Urolithin A
SupplementThe medical score and community score are similar, as both clinical studies [s1, s2] and user reports [c1, c2] show mixed but generally positive results. Community skepticism regarding the price and lack of personal benefit in a subset of users [c1, c3] reflects the still limited evidence base.
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TL;DR
Urolithin A is the most clinically grounded mitophagy activator in the supplement space: four RCTs (n ≈ 460) consistently show positive effects on muscle endurance and mitochondrial biomarkers in older and middle-aged adults. However, the evidence is limited by small sample sizes, short study duration, and heavy industry sponsorship (Amazentis/Mitopure) — independent replication is largely absent. Only around 30–40% of people naturally produce UA from food, which may explain the variable responder rate. The safety profile is favorable, but cost-effectiveness remains questionable without long-term data.
Description
Urolithin A is a gut microbiome metabolite derived from ellagitannins that activates mitophagy and improves muscle function and mitochondrial health [s1, s2].
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Legal Status (DE)
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Mechanism of Action
Urolithin A acts through several interconnected mechanisms: 1. Mitophagy activation: UA selectively stimulates the clearance of dysfunctional mitochondria via the PINK1/Parkin signaling pathway [s11]. Damaged mitochondria are ubiquitinated and recognized by autophagosomes, leading to their elimination. This improves the overall quality of the mitochondrial network [s11]. 2. mTOR inhibition: UA inhibits the mTOR signaling pathway, thereby relieving mTOR-mediated suppression of autophagy. This permits more efficient autophagic activity [s15]. 3. Mitochondrial biogenesis: Elimination of dysfunctional mitochondria and subsequent compensatory mechanisms stimulate the formation of new, functional mitochondria [s2, s6]. 4. Anti-inflammatory effects: UA exhibits dose-dependent anti-inflammatory effects, including reduction of inflammatory markers and upregulation of fatty acid oxidation genes [s6]. 5. Immunomodulation: In a 4-week study, UA increased naive CD8+ T cell counts and mitochondrial biogenesis markers while inflammatory markers declined in middle-aged adults [s14]. 6. Neuroprotective mechanisms (preclinical): In animal models and in vitro studies, UA promotes mitophagy in the brain, reduces neuroinflammation, and improves cognitive parameters in Alzheimer's models [s9, s10].
Side Effects
| Side Effect | Frequency | Severity |
|---|---|---|
| Leichte Muskel- und Gelenkbeschwerden (Myalgie, Steifheit) Some participants reported muscle pain in clinical trials; researchers attributed this largely to muscle biopsies rather than UA [s8]. Also occasionally mentioned in user reports [c1]. | gelegentlich | leicht |
| Kopfschmerzen Mild, transient headaches have been described in user reports and clinical reports as a possible adverse effect [s8, c1]. | gelegentlich | leicht |
| Verdauungsbeschwerden (Übelkeit, Durchfall, weicher Stuhl, erhöhte Schleimproduktion) Gastrointestinal complaints were mentioned in user reports and clinical reviews as mild, transient adverse effects [s8, c1, c4]. | gelegentlich | leicht |
| Ausgeprägte Tagesmüdigkeit / Energie-Crash Individual users reported pronounced fatigue approximately 4 hours after ingestion, possibly due to transient reduction in ATP production during mitochondrial remodeling [c4, c5]. | selten | leicht |
| Schwerwiegende Nebenwirkungen oder Organschäden No serious adverse events or relevant changes in hepatic, renal, or cardiac parameters were documented in clinical trials [s7, s8]. | theoretisch | leicht |
Contraindications
No safety data available for pregnant or breastfeeding women. Should be avoided as a precaution [s8].
No study data available for minors; use is not recommended [s8].
Theoretical risk of cross-reactivity; no documented cases, but caution advised with known allergies [s3, s4].
UA modulates immune function (naive CD8+ T cells) [s14]; interactions with immunosuppressive medications are theoretically possible but not clinically documented.
Interactions
Synergistic
Both substances stimulate mitophagy/autophagy via partially distinct pathways; combined effects are under discussion [s11].
A synergistic effect on mitochondrial function is theoretically possible; no RCT data on the combination are available.
Urolithin A and CoQ10 act on mitochondrial function via distinct pathways – UA stimulates mitophagy, while CoQ10 directly supports ATP production in the respiratory chain. The combination is considered complementary and well tolerated.
Fisetin and urolithin A are being investigated for senolytic and anti-aging effects in an ongoing combination study (clinical phase). Both substances target senescence and oxidative stress via partially distinct mechanisms.
Quercetin exhibits complementary anti-inflammatory and senolytic properties to urolithin A. Both are combined in longevity stacks, with no known adverse interactions.
ALCAR supports mitochondrial fatty acid transport and ATP synthesis, while UA improves mitochondrial pool quality via mitophagy. The combination is listed in expert stacks for mitochondrial health.
PQQ promotes mitochondrial biogenesis through activation of PGC-1α, while Urolithin A removes damaged mitochondria. Both compounds are considered complementary mitochondrial boosters.
Resveratrol and Urolithin A can be well combined according to available sources; no adverse interactions known. Both activate SIRT1/AMPK signaling pathways and support cellular health.
