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

Singh A, D'Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, Aebischer P, Auwerx J, Rinsch C
Cell Reports Medicine 2022 3(5):100633

Bibliography

PubMed
PMID 35584623
PubMed Central
PMC9133463
DOI
10.1016/j.xcrm.2022.100633
Funding
Not disclosed as a separate statement in the sections of the article reviewed for this entry. The study product was supplied by Amazentis SA, whose employees make up the majority of the author list — see the competing-interests note for the relevant disclosure this implies.
Competing interests
Study product (Urolithin A / Mitopure) was manufactured and supplied by Amazentis SA. The lead contacts (Drs Anurag Singh and Chris Rinsch) and the majority of the author list are Amazentis SA employees; this is a company-run and company-authored trial of the company's own product. A formal conflict-of-interest statement was not captured in the sections of the article reviewed, but this affiliation pattern is the relevant disclosure.

Study snapshot

DesignRandomised, double-blind, placebo-controlled trial (ATLAS, NCT03464500)
ModelOverweight, sedentary, middle-aged adults (40-65 years, BMI 25-34.9, VO2max <35 mL/kg/min)
Sample88 randomised (29 placebo, 29 UA 500mg, 30 UA 1,000mg); 79 completed; intent-to-treat analysis included all 88
InterventionOral Urolithin A (Mitopure) at 500mg/day or 1,000mg/day vs placebo, for 4 months
Duration4 months (120 days)
EndpointsPrimary: peak power output (PPO) on incremental cycling test; Secondary: leg muscle strength (Biodex dynamometry), hand-grip strength, VO2 peak, 6-minute walk test, gait speed; Exploratory: plasma acylcarnitines, C-reactive protein, inflammatory cytokines, skeletal muscle transcriptome/proteome

What the study showed, in plain terms

This is the landmark human trial behind most Urolithin A marketing claims: a 4-month, placebo-controlled study in 88 overweight, out-of-shape, middle-aged adults, testing whether Urolithin A (the company's own branded ingredient, Mitopure) improved muscle strength and fitness.

The honest headline: the trial's own pre-specified primary endpoint — peak power output on a cycling test — was NOT statistically significantly improved by Urolithin A. What did improve significantly was leg muscle strength (roughly 10-12% versus placebo, measured by isokinetic dynamometry) at both doses, and — at the higher 1,000mg dose only — aerobic endurance and 6-minute walk distance. Blood markers of inflammation and mitochondrial fat-burning efficiency also improved.

This is a genuinely useful, well-instrumented human trial — but read the result exactly as reported, not as the marketing summary. A real muscle-strength benefit at a secondary endpoint is meaningfully different from a confirmed win on the trial's own primary question. It is also, again, a company-run trial of the company's own product, authored by company employees.

Key findings

  • Primary endpoint (peak power output) was NOT met: both UA doses showed a non-significant ~4% increase in peak power output versus placebo (p not significant) — the trial's own pre-specified primary outcome.
  • Leg muscle strength improved significantly at both doses: hamstring peak torque rose +12% (500mg, p=0.027) and +9.8% (1,000mg, p=0.029) versus placebo; the placebo group's strength significantly declined over the same period (-9.8%).
  • Higher-dose-only benefits on endurance and walking: only the 1,000mg dose produced a statistically significant within-group rise in peak VO2 and a clinically meaningful increase in 6-minute walk distance (+33.4m, exceeding the >30m threshold considered clinically important in older adults).
  • Inflammatory and mitochondrial biomarkers improved: C-reactive protein fell significantly at the 1,000mg dose; plasma acylcarnitines fell at the 500mg dose; muscle biopsies showed dose-dependent increases in mitophagy and OXPHOS pathway proteins.
  • Body composition was unchanged: lean body mass and fat mass, measured by DEXA, did not differ between groups after 4 months.

What this study can and cannot tell us

The trial's own primary endpoint was not met. Peak power output — the pre-specified primary outcome — showed only a non-significant trend. The statistically significant strength finding is a secondary endpoint, which changes how much weight it should carry.

Sponsor-run and sponsor-authored. This is a study of Amazentis SA's own branded ingredient (Mitopure), designed, run, and authored predominantly by Amazentis employees. Independent replication by unaffiliated researchers would carry substantially more weight.

Proof-of-concept sizing. The authors themselves describe this as a proof-of-concept study, explicitly designed to identify which endpoints warrant a larger, adequately powered confirmatory trial — not as a definitive efficacy trial.

Narrow population. Results are in overweight, sedentary, middle-aged adults specifically selected for low baseline fitness — not necessarily generalisable to lean, active, or older/frailer populations.

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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