Urolithin A

Urolithin A at a Glance

Urolithin A is a small phenolic molecule — C₁₃H₈O₄, 228.2 Da, a 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one — that occupies an unusual position here. It is the destination of an entire chemical class. The twelve or so hydrolysable tannins covered here (sanguiin H-6, lambertianin C, castalagin, vescalagin, geraniin, corilagin, tellimagrandin I and II, rugosin A and D, repandusinic acid A, hamamelitannin) each run into the same wall: too large to absorb, hydrolysed in the gut to ellagic acid, which is itself barely absorbed. What actually reaches human blood is this molecule and its siblings.

No plant makes it. That is the first thing to understand and the thing most product copy gets wrong. Urolithin A is produced in the colon by bacteria, from ellagic acid, through a sequence of lactone-ring cleavage and stepwise dehydroxylations ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}. A pomegranate contains no urolithin A. A raspberry contains no urolithin A. You contain urolithin A — or you don’t, depending on which bacteria you happen to carry.

That “or you don’t” is the second thing. Human beings sort into reproducible urolithin metabotypes: metabotype A produces urolithin A only, metabotype B produces isourolithin A and urolithin B in addition, and metabotype 0 produces essentially none ^{1,2,11Reference 1Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →Reference 2Cortés-Martín A et al. · 2018The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by aging (n = 839, ages 5–90)View study →Reference 11Espín JC et al. · 2013Biological significance of urolithins, the gut microbial ellagic-acid-derived metabolites — the evidence so farView study →}. This is not a subtle effect at the margins — it is the difference between substantial systemic exposure and zero, from an identical meal. It is the single most decision-relevant fact in the whole ellagitannin area, and it is why the modern human trials give synthesised urolithin A directly rather than feeding people fruit.

The Metabotype Story

Give the same pomegranate extract to fifty people and measure their urine, and you do not get a bell curve of urolithin output. You get three discrete groups.

The three phenotypes. Across independent intervention trials — walnuts, other nuts, strawberries, raspberries, other berries, pomegranate — volunteers stratify consistently ^{1Reference 1Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →}:

• Metabotype A (UM-A): produces urolithin A conjugates only. 25–80% of volunteers depending on the trial.
• Metabotype B (UM-B): produces isourolithin A and/or urolithin B in addition to urolithin A — not instead of it, which is a common and consequential misreading. 10–50%.
• Metabotype 0 (UM-0): no urolithins detectable. 5–25%.

The three groups appeared regardless of the volunteers’ health status, age, sex, BMI, or the amount and type of ellagitannin food eaten ^{1Reference 1Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →}. That last clause matters: the split is a property of the person, not the dose.

Age is the main driver. A Caucasian cohort of 839 people aged 5 to 90 found ageing to be the principal determinant of which metabotype you land in ^{2Reference 2Cortés-Martín A et al. · 2018The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by aging (n = 839, ages 5–90)View study →}. The pattern, as summarised in the definitive review of the field: UM-0 sits at roughly 10% and stays there across the whole lifespan; UM-A falls from about 85% in early childhood to about 55% in adulthood, while UM-B rises from about 15% to about 45%, with the proportions stabilising after roughly age 35–40 ^{13,2Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →Reference 2Cortés-Martín A et al. · 2018The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by aging (n = 839, ages 5–90)View study →}. Metabotype B has also been reported more often in people with chronic conditions associated with gut dysbiosis — metabolic syndrome, colorectal cancer ^{1,3Reference 1Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →Reference 3Tomás-Barberán FA et al. · 2017Urolithins, the rescue of “old” metabolites to understand a “new” concept — metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis and host health statusView study →} — and UM-B individuals carry higher total and LDL cholesterol and higher gut alpha-diversity, with the Coriobacteriaceae family proposed as the link ^{17Reference 17Romo-Vaquero M et al. · 2019Deciphering the human gut microbiome of urolithin metabotypes — association with enterotypes and potential cardiometabolic health implications (n = 249)View study →}.

Metabotype 0 is not always permanent. In the POMEcardio crossover trial, three of six non-producers (50%) became producers after consuming pomegranate extract ^{16Reference 16González-Sarrías A et al. · 2017RCTClustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate — a randomized clinical trial (POMEcardio)View study →}. So UM-0 can mean “no producing bacteria” or “producing bacteria present but not induced”. Nobody yet knows the split.

Which bacteria. The pathway is now resolved further than most microbiome stories.

• Gordonibacter urolithinfaciens (isolated 2014 from healthy human faeces) and its relative G. pamelaeae metabolise ellagic acid in pure culture through pentahydroxy-urolithin (M-5) → tetrahydroxy (M-6) → trihydroxy (urolithin C). Critically, neither produced urolithin A, isourolithin A or urolithin B in pure culture ^{4,5Reference 4Selma MV et al. · 2014Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species — pure cultureView study →Reference 5Selma MV et al. · 2014Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gutView study →}. Gordonibacter gets you to the doorstep, not through it.
• Ellagibacter isourolithinifaciens (a new genus described in 2018) converts ellagic acid to isourolithin A — the metabotype-B branch ^{6Reference 6Beltrán D et al. · 2018Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family Eggerthellaceae isolated from human gutView study →}. Head-to-head, the catechol-dehydroxylase activity is stronger in Ellagibacter, the reductase activity stronger in Gordonibacter, and both have a narrow substrate range: they also handle caffeic, dihydrocaffeic, rosmarinic and chlorogenic acids, but not quercetin, catechin, resveratrol, gallic acid or daidzein ^{7Reference 7García-Villalba R et al. · 2020Metabolism of different dietary phenolic compounds by the urolithin-producing human-gut bacteria Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciensView study →}.
• The last step was identified in 2025. A combined transcriptomic/proteomic/comparative-genomic study found an inducible urolithin C dehydroxylase (ucd) operon in Enterocloster species, encoding a molybdopterin-dependent complex that removes the 9-OH — the exact reaction that turns urolithin C into urolithin A. In ex vivo human faecal incubations, only the samples actively transcribing ucd produced urolithin A, which is the most concrete mechanistic explanation of the metabotype split so far ^{8Reference 8Pidgeon R et al. · 2025Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species — the inducible ucd operonView study →}.
• The picture is still opening up: Enterocloster species also generate a previously unknown urolithin G (3,4,8-trihydroxy), found in 12% of volunteers and not tied to either the A or B metabotype ^{9Reference 9Beltrán D et al. · 2023NMR spectroscopic identification of urolithin G, a novel trihydroxy urolithin produced by human intestinal Enterocloster speciesView study →}, and Bifidobacterium longum, B. adolescentis and B. bifidum have been implicated in ellagic acid fermentation as well ^{10Reference 10He F et al. · 2024In vitroIn vitro conversion of ellagic acid to urolithin A by different gut microbiota of urolithin metabotype AView study →}.

