{ "checked": "2026-10-25", "page": "https://jabbitapp.com/research/urolithin-a-mitopure-mitophagy-longevity-evidence-teardown.html", "fda_gras": { "notice": "GRN 000791", "notifier": "Amazentis SA", "filed": "2018-06-15", "closed": "2018-12-20", "response": "FDA has no questions", "inventory": "https://cfsanappsexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=791", "letter": "https://www.fda.gov/media/120300/download", "quotes": [ "The Food and Drug Administration (FDA, we) completed our evaluation of GRN 000791.", "The notice informs us of Amazentis’ view that this use of urolithin A is GRAS through scientific procedures.", "Urolithin A is chemically synthesized using one of two alternative processes", "we have no questions at this time regarding Amazentis’ conclusion that urolithin A is GRAS under its intended conditions of use.", "This letter is not an affirmation that urolithin A is GRAS under 21 CFR 170.35.", "If products containing urolithin A bear any nutrient content or health claims on the label or in labeling, such claims are subject to the applicable requirements", "Food ingredient manufacturers and food producers are responsible for ensuring that marketed products are safe and compliant with all applicable legal and regulatory requirements." ] }, "eu_novel_food_application": { "submitted": "2018-08-31", "url": "https://food.ec.europa.eu/system/files/2019-05/novel-food_sum_ongoing-app_2018-0538.pdf", "quotes": [ "APPLICATION FOR THE APPROVAL OF UROLITHIN A AS A NOVEL FOOD INGREDIENT IN THE EUROPEAN UNION", "Amazentis SA’s ingredient is a synthetic version of urolithin A that is identical in structure to the compound formed endogenously following consumption of ellagic acid and ellagitannins." ], "note": "We found no EU authorisation or published EFSA opinion; status not confirmed." }, "uk_fsa": { "application": "RP-1777", "applicant": "Amazentis SA", "status": "In progress", "phase": "Risk assessment", "url": "https://data.food.gov.uk/regulated-product-applications/products-list/RP-1777" }, "swiss_fsvo": { "date": "2025-07-29", "url": "https://www.blv.admin.ch/dam/en/sd-web/b0gsH3ZLYwUB/einstufung-als-neuartiges-lebensmittel-urolithin-a-2025-en.pdf", "quotes": [ "is not known to be found in any food source", "Urolithin A is therefore subject to the authorisation requirement for novel foods under Article 17 FUAO." ] }, "registry": { "clinicaltrials_gov_intervention_urolithin": 38, "lead_sponsor_amazentis": 13, "note": "Broad search; includes pomegranate, walnut and pecan studies that measure urolithins.", "selected": { "NCT06274749": [ "RECRUITING", 180, "National Institute on Aging (NIA)", "2027-03-31", false ], "NCT07060898": [ "ACTIVE_NOT_RECRUITING", 650, "Amazentis SA", "2025-11-20", false ], "NCT07842146": [ "RECRUITING", 60, "University Hospital, Akershus", "2028-10-15", false ], "NCT06022822": [ "RECRUITING", 90, "National Cancer Institute (NCI)", "2026-11-01", false ], "NCT07231783": [ "RECRUITING", 120, "Amazentis SA", "2027-10-31", false ], "NCT05921266": [ "COMPLETED", 50, "University of Oklahoma", "2025-05-14", false ], "NCT03283462": [ "COMPLETED", 66, "Amazentis SA", "2020-09-25", false ], "NCT03464500": [ "COMPLETED", 90, "Amazentis SA", "2019-09-30", false ], "NCT05735886": [ "COMPLETED", 50, "Amazentis SA", "2024-03-31", false ], "NCT04783207": [ "COMPLETED", 42, "Amazentis SA", "2022-05-30", false ], "NCT06556706": [ "COMPLETED", 26, "Amazentis SA", "2025-04-25", false ] } }, "pubmed": { "query": "urolithin[tiab] AND randomized controlled trial[pt]", "count": 37, "idlist": [ "42853569", "42808314", "42371155", "42023516", "41794475", "41642121", "41408634", "41305622", "41174221", "40944126", "40839339", "40255128", "39487653", "39179206", "38415449", "37743489", "36175997", "35940768", "35584623", "35050355", "35021194", "34117375", "33458928", "33095939", "31496244", "30690879", "29802820", "29318244", "28513179", "27879044", "26412215", "24532260", "24410903", "23985577", "23934737", "22631214", "19885850" ], "lifespan_query": "urolithin[tiab] AND (lifespan[tiab] OR longevity[tiab] OR survival[tiab]) AND (mice[tiab] OR mouse[tiab] OR rats[tiab])", "lifespan_count": 30, "lifespan_note": "Of these, the abstracts reporting a lifespan result for urolithin A were the 2016 and 2025 worm studies and one 2023 mouse study (Buck Institute); we did not read every full text." }, "key_trials": [ { "trial": "Middle-aged adults, 2022", "n": 88, "result": "Main goal missed; strength up", "maker_funded": "Yes", "pmid": "35584623" }, { "trial": "Older adults, 2022", "n": 66, "result": "Main goals missed; endurance up", "maker_funded": "Yes", "pmid": "35050355" }, { "trial": "Immune aging, 2025", "n": 50, "result": "Immune-cell shifts", "maker_funded": "Yes", "pmid": "41174221" }, { "trial": "Adults with obesity, 