Urolithin A

updated

Urolithin A (Mitopure) is a gut-microbiome metabolite sold as a muscle and mitochondria supplement. FDA sent a no-questions letter in 2018 on a food-ingredient notice, which is not a drug approval. In 66 adults aged 65 to 90, the company-funded 4-month trial missed both primary endpoints, and a PubMed search on 11 October 2026 found no independent randomized strength trial in that age group.

Gut-microbiome metabolite of ellagitannins and ellagic acid

  • FDA's GRAS letter for GRN 000791, submitted on behalf of Amazentis SA, says the agency has no questions at this time about urolithin A in specified foods; it is not a drug approval or an efficacy finding.
  • In 66 adults aged 65 to 90, 4 months of urolithin A did not significantly change the primary endpoints: 6-minute walk rose 60.8 m versus 42.5 m on placebo, and muscle ATP production changed 0.07 versus 0.06 mM/s.
  • In ATLAS (88 randomized adults, mean age about 52), hamstring torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo, but the primary endpoint, peak power output, did not improve significantly.
  • A systematic review pooled 6-minute walk results from 2 trials: +17.03 m (95% CI -5.33 to 39.40 m), with low certainty.
  • In rats, a 90-day diet study found no target organs, with a no-observed-adverse-effect level at the highest dose tested.
  • A PubMed search on 11 October 2026 returned 26 randomized-trial records, and none was an independent randomized strength trial in adults aged 65 or older.

What is urolithin A, and what is its US status?

Urolithin A is a single defined molecule that gut bacteria make from compounds in pomegranate, nuts and certain berries, and the ingredient in FDA's letter is made synthetically. FDA sent a no-questions letter in 2018 on a food-ingredient notice from Amazentis, which is not a drug approval and not an efficacy finding.

Urolithin A (PubChem CID 5488186, C13H8O4, 228.20 g/mol, CAS 1143-70-0, 3,8-dihydroxybenzo[c]chromen-6-one) is a single defined molecule, not a salt. Gut bacteria make it from ellagitannins and ellagic acid in pomegranate, nuts and certain berries. The ingredient in FDA's letter is chemically synthesized by one of two processes the letter describes, with a specification of at least 97% urolithin A, and the rat studies used synthetic urolithin A.

Mitopure is the name the Amazentis-sponsored trials use for their product, so those trial results apply to that material at the doses given. No trial found here tests another vendor's urolithin A.

FDA GRAS Notice GRN 000791 was submitted on behalf of Amazentis SA, received on 15 June 2018 and filed on 9 July 2018. It covers urolithin A as an ingredient in protein shakes, meal replacement drinks, instant oatmeal, protein and nutrition bars and yogurt drinks at up to 500 mg per serving, and in Greek yogurts, high protein yogurts and milk-based protein shakes at up to 1000 mg per serving. FDA states it has no questions at this time about the notifier's GRAS conclusion. The letter, stamped 20 December 2018, says it is not an affirmation that urolithin A is GRAS under 21 CFR 170.35, that FDA did not evaluate labeling or health claims, and that a food use of this beige to yellow powder may be a color additive use.

This is a food-ingredient notice, not a drug approval and not an efficacy finding. On 11 October 2026, an openFDA Drugs@FDA query for urolithin A returned no match and DailyMed drug-name searches for urolithin A and Mitopure returned no labels. EU novel food status is not established here, and whether current supplement products rest on a dietary-ingredient notice is not established here.

PubChem: urolithin A identity, C13H8O4, 228.20 g/mol

Chemical identity record

National Library of Medicine. PubChem compound record CID 5488186 (urolithin A).

Urolithin A: PubChem CID 5488186, C13H8O4, 228.20 g/mol, CAS 1143-70-0, IUPAC name 3,8-dihydroxybenzo[c]chromen-6-one, with Mitopure among the listed synonyms. It is a single defined molecule, not a salt, and a gut-microbiome metabolite of ellagitannins and ellagic acid from pomegranate, nuts and certain berries.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety. Mitopure is the name the Amazentis-sponsored trials use for their product, so their results apply to that material at the doses given.

Read the original source
FDA GRN 000791 letter: no questions at this time, specific foods, not an approval

Regulatory record

U.S. Food and Drug Administration. Response letter to GRAS Notice GRN 000791 (urolithin A), submitted on behalf of Amazentis SA, received 15 June 2018 and filed 9 July 2018; digital signature stamp 20 December 2018.

FDA states it has no questions at this time about the notifier's GRAS conclusion for urolithin A as an ingredient in protein shakes, meal replacement drinks, instant oatmeal, protein and nutrition bars and yogurt drinks at up to 500 mg per serving, and in Greek yogurts, high protein yogurts and milk-based protein shakes at up to 1000 mg per serving. The letter says it is not an affirmation that urolithin A is GRAS under 21 CFR 170.35, that FDA did not evaluate labeling or health claims, that a food use of this beige to yellow powder may be a color additive use, and that FDA did not consider section 301(ll) of the FD&C Act. The ingredient is chemically synthesized by one of two processes the letter describes, with a specification of at least 97% urolithin A. On 11 October 2026 an openFDA Drugs@FDA query for urolithin A returned no match, and DailyMed drug-name searches for urolithin A and Mitopure returned no labels.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter stamped 20 December 2018
Study design
FDA response letter to a company notice
Funding
Notice submitted on behalf of Amazentis SA

A food-ingredient notice is not a drug approval and not an efficacy finding.

Read the original source

What did the randomized trials in older and middle-aged adults find?

Both company-funded trials missed their primary endpoints. In 66 adults aged 65 to 90, 4 months of urolithin A did not significantly change 6-minute walk distance or muscle ATP production, and in 88 middle-aged adults it did not significantly improve peak power output. Some other endpoints improved, including muscle endurance in the older adults and hamstring torque in the middle-aged adults.

Of 66 adults aged 65 to 90 (33 per group, mean age 71.7, mostly women) randomized to 1000 mg urolithin A daily or placebo for 4 months, the primary endpoints did not reach significance. The increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. The authors call for confirmation (NCT03283462).

Amazentis SA supported this trial. Its funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

ATLAS randomized 88 overweight healthy adults (79 completed, mean age about 52, so middle-aged, not older) to urolithin A 500 mg, 1,000 mg or placebo daily for 4 months (NCT03464500; the registry lists 90 enrolled, aged 40 to 65). Muscle strength rose about 12% on urolithin A, but the primary endpoint, peak power output, did not improve significantly. Hamstring average peak torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo (p = 0.027 and 0.029 versus placebo), while quadriceps torque and hand-grip strength were not significantly different. Plasma acylcarnitines and C-reactive protein were lower, and muscle proteins linked to mitophagy and mitochondrial metabolism were higher.

