Urolithin A

Andreux et al. (Nat Metab, 2019; PMID 32694802, n=60): a phase 1 trial whose primary outcome was safety; urolithin A 500 and 1,000 mg/day for 4 weeks improved mitochondrial gene expression and plasma acylcarnitines vs. placebo as secondary outcomes; five of nine authors are employees of the company that makes the urolithin A tested. Liu et al. (JAMA Netw Open, 2022; PMID 35050355): randomized clinical trial reporting improved muscle endurance and mitochondrial health in older adults. The pre-registered primary endpoint was not superior to placebo, so the endurance result is a secondary one. Funded by the maker, which the paper states had a role in the design and conduct of the study and in the analysis and interpretation of the data; the founder, chief executive and board chair of the company are among the authors. Singh et al. (Cell Rep Med, 2022; PMID 35584623): randomized trial in middle-aged adults reporting improved muscle strength, exercise performance and biomarkers of mitochondrial health. Here too the pre-registered primary endpoint was not superior to placebo, so these are secondary results. Sponsored by the maker; six authors are its employees and two sit on its board. Zhao et al. (J Int Soc Sports Nutr, 2024; PMID 39487653): 8-week randomized double-blind placebo-controlled trial in male resistance-trained athletes measuring muscle endurance, strength, inflammation, oxidative stress and protein metabolism; funded by the Jiangsu Province education plan, no company involvement declared, the one trial here independent of the maker. Whitfield et al. (Sports Med, 2025; PMID 40839339, n=42): highly trained male distance runners, 1,000 mg/day for 4 weeks during an altitude camp; the 3,000 m time trial did not improve and the VO2max time-by-treatment interaction was not significant, with lower perceived exertion and lower creatine kinase after the time trial; funded by the maker, with one of its staff among the authors. Denk et al. (Nature Aging, 2025; PMID 41174221, n=50): randomized double-blind placebo-controlled trial, 1,000 mg/day for 4 weeks in healthy middle-aged adults, with peripheral CD3+ T cell subsets and immune metabolic remodeling as primary outcomes; funded by the maker, which also provided the product, with three of its employees and its president among the authors. Immune-cell phenotype markers, not a clinical endpoint, and no independent replication of a clinical result. Dao et al. (Front Nutr, 2026; PMID 42559151): meta-analysis of five randomized trials, 236 participants; only the 6-minute walk test could be pooled, +17 m with a confidence interval crossing zero (-5 to 39 m), low certainty; other muscle outcomes were exploratory signals rather than reproducible effects. Monsalve Acevedo et al. (Front Nutr, 2025; PMID 41245402): single-blind pilot, 20 academy soccer players aged about 17, 1,000 mg/day for 6 weeks; the intermittent recovery running test improved; a supplement company reimbursed one author's conference travel. Jamialahmadi et al. (Rev Recent Clin Trials, 2024; PMID 38415449): crossover in 10 patients with heart failure with reduced ejection fraction, 1,000 mg/day for 4 weeks; no change in echocardiographic measures, pro-BNP or CRP. Grade C. Funding: the company that makes the urolithin A tested funded or ran five of the six trials cited (PMIDs 32694802, 35050355, 35584623, 40839339, 41174221); the sixth (PMID 39487653) was publicly funded in China.