2 detailed study records

Key findings from detailed records

Human trials of urolithin A have reported improvements in selected measures of muscle strength and endurance. The clearest signals concern specific muscle tests, rather than a general improvement in walking ability or a proven extension of human lifespan. Here we distinguish those findings from mitochondrial mechanisms, branded ingredients and patents.

KNOWLEDGE RECORD

Category
Metabolism and cellular function
Last Reviewed

Names and related search termsUrolithin A / Urolithin A / UA / Mitopure / Mitophagy

Study type: human intervention study.

Explore 10 papers by research question ↓

OUTCOME-SPECIFIC EVIDENCE

Scientific Evidence Profile

Editorial pilot · selected evidence; not a systematic review or formal GRADE assessment.

Hamstring strength in sedentary middle-aged adults with overweight

Limited

A 4-month trial in 88 randomized adults found improvement versus placebo at 500 and 1,000 mg/day. This supports a specific strength signal, with further independent confirmation needed.

Basis of this assessment
Human study quality
Randomized, blinded, placebo-controlled human trials; the positive muscle outcomes were secondary.
Scale and replication
Small trials with different tests and populations; independent confirmation of the same outcome is limited.
Consistency of findings
Selected muscle measures improved, while primary functional outcomes did not. The result depends on the test and timepoint.
Clinical relevance
A measured muscle benefit is more direct than a blood biomarker, but does not establish less disability or longer life.
Systematic reviews / meta-analyses
The 2026 review found strength and endurance measures too heterogeneous to pool. Its pooled walking result was inconclusive.
Limitations / funding / COI
The central trials were funded by Amazentis and included company-affiliated authors. Limited follow-up and independent replication constrain confidence; funding alone is not the reason for the level.

Assessment sources

Hand and leg muscle endurance in adults aged 65–90

Limited

A 66-person trial of 1,000 mg/day found a placebo-controlled benefit at 2 months, but not at 4 months. Walking distance and maximal ATP production did not show significant primary-outcome benefits.

Basis of this assessment
Human study quality
Randomized, blinded, placebo-controlled human trials; the positive muscle outcomes were secondary.
Scale and replication
Small trials with different tests and populations; independent confirmation of the same outcome is limited.
Consistency of findings
Selected muscle measures improved, while primary functional outcomes did not. The result depends on the test and timepoint.
Clinical relevance
A measured muscle benefit is more direct than a blood biomarker, but does not establish less disability or longer life.
Systematic reviews / meta-analyses
The 2026 review found strength and endurance measures too heterogeneous to pool. Its pooled walking result was inconclusive.
Limitations / funding / COI
The central trials were funded by Amazentis and included company-affiliated authors. Limited follow-up and independent replication constrain confidence; funding alone is not the reason for the level.

Assessment sources

Profile reviewed:

This profile concerns the stated outcome and population, not the ingredient as a whole. It is not a probability of benefit, a safety rating, a product efficacy rating or an indication of product adoption.

How we assess evidence

Ingredient Profile

What is it?
Urolithin A is a defined small molecule in the urolithin family. Studying an isolated molecule makes a different comparison from studying a complex food or extract. [1]
Sources for this profile

Compound properties and formulation properties are different. These sources do not establish the efficacy of a finished supplement.

  1. PubChem — Urolithin A (CID 5488186) Chemical identity reference. Maintained by NCBI, U.S. National Library of Medicine. Database record; not a clinical trial.

Profile sources checked:

Read the evidence in context
  • Evidence: what was measured in the stated population or experimental model.
  • Inference: an interpretation connecting findings; its applicability depends on the study conditions.
  • Hypothesis: a proposed explanation or effect that remains to be tested.

Research Evidence · Scientific Synthesis

Why It Matters #

Maintaining muscle function supports everyday movement. Urolithin A is being studied because it connects gut microbial metabolism with mitochondrial quality control. It offers a useful way to ask whether a cellular mechanism can translate into a measurable functional benefit.

