Urolithin A
Evidence Fact Sheet
Urolithin A is a gut-microbiome metabolite of ellagitannins (and a synthetic postbiotic) studied as a mitophagy inducer for healthy aging, muscle, and immune function. Human RCTs and a systematic review report mixed results — some muscle/immune-biomarker gains alongside null primary endpoints. US GRAS; EU novel-food pending.
Also known as: UA · Uro-A · 3,8-Dihydroxy-6H-dibenzo[b,d]pyran-6-one · CAS 1143-70-0
Overview
Urolithin A (UA, Mitopure) is a gut-microbiota metabolite of ellagitannins/ellagic acid — found in pomegranate, walnuts and berries — that is also produced synthetically, since only a minority of people host the gut bacteria needed to make meaningful amounts themselves. Mechanistically it is studied as an inducer of mitophagy (PINK1/Parkin-mediated clearance of damaged mitochondria) and an activator of mitochondrial-biogenesis pathways (AMPK, SIRT1), with NF-κB/NLRP3 anti-inflammatory signaling described in preclinical work. Human research has focused on healthy aging, muscle endurance and strength, athletic recovery, and immune aging. Typical research doses range from 500 to 1000 mg/day with food (single doses up to 2000 mg have been tolerated). Regulatory status: US FDA GRAS for food use (GRN 000791) and marketed as a DSHEA dietary supplement with the mandatory structure/function disclaimer (no authorized health claim); EU novel-food authorisation is pending with a positive EFSA safety opinion; no current ANVISA or China novel-food authorization.
Mechanism of Action
Mitophagy induction (PINK1/Parkin-mediated selective clearance of damaged mitochondria · research context) · AMPK activation supporting mitochondrial biogenesis (research context) · NF-κB / NLRP3 inflammasome suppression (preclinical) · SIRT1 upregulation / NAD+-linked mitochondrial metabolism (research context) · Gut-microbiota metabolite of ellagitannins (only ~30-40% of people are high producers)
Body systems: Mitochondrial & Cellular Energy · Musculoskeletal · Immune System · Cellular Renewal
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — Urolithin A is not characterized as a treatment for any disease.
Healthy Aging / Geroprotection (Systematic Review)
Meta-analysis supported- 5 studiessystematic review
- 250 individualshealthy adults pooled
- 10-1000 mg/daydose range · 28d-4mo
A systematic review of UA's geroprotective potential in humans pooled five trials in 250 healthy individuals. It reported a dose-dependent anti-inflammatory effect plus increased muscle strength and endurance, but explicitly noted no effect on maximal mitochondrial ATP production, biogenesis, dynamics, gut microbiota, anthropometrics, cardiovascular outcomes, or physical function — an honest mixed picture.
Reported effect: Five studies including 250 healthy individuals; UA 10-1000 mg/day for 28 days to 4 months; dose-dependent anti-inflammatory effect; increased muscle strength and endurance; no effect on mitochondrial maximal ATP production, biogenesis, dynamics, gut microbiota, anthropometrics, cardiovascular outcomes, or physical function.
“In five studies including 250 healthy individuals, UA (10-1000 mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. 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.”
Source: PMID 39002645 · Kuerec 2024 · Ageing Res Rev
Muscle Strength & Exercise Performance (Middle-Aged Adults)
RCT supported- ∼12%muscle strength gain
- peak powerprimary endpoint · not significant
In a randomized, placebo-controlled trial in middle-aged adults dosed for 4 months, UA produced significant ~12% improvements in muscle strength and lowered plasma acylcarnitines and C-reactive protein, but did NOT significantly improve peak power output, which was the trial's pre-specified primary endpoint — a notable honest negative on the primary outcome.
Reported effect: Significant improvements in muscle strength (∼12%); no significant improvement on peak power output (primary endpoint); plasma acylcarnitines and C-reactive proteins significantly lower with Urolithin A.
“The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A. We observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen consumption [VO₂]) and physical performance (6 min walk test) but do not notice a significant improvement on peak power output (primary endpoint). Levels of plasma acylcarnitines and C-reactive proteins are significantly lower with Urolithin A.”
Source: PMID 35584623 · Singh 2022 · Cell Rep Med
Muscle Endurance (Older Adults, 65-90 Y)
Null / no benefit RCT supported- 60.8 vs 42.5 m6-min walk · not significant
- P <.01muscle endurance · secondary
In a double-blind RCT of 66 adults aged 65-90, UA significantly improved muscle endurance at 2 months (a secondary endpoint), but the co-primary endpoints were null: the between-group difference in 6-minute walk distance (60.8 vs 42.5 m) was not statistically significant, and maximal ATP production did not improve versus placebo. A mixed result with null primaries.
