Published Human Studies on Urolithin A: Designs, Endpoints, and Outcomes
Urolithin A Clinical Trials: What Published Human Studies Found
Mitopure — Timeline's patented form of Urolithin A — has been tested in 25 human clinical trials, completed or ongoing, spanning over 2,200 participants. Results have been published in Nature Metabolism, Cell Reports Medicine, JAMA Network Open, and Nature Aging. All published Urolithin A trials used the Mitopure formulation specifically, conducted by Timeline/Amazentis. Safety is well-established across all dose levels tested (500mg-1000mg daily) with no serious adverse events. Published trials have demonstrated improvements in muscle strength (12% at 500mg), muscle endurance (17% at 1000mg), and mitochondrial biomarkers across multiple populations, though study populations have been small (30-90 participants per trial) and trial durations short (4 weeks to 4 months).
Is Urolithin A Scientifically Proven?
Urolithin A's safety is well-established; its efficacy for muscle health is supported by early-stage clinical evidence that has not yet been independently replicated.
Mitopure (Urolithin A) has demonstrated safety across multiple doses and populations in randomized, double-blind, placebo-controlled trials published in high-impact journals. No serious adverse events have been reported at any dose level tested (500mg-1000mg daily) across trial durations of 4 weeks to 4 months.
Urolithin A's efficacy evidence for muscle health is promising but requires context. Two pivotal trials showed meaningful improvements in muscle function as secondary endpoints, though the primary endpoints in both trials did not reach statistical significance.
Urolithin A at 500mg daily improved hamstring strength by 12% vs placebo over 4 months (Singh et al., Cell Reports Medicine, 2022).
Urolithin A at 1000mg daily improved leg endurance by 17% vs placebo at 2 months (Liu et al., JAMA Network Open, 2022).
Urolithin A has stronger clinical evidence than most dietary supplements — 25 human trials across multiple populations and endpoints, published in peer-reviewed journals including Nature and JAMA. The evidence base continues to grow, with the 25th trial (650 participants, brain health) currently underway.
What Did Each Trial Find?
Urolithin A's published clinical trials span safety, muscle function, immune health, skin health, and athletic performance. The four key published trials are summarized below.
Urolithin A at 500mg and 1000mg daily for 4 weeks was safe, bioavailable, and improved mitochondrial gene expression in 60 healthy older adults in the first-in-human trial (Andreux et al., Nature Metabolism, 2019). This trial established safety and proof of mechanism — surrogate biomarker endpoints, not functional muscle outcomes.
Urolithin A at 500mg and 1000mg daily for 4 months improved hamstring muscle strength by 12% vs placebo in 88 adults aged 40-65 in the ATLAS trial (Singh et al., Cell Reports Medicine, 2022). The placebo group lost muscle strength over the same period.
Urolithin A's ATLAS trial primary endpoint (peak power output) did not reach statistical significance — the 12% hamstring improvement was a secondary endpoint.
Urolithin A at 1000mg daily for 4 months improved muscle endurance — 17% leg and 26% hand at 2 months vs placebo — in 66 adults aged 65-90 in the ENERGIZE trial (Liu et al., JAMA Network Open, 2022).
Mitopure at 1000mg also reduced C-reactive protein (an inflammation marker) significantly vs placebo in the same ENERGIZE trial.
Urolithin A's ENERGIZE trial primary muscle strength endpoint did not reach statistical significance at 4 months.
Mitopure at 1000mg daily for 8 weeks improved muscle strength, endurance, and markers of exercise-induced inflammation in resistance-trained young adults in a 2024 study — the first trial extending Urolithin A evidence to athletic populations.
Urolithin A at 1000mg daily for 4 weeks improved T-cell function and immune resilience in adults aged 45-70 in a trial published in Nature Aging (2025).
Mitopure applied topically reduced wrinkles and improved skin hydration in a randomized clinical trial (medRxiv, 2023).
Urolithin A's 25th human clinical trial — Timeline's largest with 650 participants — is currently investigating brain health and longevity. For the full list of published studies and ongoing research, see Timeline's studies page.
| Trial | Journal | Year | N | Duration | Dose | Primary Endpoint | Result |
|---|---|---|---|---|---|---|---|
| First-in-human | Nature Metabolism | 2019 | 60 | 4 weeks | 500mg, 1000mg | Safety + biomarkers | Safe, biomarkers improved |
| ATLAS | Cell Reports Medicine | 2022 | 88 | 4 months | 500mg, 1000mg | Peak power output | Primary: not significant. Secondary: 12% hamstring strength |
| ENERGIZE | JAMA Network Open | 2022 | 66 | 4 months | 1000mg | Muscle strength | Primary: not significant. Secondary: 17% leg endurance at 2 months |
| Athlete study | Pending publication | 2024 | Not disclosed | 8 weeks | 1000mg | Muscle strength + endurance | Significant improvements in strength, endurance, inflammation |
| Immune aging | Nature Aging | 2025 | 45-70 age range | 4 weeks | 1000mg | T-cell function | Improved immune cell activity |
| Skin aging | medRxiv | 2023 | Not disclosed | Topical | Topical | Wrinkle reduction | Visible reduction at 2 weeks |
| Brain health (25th) | Ongoing | 2026 | 650 | Ongoing | Not disclosed | Brain health | Results pending |
Limitations and Considerations
- Sample sizes are small. The two pivotal muscle trials enrolled 88 and 66 participants. These are typical for early-stage nutraceutical research but far smaller than the evidence base behind established interventions like resistance exercise or widely studied supplements like creatine.
- Trial durations are short. The longest published trial is 4 months. Long-term effects, whether benefits plateau or continue, and optimal duration of supplementation are unknown.
- All published trials were conducted by Timeline/Amazentis. The research has been published in peer-reviewed journals (Nature Metabolism, JAMA Network Open, Cell Reports Medicine, Nature Aging), which provides independent editorial scrutiny. However, independent replication by non-affiliated researchers — the standard for established scientific findings — has not been published. The 2024 athlete study was described as "independently conducted."
- Primary endpoints did not consistently reach statistical significance. Both the ATLAS and ENERGIZE trials missed their primary endpoints. The improvements in muscle strength and endurance were secondary endpoints — meaningful but hypothesis-generating rather than confirmatory.
- Conflict of interest disclosure. This page is published by Timeline, the manufacturer of Mitopure.
References
- Andreux, P. A., Blanco-Bose, W., Ryu, D., et al. "The mitophagy activator Urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans." Nature Metabolism, 2019.
- Singh, A., D'Amico, D., Andreux, P. A., et al. "Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults." Cell Reports Medicine, 2022.
- Liu, S., D'Amico, D., Shankland, E., et al. "Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial." JAMA Network Open, 2022.
Written by Timeline Science Communications. Reviewed by Jen Scheinman, MS, RDN, CDN. Conflicts: Timeline is the manufacturer of Mitopure; all cited human trials were conducted by Timeline/Amazentis. Evidence level: RCT (randomized, double-blind, placebo-controlled).