What Was Studied #

Two randomized placebo-controlled trials provide the detailed muscle records below: 88 sedentary, middle-aged adults with overweight were assigned to 500 or 1,000 mg/day or placebo for 4 months; 66 adults aged 65–90 were assigned to 1,000 mg/day or placebo for 4 months. Both studied Mitopure®, but used different muscle tests.[1] [2]

What Was Found #

The middle-aged trial found improved hamstring strength versus placebo at both doses. The older-adult trial found improved hand and leg muscle endurance versus placebo at 2 months. These were secondary findings: the trials did not show significant between-group improvement in their primary peak-power, walking-distance or maximal ATP-production outcomes.[1] [2]

What the Evidence Means #

The muscle findings are encouraging but endpoint-specific. Small samples, short follow-up and limited independent replication constrain confidence. In the older-adult trial, the endurance advantage was not statistically significant at 4 months. Neither study establishes a longer human lifespan.[1]

Comparing similar populations, formulations, durations and outcomes helps identify where findings agree and where they differ.

What We Can Learn #

Ask which muscle, which test and which timepoint improved. A change in blood markers or mitophagy-related proteins answers a different question from walking farther or remaining independent. Match any conclusion to the studied preparation, population and dose.

What Remains Unknown #

Longer trials should establish whether the observed muscle changes persist, translate into daily function and generalize to other populations and preparations. The studies summarized here do not establish multi-year safety or a comprehensive drug-interaction profile.

From the gut to mitochondrial quality control

Food precursors → gut microbes → urolithin A. Ellagitannins and ellagic acid in foods such as pomegranates, berries and walnuts can be converted by gut bacteria. The ability to produce urolithin A varies between people. Direct UA intake bypasses this conversion step; greater blood exposure does not itself demonstrate a greater health benefit.

Singh et al. · 2021/2022

Mitophagy is the selective recycling of mitochondria through the cell’s autophagy machinery. UA stimulated this process in preclinical models. Human studies have found changes in mitochondrial gene expression and mitophagy-related muscle proteins, alongside selected functional outcomes. Those molecular observations support a mechanism; they are not a direct measurement of whole-body mitochondrial renewal.

Ryu et al. · 2016 Singh et al. · 2022

How the wider evidence fits together

The 2026 systematic review included 5 randomized trials with 236 participants. Only the 6-minute walk test could be pooled across 2 trials: the estimated difference was +17.03 m, with a 95% confidence interval from −5.33 to 39.40 m. This interval includes no difference. Strength and endurance findings were too heterogeneous to pool, so the review does not establish a reproducible overall muscle benefit.

Systematic review · 2026

Safety and use in context

In the 4-month older-adult trial, adverse events did not differ statistically from placebo. The middle-aged trial also reported no significant safety differences in the assessed measures. These findings support short-term tolerability in the studied adults. They do not establish safety for every population or for years of use.

[1] [2]

The evidence reviewed here is not sufficient to define drug interactions or safety during pregnancy, breastfeeding or childhood. People taking medicines or receiving treatment should discuss use with their clinician. Trial doses are research conditions, not a personal dosing recommendation.

FDA’s response to GRAS notice 791 stated that it had no questions regarding Amazentis’s conclusion for the specified food uses. This is not FDA approval of efficacy or authorization to treat disease.

FDA · GRN 791

Research, Commercialization & Intellectual Property

Amazentis is the Swiss company behind the development programme. Mitopure® is its branded urolithin A ingredient; Timeline is its consumer brand. These names describe a company, an ingredient and a brand—not three different molecules. Amazentis describes Mitopure as more than 98% pure UA. This is a manufacturer specification, not a specification for every UA ingredient.

Amazentis

The two detailed muscle trials used Mitopure. Their results belong to the tested preparation, dose and population. Another product with the same molecule should be assessed for identity, purity, formulation and exposure rather than assumed to have identical clinical evidence.

Research and commercialization milestones

  • 2016: Preclinical mitophagy research in worms and rodents. Source ↗
  • 2018: FDA response to GRAS notice 791 for specified food uses. Source ↗
  • 2019: First human study of tolerability and mitochondrial molecular signatures. Source ↗
  • 2020: Announcement of the Timeline consumer launch using Mitopure. Source ↗
  • 2022: Randomized muscle-function trials in middle-aged and older adults. Source ↗

Three different types of patent protection

US11634401B2

Process: a specified route for process-scale synthesis of UA.

United States · applicant / assignee: Amazentis SA · granted 2023-04-25.

US10442784B2

Composition: claim 1 combines a protein source with UA.

United States · applicant / assignee: Amazentis SA · granted 2019-10-15.

US9872850B2

Use: claim 1 concerns administering a urolithin to a mammal to enhance muscle performance.

United States · applicant / assignee: Amazentis SA · granted 2018-01-23.