Amazentis SA sponsored and funded ATLAS, and its employees are authors. Neither trial has an independent replication in the records found.

Adults 65 to 90: 66 randomized, 4 months, primary endpoints not significant

Randomized controlled trial

Liu S et al. JAMA Netw Open. 2022;5(1):e2144279. PMID 35050355.

The primary endpoints did not reach significance: the increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. There was no significant difference in adverse events. The authors call for confirmation.

Participants / model
66 adults aged 65 to 90 (33 per group, mean age 71.7), mostly women
Treatment
Oral urolithin A 1000 mg daily or placebo
Follow-up
4 months
Study design
Randomized placebo-controlled trial (NCT03283462)
Funding
Supported by Amazentis SA. The funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

Primary endpoints were 6-minute walk distance and muscle ATP production. Endurance and biomarker results were secondary.

Read the original source
ATLAS: 88 randomized middle-aged adults, 4 months, primary endpoint not met

Randomized controlled trial

Singh A et al. Cell Rep Med. 2022;3(5):100633. PMID 35584623.

Muscle strength rose about 12% on urolithin A, but the primary endpoint, peak power output, did not improve significantly. Hamstring average peak torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo (p = 0.027 and 0.029 versus placebo), while quadriceps torque and hand-grip strength were not significantly different. Plasma acylcarnitines and C-reactive protein were lower, and muscle proteins linked to mitophagy and mitochondrial metabolism were higher. Mitophagy was inferred from protein markers, not measured as flux.

Participants / model
88 randomized overweight healthy adults (79 completed), mean age about 52 (51 to 54 across arms), about two women for each man; the registry lists 90 enrolled, aged 40 to 65
Treatment
Oral urolithin A 500 mg or 1,000 mg daily, or placebo
Follow-up
4 months
Study design
Randomized double-blind placebo-controlled trial (NCT03464500)
Funding
Amazentis SA sponsored and funded the study, and its employees are authors

Middle-aged, not older, adults. Peak power output was the primary endpoint; torque, VO2, biomarker and muscle protein results were other endpoints.

Read the original source

What does the pooled analysis of randomized trials show?

A systematic review of randomized trials up to December 2025 found five trials (n = 236) with muscle outcomes. Only the 6-minute walk test could be pooled (2 trials): +17.03 m (95% CI -5.33 to 39.40 m), which was not significant and rated low certainty.

The review found five trials (n = 236) of oral urolithin A against placebo with muscle outcomes, in clinically heterogeneous adults. Only the 6-minute walk test could be pooled, across 2 trials: +17.03 m (95% CI -5.33 to 39.40 m; p = 0.135; I2 = 0%), with GRADE certainty rated low.

Strength, endurance, aerobic capacity and biomarker results differed across populations and doses and were reported as exploratory signals, not reproducible effects. The authors conclude that larger, longer, standardized trials are needed, and they declare no commercial relationships.

Systematic review: 5 trials, n = 236; pooled 6-minute walk +17.03 m, not significant

Systematic review and meta-analysis

Dao T et al. Front Nutr. 2026;13:1834344. PMID 42559151.

The review of randomized trials up to December 2025 found five trials (n = 236) of oral urolithin A against placebo with muscle outcomes. Only the 6-minute walk test could be pooled (2 trials): +17.03 m (95% CI -5.33 to 39.40 m; p = 0.135; I2 = 0%), with GRADE certainty rated low. Strength, endurance, aerobic capacity and biomarker results differed across populations and doses and were reported as exploratory signals, not reproducible effects. The authors conclude that larger, longer, standardized trials are needed.

Participants / model
Adults in five small randomized trials, clinically heterogeneous (n = 236)
Treatment
Oral urolithin A versus placebo
Follow-up
Trials published up to December 2025
Study design
Systematic review and meta-analysis
Funding
The authors declare no commercial relationships

Only two trials could be pooled, on one outcome.

Read the original source

What happened in athletes and other groups?

Results were mixed and none involved older adults. In 20 resistance-trained men, 1RM bench press and squat did not differ from placebo while isometric strength and repetitions to failure did. In 42 distance runners the 3000 m time trial was not significantly improved. A vascular trial and a 10-patient heart failure crossover were null.

In 20 resistance-trained men given 1 g urolithin A daily for 8 weeks, 1RM bench press and squat did not differ from placebo (p = 0.462 and 0.710), while maximum voluntary isometric contraction (p = 0.048) and repetitions to failure (p = 0.011) did. No conflict of interest was reported. In 42 competitive male distance runners given 1000 mg daily for 4 weeks at an altitude camp, the 3000 m time trial was not significantly improved (urolithin A p = 0.116, placebo p = 0.771) and the between-group aerobic capacity interaction was not significant (p = 0.138), although creatine kinase after the time trial and perceived exertion were lower. Amazentis SA funded the runner trial. Neither trial tested older adults, so neither replicates the older-adult result.

In 50 healthy middle-aged adults, 4 weeks of 1,000 mg daily expanded naive-like, less terminally exhausted CD8+ cells (treatment difference 0.50 percentage points; 95% CI 0.16 to 0.83; P = 0.0437) and raised CD8+ fatty acid oxidation capacity. Amazentis funded that trial and supplied Mitopure, and the results are immune biomarkers. PubMed flags an erratum for the paper, so its figures may change.

In 50 middle-aged adults with obesity (BMI 30 or above) given 1000 mg for 4 weeks, brachial artery flow-mediated dilation did not differ from placebo (0.3% control versus 1.3% active), and the authors call the cerebrovascular signal worth further study. In 10 patients with heart failure with reduced ejection fraction, 500 mg twice daily for 4 weeks in a crossover design showed no effect on echocardiographic measures.

Trained people: 20 resistance-trained men and 42 distance runners, mixed results

Randomized controlled trial

Zhao H et al. J Int Soc Sports Nutr. 2024;21(1):2419388. PMID 39487653.

In 20 resistance-trained men given 1 g urolithin A daily for 8 weeks, 1RM bench press and squat did not differ from placebo (p = 0.462 and 0.710), while maximum voluntary isometric contraction (p = 0.048) and repetitions to failure (p = 0.011) did. A second trial gave 1000 mg daily for 4 weeks at an altitude camp to 42 competitive male distance runners: the 3000 m time trial was not significantly improved (urolithin A p = 0.116, placebo p = 0.771) and the between-group aerobic capacity interaction was not significant (p = 0.138), although creatine kinase after the time trial and perceived exertion were lower.

