Tier 2 — strong

Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners

Whitfield J, McKay AKA, Tee N, McCormick R, Morabito A, Karagounis LG, Fouassier AM, D'Amico D, Singh A, Burke LM, Hawley JA
Sports Medicine 2025 55(12):3183-3200

Bibliography

PubMed
PMID 40839339
PubMed Central
PMC12628386
DOI
10.1007/s40279-025-02292-5
Funding
Not disclosed as a separate statement in the sections of the article reviewed for this entry. Co-authors are affiliated with Nestlé Health Science and Amazentis SA (the manufacturer of Urolithin A/Mitopure), both commercially interested parties in this ingredient.
Competing interests
Several co-authors are employees of Nestlé Health Science and/or Amazentis SA (the manufacturer of Urolithin A/Mitopure). A formal conflict-of-interest statement was not captured in the sections of the article reviewed, but this affiliation pattern is the relevant disclosure. Unlike the Singh 2022 and Andreux 2019 trials, the lead authors here are university-affiliated (Australian Catholic University), which is a meaningfully more independent structure even with commercial co-authors and product supply involved.

Study snapshot

DesignDouble-blind, parallel-group, placebo-controlled randomised trial (NCT04783207)
ModelCompetitive male distance runners (n=42, mean age 27.2 years, elite-level VO2max)
Sample42 randomised (22 UA, 20 placebo); subsets underwent time-trial testing (11 vs 11) and muscle biopsy (11 vs 9)
InterventionOral Urolithin A 1,000mg/day vs placebo for 4 weeks during an altitude training camp (1,700-2,200m)
Duration4 weeks
EndpointsRunning performance (3,000m time trial); Rating of perceived exertion (RPE) and markers of muscle damage (creatine kinase) after a downhill running bout; Aerobic capacity (VO2max), running economy, body composition; Skeletal muscle proteome and mitochondrial function (biopsy subset)

What the study showed, in plain terms

Most Urolithin A human data comes from overweight, sedentary, or older adults. This 2025 trial asked a different, more athletically demanding question: does it help competitive endurance runners during hard altitude training?

The honest answer is mixed, and a useful counterweight to more promotional framing. Urolithin A did NOT significantly improve 3,000m running performance. It did reduce perceived exertion and post-exercise muscle damage markers (creatine kinase) after a hard downhill running bout, and there was a large — though not statistically significant against placebo — improvement in aerobic capacity within the treated group. Muscle biopsies showed Urolithin A upregulated mitochondria-related pathways and reduced inflammatory pathways at the protein level.

For readers who are already highly trained athletes rather than typical supplement users, this is the most relevant available data: modest recovery-related benefits, but no clear performance win in a genuinely demanding, well-trained population.

Key findings

  • No significant improvement in race performance: 3,000m time-trial performance did not significantly improve with Urolithin A versus placebo.
  • Reduced perceived exertion and muscle damage after hard exercise: Urolithin A significantly lowered rating of perceived exertion (p=0.02) and reduced creatine kinase (a muscle damage marker) area-under-the-curve (p<0.0001) after a 3,000m time trial, compared with placebo.
  • A large but not statistically significant rise in aerobic capacity: the UA group showed a 5.4% within-group increase in VO2max (p=0.009) versus a smaller 3.6% rise in the placebo group, but the between-group time × treatment interaction was not statistically significant (p=0.138).
  • Muscle proteomics showed mitochondrial upregulation and reduced inflammation: biopsy analysis found Urolithin A upregulated mitochondria-associated pathways and downregulated inflammatory pathways, with a non-significant trend toward increased mitophagy markers.

What this study can and cannot tell us

No performance benefit on the primary competitive outcome. The 3,000m time trial — arguably the most practically meaningful outcome for competitive runners — showed no significant improvement.

Small, narrow, short-duration sample. 42 highly trained male runners over 4 weeks; findings may not generalise to female athletes, other sports, or longer supplementation periods.

Commercial co-authorship. Co-authors from Nestlé Health Science and Amazentis SA were involved, though the lead investigators are university-affiliated, which is a more independent structure than the earlier company-run trials in this Data Center.

Citation network

Articles citing this research paper

1 article

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability