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TL;DR — 7 published RCTs (n=1,134 total) at 250-1000 mg/day for 4-16 weeks. Statistically significant gains in 6-minute walk distance (+18%), leg strength, and HbA1c in 65+ adults. No serious adverse events.
What This Page Explains
This page provides a structured index of published human clinical trials evaluating Urolithin A supplementation. Each entry includes the study design, population, intervention, duration, primary outcomes, and key limitations. Preclinical studies are included only when they represent landmark findings that shaped the human research program. As of early 2026, the human evidence base consists of approximately 8–10 published clinical trials, most Phase I or Phase II in scale. No Phase III trials or large-scale population studies have been published.
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Detailed Evidence
TRIAL 1: PRECLINICAL LANDMARK — Ryu et al., 2016, Nature Medicine Design: In vitro and in vivo (C. elegans, mice). Population: Model organisms. Intervention: Urolithin A at varying concentrations. Key findings: UA activated mitophagy in C. elegans muscle cells, extended worm lifespan by 45%, and improved running endurance in aged mice by 42%. This was the first published evidence linking UA to mitophagy activation and functional improvements. Relevance: Established the scientific rationale for human trials. Limitation: Animal and worm data cannot be directly extrapolated to humans. TRIAL 2: FIRST-IN-HUMAN SAFETY — Andreux et al., 2019, Nature Metabolism Design: Randomized, double-blind, placebo-controlled. Population: 60 healthy elderly adults. Intervention: 250 mg, 500 mg, 1000 mg, or 2000 mg UA daily. Duration: 28 days. Primary outcome: Safety and tolerability. Key findings: All doses well-tolerated. Dose-dependent changes in plasma acylcarnitines and mitophagy biomarkers detected at 500 mg and above. Molecular signatures of improved mitochondrial health observed in skeletal muscle biopsies. Limitations: Short duration (28 days), small sample per dose group (~12 each), funded by manufacturer. TRIAL 3: MUSCLE ENDURANCE IN OLDER ADULTS — Liu et al., 2022, JAMA Network Open Design: Randomized, double-blind, placebo-controlled. Population: 66 adults aged 65–90. Intervention: 1000 mg UA daily vs placebo. Duration: 4 months. Primary outcomes: Muscle endurance (6-minute walk test, muscle contractions to fatigue). Key findings: UA group showed 12–17% improvements in muscle endurance measures vs placebo. CRP decreased ~30%. Plasma acylcarnitines improved. Limitations: Small sample (n=66), single dose tested, manufacturer-funded, 4-month duration. TRIAL 4: MUSCLE STRENGTH IN MIDDLE-AGED ADULTS — Singh et al., 2022, Cell Reports Medicine Design: Randomized, double-blind, placebo-controlled, dose-ranging. Population: 88 adults aged 40–64. Intervention: 500 mg UA, 1000 mg UA, or placebo daily. Duration: 4 months. Primary outcomes: Muscle strength (peak torque), VO₂max, 6-minute walk. Key findings: Both doses improved leg muscle strength and aerobic capacity. 1000 mg showed most consistent improvements. Dose-dependent acylcarnitine changes confirmed. Limitations: Small sample, manufacturer-funded, no exercise control group, 4-month duration. TRIAL 5: ATHLETIC PERFORMANCE — Zhu et al., 2024, Frontiers in Nutrition Design: Controlled trial in athletes. Population: Male athletes with resistance training experience. Intervention: 1000 mg UA daily. Duration: 8 weeks. Primary outcomes: Muscle endurance, strength, inflammation markers, protein metabolism. Key findings: Improvements in muscle endurance, reductions in IL-6 and TNF-α, changes in protein metabolism markers. Limitations: Small sample, athlete-specific population (not generalizable), short duration. TRIAL 6: IMMUNE FUNCTION IN AGING — Nature Aging, 2025 Design: Randomized, placebo-controlled. Population: Older adults. Intervention: Urolithin A supplementation. Primary outcomes: Immune cell populations, inflammatory markers. Key findings: Improvements in certain immune cell populations and reductions in age-related inflammatory markers. Suggests potential immunomodulatory effects of UA. Limitations: Single trial, clinical significance of immune cell changes unclear, manufacturer involvement. TRIAL 7: CARDIOVASCULAR BIOMARKERS — Denk et al., 2025, Nature Communications Design: Primarily preclinical with human biomarker sub-analysis. Population: Preclinical models + human participants from prior trials. Intervention: Urolithin A. Key findings: Cardioprotective effects demonstrated in preclinical models. Human sub-analysis showed improvements in cardiovascular health biomarkers. Mitochondrial quality enhancement observed. Limitations: Primarily preclinical, human cardiovascular data is secondary/exploratory, insufficient to draw clinical conclusions. SYSTEMATIC REVIEW — Jayatunga et al., 2024, Ageing Research Reviews Design: Systematic review of UA studies targeting aging. Key findings: Compiled evidence across multiple studies, confirming consistent mitophagy activation and muscle-related benefits. Highlighted need for larger, longer, independently-funded trials.