What this does to the literature. Every study that feeds people ellagitannins and measures an outcome is, unknowingly, running a subgroup analysis. The POMEcardio trial made that explicit: pomegranate extract at 640 mg phenolics/day dose-dependently reduced total cholesterol (−15.5%), LDL (−14.9%), small LDL (−47%), non-HDL, apolipoprotein B and oxidised LDL (−24%) — but only in UM-B subjects, with the effects partly correlated to urolithin production and rising Gordonibacter levels ^{16Reference 16González-Sarrías A et al. · 2017RCTClustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate — a randomized clinical trial (POMEcardio)View study →}. Read against that, “pomegranate lowers cholesterol” and “pomegranate doesn’t lower cholesterol” can both be true reports of the same experiment run on different people.

Eating Pomegranate vs. Taking Urolithin A

This is the practical payoff of the entire hydrolysable-tannin cluster, and it deserves to be stated bluntly.

	Ellagitannin-rich food	Synthesised urolithin A
What you swallow	Punicalagin, sanguiin H-6, castalagin, geraniin — 700–2,800 Da polyphenols	Urolithin A, 228 Da, ≥97% pure
Absorbed intact?	No	Partly — as the aglycone, then conjugated
Requires a competent microbiome?	Yes, absolutely	No
If you are metabotype 0	You get essentially none	You get the full dose
Typical exposure	Plasma total urolithins ~0.003–5.2 µM, highly variable 13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →	>30× higher plasma at 6 h than pomegranate juice; Tmax ~6 h; half-life ~1 day 13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →
Antibiotics / dysbiosis	Can abolish it	Irrelevant
Also delivers	Anthocyanins, other polyphenols, fibre, food	One molecule

The asymmetry runs the other way too. Whole-food ellagitannins act in the gut lumen at concentrations a supplement never produces there, and that is where several of urolithin A’s better-evidenced effects — gut-barrier and colonic ones — actually operate ^{21,26Reference 21Ryu D et al. · 2016AnimalUrolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodentsView study →Reference 26Singh R et al. · 2019Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway — urolithin A and UAS03 via AhR–Nrf2 and tight-junction proteinsView study →}. So “supplement is strictly better” is as wrong as “food is strictly better”. They are different exposures with different targets, and the metabotype question only applies to one of them.

What It's Used For

Urolithin A is, unusually for a molecule here, backed by real randomised human trials of the isolated compound. That evidence deserves to be reported at full strength — and read exactly.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — weighted by study type (human > animal > in vitro) and study volume, tempered for isolate-vs-source match, endpoint quality and sponsorship. It’s a beta, not a validated metric. Scores here are capped by primary-endpoint failures and by sponsor concentration, not by absence of human data.

01Muscle & Mitochondrial FunctionPromising55%Three sponsor-run RCTs (n=88, 66, 50) + two independent (n=20, soccer pilot); primary endpoints missed in the two largest ^{22,23,24,28,29Reference 22Andreux PA et al. · 2019The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans — first-in-human, safety as primary outcomeView study →Reference 23Singh A et al. · 2022RCTUrolithin A improves muscle strength, exercise performance and biomarkers of mitochondrial health in a randomized trial in middle-aged adults (NCT03464500) — primary endpoint peak power output not metView study →Reference 24Liu S et al. · 2022RCTEffect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults — a randomized clinical trial (NCT03283462); co-primary endpoints not metView study →Reference 28Zhao H et al. · 2024RCTAssessment 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 (n = 20)View study →Reference 29Monsalve Acevedo A et al. · 2025RCTEffects of urolithin A supplementation on performance and antioxidant status in academy soccer players during preseason — a pilot randomised controlled trialView study →}

02Inflammation & Immune AgeingPromising46%CRP reduced in two RCTs; a dedicated immune-ageing RCT with positive but small primary effects ^{23,24,27Reference 23Singh A et al. · 2022RCTUrolithin A improves muscle strength, exercise performance and biomarkers of mitochondrial health in a randomized trial in middle-aged adults (NCT03464500) — primary endpoint peak power output not metView study →Reference 24Liu S et al. · 2022RCTEffect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults — a randomized clinical trial (NCT03283462); co-primary endpoints not metView study →Reference 27Denk D et al. · 2025RCTEffect of the mitophagy inducer urolithin A on age-related immune decline — a randomized, placebo-controlled trial (NCT05735886)View study →}

03Gut Barrier & ColonShaky32%Strong mouse colitis + AhR/Nrf2 mechanism, at concentrations the colon actually reaches ^{26,20Reference 26Singh R et al. · 2019Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway — urolithin A and UAS03 via AhR–Nrf2 and tight-junction proteinsView study →Reference 20Muku GE et al. · 2018Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonistView study →}

04Senescence & AnticancerShaky22%Selective p53-dependent senescence in colon cancer cells; human tissue levels ~1,000× lower ^{18,19Reference 18Giménez-Bastida JA et al. · 2020The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cellsView study →Reference 19Ávila-Gálvez MÁ et al. · 2019Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients — urolithin A-3-O-glucuronide at 26.2 pmol/gView study →}

05NeuroprotectionShaky20%Three Alzheimer’s mouse models, long-term dosing; no human cognitive data ^{31Reference 31Hou Y et al. · 2024AnimalUrolithin A improves Alzheimer’s disease cognition and restores mitophagy and lysosomal functions — three transgenic mouse modelsView study →}

06Cardiovascular & MetabolicShaky18%One small negative independent heart-failure RCT; metabotype-B-only pomegranate lipid signal ^{16,32Reference 16González-Sarrías A et al. · 2017RCTClustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate — a randomized clinical trial (POMEcardio)View study →Reference 32Jamialahmadi T et al. · 2024RCTEvaluation of urolithin A efficacy in heart failure patients with reduced ejection fraction — a randomized, double-blind, crossover, placebo-controlled clinical trial (n = 10); negative for echocardiographic endpointsView study →}

Mechanisms

The last row governs the rest. Almost every micromolar figure above was obtained with the free aglycone; circulating urolithin A is overwhelmingly the glucuronide.

