Urolithin A is produced by gut microbiota from dietary ellagitannins in pomegranate, walnuts and berries. About 40% of people have the gut bacteria to produce it endogenously, non-producers must consume it directly. The first human RCTs (Andreux Nat Metab 2019, Singh JAMA Netw Open 2022) confirmed mitophagy marker improvements and modest muscle endurance gains in older sedentary adults at 500–1,000 mg/day. Disease-endpoint outcome data is not yet available.
How it works
Selective mitophagy inducer, promotes clearance of damaged mitochondria via PINK1/Parkin pathway. Effect documented in skeletal muscle, brain and intestinal stem cells in animal models. The first compound-class supplement to be positioned around 'mitophagy'.
Expected onset · Muscle endurance effects over 4 months in published trial; mitophagy markers within weeks
How to take
Dosage
500–1,000 mg/day, single dose. Trials use 500 mg/day for endurance endpoints.
Timing
Once daily with food
On the label
Mitopure (the Amazentis-trademarked form) is the trial-grade urolithin A. Dietary precursors (pomegranate, walnuts, berries) produce urolithin A only in the ~40% of people with the right gut microbiota.
Ideal for
Older sedentary adults exploring muscle and mitochondrial-focused interventions; people with low natural urolithin A production (non-producer phenotype).
Safety
Evidence
Andreux 2019 Nat Metab RCT (n=60 older adults): urolithin A 500–1,000 mg/day for 4 weeks induced mitophagy gene-expression signature in muscle. Singh 2022 JAMA Netw Open RCT (n=88) confirmed sustained plasma elevation and skeletal muscle mitochondrial improvements at 4 months. Preliminary evidence, no Cochrane review, EMA HMPC monograph or EFSA-authorised health claim covers this indication; cited RCTs are small or in non-tier-1 journals. Useful as honest reference rather than evidence-grade recommendation.
First-in-class mitophagy supplement, long-term outcome data not yet available. No Cochrane review, no EMA monograph. Cost is high relative to other longevity supplements.
- Andreux et al., Nat Metab 2019, the mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans (RCT)
- Singh et al., JAMA Netw Open 2022, direct supplementation with urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population (RCT)
- Ryu et al., Nat Med 2016, urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents (preclinical)
Where to get it
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