Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
Level 2 - randomized trial
Individual double-blind randomized placebo-controlled trial.
PubMed 35050355 · doi:10.1001/jamanetworkopen.2021.44279
What was done
A double-blind, placebo-controlled randomized clinical trial evaluated 66 adults aged 65 to 90 years (mean age 71.7 years, 75.8% women, 100% White) randomized 1:1 to daily oral urolithin A (1000 mg, n = 33) or placebo (n = 33) for 4 months. Primary endpoints were change from baseline to 4 months in 6-minute walk distance and maximal ATP production in hand muscle (first dorsal interosseus [FDI]) measured by magnetic resonance spectroscopy. Secondary endpoints included muscle endurance (contractions until fatigue) in the hand (FDI) and leg (tibialis anterior [TA]), plasma metabolomic and inflammatory biomarkers, and adverse events. Analysis followed intention-to-treat.
What was found
Neither primary endpoint showed a statistically significant improvement with urolithin A compared to placebo: 6-minute walk distance increased by a mean (SD) of 60.8 (67.2) m vs 42.5 (73.3) m; maximal ATP production change was 0.07 (0.23) mM/s vs 0.06 (0.20) mM/s in the FDI, and -0.03 (0.10) mM/s vs 0.03 (0.10) mM/s in the TA. For secondary endpoints, urolithin A significantly improved muscle endurance at 2 months in the FDI (increase in contractions: 95.3 [115.5] vs 11.6 [147.4]) and TA (41.4 [65.5] vs 5.7 [127.1]). Urolithin A also reduced plasma acylcarnitines, ceramides, and C-reactive protein (baseline to 4 months: 2.14 [2.15] to 2.07 [1.46] in urolithin A vs 2.17 [2.52] to 2.65 [1.86] in placebo). Adverse events did not differ significantly between groups.
Why it matters
This trial demonstrates that oral urolithin A is safe and well tolerated in older adults and can improve muscle endurance and cellular biomarkers, though it did not translate into statistically significant gains in walking capacity or in vivo ATP synthesis over 4 months.
Limits
The study was negative for both primary endpoints. The sample size was modest (n = 66) and lacked demographic diversity (all participants were White, and 75.8% were women). Muscle endurance improvements were reported at 2 months rather than sustained primary end points, and clinical translation to broader functional mobility remains unproven.