Pharmacokinetics

Urolithin A is absorbable — and then immediately disarmed. Unlike the 700–2,800 Da tannins it comes from, a 228 Da dibenzopyranone with XLogP ≈ 2.3 crosses the gut wall readily. What happens next is the problem: it is conjugated to glucuronide and sulfate forms, which are the predominant species in plasma after both oral and intravenous dosing in the rat ADME study ^{14Reference 14Heilman J et al. · 2017AnimalSafety assessment of urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant-derived ellagitannins and ellagic acid — rat genotoxicity, ADME, 28-day and 90-day studiesView study →} and the dominant compounds in every human matrix examined ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}.

That conjugation is not a technicality — it removes most of the activity. Conjugation of urolithin A to its glucuronide “dramatically hampers its activity” ^{39Reference 39Ávila-Gálvez MÁ et al. · 2019Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammationView study →}; phase-II metabolism and ABC efflux limited even the senescence effect that urolithin A alone among the urolithins produces ^{18Reference 18Giménez-Bastida JA et al. · 2020The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cellsView study →}. The one identified escape route is local deconjugation: urolithin A glucuronide is hydrolysed back to free urolithin A in tissue after LPS-induced inflammation, which the authors propose as the explanation for systemic activity in inflamed microenvironments ^{39Reference 39Ávila-Gálvez MÁ et al. · 2019Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammationView study →}. So the free aglycone concentration in an inflamed tissue may exceed the free concentration in plasma — but nobody has measured it in a person.

The numbers. After dietary ellagitannins, plasma total urolithins run about 0.003–5.2 µM, with 24-hour urine reaching up to about 50 µM; variability is extreme, driven by dose, food source and metabotype ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}. Direct supplementation is a different exposure entirely: plasma levels more than 30-fold higher at 6 hours than after pomegranate juice and still more than 2-fold higher at 24 hours, with Tmax around 6 hours and a half-life of roughly a day ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}. Urolithins persist in urine for up to 48 hours after an ellagitannin load ^{40Reference 40Seeram NP et al. · 2006Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hoursView study →}, and free ellagic acid — for comparison — peaks at only about 0.06 µmol/L with a sub-hour half-life ^{41Reference 41Seeram NP et al. · 2004Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juiceView study →}.

Tissue is where the argument is settled. Urolithin A-3-O-glucuronide in human malignant breast tissue: median 26.2 pmol/g, range 3.2–66.5 ^{19Reference 19Ávila-Gálvez MÁ et al. · 2019Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients — urolithin A-3-O-glucuronide at 26.2 pmol/gView study →}. Cell studies routinely use 10–50 µM of the free aglycone. That is a gap of roughly a thousandfold, and it is the reason the first physiologically-based pharmacokinetic model of urolithin A concluded that concentrations at which either toxic or beneficial effects have been observed in vitro are unlikely to be achieved in vivo. The same paper frames this as reassuring for safety and awkward for efficacy: it “supports the safety of UA, but also challenges the potential for readily achieving beneficial effects by postbiotic supplementation” ^{15Reference 15Aichinger G et al. · 2023Physiologically-based pharmacokinetic modeling of the postbiotic supplement urolithin A predicts its bioavailability is orders of magnitude lower than concentrations that induce toxicity, but also neuroprotective effectsView study →}.

Practical read: treat any urolithin A result obtained above ~1 µM of free aglycone as a gut-lumen or bench concentration unless the authors specifically used the glucuronide. The neutrophil ROS work at 1 µM ^{36Reference 36Piwowarski JP et al. · 2014Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils — urolithin A cut stimulated ROS by 42.6–53.7% at 1 µMView study →} and the endothelial work using urolithin A glucuronide itself at 5–15 µM ^{42Reference 42Giménez-Bastida JA et al. · 2012Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cellsView study →} are the exceptions that make the point.

Clinical Trials

Urolithin A has more genuine human isolate data than almost any other molecule here — and the pattern in it is consistent enough to state plainly: biomarkers and secondary endpoints move; primary and functional endpoints mostly do not.

Trial	Population	Dose / duration	Primary endpoint	Result
Andreux 2019 (first-in-human)	Healthy sedentary elderly	500 / 1,000 mg, single + 4 wk	Safety	Met — favourable; mitochondrial gene signature secondary 22Reference 22Andreux PA et al. · 2019The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans — first-in-human, safety as primary outcomeView study →
Singh 2022 (NCT03464500)	Middle-aged adults, 4 mo	Two doses vs placebo	Peak power output	Not met; strength +~12%, CRP ↓ (secondary) 23Reference 23Singh A et al. · 2022RCTUrolithin A improves muscle strength, exercise performance and biomarkers of mitochondrial health in a randomized trial in middle-aged adults (NCT03464500) — primary endpoint peak power output not metView study →
Liu 2022 (NCT03283462)	Adults 65–90, n=66	1,000 mg/day, 4 mo	6-min walk + max muscle ATP	Neither met; muscle endurance ↓fatigue at 2 mo (secondary) 24Reference 24Liu S et al. · 2022RCTEffect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults — a randomized clinical trial (NCT03283462); co-primary endpoints not metView study →
Jamialahmadi 2024	HFrEF, n=10, crossover	500 mg BID, 4 wk	Echocardiographic indices	Negative; HDL +6.46 mg/dL only 32Reference 32Jamialahmadi T et al. · 2024RCTEvaluation of urolithin A efficacy in heart failure patients with reduced ejection fraction — a randomized, double-blind, crossover, placebo-controlled clinical trial (n = 10); negative for echocardiographic endpointsView study →
Zhao 2024	Resistance-trained men, n=20	1 g/day, 8 wk	Strength / endurance	MVIC and reps-to-failure ↑; 1RM not significant 28Reference 28Zhao H et al. · 2024RCTAssessment 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 (n = 20)View study →
Denk 2025 (NCT05735886)	Healthy middle-aged, n=50	1,000 mg/day, 4 wk	CD3⁺ T-cell subsets, immune metabolism	Met, small effect sizes 27Reference 27Denk D et al. · 2025RCTEffect of the mitophagy inducer urolithin A on age-related immune decline — a randomized, placebo-controlled trial (NCT05735886)View study →; correction 2026 33Reference 33Denk D et al. · 2026Author correction — effect of the mitophagy inducer urolithin A on age-related immune declineView study →
Monsalve Acevedo 2025	Academy soccer players	6 wk	Yo-Yo IRT1	+239 m (95% CI 20–454) 29Reference 29Monsalve Acevedo A et al. · 2025RCTEffects of urolithin A supplementation on performance and antioxidant status in academy soccer players during preseason — a pilot randomised controlled trialView study →
URO-PRO (NCT06022822)	Prostate cancer, pre-prostatectomy	—	—	Recruiting
NCT06556706	Frail older adults	—	—	Completed, not yet reported here

