Urolithin A
Gut-derived pomegranate metabolite that triggers mitophagy; early trials hint at better muscle endurance.
Preliminary evidence
⏳Longevity
Evidence tier
Preliminary
Research weight
Citations
10 verified / 10
Classification
Longevity
❝
What the evidence says. Early or small human trials; promising but not yet conclusive.
What is Urolithin A?
Urolithin A is a longevity supplement used for improved skeletal muscle endurance (more contractions to fatigue) in older and resistance-trained adults in small rcts. NutriDex grades the human evidence as Preliminary. Urolithin A is a metabolite produced by gut bacteria from ellagitannins found in pomegranate, walnuts, and certain berries, though only some people carry the microbes needed to make it efficiently. Its main mechanism of interest is stimulating mitophagy, the cellular clearance of damaged mitochondria, which has driven its marketing as a longevity and muscle-health supplement (commonly as the standardized ingredient Mitopure). Small, mostly industry-supported randomized trials in older, middle-aged, and athletic adults report improvements in muscle endurance and favorable shifts in mitochondrial and inflammatory blood biomarkers, but results on hard endpoints like muscle strength, peak ATP production, and the 6-minute walk test have been inconsistent and sometimes not statistically significant. No trial has demonstrated long-term clinical outcomes such as reduced disability, falls, or improved survival. Short-term safety in studies up to several months appears good, but the overall evidence base remains preliminary and limited in size, duration, and independent replication.
Purported Benefits
✓Improved skeletal muscle endurance (more contractions to fatigue) in older and resistance-trained adults in small RCTs
✓Favorably shifted mitochondrial-health blood markers (acylcarnitines, ceramides) and reduced C-reactive protein
✓Modest gains in muscle strength and exercise performance reported in middle-aged adults, though not consistent across endpoints
✓Stimulates mitophagy (recycling of damaged mitochondria), a mechanism of interest for healthy aging
✓Generally well tolerated with a favorable short-term safety profile at studied doses
Evidence by outcome
The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.
| Outcome | Evidence | Effect | Studies |
|---|---|---|---|
| Muscle endurance (contractions to fatigue)Multiple small RCTs (ENERGIZE, athletes) consistently improved endurance, though most are industry-supported. | Moderate | ↑ benefit · moderate | 4 |
| Mitochondrial/inflammatory biomarkers (acylcarnitines, CRP)Reproducible favorable shifts in plasma acylcarnitines, ceramides and CRP across trials and a systematic review. | Moderate | ↑ benefit · moderate | 4 |
| Muscle strength / peak performanceATLAS showed ~12% strength gain but ENERGIZE/athlete trials missed 1-RM and 6-min-walk endpoints; inconsistent. | Mixed | ↔ mixed · small | 4 |
| Exercise recovery markers (CK, perceived exertion)Trained-runner RCT lowered creatine kinase AUC and exertion but did not improve actual time-trial performance. | Preliminary | ↑ benefit · small | 2 |
| Safety / tolerabilitySafe and bioavailable up to 1000 mg/day over weeks to months; no long-term safety data. | Moderate | ↑ benefit | 2 |
| Maximal ATP production / physical functionENERGIZE co-primary ATP endpoint and a systematic review found no effect on peak ATP or physical function. | Moderate | — no effect · negligible | 2 |
Dosing & Compounds
Typical Dose
500–1000 mg once daily of standardized urolithin A (e.g., Mitopure), taken with food; most trials used 1000 mg/day for 4 months.