As reviewed on 2026-10-25, Google Patents lists these US grants as Active. This records the database status, not an independent legal determination of validity, enforceability or current maintenance fees. Rights in Japan, Vietnam and other jurisdictions have not been assessed here. Patent scope depends on the granted claims and jurisdiction, not the title alone.

A patent protects a claimed invention; it does not prove clinical efficacy or imply exclusive ownership of every use of urolithin A. Mitopure® is a trademark. Research evidence, intellectual property and product adoption are separate questions. Inclusion in LÍFSVARÐA Knowledge does not indicate use or planned use in a LÍFSVARÐA product.

LITERATURE MAP / 10 PAPERS

Compare papers by conditions and findings.

A map focused on direct UA supplementation trials, comparing muscle function, pharmacokinetics, immunity, exercise and populations with disease. Gut microbial metabotype studies are distinguished from supplementation trials.

Selected: 2026-09-21. Bibliographic information checked against Europe PMC / PubMed. Editorial selection considered major papers and a range of populations and questions. This is not a systematic search covering all recent research.

10 RECORDS

A dash marks fields outside the bibliographic record. Use detailed records to compare findings and design records to connect mechanisms.

Research comparison table
Paper and topicStudy conditionsFindings and scope
Exercise and muscle functionEffect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.2022 JAMA network openPMID 35050355 #Study conditions

Randomized, double-blind, placebo-controlled trial

Population
66 adults aged 65–90, mean age 71.7; approximately 76% women, all White.
Dose
Urolithin A 1,000 mg/day
Duration
4 months
Outcomes
Primary: six-minute walk distance and maximal ATP production in hand skeletal muscle. Secondary: muscle endurance and other measures.
Findings and scope

Secondary hand and leg muscle endurance improved versus placebo at 2 months; selected blood markers improved at 4 months. Neither primary outcome—6-minute walk distance or maximal ATP production—showed a significant between-group benefit at 4 months.

View findings and limitations

DOI

Authors

Liu S, D'Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P et al.

Exercise and muscle functionUrolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.2022 Cell reports. MedicinePMID 35584623 #Study conditions

Randomized placebo-controlled trial

Population
88 sedentary middle-aged adults with overweight; 79 completed the trial.
Dose
Urolithin A 500 mg/day or 1,000 mg/day versus placebo.
Duration
4 months
Outcomes
Primary: peak power. Strength, aerobic capacity and other measures were also assessed.
Findings and scope

Hamstring strength improved versus placebo at 500 and 1,000 mg/day after 4 months. The primary peak-power outcome did not differ significantly. Walking-distance and aerobic-capacity changes included within-group improvements, not statistically significant superiority over placebo.

View findings and limitations

DOI

Authors

Singh A, D'Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M et al.

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.2019 Nature metabolismPMID 32694802 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Andreux PA, Blanco-Bose W, Ryu D, Burdet F, Ibberson M, Aebischer P et al.

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population.2022 European journal of clinical nutritionPMID 34117375 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Singh A, D'Amico D, Andreux PA, Dunngalvin G, Kern T, Blanco-Bose W et al.

Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial.2025 Nature agingPMID 41174221 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Denk D, Singh A, Kasler HG, D'Amico D, Rey J, Alcober-Boquet L et al.

Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study.2024 Journal of the International Society of Sports NutritionPMID 39487653 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Zhao H, Zhu H, Yun H, Liu J, Song G, Teng J et al.

Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial.2024 Reviews on recent clinical trialsPMID 38415449 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Jamialahmadi T, Hasanpour M, Vakilian F, Penson PE, Iranshahy M, Sahebkar A

Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners.2025 Sports medicine (Auckland, N.Z.)PMID 40839339 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Whitfield J, McKay AKA, Tee N, McCormick R, Morabito A, Karagounis LG et al.

Effects of Urolithin A supplementation on performance and antioxidant status in academy soccer players during preseason: a pilot randomised controlled trial.2025 Frontiers in nutritionPMID 41245402 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Monsalve Acevedo A, Sanctuary C, Aitken RJ, Wilkins A, Harrison N, Naughton M

Deciphering the Human Gut Microbiome of Urolithin Metabotypes: Association with Enterotypes and Potential Cardiometabolic Health Implications.2019 Molecular nutrition & food researchPMID 30471188 #Study conditions

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Findings and scope

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Open original paper

DOI

Authors

Romo-Vaquero M, Cortés-Martín A, Loria-Kohen V, Ramírez-de-Molina A, García-Mantrana I, Collado MC et al.