Last checked: August 2026.

Isolate vs. Plant Studies

The usual attribution problem here runs from plant to molecule. Here it runs the opposite way, and it is worth being precise about the direction.

The isolate evidence is the strong evidence. Every human trial above dosed synthesised urolithin A at defined purity. That is the reverse of the situation on the ellagitannin pages, where the molecule is never the thing tested.

But the isolate evidence does not transfer back to the foods. A pomegranate, a handful of walnuts or a cup of raspberry-leaf infusion delivers ellagitannins, which deliver ellagic acid, which delivers urolithin A only in some people and at concentrations an order of magnitude or more below a 500 mg capsule ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}. Citing the Mitopure muscle trials as evidence that pomegranate juice improves muscle strength is the central error in this area, and our own ellagic acid page is right to say the flashy human data belong to a different molecule.

Nor does it transfer forward to the mechanism. The mouse and cell work that supplies urolithin A’s mechanistic narrative — mitophagy, senescence, AhR, lysosomes — was done with the free aglycone at 10–50 µM. Human tissue sees the glucuronide at tens of nanomolar ^{19,15Reference 19Ávila-Gálvez MÁ et al. · 2019Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients — urolithin A-3-O-glucuronide at 26.2 pmol/gView study →Reference 15Aichinger G et al. · 2023Physiologically-based pharmacokinetic modeling of the postbiotic supplement urolithin A predicts its bioavailability is orders of magnitude lower than concentrations that induce toxicity, but also neuroprotective effectsView study →}. The mechanism is real; whether it is the mechanism operating in a person taking a capsule is unresolved.

And the siblings are not interchangeable. Urolithin A, isourolithin A, urolithin B and urolithin C differ in activity, sometimes sharply: urolithin A alone induced senescence in colon cancer cells ^{18Reference 18Giménez-Bastida JA et al. · 2020The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cellsView study →}; urolithin C alone inhibited neutrophil elastase release; urolithin B was the one active on IL-8 and MMP-9 ^{36Reference 36Piwowarski JP et al. · 2014Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils — urolithin A cut stimulated ROS by 42.6–53.7% at 1 µMView study →}. “Urolithins are anti-inflammatory” is a class statement covering four molecules with four profiles — which matters because a metabotype-B person produces a different mixture than a metabotype-A person from the same fruit.

How It Is Made

Urolithin A has no biosynthesis in the botanical sense. It is a catabolite — the product of bacteria dismantling a plant defence molecule to make it metabolically tractable.

The route starts with an ellagitannin — punicalagin from pomegranate, sanguiin H-6 from raspberry, castalagin from an oak barrel: a galloyl/hexahydroxydiphenoyl ester of glucose, built in the plant by oxidative C–C coupling of two adjacent galloyl groups. In the gut, ester bonds hydrolyse, and the freed hexahydroxydiphenoyl acid spontaneously lactonises into ellagic acid — a flat, poorly soluble, barely absorbable dilactone. That is where plant chemistry stops and microbial chemistry begins.

Colonic bacteria then perform, in sequence: lactone-ring cleavage, decarboxylation, and a series of dehydroxylations, walking the molecule down from pentahydroxy urolithin M-5 → tetrahydroxy M-6 → trihydroxy urolithin C → dihydroxy urolithin A, mostly in the distal colon ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}. Each dehydroxylation is a distinct enzymatic step in a distinct organism, which is exactly why the pathway can stall partway and why metabotypes exist at all: Gordonibacter reliably gets to urolithin C and stops there ^{4Reference 4Selma MV et al. · 2014Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species — pure cultureView study →}, and only a microbiota carrying the Enterocloster ucd operon removes the 9-OH to finish the job ^{8Reference 8Pidgeon R et al. · 2025Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species — the inducible ucd operonView study →}. Branch off at the wrong hydroxyl and you get isourolithin A (Ellagibacter) ^{6Reference 6Beltrán D et al. · 2018Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family Eggerthellaceae isolated from human gutView study →}; remove one more and you get urolithin B; take a different route from urolithin D and you get the recently described urolithin G ^{9Reference 9Beltrán D et al. · 2023NMR spectroscopic identification of urolithin G, a novel trihydroxy urolithin produced by human intestinal Enterocloster speciesView study →}.

The commercial supplement short-circuits all of this. The Amazentis ingredient is a chemically synthesised compound, structurally identical to the microbial product, manufactured and purified to a specification of at least 97% purity — which is why a capsule works the same in a metabotype-0 person as in anyone else.

Prevalence in Nature

Urolithin A does not occur in plants. Searches pairing it with the botanical binomials of its supposed “sources” return studies of the precursor chemistry, not of the molecule. Any product label listing urolithin A as a pomegranate or berry constituent is describing something the fruit does not contain.