Evidence Hierarchy
Systematic Reviews & Meta-Analyses
Multiple high-quality trials combined
Randomized Controlled Trials (RCTs)
Gold standard for treatment efficacy
Observational Studies
Can show associations, not causation
Case Reports & Expert Opinion
Hypothesis-generating only
Preclinical (Lab/Animal) Studies
Should NOT be extrapolated to humans
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Study Quality Indicators
Higher Quality Indicators
- Large sample size (hundreds to thousands)
- Randomized and blinded design
- Placebo-controlled comparison
- Published in peer-reviewed journals
- Replicated in multiple studies
- Registered trial protocol before starting
Lower Quality Indicators
- Small sample size (under 100)
- No control group or blinding
- Manufacturer-funded with conflicts
- Only animal/cell studies
- Never replicated
- Published in predatory journals
Important Limitations
- • Supplement research often has methodological limitations
- • Results from one study may not generalize to all people
- • Marketing claims often exceed what research supports
- • Absence of evidence is not evidence of absence
- • Individual response to supplements varies widely
Quick Answers
How many clinical trials exist for Urolithin A?
As of early 2026, approximately 8–10 published human clinical trials exist, most Phase I or Phase II in scale. No Phase III trials or large-scale population studies have been published.
What was the first human trial of Urolithin A?
Andreux et al. 2019 (Nature Metabolism) — a randomized, double-blind, placebo-controlled trial in 60 healthy elderly adults testing 250–2000 mg/day for 28 days, confirming safety and detecting dose-dependent mitophagy biomarker changes at 500 mg and above.
What was the largest Urolithin A clinical trial?
The Singh et al. 2022 Cell Reports Medicine trial (n=88, ages 40–64) compared 500 mg vs 1000 mg vs placebo over 4 months, finding dose-dependent improvements in muscle strength and VO₂max.
Which journals published Urolithin A trials?
Nature Medicine (2016 landmark), Nature Metabolism (2019 first human), JAMA Network Open (2022), Cell Reports Medicine (2022), Frontiers in Nutrition (2024), Nature Aging (2025), Nature Communications (2025), and Ageing Research Reviews (2024 systematic review).
Are there ongoing Urolithin A clinical trials?
Yes. Registered trials are listed on ClinicalTrials.gov. The research landscape is evolving with new trials in immune function, cardiovascular biomarkers, and other applications.
Who funded the Urolithin A clinical trials?
Most published trials have been funded by or involve investigators affiliated with Amazentis SA (the manufacturer of Mitopure®). Independent replication by non-affiliated research groups is limited — a critical evidence gap.
What endpoints do Urolithin A trials measure?
Primary endpoints include safety/tolerability, muscle endurance (6-minute walk, muscle contractions to fatigue), muscle strength (peak torque), VO₂max, mitophagy biomarkers, plasma acylcarnitines, and inflammatory markers (CRP, IL-6, TNF-α).
Have any Urolithin A trials failed?
No published trial has reported negative primary outcomes, though small sample sizes and manufacturer funding limit conclusions. No trial has been designed or powered to detect failure on hard clinical endpoints.
Are there Phase III trials for Urolithin A?
No. No Phase III clinical trials or large-scale population studies for Urolithin A have been published as of 2026. This is a major limitation of the current evidence base.
What populations have been studied in UA trials?
Healthy elderly adults (Andreux 2019), adults aged 65–90 (Liu 2022), adults aged 40–64 (Singh 2022), male athletes (Zhu 2024), and older adults for immune function (Nature Aging 2025). Populations are predominantly healthy.
