{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:57:35Z","timestamp":1790013455298,"version":"4.0.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100032744","name":"Amazentis SA","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032744","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian Catholic University Limited"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sports Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Urolithin A (UA) is a metabolite produced by gut bacteria following the consumption of ellagitannin-rich foods. Clinical trials in middle-aged and older adults demonstrated that supplementation with UA improves muscle strength, endurance, and biomarkers of mitochondrial health, suggesting that UA may be an effective ergogenic aid in other populations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this double-blind, parallel group, placebo-controlled clinical trial (NCT04783207), competitive male distance runners (\n n<\/jats:italic>\n \u2009=\u200942, 27.2\u2009\u00b1\u20091.0\u00a0years,\n \n \n $$\\dot{V}{\\text{O}}_{{{\\text{2max}}}}$$<\/jats:tex-math>\n \n \n \n V<\/mml:mi>\n \u02d9<\/mml:mo>\n <\/mml:mover>\n \n O<\/mml:mtext>\n 2max<\/mml:mtext>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 66.4\u2009\u00b1\u20090.6\u00a0mL\u00b7kg\n \u22121<\/jats:sup>\n \u00b7min\n \u22121<\/jats:sup>\n , mean\u2009\u00b1\u2009SEM) were randomized to consume either 1000\u00a0mg\u00b7day\n \u22121<\/jats:sup>\n UA (\n n<\/jats:italic>\n \u2009=\u200922) or placebo (PL;\n n<\/jats:italic>\n \u2009=\u200920) for 4\u00a0weeks during an altitude training camp (~\u20091700\u20132200\u00a0m). Physiological outcomes including body composition, hemoglobin mass, running economy, and maximal aerobic capacity (\n \n \n $$\\dot{V}{\\text{O}}_{{{\\text{2max}}}}$$<\/jats:tex-math>\n \n \n \n V<\/mml:mi>\n \u02d9<\/mml:mo>\n <\/mml:mover>\n \n O<\/mml:mtext>\n 2max<\/mml:mtext>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n ) were measured in all subjects at baseline and at the end of the 4-week camp to assess training- and supplementation-induced adaptations. During the camp, a weekly downhill running bout was performed to challenge skeletal muscle, with capillary blood samples collected to assess inflammation (C-reactive protein; CRP) and indirect markers of muscle damage (creatine kinase; CK). A subset of athletes also either completed a 3000\u00a0m track time trial (\n n<\/jats:italic>\n \u2009=\u200911 PL,\n n<\/jats:italic>\n \u2009=\u200911 UA) or had skeletal muscle biopsies taken (\n n<\/jats:italic>\n \u2009=\u20099 PL,\n n<\/jats:italic>\n \u2009=\u200911 UA) pre\/post supplementation to determine the effect of UA on running performance and for exploration of alterations in skeletal muscle proteome and mitochondrial function, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Running performance (3000\u00a0m time trial) was not significantly improved in either treatment group (UA;\n p<\/jats:italic>\n \u2009=\u20090.116, PL;\n p<\/jats:italic>\n \u2009=\u20090.771), although UA supplementation significantly lowered ratings of perceived exertion (RPE,\n p<\/jats:italic>\n \u2009=\u20090.02) and reduced indirect markers of post-exercise muscle damage (CK, total\u00a0area under the curve\n p<\/jats:italic>\n \u2009<\u20090.0001) following the 3000\u00a0m time trial compared with PL. Although there was no statistically significant time\u2009\u00d7\u2009treatment interaction for aerobic capacity (\n p<\/jats:italic>\n \u2009=\u20090.138), UA supplementation showed a large within-group increase in\n \n \n $$\\dot{V}{\\text{O}}_{{{\\text{2max}}}}$$<\/jats:tex-math>\n \n \n \n V<\/mml:mi>\n \u02d9<\/mml:mo>\n <\/mml:mover>\n \n O<\/mml:mtext>\n 2max<\/mml:mtext>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n (5.4\u2009\u00b1\u20090.9%, 66.4\u2009\u00b1\u20090.8 to 70.0\u2009\u00b1\u20091.0\u00a0mL\u00b7kg\n \u22121<\/jats:sup>\n \u00b7min\n \u22121<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009=\u20090.009,\n d<\/jats:italic>\n \u2009= \u2212\u20090.83), with a smaller increase in the PL group (3.6\u2009\u00b1\u20091.3%, 66.4\u2009\u00b1\u20090.9 to 68.7\u2009\u00b1\u20091.0\u00a0mL\u00b7kg\n \u22121<\/jats:sup>\n \u00b7min\n \u22121<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009=\u20090.098,\n d<\/jats:italic>\n \u2009= \u2212\u20090.54). Proteomic screening of skeletal muscle biopsies revealed UA upregulated pathways associated with mitochondria, while downregulating inflammatory pathways. While not statistically significant, UA led to a medium effect for increased markers of mitophagy (\n d<\/jats:italic>\n \u2009= \u2212\u20090.74), without changes in mitochondrial function.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results show that 4\u00a0weeks of daily UA supplementation facilitates recovery by downregulating inflammatory pathways and indirect markers of muscle damage. However, despite a reduction in rating of exertion and increased aerobic capacity, UA supplementation did not further enhance performance in highly trained male endurance athletes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s40279-025-02292-5","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T14:29:45Z","timestamp":1755786585000},"page":"3183-3200","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners"],"prefix":"10.1007","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-8872","authenticated-orcid":false,"given":"Jamie","family":"Whitfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4184-3886","authenticated-orcid":false,"given":"Alannah K. 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This work was supported by research funding from Amazentis SA awarded to L.M.B. and J.A.H.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Ethics approval was obtained from the Australian Catholic University\u2019s Human Research Ethics Committee (2021-36HC), and the study was prospectively registered as a clinical trial (NCT04783207). All procedures were performed in accordance with the standards of ethics outlined in the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All participants completed medical history screening to ensure they were free from illness and injury. Comprehensive details of the study protocol were explained orally and provided in writing prior to athletes providing their written informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information files. All raw data are available from the corresponding authors upon reasonable request.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"The authors declare the following competing interests: A.M.F., D.D., and A.S. are employees of Amazentis SA, the sponsor of this clinical study. J.W. has received travel support from Amazentis SA to present findings related to this project at scientific conferences. L.G.K. was an employee of Nestl\u00e9 Research and Nestl\u00e9 Health Science, is on the scientific advisory boards of Vital Proteins, NUUN, and RNWY, is a board member of Siftlink, and reports personal fees from Nestl\u00e9 Health Science, Liquid I.V. and RNWY. J.A.H. is an Editorial Board member of\n Sports Medicine\n . J.A.H. was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. The other authors declare no competing interests.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"J.W., A.K.A.M., L.G.K., D.D., A.S., L.M.B., and J.A.H contributed to the design of the study. J.W., A.K.A.M., N.T., R.M., A.M., and L.M.B collected and analyzed the whole-body data. J.W. and D.D. analyzed the muscle data. J.W. created the figures and wrote the manuscript with the critical input from the other co-authors. All authors reviewed and approved the final manuscript.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}]}}