What food supplies is the ellagitannin/ellagic-acid substrate, and that distribution is genuinely narrow:

Precursor source	Part	Ellagitannin chemistry
Pomegranate (Punica granatum)	peel/rind, juice	Punicalagin; peel carries ~50× the arils and is the commercial extraction source
Walnut and pecan	kernel	Pedunculagin; the food most associated with urolithin production in cohort studies 38Reference 38Selma MV et al. · 2018The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkersView study →
Raspberry, blackberry, cloudberry	fruit, leaf, shoot	Sanguiin H-6, lambertianin C
Strawberry	fruit	Agrimoniin-dominant
Oak-aged wine and whisky	beverage	Vescalagin / castalagin migrating from the barrel
Muscadine grapes	fruit	Unusual among grapes in carrying ellagitannins
Camu-camu, meadowsweet, chanca piedra, bearberry, witch hazel	various	Ellagitannin-bearing herbal materials whose infusions yield urolithins on faecal incubation 37Reference 37Piwowarski JP et al. · 2014Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — ex vivo faecal incubation and macrophage assayView study →

Urolithin A has been detected in human plasma, urine, faeces, breast milk, and prostate, colon and breast tissue ^{13,19Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →Reference 19Ávila-Gálvez MÁ et al. · 2019Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients — urolithin A-3-O-glucuronide at 26.2 pmol/gView study →} — which is to say, its “natural distribution” is a distribution inside people, not inside plants.

Discovery & Synthesis

Urolithin A entered the modern literature through pharmacokinetics, not phytochemistry. It was the pomegranate-juice bioavailability studies of the mid-2000s that established the pattern the whole field now works from: free ellagic acid peaks in plasma at a trivial ~0.06 µmol/L and clears within hours ^{41Reference 41Seeram NP et al. · 2004Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juiceView study →}, while ellagitannin metabolites appear in plasma and persist in urine for up to 48 hours ^{40Reference 40Seeram NP et al. · 2006Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hoursView study →}. Naming the responsible organisms took another decade — Gordonibacter urolithinfaciens in 2014 ^{5Reference 5Selma MV et al. · 2014Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gutView study →}, Ellagibacter isourolithinifaciens in 2018 ^{6Reference 6Beltrán D et al. · 2018Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family Eggerthellaceae isolated from human gutView study →} — and identifying the enzyme that actually makes urolithin A took until 2025 ^{8Reference 8Pidgeon R et al. · 2025Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species — the inducible ucd operonView study →}.

Structurally the molecule is a 6H-dibenzo[b,d]pyran-6-one: a benzene ring fused across a coumarin (2H-chromen-2-one) system, with hydroxyls at positions 3 and 8. Formula C₁₃H₈O₄, MW 228.20, XLogP 2.3. Its siblings differ only in hydroxylation pattern — isourolithin A is the 3,9-dihydroxy isomer, urolithin B the 3-monohydroxy, urolithin C the 3,8,9-trihydroxy. That small difference is enough to change which bioactivities each one has ^{18,36Reference 18Giménez-Bastida JA et al. · 2020The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cellsView study →Reference 36Piwowarski JP et al. · 2014Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils — urolithin A cut stimulated ROS by 42.6–53.7% at 1 µMView study →}.

Supply is entirely synthetic. There is no extraction route, because there is nothing to extract it from: the manufacturer’s ingredient is a laboratory synthesis “identical in structure to the compound formed endogenously”, produced in several steps to ≥97% purity. This is one of the few molecules here where the synthetic article is not a compromise — it is the only practical form, and it is what every human trial has used.

Patents: not yet researched.

Regulatory Status

Worth stating precisely, because “FDA approved” appears in a great deal of marketing copy and is not what happened.

United States. Amazentis SA filed a GRAS notice for urolithin A (GRN 000791) in June 2018. FDA closed the notice on 20 December 2018 with a “no questions” letter for use as an ingredient in powdered and ready-to-drink protein shakes, non-milk meal-replacement beverages, instant oatmeal, protein and nutrition bars and yogurts, at maximum levels of 500 mg or 1,000 mg per serving depending on the category ^{43Reference 43US Food et al. · 2018GRAS Notice NoView study →}. GRAS is a notification that FDA declines to question, not an approval, and it certifies safety at the notified food-ingredient levels — not efficacy, and not any health claim.

Elsewhere. An EU novel-food application (Amazentis, 2018-0538) was filed and the manufacturer states that authorisation followed; I was unable to verify a Union-list entry for urolithin A on EUR-Lex, so none is asserted an EU authorisation. Treat non-US regulatory claims as unconfirmed here until checked against the official register.

Toxicity & Safety

Urolithin A carries a low flag, and unusually for this database that flag rests on an actual dataset rather than on dietary familiarity: a purpose-built rat toxicology package, a closed FDA GRAS notice, and several months of randomised human dosing at 500–1,000 mg/day with adverse-event reporting.

Safety at a Glance

✅ Low / no toxicity

• A real toxicology package exists. Genotoxicity battery negative; 28-day and 90-day oral rat studies showed no changes in clinical parameters, blood chemistry or haematology, no target organs and no specific toxic mechanism. NOAEL = the highest dose tested, 5% of diet — 3,451 mg/kg/day in males and 3,826 mg/kg/day in females ^{14Reference 14Heilman J et al. · 2017AnimalSafety assessment of urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant-derived ellagitannins and ellagic acid — rat genotoxicity, ADME, 28-day and 90-day studiesView study →}.
• Human tolerability at trial doses. No statistically different adverse events versus placebo in the 4-month older-adult trial ^{24Reference 24Liu S et al. · 2022RCTEffect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults — a randomized clinical trial (NCT03283462); co-primary endpoints not metView study →}; adverse events across the trial set were mild or moderate and judged unrelated ^{25Reference 25Kuerec AH et al. · 2024Systematic reviewTargeting aging with urolithin A in humans — a systematic review (5 studies, 250 participants)View study →}.
• The bioavailability ceiling cuts both ways. The PBPK model concludes achievable plasma concentrations sit orders of magnitude below those that produced toxicity in vitro ^{15Reference 15Aichinger G et al. · 2023Physiologically-based pharmacokinetic modeling of the postbiotic supplement urolithin A predicts its bioavailability is orders of magnitude lower than concentrations that induce toxicity, but also neuroprotective effectsView study →}.
• Reported human kidney stones — from food, not supplements. Eight patients (seven women, aged 59–87) had renal calculi containing urolithin A at 5–80% of stone composition, confirmed by infrared spectroscopy, LC-MS and NMR. None were taking urolithin A supplements; all six with dietary histories ate walnuts daily or near-daily, often blended in smoothies. The authors recommend adding urolithin A to stone-analysis reference libraries and flag rising supplement use as a reason to watch ^{12Reference 12Best SL et al. · 2026First reported human cases of urolithin A renal calculi — eight patients, none taking supplementsView study →}. Eight cases with no denominator is a signal, not a rate — but it is a real one, and it is new.
• Nothing is longer than four months. Every human trial to date is 4 weeks to 4 months in tens of participants. A compound marketed for lifelong use has no long-term safety data.
• AhR antagonism is a plausible interaction mechanism. Urolithin A binds AhR directly and blocks TCDD-induced CYP1A1 transcription ^{20Reference 20Muku GE et al. · 2018Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonistView study →}. No clinical drug-interaction study has been done; whether this matters at achievable concentrations is unknown.
• No reproductive or developmental data. None exists for the isolated molecule at supplement doses.