Participants / model
20 resistance-trained men; 42 highly trained male distance runners
Treatment
Oral urolithin A 1 g daily for 8 weeks; 1000 mg daily for 4 weeks
Follow-up
8 weeks; 4 weeks
Study design
Two randomized trials
Funding
No conflict of interest was reported for the 20-man trial; the 42-runner trial was funded by Amazentis SA

Neither trial tested older adults, so neither replicates the older-adult result.

Read the original source
Other groups: CD8+ cell markers (50), vascular function (50), heart failure (10)

Randomized controlled trial

Denk D et al. Nat Aging. 2025;5(11):2309-2322. PMID 41174221.

A 4-week trial of 50 healthy middle-aged adults on 1,000 mg daily found urolithin A expanded naive-like, less terminally exhausted CD8+ cells (treatment difference 0.50 percentage points; 95% CI 0.16 to 0.83; P = 0.0437) and raised CD8+ fatty acid oxidation capacity. In 50 middle-aged adults with obesity (BMI 30 or above) given 1000 mg for 4 weeks, brachial artery flow-mediated dilation did not differ from placebo (0.3% control versus 1.3% active), and the authors call the cerebrovascular signal worth further study. In 10 patients with heart failure with reduced ejection fraction, 500 mg twice daily for 4 weeks in a crossover design showed no effect on echocardiographic measures.

Participants / model
50 healthy middle-aged adults; 50 middle-aged adults with obesity; 10 patients with heart failure with reduced ejection fraction
Treatment
Oral urolithin A 1,000 mg daily for 4 weeks; 500 mg twice daily for 4 weeks
Follow-up
4 weeks in each trial
Study design
Three randomized trials, the heart failure study as a crossover
Funding
Amazentis funded the CD8+ trial and supplied Mitopure; no conflict of interest was reported for the obesity trial; funding is not stated in the source for the heart failure study

PubMed flags an erratum for the CD8+ paper (Nat Aging 2026), so its figures may change. The CD8+ results are immune biomarkers, not strength or endurance outcomes.

Read the original source

Does urolithin A improve muscle endurance and strength in older adults?

Partly. The only trial in adults aged 65 or older is company-funded and missed its primary endpoints, with muscle endurance improving as a secondary endpoint, and no independent randomized strength trial in that age group was found. A PubMed search on 11 October 2026 returned 26 randomized-trial records, 8 of them direct urolithin A supplementation trials.

Sellers say urolithin A (Mitopure) activates mitophagy and improves muscle endurance and strength in older adults. The claim is partly supported: secondary endpoints improved in one company-funded trial in people aged 65 to 90, and a company-funded trial in middle-aged adults found a strength signal while missing its primary endpoint. Neither has an independent replication in the records found.

A PubMed search on 11 October 2026 for urolithin A in the title or abstract with randomized controlled trial as publication type returned 26 records, and all 26 titles were reviewed. Eight were trials of direct urolithin A supplementation, and the other 18 were food, polyphenol or synbiotic trials (pomegranate, walnuts, raspberries, Mediterranean diet, croissants and similar). The only trial in adults aged 65 or older is company-funded and missed its primary endpoints, and no independent randomized strength trial in that age group was found.

A ClinicalTrials.gov search the same day returned NCT07231783 (Amazentis SA, recruiting, an estimated 120 healthy adults aged 40 to 65, primary outcome maximum isokinetic knee flexion strength, primary completion listed as 31 October 2027, no results) and NCT05814705 (McMaster University, 24 young men, mitochondrial respiration during leg immobilization, no results). Registered trials without results show that a study was registered, not that it works.

The mitophagy part of the claim rests on gene and protein markers, not on measured mitophagic flux.

PubMed search, 11 October 2026: 26 records, 8 supplementation trials, no independent trial in adults 65 and older

PubMed search record

PubMed search run on 11 October 2026: "urolithin A"[tiab] AND randomized controlled trial[pt]. 26 records returned. ClinicalTrials.gov search for "urolithin A" run the same day.

The search returned 26 records, and all 26 titles were reviewed. Eight were trials of direct urolithin A supplementation: the older-adult, ATLAS, trained-men, distance-runner, CD8+, obesity and heart failure trials and a 2022 exposure study (PMID 34117375). The other 18 were food, polyphenol or synbiotic trials (pomegranate, walnuts, raspberries, Mediterranean diet, croissants and similar). The only trial in adults aged 65 or older is company-funded and missed its primary endpoints. The clearest strength result against placebo came from a company-funded trial in middle-aged adults that also missed its primary endpoint. No independent randomized strength trial in adults aged 65 or older was found in these records. A ClinicalTrials.gov search returned records including NCT07231783 (Amazentis SA, recruiting, estimated 120 healthy adults aged 40 to 65, primary outcome maximum isokinetic knee flexion strength, primary completion listed as 31 October 2027, no results) and NCT05814705 (McMaster University, 24 young men, mitochondrial respiration primary outcome during leg immobilization, no results).

Participants / model
Records reviewed and registered trials, not a population
Treatment
Not applicable
Follow-up
Search run on 11 October 2026
Study design
Literature search and trial registry
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists. Registered trials without results show that a study was registered, not that it works.

Read the original source
Adults 65 to 90: 66 randomized, 4 months, primary endpoints not significant

Randomized controlled trial

Liu S et al. JAMA Netw Open. 2022;5(1):e2144279. PMID 35050355.

The primary endpoints did not reach significance: the increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. There was no significant difference in adverse events. The authors call for confirmation.

Participants / model
66 adults aged 65 to 90 (33 per group, mean age 71.7), mostly women
Treatment
Oral urolithin A 1000 mg daily or placebo
Follow-up
4 months
Study design
Randomized placebo-controlled trial (NCT03283462)
Funding
Supported by Amazentis SA. The funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

Primary endpoints were 6-minute walk distance and muscle ATP production. Endurance and biomarker results were secondary.

Read the original source
ATLAS: 88 randomized middle-aged adults, 4 months, primary endpoint not met

Randomized controlled trial

Singh A et al. Cell Rep Med. 2022;3(5):100633. PMID 35584623.

Muscle strength rose about 12% on urolithin A, but the primary endpoint, peak power output, did not improve significantly. Hamstring average peak torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo (p = 0.027 and 0.029 versus placebo), while quadriceps torque and hand-grip strength were not significantly different. Plasma acylcarnitines and C-reactive protein were lower, and muscle proteins linked to mitophagy and mitochondrial metabolism were higher. Mitophagy was inferred from protein markers, not measured as flux.

