Urolithin A (Mitopure)

MitochondrialMuscleLongevity

Triggers mitophagy — the cell's housekeeping process that clears out damaged mitochondria. The first supplement with proper RCT evidence for measurably better muscle function in older adults.

EvidenceModerate (rising fast)

Two well-designed RCTs in older adults showed improved muscle endurance and strength after 4 months of 500 mg/day. Animal data shows extended healthspan and improved muscle / mitochondrial markers. Effects: 8–16 weeks for muscle function.

Urolithin A is a metabolite the gut microbiome makes from ellagitannins found in pomegranate, walnuts, and some berries. Critically, only ~30–40% of people have the right gut bacteria to actually produce it from those foods — for the other 60%, eating pomegranate doesn't deliver any urolithin A at all. Direct supplementation bypasses the gut variability. Its primary effect: triggering mitophagy, the quality-control process that clears out damaged mitochondria so cells can make healthy new ones. Two well-designed human trials (Andreux et al. 2019, 2022) showed measurable improvements in muscle endurance and strength in older adults. Sold under the Mitopure brand (Amazentis / Timeline).

Form
Mitopure (Timeline brand) — the only commercial pure-urolithin-A product with completed RCTs. Generic urolithin A is increasingly available. Pomegranate extracts high in ellagitannins are a precursor-only approach — only works if your microbiome converts.
Dose
500 mg/day (the dose used in published trials). 250 mg is the lower-bound effective dose.
Timing
With a fat-containing meal for absorption. AM typical.
Schedule
Daily.
Side effects
Very well-tolerated in trials. Rare GI upset.
Interactions
Generally clean. Limited interaction data.
Contraindications
Pregnancy / lactation (no data). Active cancer / chemotherapy (theoretical mitochondrial-modulation concern — discuss with oncologist).
Lab markers
Plasma urolithin A (sometimes offered by Timeline as a producer-status test). Functional muscle markers: 6-minute walk distance, grip strength.
Food sources
Pomegranate (juice and arils), walnuts, raspberries, strawberries, blackberries, certain teas. But only converted to urolithin A by ~30–40% of people — most need to supplement directly to see the effect, regardless of how many pomegranates they eat.

Pairs with

CoQ10 + PQQ (mitochondrial trio — supports existing mitochondria, builds new ones, clears damaged ones). NMN / NR (NAD+ support — mitophagy is energy-intensive). Creatine + resistance training for muscle outcomes.