Full Safety & Interactions Detail

What the rat package covers, and what it doesn’t. Heilman and colleagues ran the first published safety assessment of directly administered urolithin A: a genotoxicity battery (negative), an ADME study showing glucuronidated and sulfonated forms predominate after both oral and intravenous dosing, and 28-day and 90-day dietary studies at up to 5% of diet. No adverse effects, no target organs, NOAEL at the top dose ^{14Reference 14Heilman J et al. · 2017AnimalSafety assessment of urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant-derived ellagitannins and ellagic acid — rat genotoxicity, ADME, 28-day and 90-day studiesView study →}. Two caveats belong with that. First, the study was authored by Amazentis staff and a consultancy engaged by them — which does not invalidate it, but it is the same sponsor as the efficacy programme. Second, a subsequent independent PBPK analysis noted that “few studies raise possible adverse effects at high doses, including genotoxicity and estrogenic effects” and set out to resolve the question by modelling exposure; its answer was that neither the toxic nor the beneficial in vitro concentrations are plausibly reached ^{15Reference 15Aichinger G et al. · 2023Physiologically-based pharmacokinetic modeling of the postbiotic supplement urolithin A predicts its bioavailability is orders of magnitude lower than concentrations that induce toxicity, but also neuroprotective effectsView study →}. Those two positions are compatible — the reassurance in both cases comes from low systemic exposure.

The estrogenicity question, answered where it counts. Urolithins have a phenolic, planar structure that invites the phytoestrogen question. The most relevant test measured the metabolites as they actually occur in human breast tissue — urolithin A-3-O-glucuronide at a median 26.2 pmol/g — and found no estrogenic or antiestrogenic activity in MCF-7 cells at those concentrations and in those molecular forms ^{19Reference 19Ávila-Gálvez MÁ et al. · 2019Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients — urolithin A-3-O-glucuronide at 26.2 pmol/gView study →}. That is a better answer than a receptor-binding assay.

The stone finding in context. The name “urolithin” derives from urinary stones, so there is an irony in the 2026 report, but the substance of it is straightforward: urolithin A is sufficiently insoluble that it can crystallise in urine, and this had never been documented in humans before. The exposure was dietary — daily walnuts — not supplemental, which is itself interesting, because it means high urolithin production from food can reach stone-forming concentrations in the urine of a metabotype-A individual. The authors’ concern about the growing supplement market is explicitly forward-looking, not a finding about supplement users ^{12Reference 12Best SL et al. · 2026First reported human cases of urolithin A renal calculi — eight patients, none taking supplementsView study →}. Anyone with a stone history taking urolithin A should know this exists.

Interactions. No clinical drug-interaction study has been performed. The two mechanistically plausible flags are (a) AhR/CYP1A1: urolithin A is a direct AhR ligand and a selective antagonist that suppresses CYP1A1 induction ^{20Reference 20Muku GE et al. · 2018Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonistView study →}, which in principle touches the metabolism of CYP1A1/1A2 substrates; and (b) anything that reshapes the colonic microbiota — antibiotics above all — which will alter endogenous urolithin production far more than any pharmacokinetic interaction would, though it has no effect on a synthesised supplement ^{1,2Reference 1Tomás-Barberán FA et al. · 2014Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health statusView study →Reference 2Cortés-Martín A et al. · 2018The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by aging (n = 839, ages 5–90)View study →}.

Reproductive and developmental note (prose only). No reproductive or developmental toxicity study of isolated urolithin A has been published, and no trial has enrolled pregnant or lactating participants. Urolithin conjugates have been detected in human breast milk ^{13Reference 13García-Villalba R et al. · 2022Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiotaView study →}, so transfer occurs at dietary exposures. Decisions about supplementation in pregnancy belong to a clinician, not to a phytochemistry page.

Dosage

There is no established therapeutic dose of urolithin A. The figures below are what the research used.

The last three rows are the ones to keep in view. The gap between the dietary route and the supplement route is a microbiome; the gap between the supplement route and the cell literature is three orders of magnitude. These are descriptive research figures, not a recommendation.