Participants / model
88 randomized overweight healthy adults (79 completed), mean age about 52 (51 to 54 across arms), about two women for each man; the registry lists 90 enrolled, aged 40 to 65
Treatment
Oral urolithin A 500 mg or 1,000 mg daily, or placebo
Follow-up
4 months
Study design
Randomized double-blind placebo-controlled trial (NCT03464500)
Funding
Amazentis SA sponsored and funded the study, and its employees are authors

Middle-aged, not older, adults. Peak power output was the primary endpoint; torque, VO2, biomarker and muscle protein results were other endpoints.

Read the original source

How does urolithin A work, and what reaches the blood?

Sellers describe urolithin A as activating mitophagy, but in the trials that is inferred from gene and protein markers, not measured as flux. In the first-in-human trial it was bioavailable in plasma at all doses, and 4 weeks at 500 mg and 1,000 mg changed plasma acylcarnitines and muscle mitochondrial gene expression.

The supplier description is that urolithin A activates mitophagy. In ATLAS, muscle proteins linked to mitophagy and mitochondrial metabolism were higher on urolithin A, and mitophagy was inferred from those protein markers, not measured as flux. Plasma acylcarnitines and C-reactive protein were lower in both company-funded randomized trials, a consistent direction for those biomarkers.

In the first-in-human trial, healthy sedentary elderly people took urolithin A as a single dose or as multiple doses over 4 weeks. Safety, the primary outcome, was favorable, and urolithin A was bioavailable in plasma at all doses tested. Four weeks at 500 mg and 1,000 mg changed plasma acylcarnitines and skeletal muscle mitochondrial gene expression, which were secondary outcomes. These are biomarker changes, not strength or endurance outcomes. The abstract gives no sample size, and no half-life appears in the sources reviewed here.

An independent physiologically based pharmacokinetic model from ETH Zurich and Wageningen predicted that the concentrations linked to beneficial effects in vitro are hard to reach by supplementation. It is a prediction, not a human measurement.

ATLAS: 88 randomized middle-aged adults, 4 months, primary endpoint not met

Randomized controlled trial

Singh A et al. Cell Rep Med. 2022;3(5):100633. PMID 35584623.

Muscle strength rose about 12% on urolithin A, but the primary endpoint, peak power output, did not improve significantly. Hamstring average peak torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo (p = 0.027 and 0.029 versus placebo), while quadriceps torque and hand-grip strength were not significantly different. Plasma acylcarnitines and C-reactive protein were lower, and muscle proteins linked to mitophagy and mitochondrial metabolism were higher. Mitophagy was inferred from protein markers, not measured as flux.

Participants / model
88 randomized overweight healthy adults (79 completed), mean age about 52 (51 to 54 across arms), about two women for each man; the registry lists 90 enrolled, aged 40 to 65
Treatment
Oral urolithin A 500 mg or 1,000 mg daily, or placebo
Follow-up
4 months
Study design
Randomized double-blind placebo-controlled trial (NCT03464500)
Funding
Amazentis SA sponsored and funded the study, and its employees are authors

Middle-aged, not older, adults. Peak power output was the primary endpoint; torque, VO2, biomarker and muscle protein results were other endpoints.

Read the original source
Adults 65 to 90: 66 randomized, 4 months, primary endpoints not significant

Randomized controlled trial

Liu S et al. JAMA Netw Open. 2022;5(1):e2144279. PMID 35050355.

The primary endpoints did not reach significance: the increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. There was no significant difference in adverse events. The authors call for confirmation.

Participants / model
66 adults aged 65 to 90 (33 per group, mean age 71.7), mostly women
Treatment
Oral urolithin A 1000 mg daily or placebo
Follow-up
4 months
Study design
Randomized placebo-controlled trial (NCT03283462)
Funding
Supported by Amazentis SA. The funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

Primary endpoints were 6-minute walk distance and muscle ATP production. Endurance and biomarker results were secondary.

Read the original source
First-in-human trial: favorable safety, plasma exposure, muscle gene expression changes

Randomized controlled trial

Andreux PA et al. Nat Metab. 2019;1(6):595-603. PMID 32694802.

Healthy, sedentary elderly people took urolithin A as a single dose or as multiple doses over 4 weeks. Safety, the primary outcome, was favorable. Urolithin A was bioavailable in plasma at all doses tested, and 4 weeks at 500 mg and 1,000 mg changed plasma acylcarnitines and skeletal muscle mitochondrial gene expression (secondary outcomes).

Participants / model
Healthy sedentary elderly adults; sample size not stated in the source
Treatment
Oral urolithin A, single dose or multiple doses over 4 weeks (500 mg and 1,000 mg named for the 4-week effects)
Follow-up
Single dose, or multiple doses over 4 weeks
Study design
Randomized trial; safety was the primary outcome
Funding
not stated in the source; the authors are affiliated with Amazentis SA

These are biomarker changes, not strength or endurance outcomes. The abstract gives no sample size, so none is stated here.

Read the original source
Rat toxicology: no target organs, NOAEL at the highest dose tested; modeled human exposure

Animal study

Heilman J et al. Food Chem Toxicol. 2017;108(Pt A):289-297. PMID 28757461.

In rats, synthetic urolithin A was not genotoxic in a battery of assays, and 28-day and 90-day diet studies showed no changes in clinical parameters, blood chemistry or hematology and no target organs. The NOAEL was the highest dose tested, 5% urolithin A by weight in the diet, or 3451 mg/kg bw/day in males and 3826 mg/kg bw/day in females in the 90-day study. An independent physiologically based pharmacokinetic model from ETH Zurich and Wageningen predicted that concentrations at which toxic effects were seen in vitro are unlikely to be reached in vivo, and that the concentrations linked to beneficial effects in vitro are hard to reach by supplementation.

Participants / model
Rats (toxicology); human exposure predicted by a model
Treatment
Dietary synthetic urolithin A in rats; modeled oral supplementation
Follow-up
28-day and 90-day diet studies
Study design
Animal toxicology study plus an independent modeling study
Funding
Three authors list Amazentis SA and two list Exponent, Inc.

The model is a prediction, not a human measurement. The rat result is company-linked and applies to rats.

Read the original source

What do the toxicology and trial safety data show?

No safety signal was reported in the studies found: rat studies showed no target organs, and the 66-adult trial found no significant difference in adverse events. The human trials ran 4 months or less, the toxicology is company-linked, and no human data beyond 4 months were found.

In rats, synthetic urolithin A was not genotoxic in a battery of assays, and 28-day and 90-day diet studies showed no changes in clinical parameters, blood chemistry or hematology and no target organs. The no-observed-adverse-effect level was the highest dose tested, 5% urolithin A by weight in the diet, or 3451 mg/kg bw/day in males and 3826 mg/kg bw/day in females in the 90-day study. Three authors list Amazentis SA and two list Exponent, Inc.