Reported effect: 6-minute walk distance increase 60.8 (67.2) m UA vs 42.5 (73.3) m placebo (not significant); maximal ATP production change 0.07 (0.23) vs 0.06 (0.20) mM/s (no significant improvement); muscle endurance significantly improved at 2 months (P <.01).
“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. ... The mean (SD) change from baseline to 4 months in maximal ATP production in the FDI was 0.07 (0.23) mM/s in the urolithin A group and 0.06 (0.20) mM/s in the placebo group. ... Urolithin A, compared with placebo, significantly improved muscle endurance in the FDI and TA at 2 months (P <.01).”
Source: PMID 35050355 · Liu 2022 · JAMA Netw Open
Resistance-Trained Male Athletes (8 Weeks)
RCT supported- p = 0.000isometric strength (MVIC)
- p = 0.001reps to failure
- p = 0.0511RM bench · not significant
In an 8-week double-blind RCT in resistance-trained male athletes, UA significantly improved maximum voluntary isometric contraction and repetitions to failure versus baseline, while gains in 1RM bench press and squat did not reach statistical significance. UA also lowered a muscle-breakdown marker (3-methylhistidine) but, notably, increased C-reactive protein versus baseline.
Reported effect: MVIC Δ = 36.10 ± 0.62 NM, p = 0.000 and repetitions-to-failure Δ = 2.00 ± 0.56, p = 0.001 (significant); 1RM bench press Δ = 3.00 ± 0.17 kg, p = 0.051 and squat Δ = 1.35 ± 2.73 kg, p = 0.499 (not significant); 3-methylhistidine Δ = -2.38 ± 1.96 μmol/L, p = 0.049; CRP Δ = 0.71 ± 0.21 mg/L, p = 0.001.
“After 8 weeks of UA supplementation, compared to baseline measurements, the UA group exhibited increases in 1RM bench press and squat, although these changes were not statistically significant (Δ = 3.00 ± 0.17 kg, p = 0.051, Δ = 1.35 ± 2.73 kg, p = 0.499). Significant improvements were noted in Maximum Voluntary Isometric Contraction (MVIC) and repetitions to failure (RTF) performance (Δ = 36.10 ± 0.62 NM, p = 0.000; Δ = 2.00 ± 0.56, p = 0.001).”
Source: PMID 39487653 · Zhao 2024 · J Int Soc Sports Nutr
Immune Aging / Inflammaging (Middle-Aged Adults)
RCT supported- 14.72 ppCD8+ fat-oxidation · P=0.0061
- 0.50 ppnaive-like CD8+ · P=0.0437
In a randomized, placebo-controlled trial in healthy middle-aged adults (1000 mg/day for 4 weeks), UA expanded naive-like, less terminally exhausted CD8+ T cells and increased CD8+ fatty-acid-oxidation capacity versus placebo, an early signal that the mitophagy inducer may counter age-related immune decline.
Reported effect: Naive-like, less terminally exhausted CD8+ cells expanded (treatment difference 0.50 percentage points; P = 0.0437); CD8+ fatty acid oxidation capacity increased (treatment difference = 14.72 percentage points; P = 0.0061).
“UA expanded naive-like, less terminally exhausted CD8+ cells (treatment difference 0.50 percentage points; P = 0.0437) ... increasing CD8+ fatty acid oxidation capacity (treatment difference = 14.72 percentage points; P = 0.0061).”
Source: PMID 41174221 · Denk 2025 · Nat Aging
Endurance Running Performance & Recovery (Trained Runners)
Null / no benefit RCT supportedIn a double-blind RCT in 42 highly trained male distance runners (1000 mg/day for 4 weeks during an altitude training camp), UA lowered perceived exertion and reduced indirect markers of post-exercise muscle damage, but did NOT enhance running performance versus placebo — an honest negative on the performance endpoint.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“UA supplementation did not further enhance performance in highly trained male endurance athletes.”
Source: PMID 40839339 · Whitfield 2025 · Sports Med
Dosage (research context · not a recommendation)
500-1000 mg/day with food (educational reference · RCT range; mitophagy/muscle-biomarker signals from 4 weeks, muscle-function trials run 4 months · single human dose to 2000 mg tolerated)
Regulatory Status · 4 Markets
- US · FDA
- GRAS for food use (GRN 000791 · Amazentis SA · FDA no-questions 2018-12-20 · 500 mg/serving general food, 1000 mg/serving high-protein food). Marketed as a dietary supplement under DSHEA via NDI self-affirmation; NO FDA-authorized health claim — structure/function statements require the mandatory FDA disclaimer. 'FDA approved/certified' is prohibited.