References

1. Tomás-Barberán FA, García-Villalba R, González-Sarrías A, Selma MV, Espín JC (2014). Ellagic acid metabolism by human gut microbiota — consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age and health status. Journal of Agricultural and Food Chemistry, 62(28), 6535–6538. https://pubmed.ncbi.nlm.nih.gov/24976365/
2. Cortés-Martín A, García-Villalba R, González-Sarrías A, Romo-Vaquero M, Loria-Kohen V, Ramírez-de-Molina A, Tomás-Barberán FA, Selma MV, Espín JC (2018). The gut microbiota urolithin metabotypes revisited — the human metabolism of ellagic acid is mainly determined by aging (n = 839, ages 5–90). Food & Function, 9(8), 4100–4106. https://pubmed.ncbi.nlm.nih.gov/30004553/
3. Tomás-Barberán FA, González-Sarrías A, García-Villalba R, Núñez-Sánchez MA, Selma MV, García-Conesa MT, Espín JC (2017). Urolithins, the rescue of “old” metabolites to understand a “new” concept — metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis and host health status. Molecular Nutrition & Food Research, 61(1). https://pubmed.ncbi.nlm.nih.gov/27158799/
4. Selma MV, Beltrán D, García-Villalba R, Espín JC, Tomás-Barberán FA (2014). Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species — pure culture. Food & Function, 5(8), 1779–1784. https://pubmed.ncbi.nlm.nih.gov/24909569/
5. Selma MV, Tomás-Barberán FA, Beltrán D, García-Villalba R, Espín JC (2014). Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut. International Journal of Systematic and Evolutionary Microbiology, 64(7), 2346–2352. https://pubmed.ncbi.nlm.nih.gov/24744017/
6. Beltrán D, Romo-Vaquero M, Espín JC, Tomás-Barberán FA, Selma MV (2018). Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family Eggerthellaceae isolated from human gut. International Journal of Systematic and Evolutionary Microbiology, 68(5), 1707–1712. https://pubmed.ncbi.nlm.nih.gov/29583112/
7. García-Villalba R, Beltrán D, Frutos MD, Selma MV, Espín JC, Tomás-Barberán FA (2020). Metabolism of different dietary phenolic compounds by the urolithin-producing human-gut bacteria Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciens. Food & Function, 11(8), 7012–7022. https://pubmed.ncbi.nlm.nih.gov/32716447/
8. Pidgeon R, Mitchell S, Shamash M, Suleiman L, Dridi L, Maurice CF, Castagner B (2025). Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species — the inducible ucd operon. Nature Communications, 16(1), 999. https://pubmed.ncbi.nlm.nih.gov/39856097/
9. Beltrán D, Frutos-Lisón MD, García-Villalba R, Yuste JE, García V, Espín JC, Selma MV, Tomás-Barberán FA (2023). NMR spectroscopic identification of urolithin G, a novel trihydroxy urolithin produced by human intestinal Enterocloster species. Journal of Agricultural and Food Chemistry, 71(31), 11921–11928. https://pubmed.ncbi.nlm.nih.gov/37494568/
10. He F, Bian Y, Zhao Y, Xia M, Liu S, Gui J, Hou X, Fang Y (2024). In vitro conversion of ellagic acid to urolithin A by different gut microbiota of urolithin metabotype A. Applied Microbiology and Biotechnology, 108(1), 215. https://pubmed.ncbi.nlm.nih.gov/38363367/
11. Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F (2013). Biological significance of urolithins, the gut microbial ellagic-acid-derived metabolites — the evidence so far. Evidence-Based Complementary and Alternative Medicine, 2013, 270418. https://pubmed.ncbi.nlm.nih.gov/23781257/
12. Best SL, Gruzdys V, White M, Gromadzka N, Owen B, Zhang Y, Asplin JR (2026). First reported human cases of urolithin A renal calculi — eight patients, none taking supplements. Kidney International Reports, 11(6), 106515. https://pubmed.ncbi.nlm.nih.gov/42058113/
13. García-Villalba R, Giménez-Bastida JA, Cortés-Martín A, Ávila-Gálvez MÁ, Tomás-Barberán FA, Selma MV, Espín JC, González-Sarrías A (2022). Urolithins — a comprehensive update on their metabolism, bioactivity and associated gut microbiota. Molecular Nutrition & Food Research, 66(21), e2101019. https://pubmed.ncbi.nlm.nih.gov/35118817/
14. Heilman J, Andreux P, Tran N, Rinsch C, Blanco-Bose W (2017). Safety assessment of urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant-derived ellagitannins and ellagic acid — rat genotoxicity, ADME, 28-day and 90-day studies. Food and Chemical Toxicology, 108(Pt A), 289–297. https://pubmed.ncbi.nlm.nih.gov/28757461/
15. Aichinger G, Stevanoska M, Beekmann K, Sturla SJ (2023). Physiologically-based pharmacokinetic modeling of the postbiotic supplement urolithin A predicts its bioavailability is orders of magnitude lower than concentrations that induce toxicity, but also neuroprotective effects. Molecular Nutrition & Food Research, 67(15), e2300009. https://pubmed.ncbi.nlm.nih.gov/37195009/
16. González-Sarrías A, García-Villalba R, Romo-Vaquero M, Alasalvar C, Örem A, Zafrilla P, Tomás-Barberán FA, Selma MV, Espín JC (2017). Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate — a randomized clinical trial (POMEcardio). Molecular Nutrition & Food Research, 61(5). https://pubmed.ncbi.nlm.nih.gov/27879044/
17. Romo-Vaquero M, Cortés-Martín A, Loria-Kohen V, Ramírez-de-Molina A, García-Mantrana I, Collado MC, Espín JC, Selma MV (2019). Deciphering the human gut microbiome of urolithin metabotypes — association with enterotypes and potential cardiometabolic health implications (n = 249). Molecular Nutrition & Food Research, 63(4), e1800958. https://pubmed.ncbi.nlm.nih.gov/30471188/
18. Giménez-Bastida JA, Ávila-Gálvez MÁ, Espín JC, González-Sarrías A (2020). The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells. Food and Chemical Toxicology, 139, 111260. https://pubmed.ncbi.nlm.nih.gov/32179165/
19. Ávila-Gálvez MÁ, García-Villalba R, Martínez-Díaz F, Ocaña-Castillo B, Monedero-Saiz T, Torrecillas-Sánchez A, Abellán B, González-Sarrías A, Espín JC (2019). Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients — urolithin A-3-O-glucuronide at 26.2 pmol/g. Molecular Nutrition & Food Research, 63(9), e1801239. https://pubmed.ncbi.nlm.nih.gov/30690879/
20. Muku GE, Murray IA, Espín JC, Perdew GH (2018). Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonist. Metabolites, 8(4), 86. https://pubmed.ncbi.nlm.nih.gov/30501068/
21. Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J (2016). Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, 22(8), 879–888. https://pubmed.ncbi.nlm.nih.gov/27400265/
22. Andreux PA, Blanco-Bose W, Ryu D, Burdet F, Ibberson M, Aebischer P, Auwerx J, Singh A, Rinsch C (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans — first-in-human, safety as primary outcome. Nature Metabolism, 1(6), 595–603. https://pubmed.ncbi.nlm.nih.gov/32694802/
23. Singh A, D’Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, Aebischer P, Auwerx J, Rinsch C (2022). Urolithin A improves muscle strength, exercise performance and biomarkers of mitochondrial health in a randomized trial in middle-aged adults (NCT03464500) — primary endpoint peak power output not met. Cell Reports Medicine, 3(5), 100633. https://pubmed.ncbi.nlm.nih.gov/35584623/
24. Liu S, D’Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, Rinsch C, Singh A, Marcinek DJ (2022). Effect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults — a randomized clinical trial (NCT03283462); co-primary endpoints not met. JAMA Network Open, 5(1), e2144279. https://pubmed.ncbi.nlm.nih.gov/35050355/
25. Kuerec AH, Lim XK, Khoo AL, Sandalova E, Guan L, Feng L, Maier AB (2024). Targeting aging with urolithin A in humans — a systematic review (5 studies, 250 participants). Ageing Research Reviews, 100, 102406. https://pubmed.ncbi.nlm.nih.gov/39002645/
26. Singh R, Chandrashekharappa S, Bodduluri SR, et al. (2019). Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway — urolithin A and UAS03 via AhR–Nrf2 and tight-junction proteins. Nature Communications, 10(1), 89. https://pubmed.ncbi.nlm.nih.gov/30626868/
27. Denk D, Singh A, Kasler HG, D’Amico D, et al. (2025). Effect of the mitophagy inducer urolithin A on age-related immune decline — a randomized, placebo-controlled trial (NCT05735886). Nature Aging, 5(11), 2309–2322. https://pubmed.ncbi.nlm.nih.gov/41174221/
28. Zhao H, Zhu H, Yun H, Liu J, Song G, Teng J, Zou D, Lu N, Liu C (2024). 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 (n = 20). Journal of the International Society of Sports Nutrition, 21(1), 2419388. https://pubmed.ncbi.nlm.nih.gov/39487653/
29. Monsalve Acevedo A, Sanctuary C, Aitken RJ, Wilkins A, Harrison N, Naughton M (2025). Effects of urolithin A supplementation on performance and antioxidant status in academy soccer players during preseason — a pilot randomised controlled trial. Frontiers in Nutrition, 12, 1674446. https://pubmed.ncbi.nlm.nih.gov/41245402/
30. D’Amico D, Olmer M, Fouassier AM, Valdés P, Andreux PA, Rinsch C, Lotz M (2022). Urolithin A improves mitochondrial health, reduces cartilage degeneration and alleviates pain in osteoarthritis — mouse model and human chondrocytes. Aging Cell, 21(8), e13662. https://pubmed.ncbi.nlm.nih.gov/35778837/
31. Hou Y, Chu X, Park JH, Zhu Q, Hussain M, Li Z, Madsen HB, Yang B, Wei Y, Wang Y, Fang EF, Croteau DL, Bohr VA (2024). Urolithin A improves Alzheimer’s disease cognition and restores mitophagy and lysosomal functions — three transgenic mouse models. Alzheimer’s & Dementia, 20(6), 4212–4233. https://pubmed.ncbi.nlm.nih.gov/38753870/
32. Jamialahmadi T, Hasanpour M, Vakilian F, Penson PE, Iranshahy M, Sahebkar A (2024). Evaluation of urolithin A efficacy in heart failure patients with reduced ejection fraction — a randomized, double-blind, crossover, placebo-controlled clinical trial (n = 10); negative for echocardiographic endpoints. Reviews on Recent Clinical Trials, 19(3), 221–228. https://pubmed.ncbi.nlm.nih.gov/38415449/
33. Denk D, Singh A, Kasler HG, et al. (2026). Author correction — effect of the mitophagy inducer urolithin A on age-related immune decline. Nature Aging, 6(2), 463. https://pubmed.ncbi.nlm.nih.gov/41491872/
34. Ishimoto H, Shibata M, Myojin Y, Ito H, Sugimoto Y, Tai A, Hatano T (2011). In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A. Bioorganic & Medicinal Chemistry Letters, 21(19), 5901–5904. https://pubmed.ncbi.nlm.nih.gov/21843938/
35. Piwowarski JP, Kiss AK, Granica S, Moeslinger T (2015). Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages — active at ≥40 µM. Molecular Nutrition & Food Research, 59(11), 2168–2177. https://pubmed.ncbi.nlm.nih.gov/26202092/
36. Piwowarski JP, Granica S, Kiss AK (2014). Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils — urolithin A cut stimulated ROS by 42.6–53.7% at 1 µM. Planta Medica, 80(11), 887–895. https://pubmed.ncbi.nlm.nih.gov/24995502/
37. Piwowarski JP, Granica S, Zwierzyńska M, Stefańska J, Schopohl P, Melzig MF, Kiss AK (2014). Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — ex vivo faecal incubation and macrophage assay. Journal of Ethnopharmacology, 155(1), 801–809. https://pubmed.ncbi.nlm.nih.gov/24969824/
38. Selma MV, González-Sarrías A, Salas-Salvadó J, Andrés-Lacueva C, Alasalvar C, Örem A, Tomás-Barberán FA, Espín JC (2018). The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers. Clinical Nutrition, 37(3), 897–905. https://pubmed.ncbi.nlm.nih.gov/28347564/
39. Ávila-Gálvez MÁ, Giménez-Bastida JA, González-Sarrías A, Espín JC (2019). Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammation. Food & Function, 10(6), 3135–3141. https://pubmed.ncbi.nlm.nih.gov/31041969/
40. Seeram NP, Henning SM, Zhang Y, Suchard M, Li Z, Heber D (2006). Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. The Journal of Nutrition, 136(10), 2481–2485. https://pubmed.ncbi.nlm.nih.gov/16988113/
41. Seeram NP, Lee R, Heber D (2004). Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clinica Chimica Acta, 348(1–2), 63–68. https://pubmed.ncbi.nlm.nih.gov/15369737/
42. Giménez-Bastida JA, González-Sarrías A, Larrosa M, Tomás-Barberán F, Espín JC, García-Conesa MT (2012). Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells. Molecular Nutrition & Food Research, 56(5), 784–796. https://pubmed.ncbi.nlm.nih.gov/22648625/
43. US Food and Drug Administration. GRAS Notice No. GRN 000791 — urolithin A (Amazentis SA); closed 20 December 2018, “FDA has no questions”. https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=grasnotices&id=791

View all 43 references▾