In people, safety was the primary outcome of the first-in-human trial and was favorable, and the 66-adult older-adult trial found no significant difference in adverse events. The longest human trials found ran 4 months, so long-term human data are not available.

The independent model predicted that concentrations at which toxic effects were seen in vitro are unlikely to be reached in vivo. That supports safety but is a prediction. FDA's no-questions letter covers specific foods, does not evaluate labeling or health claims, and is not an affirmation that urolithin A is GRAS.

Rat toxicology: no target organs, NOAEL at the highest dose tested; modeled human exposure

Animal study

Heilman J et al. Food Chem Toxicol. 2017;108(Pt A):289-297. PMID 28757461.

In rats, synthetic urolithin A was not genotoxic in a battery of assays, and 28-day and 90-day diet studies showed no changes in clinical parameters, blood chemistry or hematology and no target organs. The NOAEL was the highest dose tested, 5% urolithin A by weight in the diet, or 3451 mg/kg bw/day in males and 3826 mg/kg bw/day in females in the 90-day study. An independent physiologically based pharmacokinetic model from ETH Zurich and Wageningen predicted that concentrations at which toxic effects were seen in vitro are unlikely to be reached in vivo, and that the concentrations linked to beneficial effects in vitro are hard to reach by supplementation.

Participants / model
Rats (toxicology); human exposure predicted by a model
Treatment
Dietary synthetic urolithin A in rats; modeled oral supplementation
Follow-up
28-day and 90-day diet studies
Study design
Animal toxicology study plus an independent modeling study
Funding
Three authors list Amazentis SA and two list Exponent, Inc.

The model is a prediction, not a human measurement. The rat result is company-linked and applies to rats.

Read the original source
First-in-human trial: favorable safety, plasma exposure, muscle gene expression changes

Randomized controlled trial

Andreux PA et al. Nat Metab. 2019;1(6):595-603. PMID 32694802.

Healthy, sedentary elderly people took urolithin A as a single dose or as multiple doses over 4 weeks. Safety, the primary outcome, was favorable. Urolithin A was bioavailable in plasma at all doses tested, and 4 weeks at 500 mg and 1,000 mg changed plasma acylcarnitines and skeletal muscle mitochondrial gene expression (secondary outcomes).

Participants / model
Healthy sedentary elderly adults; sample size not stated in the source
Treatment
Oral urolithin A, single dose or multiple doses over 4 weeks (500 mg and 1,000 mg named for the 4-week effects)
Follow-up
Single dose, or multiple doses over 4 weeks
Study design
Randomized trial; safety was the primary outcome
Funding
not stated in the source; the authors are affiliated with Amazentis SA

These are biomarker changes, not strength or endurance outcomes. The abstract gives no sample size, so none is stated here.

Read the original source
Adults 65 to 90: 66 randomized, 4 months, primary endpoints not significant

Randomized controlled trial

Liu S et al. JAMA Netw Open. 2022;5(1):e2144279. PMID 35050355.

The primary endpoints did not reach significance: the increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. There was no significant difference in adverse events. The authors call for confirmation.

Participants / model
66 adults aged 65 to 90 (33 per group, mean age 71.7), mostly women
Treatment
Oral urolithin A 1000 mg daily or placebo
Follow-up
4 months
Study design
Randomized placebo-controlled trial (NCT03283462)
Funding
Supported by Amazentis SA. The funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

Primary endpoints were 6-minute walk distance and muscle ATP production. Endurance and biomarker results were secondary.

Read the original source
FDA GRN 000791 letter: no questions at this time, specific foods, not an approval

Regulatory record

U.S. Food and Drug Administration. Response letter to GRAS Notice GRN 000791 (urolithin A), submitted on behalf of Amazentis SA, received 15 June 2018 and filed 9 July 2018; digital signature stamp 20 December 2018.

FDA states it has no questions at this time about the notifier's GRAS conclusion for urolithin A as an ingredient in protein shakes, meal replacement drinks, instant oatmeal, protein and nutrition bars and yogurt drinks at up to 500 mg per serving, and in Greek yogurts, high protein yogurts and milk-based protein shakes at up to 1000 mg per serving. The letter says it is not an affirmation that urolithin A is GRAS under 21 CFR 170.35, that FDA did not evaluate labeling or health claims, that a food use of this beige to yellow powder may be a color additive use, and that FDA did not consider section 301(ll) of the FD&C Act. The ingredient is chemically synthesized by one of two processes the letter describes, with a specification of at least 97% urolithin A. On 11 October 2026 an openFDA Drugs@FDA query for urolithin A returned no match, and DailyMed drug-name searches for urolithin A and Mitopure returned no labels.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter stamped 20 December 2018
Study design
FDA response letter to a company notice
Funding
Notice submitted on behalf of Amazentis SA

A food-ingredient notice is not a drug approval and not an efficacy finding.

Read the original source

Why does urolithin A sit in C tier?

C fits a compound that is well tolerated in short trials and clean in rat toxicology, with thin and mostly company-sponsored outcome data. Both Amazentis trials missed their primary endpoints, and the pooled 6-minute walk difference was not significant, with low certainty.

The tolerability record is good so far: an FDA no-questions letter for specific foods, rat studies with no target organs, and human trials of 4 months or less with no adverse-event difference in the 66-adult trial. The outcome data are thin. Both company-funded trials missed their primary endpoints, the pooled walk-distance difference was +17.03 m (95% CI -5.33 to 39.40 m) with low certainty, and the athlete, vascular and heart failure trials were null or mixed.

The grade covers urolithin A as sold for muscle and mitochondrial support. The mitophagy claim rests on gene and protein markers, and no independent randomized strength trial in adults aged 65 or older was found.

FDA GRN 000791 letter: no questions at this time, specific foods, not an approval

Regulatory record

U.S. Food and Drug Administration. Response letter to GRAS Notice GRN 000791 (urolithin A), submitted on behalf of Amazentis SA, received 15 June 2018 and filed 9 July 2018; digital signature stamp 20 December 2018.

FDA states it has no questions at this time about the notifier's GRAS conclusion for urolithin A as an ingredient in protein shakes, meal replacement drinks, instant oatmeal, protein and nutrition bars and yogurt drinks at up to 500 mg per serving, and in Greek yogurts, high protein yogurts and milk-based protein shakes at up to 1000 mg per serving. The letter says it is not an affirmation that urolithin A is GRAS under 21 CFR 170.35, that FDA did not evaluate labeling or health claims, that a food use of this beige to yellow powder may be a color additive use, and that FDA did not consider section 301(ll) of the FD&C Act. The ingredient is chemically synthesized by one of two processes the letter describes, with a specification of at least 97% urolithin A. On 11 October 2026 an openFDA Drugs@FDA query for urolithin A returned no match, and DailyMed drug-name searches for urolithin A and Mitopure returned no labels.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter stamped 20 December 2018
Study design
FDA response letter to a company notice
Funding
Notice submitted on behalf of Amazentis SA

A food-ingredient notice is not a drug approval and not an efficacy finding.