- EU · EFSA
- EU novel-food authorisation is pending/ongoing (Amazentis/Mitopure dossier; EFSA 2021 positive safety opinion, but not yet a granted Union authorisation) in specified food categories (cereal/protein/nutrition products); EFSA 2021 positive safety opinion at ≤500 mg/day for adults. NO authorized health claim under Reg 432/2012. Not for children, pregnant or lactating women (not assessed).
- CN · China
- No record of approval as a China novel food ingredient; synthetic urolithin A (Mitopure) lacks Chinese food-use history and novel-food authorization — not lawfully marketable as a food/supplement ingredient in China at present.
- BR · ANVISA
- No public ANVISA approval record for synthetic urolithin A as a food supplement constituent; no Anexo V alegação funcional. Status to be confirmed via official channel — treat as not authorized.
Safety
Generally well tolerated in trials up to 1000 mg/day for 4 months and a single 2000 mg dose, with no serious adverse events and only occasional mild GI discomfort. Rat 90-day NOAEL = highest dose tested (≥3451 mg/kg bw/day); Ames-negative. No data in pregnancy, lactation, or children — EFSA assessment limited to adults; consult a healthcare provider. Pomegranate juice/extract or ellagic-acid supplements are NOT equivalent to direct UA (~60-70% of people lack the gut microbiota to form enough UA · key caveat). Non-Mitopure raw material is not automatically equivalent to clinical-grade UA (purity/patent caveat).
Related
Goals: longevity-stack · athletic-performance
Lifestyles: senior-60-plus · athletic-performance
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 39002645 · Kuerec 2024 · Ageing Res Rev — Healthy Aging / Geroprotection (Systematic Review)
- PMID 35584623 · Singh 2022 · Cell Rep Med — Muscle Strength & Exercise Performance (Middle-Aged Adults)
- PMID 35050355 · Liu 2022 · JAMA Netw Open — Muscle Endurance (Older Adults, 65-90 Y)
- PMID 39487653 · Zhao 2024 · J Int Soc Sports Nutr — Resistance-Trained Male Athletes (8 Weeks)
- PMID 41174221 · Denk 2025 · Nat Aging — Immune Aging / Inflammaging (Middle-Aged Adults)
- PMID 40839339 · Whitfield 2025 · Sports Med — Endurance Running Performance & Recovery (Trained Runners)
Frequently Asked Questions
1. What is Urolithin A and where does it come from?
Urolithin A (UA, sold as Mitopure) is a compound your gut bacteria make from ellagitannins and ellagic acid — the polyphenols in pomegranate, walnuts and berries. Because only a minority of people host the gut microbes needed to produce meaningful amounts, it is also manufactured synthetically and taken as a postbiotic supplement. It is studied mainly as a mitophagy inducer (helping clear damaged mitochondria).
2. Does Urolithin A actually improve muscle and exercise performance?
The human evidence is genuinely mixed. A 4-month RCT in middle-aged adults found a significant ∼12% gain in muscle strength but no significant improvement in its primary endpoint, peak power output (Singh 2022, PMID 35584623). In older adults aged 65-90, UA significantly improved muscle endurance but the co-primary 6-minute walk and ATP endpoints were null (Liu 2022, PMID 35050355). In trained athletes, isometric strength and reps-to-failure improved while 1RM did not (Zhao 2024, PMID 39487653), and in highly trained runners it aided recovery but did not enhance running performance (Whitfield 2025, PMID 40839339).
3. Is there evidence for healthy aging or immune benefits?
A systematic review of five trials in 250 healthy individuals (Kuerec 2024, PMID 39002645) reported a dose-dependent anti-inflammatory effect and gains in muscle strength and endurance, but no effect on maximal mitochondrial ATP production, biogenesis, cardiovascular outcomes, or physical function. A separate RCT in middle-aged adults found UA expanded naive-like CD8+ T cells and increased their fatty-acid-oxidation capacity (Denk 2025, PMID 41174221), an early immune-aging signal. These are research findings in studied populations, not proof of disease prevention or treatment.
4. Is Urolithin A approved, and is pomegranate juice the same thing?
In the US, Urolithin A is GRAS for food use (GRN 000791) and sold as a DSHEA dietary supplement with the mandatory structure/function disclaimer — there is no FDA-authorized health claim. EU novel-food authorisation is pending with a positive EFSA safety opinion, and there is no current ANVISA or China novel-food authorization. Pomegranate juice or ellagic-acid supplements are NOT equivalent to direct UA, because most people lack the gut microbiota to convert them into enough Urolithin A.
Last evidence review: 2026-06-13