Urolithin A

Urolithin A is not found directly in food — it is produced by specific gut bacteria (Gordonibacter and Ellagibacter species) when they metabolize ellagitannins, polyphenols found in pomegranates, walnuts, and berries. However, only about 30-40% of people have the gut microbiome composition to produce meaningful amounts naturally — making direct supplementation valuable for the majority.

First brought to widespread attention through research from the Amazentis company and the Ecole Polytechnique Fédérale de Lausanne (EPFL), Urolithin A has been clinically studied in humans and shown to improve mitochondrial function and muscle health in ways previously only achievable through caloric restriction or intense exercise.

Urolithin A's primary mechanism is the activation of mitophagy — the cellular process of selectively
clearing damaged mitochondria and replacing them with healthy new ones:

- Mitophagy activation — triggers PINK1/Parkin pathway, the cellular quality control system that identifies
and removes dysfunctional mitochondria
- Mitochondrial biogenesis — promotes the growth of new, healthy mitochondria through AMPK and PGC-1α
activation
- Muscle health — clinical studies show improved muscle endurance, strength, and reduced
inflammatory markers in older adults
- Cellular energy — by improving mitochondrial quality and quantity, cells produce ATP more
efficiently
- Anti-inflammatory — reduces systemic inflammatory markers through NF-κB inhibition and other pathways
- Longevity signaling — activates several pathways associated with healthy aging and cellular resilience

Urolithin A has an excellent safety profile with growing clinical validation:

- Very well tolerated in all published human clinical trials to date
- No significant adverse effects reported at doses up to 2,000mg daily in safety studies
- One of the few longevity compounds with actual human clinical trial data
- Generally recognized as safe — received GRAS status in the United States
- May interact with immunosuppressant medications — consult your doctor
- Long-term human safety data still accumulating as a relatively novel supplement ingredient
- Pregnant or nursing women should consult a healthcare provider before use

- Andreux et al. (2019) — Landmark randomized controlled trial published in Nature Metabolism found
Urolithin A supplementation (500-1000mg daily) significantly improved mitochondrial gene expression
and muscle endurance in older adults — the first human evidence of mitophagy activation by a
nutritional compound.

- Singh et al. (2022) — Randomized double-blind trial in European Journal of Sport Science found Urolithin A supplementation significantly improved muscle strength and endurance performance in middle-aged adults compared to placebo.

- Ryu et al. (2016) — Published in Nature Medicine, showed Urolithin A extended lifespan and improved
muscle function in C. elegans and rodent models through mitophagy activation.

- Liu et al. (2020) — Research demonstrated Urolithin A reduced neuroinflammation and amyloid-beta
accumulation in Alzheimer's disease models, suggesting neuroprotective potential.