Read the original source
Rat toxicology: no target organs, NOAEL at the highest dose tested; modeled human exposure

Animal study

Heilman J et al. Food Chem Toxicol. 2017;108(Pt A):289-297. PMID 28757461.

In rats, synthetic urolithin A was not genotoxic in a battery of assays, and 28-day and 90-day diet studies showed no changes in clinical parameters, blood chemistry or hematology and no target organs. The NOAEL was the highest dose tested, 5% urolithin A by weight in the diet, or 3451 mg/kg bw/day in males and 3826 mg/kg bw/day in females in the 90-day study. An independent physiologically based pharmacokinetic model from ETH Zurich and Wageningen predicted that concentrations at which toxic effects were seen in vitro are unlikely to be reached in vivo, and that the concentrations linked to beneficial effects in vitro are hard to reach by supplementation.

Participants / model
Rats (toxicology); human exposure predicted by a model
Treatment
Dietary synthetic urolithin A in rats; modeled oral supplementation
Follow-up
28-day and 90-day diet studies
Study design
Animal toxicology study plus an independent modeling study
Funding
Three authors list Amazentis SA and two list Exponent, Inc.

The model is a prediction, not a human measurement. The rat result is company-linked and applies to rats.

Read the original source
Adults 65 to 90: 66 randomized, 4 months, primary endpoints not significant

Randomized controlled trial

Liu S et al. JAMA Netw Open. 2022;5(1):e2144279. PMID 35050355.

The primary endpoints did not reach significance: the increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. There was no significant difference in adverse events. The authors call for confirmation.

Participants / model
66 adults aged 65 to 90 (33 per group, mean age 71.7), mostly women
Treatment
Oral urolithin A 1000 mg daily or placebo
Follow-up
4 months
Study design
Randomized placebo-controlled trial (NCT03283462)
Funding
Supported by Amazentis SA. The funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

Primary endpoints were 6-minute walk distance and muscle ATP production. Endurance and biomarker results were secondary.

Read the original source
ATLAS: 88 randomized middle-aged adults, 4 months, primary endpoint not met

Randomized controlled trial

Singh A et al. Cell Rep Med. 2022;3(5):100633. PMID 35584623.

Muscle strength rose about 12% on urolithin A, but the primary endpoint, peak power output, did not improve significantly. Hamstring average peak torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo (p = 0.027 and 0.029 versus placebo), while quadriceps torque and hand-grip strength were not significantly different. Plasma acylcarnitines and C-reactive protein were lower, and muscle proteins linked to mitophagy and mitochondrial metabolism were higher. Mitophagy was inferred from protein markers, not measured as flux.

Participants / model
88 randomized overweight healthy adults (79 completed), mean age about 52 (51 to 54 across arms), about two women for each man; the registry lists 90 enrolled, aged 40 to 65
Treatment
Oral urolithin A 500 mg or 1,000 mg daily, or placebo
Follow-up
4 months
Study design
Randomized double-blind placebo-controlled trial (NCT03464500)
Funding
Amazentis SA sponsored and funded the study, and its employees are authors

Middle-aged, not older, adults. Peak power output was the primary endpoint; torque, VO2, biomarker and muscle protein results were other endpoints.

Read the original source
Systematic review: 5 trials, n = 236; pooled 6-minute walk +17.03 m, not significant

Systematic review and meta-analysis

Dao T et al. Front Nutr. 2026;13:1834344. PMID 42559151.

The review of randomized trials up to December 2025 found five trials (n = 236) of oral urolithin A against placebo with muscle outcomes. Only the 6-minute walk test could be pooled (2 trials): +17.03 m (95% CI -5.33 to 39.40 m; p = 0.135; I2 = 0%), with GRADE certainty rated low. Strength, endurance, aerobic capacity and biomarker results differed across populations and doses and were reported as exploratory signals, not reproducible effects. The authors conclude that larger, longer, standardized trials are needed.

Participants / model
Adults in five small randomized trials, clinically heterogeneous (n = 236)
Treatment
Oral urolithin A versus placebo
Follow-up
Trials published up to December 2025
Study design
Systematic review and meta-analysis
Funding
The authors declare no commercial relationships

Only two trials could be pooled, on one outcome.

Read the original source
Trained people: 20 resistance-trained men and 42 distance runners, mixed results

Randomized controlled trial

Zhao H et al. J Int Soc Sports Nutr. 2024;21(1):2419388. PMID 39487653.

In 20 resistance-trained men given 1 g urolithin A daily for 8 weeks, 1RM bench press and squat did not differ from placebo (p = 0.462 and 0.710), while maximum voluntary isometric contraction (p = 0.048) and repetitions to failure (p = 0.011) did. A second trial gave 1000 mg daily for 4 weeks at an altitude camp to 42 competitive male distance runners: the 3000 m time trial was not significantly improved (urolithin A p = 0.116, placebo p = 0.771) and the between-group aerobic capacity interaction was not significant (p = 0.138), although creatine kinase after the time trial and perceived exertion were lower.

Participants / model
20 resistance-trained men; 42 highly trained male distance runners
Treatment
Oral urolithin A 1 g daily for 8 weeks; 1000 mg daily for 4 weeks
Follow-up
8 weeks; 4 weeks
Study design
Two randomized trials
Funding
No conflict of interest was reported for the 20-man trial; the 42-runner trial was funded by Amazentis SA

Neither trial tested older adults, so neither replicates the older-adult result.

Read the original source
Other groups: CD8+ cell markers (50), vascular function (50), heart failure (10)

Randomized controlled trial

Denk D et al. Nat Aging. 2025;5(11):2309-2322. PMID 41174221.

A 4-week trial of 50 healthy middle-aged adults on 1,000 mg daily found urolithin A expanded naive-like, less terminally exhausted CD8+ cells (treatment difference 0.50 percentage points; 95% CI 0.16 to 0.83; P = 0.0437) and raised CD8+ fatty acid oxidation capacity. In 50 middle-aged adults with obesity (BMI 30 or above) given 1000 mg for 4 weeks, brachial artery flow-mediated dilation did not differ from placebo (0.3% control versus 1.3% active), and the authors call the cerebrovascular signal worth further study. In 10 patients with heart failure with reduced ejection fraction, 500 mg twice daily for 4 weeks in a crossover design showed no effect on echocardiographic measures.

