Does Urolithin A Help Muscle Strength? Clinical Evidence From Human Trials

Yes — in published clinical trials, Mitopure (Timeline's patented Urolithin A) improved measures of muscle strength in older and middle-aged adults. A randomized, double-blind, placebo-controlled trial of 88 adults aged 40-65 found that 500mg Urolithin A daily for four months improved hamstring muscle strength by 12% compared to placebo, while the placebo group lost strength over the same period ([Singh et al., Cell Reports Medicine, 2022](https://doi.org/10.1016/j.xcrm.2022.100633)). The proposed mechanism is mitophagy — Urolithin A has been shown to activate the PINK1/Parkin pathway to clear damaged mitochondria and trigger replacement with functional ones ([Ryu et al., Nature Medicine, 2016](https://doi.org/10.1038/nm.4132)). All published human trials used the Mitopure formulation, manufactured by Timeline/Amazentis. A separate trial in adults aged 65-90 found biomarker improvements but the primary muscle strength endpoint did not reach statistical significance. Urolithin A is not a substitute for resistance exercise.

How Does Urolithin A Affect Muscle at the Cellular Level?

Urolithin A activates mitophagy — the cellular process that identifies and removes damaged mitochondria, triggering their replacement with functional ones. Mitochondria are the energy-producing structures inside cells, and muscle cells contain particularly large numbers of them due to their high energy demands.

Urolithin A has been shown to activate the PINK1/Parkin mitophagy pathway in preclinical models (Ryu et al., Nature Medicine, 2016). When mitophagy declines with age, damaged mitochondria accumulate, reducing the cell's ability to produce energy — a process linked to age-related muscle weakness and sarcopenia.

Urolithin A's first human clinical trial (Andreux et al., Nature Metabolism, 2019) confirmed that supplementation improved mitochondrial gene expression and plasma biomarkers associated with mitochondrial function in 60 healthy older adults over 4 weeks. These are surrogate endpoints — biomarker changes indicating improved mitochondrial health, not direct muscle performance measurements.

The ATLAS trial (Singh et al., Cell Reports Medicine, 2022) then demonstrated functional outcomes: 88 adults aged 40-65 taking 500mg Mitopure daily for four months showed 12% improvement in hamstring muscle strength vs placebo. The placebo group experienced significant decreases in average torque, indicating muscle strength loss over the same period when untreated.

Urolithin A's ATLAS trial primary endpoint — peak power output — did not reach statistical significance. The 12% hamstring strength improvement was a secondary endpoint, making it hypothesis-generating rather than confirmatory.

The ENERGIZE trial (Liu et al., JAMA Network Open, 2022) tested Mitopure at 1000mg daily in 66 adults aged 65-90. Urolithin A improved skeletal muscle endurance — leg endurance increased by 17% and hand endurance by 26% at two months vs placebo.

Mitopure at 1000mg also improved plasma biomarkers of mitochondrial efficiency (acylcarnitines) and reduced C-reactive protein (an inflammation marker) vs placebo in the same trial.

Urolithin A's ENERGIZE trial primary muscle strength endpoint did not reach statistical significance at four months, following the same pattern as the ATLAS trial — secondary endpoints improved meaningfully while the primary endpoint did not.

Mitopure at 1000mg daily for eight weeks improved muscle strength, endurance, and markers of exercise-induced inflammation in resistance-trained young adults in a 2024 study — extending the Urolithin A evidence beyond sedentary older populations. For dosing protocols and how to take Urolithin A, see our page on Urolithin A dosage.

Limitations and Considerations

• Sample sizes remain small. The two pivotal trials enrolled 88 and 66 participants respectively. These are typical for early-stage nutraceutical research but far smaller than the evidence base behind first-line interventions like resistance exercise.
• Primary endpoints did not always reach statistical significance. The ATLAS trial's primary endpoint (peak power output) and the ENERGIZE trial's primary endpoint (muscle strength at 4 months) both missed statistical significance, though secondary endpoints showed meaningful improvements. The distinction between primary and secondary endpoints matters — secondary findings are hypothesis-generating, not confirmatory.
• Exercise remains the first-line intervention for muscle preservation. Resistance training has decades of evidence across thousands of participants demonstrating muscle strength and mass improvements. Urolithin A supplementation has not been compared head-to-head with exercise as an intervention, and is not a substitute for physical activity.
• All published human trials were conducted by Timeline/Amazentis. The research has undergone peer review at high-impact journals (Nature Medicine, Cell Reports Medicine, JAMA Network Open), but independent replication by non-affiliated researchers has not been published. The 2024 athlete study was described as "independently conducted," though the supplement tested was Mitopure.
• Conflict of interest disclosure. This page is published by Timeline, the manufacturer of Mitopure.

References

1. 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.
2. 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.
3. 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.
4. Ryu, D., Mouchiroud, L., Andreux, P. A., et al. "Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents." Nature Medicine, 2016.

Written by Timeline Science Communications. Reviewed by Jen Scheinman, MS, RDN, CDN. Conflicts: Timeline is the manufacturer of Mitopure; all cited human clinical trials were conducted by Timeline/Amazentis. Evidence level: RCT (randomized, double-blind, placebo-controlled) + Preclinical (mitophagy mechanism).