The literature map is an index of research questions and references. Individual assessment of results, doses, funding and COI is limited to the detailed study records. Related reports from the same trial may be included; paper counts are not counts of independent trials.

Explore the research Study Records

Listed doses describe study conditions, not recommended intake.

Study RecordPMID 35584623

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.

Authors
Singh A, D'Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, Aebischer P, Auwerx J, Rinsch C.
Journal
Cell reports. Medicine
Publication year
2022
Study design
Randomized placebo-controlled trial
Participants
88 sedentary middle-aged adults with overweight; 79 completed the trial.
Dose and intervention
Urolithin A 500 mg/day or 1,000 mg/day versus placebo.
Duration
4 months
Outcomes and their role in the study
Primary: peak power. Strength, aerobic capacity and other measures were also assessed.
Findings
Hamstring strength improved versus placebo at 500 and 1,000 mg/day after 4 months. The primary peak-power outcome did not differ significantly. Walking-distance and aerobic-capacity changes included within-group improvements, not statistically significant superiority over placebo.
Limitations
Secondary strength findings were positive, while the primary peak-power outcome was not significant. Walking and aerobic measures included within-group changes rather than significant superiority to placebo. The trial was small, sponsor-funded and limited to 4 months.
Funding
Amazentis SA.
Conflict of Interest
Authors included sponsor employees, officers and scientific advisers.
Scope of source review
Relevant primary methods, endpoint hierarchy, timepoints, results, safety and disclosures checked on 2026-10-24. Secondary and within-group findings are distinguished from primary between-group outcomes.
Study RecordPMID 35050355

Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.

Authors
Liu S, D'Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, Rinsch C, Singh A, Marcinek DJ.
Journal
JAMA network open
Publication year
2022
Study design
Randomized, double-blind, placebo-controlled trial
Participants
66 adults aged 65–90, mean age 71.7; approximately 76% women, all White.
Dose and intervention
Urolithin A 1,000 mg/day
Duration
4 months
Outcomes and their role in the study
Primary: six-minute walk distance and maximal ATP production in hand skeletal muscle. Secondary: muscle endurance and other measures.
Findings
Secondary hand and leg muscle endurance improved versus placebo at 2 months; selected blood markers improved at 4 months. Neither primary outcome—6-minute walk distance or maximal ATP production—showed a significant between-group benefit at 4 months.
Limitations
The muscle findings are encouraging but endpoint-specific. Small samples, short follow-up and limited independent replication constrain confidence. In the older-adult trial, the endurance advantage was not statistically significant at 4 months. Neither study establishes a longer human lifespan.
Funding
Amazentis SA. Involvement in design, conduct, analysis, manuscript preparation and publication decisions was described.
Conflict of Interest
Authors included sponsor employees, officers, shareholders and individuals with patent-related interests. See the original disclosures.
Scope of source review
Relevant primary methods, endpoint hierarchy, timepoints, results, safety and disclosures checked on 2026-10-24. Secondary and within-group findings are distinguished from primary between-group outcomes.

Cite this page

Urolithin A: muscle function, mitophagy and the research behind Mitopure®. LÍFSVARÐA. Version 2.0 / Updated 2026-10-25.

https://lifsvarda.com/knowledge/urolithin-a/

Edited by LÍFSVARÐA (product brand).Editorial policy

Sources and updates

  1. Liu S, D'Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, Rinsch C, Singh A, Marcinek DJ. (2022). Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.Relevant primary methods, endpoint hierarchy, timepoints, results, safety and disclosures checked on 2026-10-24. Secondary and within-group findings are distinguished from primary between-group outcomes.
  2. Singh A, D'Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, Aebischer P, Auwerx J, Rinsch C. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.Relevant primary methods, endpoint hierarchy, timepoints, results, safety and disclosures checked on 2026-10-24. Secondary and within-group findings are distinguished from primary between-group outcomes.

2026-10-25 · Version 2.0: Expanded the muscle-evidence summary, mechanism, safety, research history and representative US patent examples; added an outcome-specific evidence profile. Central trial methods, results and disclosures and the 2026 synthesis were checked. Historical entries below are retained.

First published: 2026-09-21 / Version 1.1. Updated 2026-09-23: Added a research comparison table and links to design records. Source notes identify the scope of verification when the full paper has not been reviewed. Research summaries and LÍFSVARÐA’s interpretation are distinguished.