Participants / model
50 healthy middle-aged adults; 50 middle-aged adults with obesity; 10 patients with heart failure with reduced ejection fraction
Treatment
Oral urolithin A 1,000 mg daily for 4 weeks; 500 mg twice daily for 4 weeks
Follow-up
4 weeks in each trial
Study design
Three randomized trials, the heart failure study as a crossover
Funding
Amazentis funded the CD8+ trial and supplied Mitopure; no conflict of interest was reported for the obesity trial; funding is not stated in the source for the heart failure study

PubMed flags an erratum for the CD8+ paper (Nat Aging 2026), so its figures may change. The CD8+ results are immune biomarkers, not strength or endurance outcomes.

Read the original source
PubMed search, 11 October 2026: 26 records, 8 supplementation trials, no independent trial in adults 65 and older

PubMed search record

PubMed search run on 11 October 2026: "urolithin A"[tiab] AND randomized controlled trial[pt]. 26 records returned. ClinicalTrials.gov search for "urolithin A" run the same day.

The search returned 26 records, and all 26 titles were reviewed. Eight were trials of direct urolithin A supplementation: the older-adult, ATLAS, trained-men, distance-runner, CD8+, obesity and heart failure trials and a 2022 exposure study (PMID 34117375). The other 18 were food, polyphenol or synbiotic trials (pomegranate, walnuts, raspberries, Mediterranean diet, croissants and similar). The only trial in adults aged 65 or older is company-funded and missed its primary endpoints. The clearest strength result against placebo came from a company-funded trial in middle-aged adults that also missed its primary endpoint. No independent randomized strength trial in adults aged 65 or older was found in these records. A ClinicalTrials.gov search returned records including NCT07231783 (Amazentis SA, recruiting, estimated 120 healthy adults aged 40 to 65, primary outcome maximum isokinetic knee flexion strength, primary completion listed as 31 October 2027, no results) and NCT05814705 (McMaster University, 24 young men, mitochondrial respiration primary outcome during leg immobilization, no results).

Participants / model
Records reviewed and registered trials, not a population
Treatment
Not applicable
Follow-up
Search run on 11 October 2026
Study design
Literature search and trial registry
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists. Registered trials without results show that a study was registered, not that it works.

Read the original source

Studies and sources

PubChem: urolithin A identity, C13H8O4, 228.20 g/mol

Chemical identity record

National Library of Medicine. PubChem compound record CID 5488186 (urolithin A).

Urolithin A: PubChem CID 5488186, C13H8O4, 228.20 g/mol, CAS 1143-70-0, IUPAC name 3,8-dihydroxybenzo[c]chromen-6-one, with Mitopure among the listed synonyms. It is a single defined molecule, not a salt, and a gut-microbiome metabolite of ellagitannins and ellagic acid from pomegranate, nuts and certain berries.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety. Mitopure is the name the Amazentis-sponsored trials use for their product, so their results apply to that material at the doses given.

Read the original source
FDA GRN 000791 letter: no questions at this time, specific foods, not an approval

Regulatory record

U.S. Food and Drug Administration. Response letter to GRAS Notice GRN 000791 (urolithin A), submitted on behalf of Amazentis SA, received 15 June 2018 and filed 9 July 2018; digital signature stamp 20 December 2018.

FDA states it has no questions at this time about the notifier's GRAS conclusion for urolithin A as an ingredient in protein shakes, meal replacement drinks, instant oatmeal, protein and nutrition bars and yogurt drinks at up to 500 mg per serving, and in Greek yogurts, high protein yogurts and milk-based protein shakes at up to 1000 mg per serving. The letter says it is not an affirmation that urolithin A is GRAS under 21 CFR 170.35, that FDA did not evaluate labeling or health claims, that a food use of this beige to yellow powder may be a color additive use, and that FDA did not consider section 301(ll) of the FD&C Act. The ingredient is chemically synthesized by one of two processes the letter describes, with a specification of at least 97% urolithin A. On 11 October 2026 an openFDA Drugs@FDA query for urolithin A returned no match, and DailyMed drug-name searches for urolithin A and Mitopure returned no labels.

Participants / model
Not a clinical population
Treatment
Food ingredient notice; no drug application
Follow-up
Letter stamped 20 December 2018
Study design
FDA response letter to a company notice
Funding
Notice submitted on behalf of Amazentis SA

A food-ingredient notice is not a drug approval and not an efficacy finding.

Read the original source
Rat toxicology: no target organs, NOAEL at the highest dose tested; modeled human exposure

Animal study

Heilman J et al. Food Chem Toxicol. 2017;108(Pt A):289-297. PMID 28757461.

In rats, synthetic urolithin A was not genotoxic in a battery of assays, and 28-day and 90-day diet studies showed no changes in clinical parameters, blood chemistry or hematology and no target organs. The NOAEL was the highest dose tested, 5% urolithin A by weight in the diet, or 3451 mg/kg bw/day in males and 3826 mg/kg bw/day in females in the 90-day study. An independent physiologically based pharmacokinetic model from ETH Zurich and Wageningen predicted that concentrations at which toxic effects were seen in vitro are unlikely to be reached in vivo, and that the concentrations linked to beneficial effects in vitro are hard to reach by supplementation.

Participants / model
Rats (toxicology); human exposure predicted by a model
Treatment
Dietary synthetic urolithin A in rats; modeled oral supplementation
Follow-up
28-day and 90-day diet studies
Study design
Animal toxicology study plus an independent modeling study
Funding
Three authors list Amazentis SA and two list Exponent, Inc.

The model is a prediction, not a human measurement. The rat result is company-linked and applies to rats.

Read the original source
First-in-human trial: favorable safety, plasma exposure, muscle gene expression changes

Randomized controlled trial

Andreux PA et al. Nat Metab. 2019;1(6):595-603. PMID 32694802.

Healthy, sedentary elderly people took urolithin A as a single dose or as multiple doses over 4 weeks. Safety, the primary outcome, was favorable. Urolithin A was bioavailable in plasma at all doses tested, and 4 weeks at 500 mg and 1,000 mg changed plasma acylcarnitines and skeletal muscle mitochondrial gene expression (secondary outcomes).

Participants / model
Healthy sedentary elderly adults; sample size not stated in the source
Treatment
Oral urolithin A, single dose or multiple doses over 4 weeks (500 mg and 1,000 mg named for the 4-week effects)
Follow-up
Single dose, or multiple doses over 4 weeks
Study design
Randomized trial; safety was the primary outcome
Funding
not stated in the source; the authors are affiliated with Amazentis SA

These are biomarker changes, not strength or endurance outcomes. The abstract gives no sample size, so none is stated here.

Read the original source
Adults 65 to 90: 66 randomized, 4 months, primary endpoints not significant

Randomized controlled trial

Liu S et al. JAMA Netw Open. 2022;5(1):e2144279. PMID 35050355.