2026", "n": 50, "result": "Main goal missed", "maker_funded": "No", "pmid": "42853569" }, { "trial": "Elite runners, 2025", "n": 42, "result": "Race time not improved", "maker_funded": "Yes", "pmid": "40839339" }, { "trial": "Strength athletes, 2024", "n": 20, "result": "Some strength gains", "maker_funded": "None reported", "pmid": "39487653" }, { "trial": "Heart failure, 2024", "n": 10, "result": "No heart benefit", "maker_funded": "Not stated", "pmid": "38415449" } ], "key_trials_total_n": 326, "full_text_quotes": { "PMC8777576": [ "Funding/Support: This research was supported by Amazentis SA.", "After the study started, the original primary end points of change from baseline of hand maximal ATP production and of hand muscle endurance were replaced by change from baseline of 6-minute walk distance and hand maximal ATP production", "The funder had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication." ], "PMC13653284": [ "Conflict of Interest Disclosures: None reported.", "Research reported in this publication was supported by the American Heart Association", "The sponsor had no role in the design and conduct of the study", "Published: October 9, 2026.", "Second, this study had a small sample size, short duration, and was conducted at a single site." ] }, "abstract_quotes": { "27400265": { "title": "Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents", "journal": "Nat Med", "year": "2016", "quotes": [ "In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan.", "UA improved exercise capacity in two different mouse models of age-related decline of muscle function, as well as in young rats" ] }, "28757461": { "title": "Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid", "journal": "Food Chem Toxicol", "year": "2017", "quotes": [ "The battery of genotoxicity assays demonstrated that UA is not genotoxic.", "showed no alterations in clinical parameters, blood chemistry, or hematology, and did not indicate any target organs, or any specific toxic mechanisms" ] }, "32694802": { "title": "The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans", "journal": "Nat Metab", "year": "2019", "quotes": [ "first-in-human clinical trial", "to healthy, sedentary elderly individuals", "We show that UA has a favourable safety profile (primary outcome)." ] }, "34117375": { "title": "Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population", "journal": "Eur J Clin Nutr", "year": "2022", "quotes": [ "Only 12% of subjects had detectable levels of UA at baseline.", "Following PJ intake ~40% of the subjects converted significantly the precursor compounds into UA.", "provided a >6-fold exposure to UA vs. PJ (p < 0.0001)" ] }, "35050355": { "title": "Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial", "journal": "JAMA Netw Open", "year": "2022", "quotes": [ "A total of 66 participants were randomized", "were predominantly women (50 [75.8%]), and were all White individuals", "The mean (SD) increase from baseline in the 6-minute walk distance was 60.8 (67.2) m in the urolithin A group and 42.5 (73.3) m in the placebo group.", "These results showed no significant improvement with urolithin A supplementation compared with placebo.", "Urolithin A, compared with placebo, significantly improved muscle endurance", "No statistical differences in adverse events were observed between the 2 groups.", "however, future work is needed to confirm this finding" ] }, "35584623": { "title": "Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults", "journal": "Cell Rep Med", "year": "2022", "quotes": [ "The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A.", "but do not notice a significant improvement on peak power output (primary endpoint)", "We observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen oxygen consumption [VO2]) and physical performance (6 min walk test)" ] }, "38415449": { "title": "Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial", "journal": "Rev Recent Clin Trials", "year": "2024", "quotes": [ "conducted on 10 patients with HF with reduced ejection fraction (HFrEF)", "The results failed to reveal any significant effect of UA supplementation on echocardiographic measures", "The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF." ] }, "39487653": { "title": "Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study", "journal": "J Int Soc Sports Nutr", "year": "2024", "quotes": [ "with twenty resistance-trained male athletes", "although statistical significance was not reached", "the group receiving UA supplementation, compared to the placebo group, showed significant improvements in MVIC and RTF" ] }, "40839339": { "title": "Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners", "journal": "Sports Med", "year": "2025", "quotes": [ "competitive male distance runners (n = 42", "Running performance (3000 