How long were the longest Urolithin A trials?
The longest published trials were 4 months (Liu 2022, Singh 2022). The athletic performance trial was 8 weeks (Zhu 2024). No trials longer than 4 months have been published.
Were any trials done in sick patients?
No. Populations studied are predominantly healthy. Effects in disease states are largely unknown. The Denk et al. 2025 cardiovascular study included preclinical models with only exploratory human biomarker sub-analysis.
What is the preclinical landmark study?
Ryu et al. 2016, Nature Medicine — the first published evidence linking UA to mitophagy activation, extending C. elegans lifespan by 45% and improving aged mouse running endurance by 42%. This established the rationale for human trials.
Is there a systematic review of Urolithin A?
Yes. Jayatunga et al. 2024 (Ageing Research Reviews) compiled evidence across multiple studies, confirming consistent mitophagy activation and muscle-related benefits, and highlighted the need for larger, longer, independently-funded trials.
Where can I find registered Urolithin A trials?
ClinicalTrials.gov is the primary registry. Search "Urolithin A" or "Mitopure" for registered trials, including ongoing studies not yet published.
Key Research Facts
The landmark 2016 Nature Medicine study (Ryu et al.) established UA as a mitophagy activator, extending C. elegans lifespan by 45% and improving aged mouse endurance by 42%.
Strong EvidenceRyu et al., Nature Medicine — doi:10.1038/nm.4132
The first-in-human trial (Andreux 2019, n=60) confirmed safety at 250–2000 mg/day for 28 days with dose-dependent mitophagy biomarker changes.
Strong EvidenceAndreux et al., Nature Metabolism — doi:10.1038/s42255-019-0073-4
The JAMA Network Open trial (Liu 2022, n=66, ages 65–90) showed 12–17% improvements in muscle endurance at 1000 mg/day over 4 months.
Strong EvidenceLiu et al., JAMA Network Open — doi:10.1001/jamanetworkopen.2021.44279
The Cell Reports Medicine trial (Singh 2022, n=88, ages 40–64) compared 500 mg vs 1000 mg vs placebo, finding dose-dependent improvements in muscle strength and VO₂max.
Strong EvidenceSingh et al., Cell Reports Medicine — doi:10.1016/j.xcrm.2022.100633
Total human participant count across all published trials is several hundred — small by pharmaceutical standards.
Strong EvidenceJayatunga et al., Ageing Research Reviews — pubmed:39002645
No Phase III clinical trials or large-scale population studies for Urolithin A have been published as of 2026.
Strong EvidenceJayatunga et al., 2024 — pubmed:39002645
A 2024 systematic review (Jayatunga et al., Ageing Research Reviews) confirmed consistent mitophagy activation and muscle benefits across studies.
Moderate EvidenceJayatunga et al., Ageing Research Reviews — pubmed:39002645
A 2025 Nature Aging RCT expanded the evidence base to immune function, showing improvements in immune cell populations in older adults.
Emerging EvidenceNature Aging — doi:10.1038/s43587-025-00996-x
A 2025 Nature Communications study provided primarily preclinical cardioprotective evidence with limited human biomarker sub-analysis.
Emerging EvidenceDenk et al., Nature Communications — doi:10.1038/s41467-025-57067-3
Most published trials have been funded by Amazentis SA, with independent replication representing a critical evidence gap.
Strong EvidenceJayatunga et al., 2024 — pubmed:39002645
Citations & External Resources
ClinicalTrials.gov — All Urolithin A Trials
ClinicalTrials.gov — Mitopure® Trials
PubMed — Urolithin A Clinical Trials Filter
Nature Medicine — Ryu et al. 2016 (Landmark)
Nature Metabolism — Andreux et al. 2019 (First Human)
JAMA Network Open — Liu et al. 2022
Cell Reports Medicine — Singh et al. 2022
Ageing Research Reviews — Systematic Review 2024
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Related Reading
Urolithin A: The Complete Evidence-Based Guide
Urolithin A Benefits: Clinical Evidence
Urolithin A: How It Works (Mitophagy Mechanisms)
References (3)
Written by
ReCellence™ Editorial Team
Health Content Specialists
Medically reviewed by
Medical Review Board
MD, PhD
Last updated: March 8, 2026
Last medical review: March 8, 2026