Urolithin A

What is urolithin A?

Urolithin A is a postbiotic compound your body makes when certain gut bacteria break down ellagitannins and ellagic acid from foods like pomegranates, walnuts, raspberries, and strawberries. It doesn't exist in any food directly. Instead, it's produced through a multi-step microbial conversion in the colon: punicalagin (concentrated in pomegranate) gets hydrolyzed to ellagic acid, which gut bacteria then transform into several urolithins. Urolithin A is the most bioactive of these.

Here's the catch: only about 40% of people have the right gut bacteria to make urolithin A efficiently ^[1]. The key species include Gordonibacter urolithinfaciens, certain Bifidobacterium strains, and Enterocloster species that carry a specific dehydroxylase enzyme. People who do produce it tend to have greater microbiome diversity and more Firmicutes relative to Bacteroidetes. This huge variability in natural production is exactly why direct urolithin A supplementation has gained traction.

How urolithin A works: mitophagy activation

The main reason urolithin A matters for aging is its ability to trigger mitophagy, the process by which cells identify and recycle damaged mitochondria. With age, mitophagy slows down. Broken mitochondria pile up, cellular energy production drops, oxidative stress rises, and chronic low-grade inflammation sets in. These are textbook hallmarks of aging.

Urolithin A ramps up mitophagy through two routes. First, it boosts the PINK1/Parkin pathway, where PINK1 and Parkin proteins tag damaged mitochondria with ubiquitin for disposal. Second, it activates PINK1/Parkin-independent mitophagy receptors. On top of clearing out the old, urolithin A also dials down mTOR signaling (shifting cells from growth mode to maintenance), activates AMPK, and raises PGC-1a levels to stimulate the production of fresh mitochondria ^[2].

Clinical evidence for muscle strength and endurance

Human trial data is what sets urolithin A apart from many other longevity supplements. In a randomized, placebo-controlled trial, middle-aged adults taking 500 mg or 1,000 mg daily for four months saw a 12% improvement in hamstring muscle strength versus placebo. They also showed gains in aerobic endurance (VO2 peak) and six-minute walk distance. Blood markers confirmed the mechanism: acylcarnitine and C-reactive protein both dropped, pointing to better mitochondrial efficiency and less systemic inflammation ^[3].

A 2024 systematic review covering five human studies with 250 participants (doses from 10 to 1,000 mg/day) confirmed the dose-dependent anti-inflammatory effect and improvements in muscle strength and endurance ^[4]. A separate 2025 meta-analysis on muscle outcomes found a pooled +23 meter gain in six-minute walk distance, though this didn't reach statistical significance. In athletes, an 8-week trial in resistance-trained men showed improvements in protein metabolism markers and reduced exercise-induced inflammation ^[5].

Benefits beyond muscle: heart, brain, and immune system

Recent research has expanded well beyond muscle health. A 2025 study published in iScience found that urolithin A reduced both systolic and diastolic cardiac dysfunction in aging models and heart failure, with recovery of mitochondrial structural defects. In humans, four months of supplementation significantly lowered plasma ceramides, which are validated predictors of cardiovascular disease risk ^[6].

For immune function, a randomized trial showed that 1,000 mg/day for four weeks expanded naive CD8+ T cells, increased natural killer cell populations, and improved monocyte bacterial uptake in healthy middle-aged adults ^[7]. This matters because immune decline (immunosenescence) is a major driver of age-related disease.

Neurological research is earlier-stage but promising. A 2024 study showed five months of urolithin A treatment improved learning, memory, and olfactory function in Alzheimer's disease mouse models while reducing tau pathology and neuroinflammation ^[8]. Urolithin A can cross the blood-brain barrier, making it a candidate for human neurodegenerative disease trials now underway.

Urolithin A food sources and supplementation

The richest dietary precursors are pomegranate (juice and peel), walnuts, pecans, raspberries, strawberries, and blackberries. But eating these foods doesn't guarantee adequate urolithin A production. Direct supplementation delivers over six times the plasma exposure of pomegranate juice ^[9].

Mitopure, made by the Swiss company Amazentis and sold under the brand Timeline, is the most-studied urolithin A supplement. It received FDA GRAS status in 2018 for doses up to 1,000 mg per serving. Clinical trials have tested single doses from 250 to 2,000 mg and daily doses of 250, 500, and 1,000 mg for up to four months with no serious side effects. The typical study dose is 500 to 1,000 mg daily ^[1]. Urolithin A can be taken with or without food, though absorption tends to be better with meals containing some fat.

Safety and side effects

Across all published human trials, urolithin A has shown a clean safety profile. No serious adverse events were linked to the compound. Mild side effects reported occasionally include digestive discomfort, bloating, or loose stools, all of which resolved on their own. Liver and kidney function tests showed no abnormalities ^[4]. Preclinical studies actually found that urolithin A protects the liver against drug-induced damage through Nrf2 activation ^[10]. That said, most trials lasted only two to four months with relatively small groups of healthy adults, so long-term safety data in diverse populations is still needed.