Caution
Theoretical interaction due to immunomodulatory effects of UA [s14]; no clinical data available.
Metabolism of UA and potential enzyme interactions are not fully characterized; caution advised with polypharmacy.
Community Evidence
Top reported benefits
- Improved endurance and physical performance
- Increased heart rate variability (HRV)
- Subjectively increased energy in daily life
- Reduction of headaches (single case report)
Top reported issues
- No noticeable effect in a substantial proportion of users
- Transient daytime drowsiness or energy crash
- High cost relative to perceived benefit
- Mild gastrointestinal discomfort
Many users report no perceivable effect [c1, c3]. The close association of most studies with manufacturer Amazentis/Timeline (Mitopure) is discussed in the community as a potential source of bias [c1, c2]. Some users suspect that effects only occur in those who lack a functional gut microbiome for endogenous UA production [c2]. Cost-effectiveness is viewed critically given the unclear long-term data [c1].
Scientific Sources
- Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial
Liu S, D'Amico D, Shankland E, et al. (2022). JAMA Network OpenAPMID:35050355DOI - Methylated urolithin A mitigates cognitive impairment by inhibiting NLRP3 inflammasome and ameliorating mitochondrial dysfunction in aging mice
Wang Y, Zhang X, Chen L, et al. (2024). NeuropharmacologyCDOI - Distinct roles of urolithin A and spermidine in mitophagy and autophagy: implications for dietary supplementation
Madeo F, Carmona-Gutierrez D, Hofer SJ, et al. (2024). Nutrition Research ReviewsBDOI - Novel Food Regulation and Urolithin A EU authorization – Longevity ingredients under the EU regulatory spotlight
NutraIngredients-Redaktion (2026). nutraingredients.comBLink - Agency Response Letter GRAS Notice No. GRN 000791 – Urolithin A (Amazentis SA)
U.S. Food and Drug Administration (2018). FDAALink - Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial
Andreux PA, Blanco-Bose W, Ryu D, et al. (2025). Nature AgingADOI - The Science of Mitophagy: Urolithin A's Impact on Mitochondrial Function and Aging
Healthspan-Redaktion (2024). gethealthspan.comDLink - The effects of urolithin A supplementation on muscle strength, muscle mass and physical performance in humans – a systematic review
Preprint-Autoren (medRxiv) (2025). medRxiv (Preprint)BDOI - Emerging evidence of Urolithin A in sports nutrition: bridging preclinical findings to athletic applications
Domínguez R, Ramos-Álvarez JJ, Llorente-Cantarero FJ, et al. (2025). Frontiers in NutritionBDOI - Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review
Tripolt NJ, Stekovic S, Abdellatif M, et al. (2023). NutrientsADOI - The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: comparison between normoweight, overweight-obesity and metabolic syndrome
Selma MV, González-Sarrías A, Salas-Salvadó J, Andrés-Lacueva C, Alasalvar C, Örem A et al. (2017). Clinical NutritionCPMID:28347564DOI - Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults
Singh A, D'Amico D, Andreux PA, et al. (2022). Cell Reports MedicineAPMID:35584623DOI - Commission Implementing Regulation (EU) 2022/1452 of 4 August 2022 authorising the placing on the market of urolithin A as a novel food under Regulation (EU) 2015/2283 of the European Parliament and of the Council
Unbekannt (2022). CLink - Safety of urolithin A as a novel food pursuant to Regulation (EU) 2015/2283
EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) (2022). EFSA JournalCDOI - A Synergistic Combination of DHA, Luteolin, and Urolithin A Against Alzheimer's Disease
Jayatunga DPW, Hone E, Fernando W, Garg ML, Verdile G, Martins RN (2022). Frontiers in Aging NeuroscienceCDOI - Gut Bacteria Involved in Ellagic Acid Metabolism To Yield Human Urolithin Metabotypes Revealed
Cortez-Trejo MC, Wall-Medrano A, Garay-Martínez LE, et al. (2023). Journal of Agricultural and Food ChemistryBDOI - The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers
García-Villalba R, Giménez-Bastida JA, Cortés-Martín A, et al. (2017). Clinical NutritionBPMID:28347564DOI - Urolithin A: Das Postbiotikum für junge Mitochondrien 2026
Kuukivi-Redaktion (2026). kuukivi.deDLink - Targeting aging with urolithin A in humans: A systematic review
Ghosh N, Das A, Biswas N, et al. (2024). Ageing Research ReviewsAPMID:39002645DOI - Urolithin A Side Effects: Is It Really Safe to Take?
omre-Redaktion (2024). omre.coDLink - Urolithin A – Cognitive Vitality Report (Alzheimer's Drug Discovery Foundation)
Alzheimer's Drug Discovery Foundation (2023). alzdiscovery.orgBLink - Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions
Hou Y, Singh A, Andreux PA, et al. (2024). Alzheimer's & DementiaCDOI
Community Sources
Storage
Unopened
Store in a dry, cool place at room temperature (15–25 °C), protected from direct sunlight and moisture.
Opened
Keep container tightly closed; avoid moisture when in powder or capsule form.
Notes
Follow manufacturer instructions on packaging; no special refrigeration requirements known.