m time trial) was not significantly improved in either treatment group", "reduced indirect markers of post-exercise muscle damage", "UA supplementation did not further enhance performance in highly trained male endurance athletes" ] }, "41174221": { "title": "Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial", "journal": "Nat Aging", "year": "2025", "quotes": [ "50 healthy middle-aged adults", "UA expanded peripheral naive-like, less terminally exhausted CD8+ cells (treatment difference 0.50 percentage points; 95% CI = 0.16 to 0.83; P = 0.0437)", "supporting its potential to counteract age-related immune decline and inflammaging" ] }, "42853569": { "title": "Urolithin A and Endothelial and Cerebrovascular Function in Middle-Aged Adults With Obesity: A Randomized Clinical Trial", "journal": "JAMA Netw Open", "year": "2026", "quotes": [ "Overall, 50 participants were included", "Seven participants were lost to follow-up (14% dropout rate).", "Change in mean (SD) FMD did not differ significantly based on group allocation", "there was no significant treatment effect on secondary peripheral endothelial function outcomes", "while task performance remained unchanged", "4 weeks of UA supplementation did not significantly improve peripheral endothelial function in middle-aged adults with obesity", "supplementation was well tolerated and feasible, and its effect on task-evoked cerebrovascular hemodynamic responses warrants further investigation" ] }, "42559151": { "title": "Effects of Urolithin A supplementation on muscle health outcomes in humans from randomized controlled trials", "journal": "Front Nutr", "year": "2026", "quotes": [ "Five randomized controlled trials (n = 236) were included.", "The certainty of evidence for the 6MWT outcome was rated as low (GRADE).", "showed a directionally favorable but statistically inconclusive effect with low GRADE certainty", "are exploratory and hypothesis-generating, not reproducible evidence of efficacy", "Larger, longer, and methodologically standardized trials in better-defined populations are required before firm clinical recommendations can be made." ] }, "39002645": { "title": "Targeting aging with urolithin A in humans: A systematic review", "journal": "Ageing Res Rev", "year": "2024", "quotes": [ "In five studies including 250 healthy individuals", "It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition.", "UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function.", "Unrelated adverse events were mild or moderate." ] }, "36576642": { "title": "Urolithin A reduces amyloid-beta load and improves cognitive deficits uncorrelated with plaque burden in a mouse model of Alzheimer's disease", "journal": "Geroscience", "year": "2023", "quotes": [ "WT and 3xTg-AD mice were administered long-term intermittent dietary supplementation with UA.", "UA was also found to extend lifespan in normal aging mice." ] }, "40944367": { "title": "Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing", "journal": "Autophagy", "year": "2025", "quotes": [ "Calcium chelation abolishes UA-induced mitophagy, blocking its beneficial impact on muscle function and lifespan" ] }, "42866687": { "title": "Topical application of urolithin A activates mitophagy and enhances mitochondrial function to promote skin longevity", "journal": "iScience", "year": "2026", "quotes": [ "In randomized, placebo-controlled clinical studies, UA reduced periorbital wrinkle depth after 8 weeks and attenuated UVB-induced erythema." ] } }, "conflict_statements": { "34117375": "Amazentis SA, who is the sponsor of this clinical study", "35584623": "Amazentis SA, who is the sponsor of this clinical study", "41174221": "Amazentis SA, which funded this clinical study and provided the investigational product (Mitopure)", "40839339": "This work was supported by research funding from Amazentis SA", "42866687": "commercializes its products under the brand Timeline", "39487653": "No potential conflict of interest was reported by the author(s).", "36576642": "The authors declare no competing interests.", "42559151": "conducted in the absence of any commercial or financial relationships" }, "amazentis_affiliated_authors": [ "27400265", "28757461", "32694802" ], "analysis": { "note": "Jabbit analysis. Urolithin A is a gut-microbe metabolite of ellagitannins sold as a supplement ingredient (Mitopure). It extended lifespan in worms, and one 2023 mouse study reported longer life in normal aging mice; no human trial has measured lifespan. Human trials are small (10 to 88 people) and short (4 weeks to 4 months); most were funded by the ingredient's maker; several missed their main goals while reporting secondary signals in strength, endurance, inflammation or immune markers. Reported tolerability was good, but long-term safety data are lacking." } }