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SOURCE-LINKED STUDY SUMMARY

Urolithin A Muscle Trial: Endurance Signal, Mixed Results

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

JAMA network open ·

Human

PED EVIDENCE INTERPRETATION

Did urolithin A improve muscle performance?

In 66 older adults, urolithin A did not significantly outperform placebo on the primary walking-distance or ATP-production outcomes. A secondary endurance advantage appeared at two months, not four. [1]

Design
Double-blind randomized trial
Population
66 adults aged 65–90; 33 per group
Comparison
Oral urolithin A 1,000 mg/day vs placebo
Duration
4 months; endurance also tested at month 2

The evidence at a glance

Primary outcomes and the secondary endurance signal [1]
Outcome / timingUrolithin APlaceboUncertainty / meaning
6-minute walk, month 4 [1]+60.8 m+42.5 mPrimary; no significant between-group difference
Hand ATP production, month 4 [1]+0.07 mM/s+0.06 mM/sPrimary; no significant between-group difference
Hand endurance, month 2 [1]+95.3 contractions+11.6 contractionsSecondary; significant at month 2, not month 4

Changes from baseline. Walking-distance SD: 67.2 vs 73.3 m; hand-endurance SD: 115.5 vs 147.4 contractions. These are variability measures, not confidence intervals.

OUR READING OF THE EVIDENCE

What this changes

The signal merits confirmation using a prespecified functional outcome and follow-up long enough to test persistence. [1][2]

What it does not establish

It does not establish better everyday mobility, muscle growth or longer life. A null comparison also does not establish equivalence. [1]

Put it in context

The related trial also had a null primary endpoint

A separate four-month trial in untrained adults aged 40–64 reported improvements in some strength measures, but not its primary endpoint, peak power output. Different tests and populations mean it is not a direct replication of the older-adult endurance finding. [2]

What would strengthen the case?

An independently conducted trial that replicates a meaningful functional improvement would be more persuasive than accumulating favorable biomarker changes. Biomarker movement alone does not tell a reader how much better they will move or feel.

Sources and transparency

Interpretation added . Full-text older-adult trial, including endpoint timing, plus a related middle-aged-adult trial.

Amazentis funded and participated in the older-adult trial. The small, predominantly female, all-White sample limits generalizability. Short follow-up cannot settle long-term safety. [1]

  1. Liu et al., older-adult randomized trial (2022)DOI 10.1001/jamanetworkopen.2021.44279 · Primary and secondary results, including month 4
  2. Singh et al., middle-aged-adult randomized trial (2022)DOI 10.1016/j.xcrm.2022.100633 · Primary peak-power outcome and strength measures

AI-assisted editorial analysis by PED Evidence. Sources are linked for verification; no independent clinician review or formal risk-of-bias assessment is claimed. Studied exposures describe the research, not a recommended regimen. Editorial and correction policy.

Questions this study helps answer

Did this trial show that urolithin A builds muscle?

No. It assessed mitochondrial and performance outcomes; the results do not establish hypertrophy. An endurance finding is different from increased muscle size. [1]

Why does the two-month versus four-month distinction matter?

A benefit observed at one assessment may not persist. The primary four-month comparisons and later endurance assessment should be considered alongside the favorable two-month result. [1]

Original compact summary and study details
Abstract summarizedQuality not appraised
What was studied
A blinded, randomized trial tested urolithin A against placebo for walking ability, muscle endurance and cellular energy production.
Who / model studied
66 adults aged 65 to 90 took part in a 4-month trial.
Studied dose & schedule
In this randomized study of adults aged 65 to 90 years, participants received 1000 mg urolithin A orally each day or placebo for 4 months. This was the assigned study intervention; the abstract does not describe a starting-dose adjustment or any individualized regimen.
What the study found
Muscle endurance measures improved, but walking distance and the primary cellular-energy measure did not improve significantly versus placebo.
Limitations & context
This was a small study, predominantly in women, and all participants were White. The authors called for further confirmation.

Read summary source ↗ · Prepared 9/15/2026 · AI-assisted, source-based summary

Review record & corrections

Summary prepared: . Source scope: abstract. This is an AI-assisted source summary, not an independent clinician sign-off.

No public field-by-field revision history is available for this card yet. The date above is the summary date, not proof that every field was updated then.

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Research findings apply to the population and conditions studied. This educational summary is not a treatment recommendation or a formal assessment of study quality.

Original publication ↗ · DOI: 10.1001/jamanetworkopen.2021.44279

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