Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners.
Level 2 - randomized trial
Double-blind, parallel-group, placebo-controlled randomized trial
PubMed 40839339 · doi:10.1007/s40279-025-02292-5
What was done
In a double-blind, parallel-group, placebo-controlled trial (NCT04783207), 42 competitive male distance runners (mean age 27.2 ± 1.0 years, VO2max 66.4 ± 0.6 mL·kg⁻¹·min⁻¹) were randomized to receive 1000 mg/day Urolithin A (n = 22) or placebo (n = 20) for 4 weeks during an altitude training camp (~1700–2200 m). Body composition, hemoglobin mass, running economy, and VO2max were measured at baseline and post-intervention. Muscle damage (creatine kinase, CK) and inflammation (C-reactive protein) were assessed following weekly downhill running bouts. Subsets completed a 3000 m track time trial (n = 11 per group) or underwent skeletal muscle biopsies (n = 11 UA, n = 9 placebo) for proteomic and mitochondrial assessments.
What was found
Running performance on the 3000 m time trial was not significantly improved in either group (UA: p = 0.116; placebo: p = 0.771). However, UA significantly lowered ratings of perceived exertion (p = 0.02) and reduced post-exercise CK total area under the curve (p < 0.0001) compared with placebo. Aerobic capacity showed no statistically significant time × treatment interaction (p = 0.138), though UA supplementation produced a within-group VO2max increase of 5.4 ± 0.9% (66.4 ± 0.8 to 70.0 ± 1.0 mL·kg⁻¹·min⁻¹, p = 0.009, d = -0.83) compared to 3.6 ± 1.3% in placebo (66.4 ± 0.9 to 68.7 ± 1.0 mL·kg⁻¹·min⁻¹, p = 0.098, d = -0.54). Muscle proteomics indicated UA upregulated mitochondrial pathways and downregulated inflammatory pathways, with a non-significant medium effect for mitophagy markers (d = -0.74) and no change in mitochondrial function.
Why it matters
This study provides evidence that Urolithin A can reduce muscle damage markers and perceived exertion during intense endurance training, though these physiological benefits did not translate to superior time-trial performance in elite runners.
Limits
The total sample size was small (n = 42), and key endpoints like the 3000 m time trial and muscle biopsies were assessed in even smaller subsets (n = 20–22). The study was limited to competitive male runners across a short 4-week window at altitude, limiting generalizability to females, recreational athletes, or longer supplementation periods.