Urolithin A
A gut microbiome metabolite produced from ellagitannins in pomegranate and walnuts. The most clinically validated mitophagy inducer — clears damaged mitochondria and drives mitochondrial biogenesis. Phase 2 clinical trial data demonstrates improved muscle endurance in older adults.
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What Is Urolithin A?
Urolithin A is a compound produced by gut bacteria when they metabolise ellagitannins — polyphenols found in pomegranates, walnuts, and certain berries. The critical insight is that only ~40% of people have the gut microbiome composition needed to produce meaningful amounts of Urolithin A from dietary sources — making supplementation relevant even for those eating polyphenol-rich diets.
It is the most clinically validated mitophagy inducer currently available as a supplement, with Phase 1 and Phase 2 human trial data supporting both safety and efficacy.
Mechanism: Mitophagy
Mitophagy is the selective autophagy of damaged mitochondria. As mitochondria age or sustain damage, they become less efficient and begin producing excess reactive oxygen species (ROS). The cell's quality control system — the PINK1/Parkin pathway — tags these dysfunctional mitochondria for removal.
Urolithin A is a potent activator of this PINK1/Parkin pathway. By clearing damaged mitochondria and stimulating biogenesis of new ones (via PGC-1α upregulation), it effectively rejuvenates the cellular energy infrastructure.
Clinical Evidence
Phase 1 trial (Ryu et al., Nature Medicine, 2016): Demonstrated safe oral bioavailability and dose-dependent mitophagy gene expression in human muscle biopsies. First human proof-of-concept for dietary mitophagy induction.
Phase 2 RCT (Singh et al., European Urology, 2022): 66 sedentary older adults randomised to Urolithin A 500mg, 1000mg, or placebo for 4 months. The 1000mg group showed significantly improved muscle endurance (walking distance), increased mitochondrial gene expression, and reduced inflammatory markers.
This is Oxford Level 2b evidence — the highest available for any supplement-grade mitophagy inducer.
Dosage
| Parameter | Recommendation |
|---|---|
| Dose | 500–1000 mg/day |
| Timing | Morning |
| Cycling | Daily, continuous |
| Form | Standardised supplement (Timeline Nutrition, etc.) |
Related Research
Stacking Interactions
How Urolithin A interacts with other compounds
Safety Profile — Tier A
Well-tolerated — strong human evidence
Contraindications
- ●Pregnancy and breastfeeding (insufficient data)
Side Effects
- ●Excellent safety profile in human trials
- ●Mild GI discomfort in a small percentage of users
- ●No serious adverse events in Phase 1/2 trials