Active Compounds
Safety & Cautions
Urolithin A has a favorable short-term safety profile in trials up to about 4 months at 250–1000 mg/day, with adverse-event rates similar to placebo and no serious adverse events reported; mild gastrointestinal complaints are the most common issue. Long-term safety beyond a few months is unstudied. Safety has not been established in pregnancy or breastfeeding, or in children, so these groups should avoid it. People with significant liver or kidney disease and those on multiple medications should consult a clinician first, as metabolism, drug interactions, and effects on disease are not well characterized; theoretical interactions with drugs cleared by the liver cannot be excluded. It is a dietary supplement and is not regulated as a drug, so product purity and dosing accuracy vary by brand—choose standardized products (e.g., Mitopure). It is not a treatment for any disease, and anyone with a medical condition or taking prescription medications should discuss use with a healthcare provider before starting. Educational only — always check with your doctor or pharmacist before combining Urolithin A with any medicine.
Key Studies ★ 10 studies
Systematic review
Kuerec et al. 2024, Ageing Res Rev
✓ PubMed
Systematic review of 5 studies (250 healthy adults; UA 10-1000 mg/day, 28 days-4 months): UA showed dose-dependent anti-inflammatory effects, upregulated mitochondrial/autophagy/fatty-acid-oxidation genes, and increased muscle strength and endurance, but did NOT affect maximal ATP production, mitochondrial biogenesis/dynamics, gut microbiota, anthropometrics, cardiovascular outcomes, or physical function.
RCT
Sports Medicine 2025
✓ PubMed
In a double-blind RCT of 42 highly trained male distance runners during altitude training, 1000 mg/day urolithin A for 4 weeks lowered perceived exertion (p=0.02) and reduced post-exercise creatine kinase AUC (p<0.0001), but did not significantly improve 3000m time-trial performance.
RCT
JISSN 2024
✓ Full text
8-week double-blind RCT in 20 resistance-trained male athletes (1 g/d UA) significantly improved maximal voluntary isometric contraction and repetitions-to-failure and reduced CRP and 3-methylhistidine vs placebo.
RCT
Frontiers Nutr 2025
✓ Source
Pilot RCT in academy soccer players during preseason evaluated UA effects on performance and antioxidant status, extending evidence to a younger trained-athlete population.
RCT
Liu 2022
✓ Full text
In a randomized clinical trial of 66 older adults, 1000 mg urolithin A significantly improved hand and leg muscle endurance versus placebo and decreased plasma acylcarnitines, ceramides, and C-reactive protein.
RCT
Andreux et al. 2019, Nat Metab
✓ PubMed
First-in-human RCT in healthy sedentary elderly: single and 4-week dosing of Urolithin A (up to 1000 mg) was safe and bioavailable; 500 and 1000 mg/day modulated plasma acylcarnitines and upregulated skeletal-muscle mitochondrial gene expression, a molecular signature of improved mitochondrial health (secondary outcomes).
Randomized controlled trial (first-in-human)
28 healthy elderly adults
✓ Full text
In this first-in-human randomized trial, oral urolithin A (up to 1000 mg) was safe and well tolerated, was bioavailable in plasma, and at 500–1000 mg/day for 4 weeks modulated plasma acylcarnitines and skeletal-muscle mitochondrial gene expression consistent with improved mitochondrial health.
Randomized controlled trial
66 older adults (mean age ~72)
✓ PubMed
In the ENERGIZE RCT, 1000 mg/day urolithin A for 4 months did not significantly beat placebo on co-primary endpoints (6-minute walk distance, hand-muscle ATP production) but significantly improved muscle endurance (contractions to fatigue) and lowered C-reactive protein, with no serious adverse events.
Randomized controlled trial
88 overweight, untrained middle-aged adults
✓ PubMed
In the ATLAS RCT, 500 or 1000 mg/day urolithin A for 4 months improved muscle strength by roughly 12% versus baseline and produced clinically meaningful gains in aerobic endurance (peak VO2) and the 6-minute walk, alongside favorable mitochondrial biomarker changes.
Randomized controlled trial
20 resistance-trained male athletes (~24 yr)
✓ PubMed
In an 8-week double-blind RCT, 1000 mg/day urolithin A significantly improved muscle endurance (repetitions to failure) and maximal isometric contraction and reduced inflammatory/oxidative markers versus placebo, but did not significantly increase 1-rep-max strength.