The primary endpoints did not reach significance: the increase in 6-minute walk distance was 60.8 m on urolithin A and 42.5 m on placebo, and the change in maximal ATP production in hand muscle was 0.07 mM/s versus 0.06 mM/s. Muscle endurance, a secondary endpoint, improved in the first dorsal interosseus and tibialis anterior at 2 months, and plasma acylcarnitines, ceramides and C-reactive protein were lower at 4 months. There was no significant difference in adverse events. The authors call for confirmation.

Participants / model
66 adults aged 65 to 90 (33 per group, mean age 71.7), mostly women
Treatment
Oral urolithin A 1000 mg daily or placebo
Follow-up
4 months
Study design
Randomized placebo-controlled trial (NCT03283462)
Funding
Supported by Amazentis SA. The funding statement says the funder had a role in design and conduct, data collection and analysis, manuscript approval and the decision to submit, and the disclosures list the founder and chief executive, the board chair and shareholder, and employees among the authors.

Primary endpoints were 6-minute walk distance and muscle ATP production. Endurance and biomarker results were secondary.

Read the original source
ATLAS: 88 randomized middle-aged adults, 4 months, primary endpoint not met

Randomized controlled trial

Singh A et al. Cell Rep Med. 2022;3(5):100633. PMID 35584623.

Muscle strength rose about 12% on urolithin A, but the primary endpoint, peak power output, did not improve significantly. Hamstring average peak torque rose 12% at 500 mg and 9.8% at 1,000 mg against a 9.8% fall on placebo (p = 0.027 and 0.029 versus placebo), while quadriceps torque and hand-grip strength were not significantly different. Plasma acylcarnitines and C-reactive protein were lower, and muscle proteins linked to mitophagy and mitochondrial metabolism were higher. Mitophagy was inferred from protein markers, not measured as flux.

Participants / model
88 randomized overweight healthy adults (79 completed), mean age about 52 (51 to 54 across arms), about two women for each man; the registry lists 90 enrolled, aged 40 to 65
Treatment
Oral urolithin A 500 mg or 1,000 mg daily, or placebo
Follow-up
4 months
Study design
Randomized double-blind placebo-controlled trial (NCT03464500)
Funding
Amazentis SA sponsored and funded the study, and its employees are authors

Middle-aged, not older, adults. Peak power output was the primary endpoint; torque, VO2, biomarker and muscle protein results were other endpoints.

Read the original source
Systematic review: 5 trials, n = 236; pooled 6-minute walk +17.03 m, not significant

Systematic review and meta-analysis

Dao T et al. Front Nutr. 2026;13:1834344. PMID 42559151.

The review of randomized trials up to December 2025 found five trials (n = 236) of oral urolithin A against placebo with muscle outcomes. Only the 6-minute walk test could be pooled (2 trials): +17.03 m (95% CI -5.33 to 39.40 m; p = 0.135; I2 = 0%), with GRADE certainty rated low. Strength, endurance, aerobic capacity and biomarker results differed across populations and doses and were reported as exploratory signals, not reproducible effects. The authors conclude that larger, longer, standardized trials are needed.

Participants / model
Adults in five small randomized trials, clinically heterogeneous (n = 236)
Treatment
Oral urolithin A versus placebo
Follow-up
Trials published up to December 2025
Study design
Systematic review and meta-analysis
Funding
The authors declare no commercial relationships

Only two trials could be pooled, on one outcome.

Read the original source
Trained people: 20 resistance-trained men and 42 distance runners, mixed results

Randomized controlled trial

Zhao H et al. J Int Soc Sports Nutr. 2024;21(1):2419388. PMID 39487653.

In 20 resistance-trained men given 1 g urolithin A daily for 8 weeks, 1RM bench press and squat did not differ from placebo (p = 0.462 and 0.710), while maximum voluntary isometric contraction (p = 0.048) and repetitions to failure (p = 0.011) did. A second trial gave 1000 mg daily for 4 weeks at an altitude camp to 42 competitive male distance runners: the 3000 m time trial was not significantly improved (urolithin A p = 0.116, placebo p = 0.771) and the between-group aerobic capacity interaction was not significant (p = 0.138), although creatine kinase after the time trial and perceived exertion were lower.

Participants / model
20 resistance-trained men; 42 highly trained male distance runners
Treatment
Oral urolithin A 1 g daily for 8 weeks; 1000 mg daily for 4 weeks
Follow-up
8 weeks; 4 weeks
Study design
Two randomized trials
Funding
No conflict of interest was reported for the 20-man trial; the 42-runner trial was funded by Amazentis SA

Neither trial tested older adults, so neither replicates the older-adult result.

Read the original source
Other groups: CD8+ cell markers (50), vascular function (50), heart failure (10)

Randomized controlled trial

Denk D et al. Nat Aging. 2025;5(11):2309-2322. PMID 41174221.

A 4-week trial of 50 healthy middle-aged adults on 1,000 mg daily found urolithin A expanded naive-like, less terminally exhausted CD8+ cells (treatment difference 0.50 percentage points; 95% CI 0.16 to 0.83; P = 0.0437) and raised CD8+ fatty acid oxidation capacity. In 50 middle-aged adults with obesity (BMI 30 or above) given 1000 mg for 4 weeks, brachial artery flow-mediated dilation did not differ from placebo (0.3% control versus 1.3% active), and the authors call the cerebrovascular signal worth further study. In 10 patients with heart failure with reduced ejection fraction, 500 mg twice daily for 4 weeks in a crossover design showed no effect on echocardiographic measures.

Participants / model
50 healthy middle-aged adults; 50 middle-aged adults with obesity; 10 patients with heart failure with reduced ejection fraction
Treatment
Oral urolithin A 1,000 mg daily for 4 weeks; 500 mg twice daily for 4 weeks
Follow-up
4 weeks in each trial
Study design
Three randomized trials, the heart failure study as a crossover
Funding
Amazentis funded the CD8+ trial and supplied Mitopure; no conflict of interest was reported for the obesity trial; funding is not stated in the source for the heart failure study

PubMed flags an erratum for the CD8+ paper (Nat Aging 2026), so its figures may change. The CD8+ results are immune biomarkers, not strength or endurance outcomes.

Read the original source

Why is Urolithin A in C tier?

C fits a well-tolerated compound whose outcome data are thin and come mostly from company-sponsored trials. Both Amazentis trials missed their primary endpoints, the pooled walking-distance result was not significant with low certainty, and trials in athletes, vascular function and heart failure were null or mixed. The grade covers the supplier's muscle and mitochondrial claims, and the mitophagy part of them rests on gene and protein markers.