Ura8.5

Urolithin A Research

37 peer-reviewed studies · Evidence score: 8.5/10

Unveiling the Anticancer Potential of Urolithin A in Colorectal Cancer: A Systematic Review

Francisco M et al. • Oncology research (2026)

Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.

Systematic review examining Urolithin A efficacy
Further research warranted to confirm findings

Systematic Review

DOI

The anti-obesity effects of postbiotics: A systematic review of pre-clinical and clinical studies

Eslami M et al. • Clinical nutrition ESPEN (2024)

Postbiotics seem to be a safe intervention and the results were in favor of a reduction in adipogenesis as well as an increase in energy expenditure.

Postbiotics seem to be a safe intervention and the results were in favor of a reduction in adipogenesis as well as an increase in energy expenditure.
Further high-quality studies are required in this relatively new topic.
Further research warranted to confirm findings

Systematic Reviewn=49

DOI

Impact of nutraceuticals and dietary supplements on mitochondria modifications in healthy aging: a systematic review of randomized controlled trials

Lippi L et al. • Aging clinical and experimental research (2022)

Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults.

Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults.
Further research warranted to confirm findings

Systematic Reviewn=201

DOI

Targeting aging with urolithin A in humans: A systematic review

Kuerec AH et al. • Ageing research reviews (2024)

Unrelated adverse events were mild or moderate.

Unrelated adverse events were mild or moderate.
Further research across more physiological systems and longer intervention periods is required.

Systematic Review

DOI

Age-related sarcopenia and altered gut microbiota: A systematic review

Wang M et al. • Microbial pathogenesis (2024)

Age-related sarcopenia and gut microbiota alterations are intricately linked.

Age-related sarcopenia and gut microbiota alterations are intricately linked.
Short-chain fatty acid metabolism, urolithin A, and bile acid production may be pivotal factors in the gut-muscle axis pathway.
Supplementation with beneficial metabolite-associated microorganisms could enhance muscle function, mitigate muscle atrophy, and decelerate sarcopenia progression.

Systematic Review

DOI

Pharmacological Regulation of Mitophagy by Natural Plant Products as a Therapeutic Target for Alzheimer's Disease

Shao S et al. • Phytotherapy research : PTR (2026)

This review explores the mechanistic hypotheses linking mitophagy to AD pathology and provides a systematic overview of recent advances in representative NPPs that regulate mitophagy to alleviate AD-related impairments, offering new perspectives for the development of therapeutic strategies against AD.© 2025 John Wiley & Sons Ltd.

Notably, a number of natural plant products (NPPs) have been demonstrated to modulate mitophagy and intervene in the pathological process of AD.
For instance, NPPs such as urolithin A and β-asarone have been reported to enhance mitophagy by activating the PINK1/Parkin pathway, thereby alleviating Aβ-induced neurotoxicity.
The distinctive multi-target properties and favorable safety profiles of NPPs endow them with significant research potential and developmental value, establishing them as a vital resource for novel drug discovery.

Systematic ReviewAI-discovered

DOI

Urinary polyphenol signature of the Mediterranean diet is associated with lower cardiovascular disease risk: the PREDIMED trial

Domínguez-López I et al. • BMC medicine (2025)

We identified a urinary multi-metabolite signature of MedDiet adherence that is prospectively associated with lower CVD incidence.

After 1 year, MedDiet interventions significantly increased urolithin A metabolites (derived from walnuts) compared to the control group.
We identified a urinary multi-metabolite signature of MedDiet adherence that is prospectively associated with lower CVD incidence.
These findings support that polyphenols derived from the MedDiet showed inverse associations with cardiovascular outcomes.

RCTn=603

DOI

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

Zhao H et al. • Journal of the International Society of Sports Nutrition (2024)

After 8 weeks of UA supplementation at 1 g/day, resistance-trained male athletes showed improvements in muscle strength and endurance.

After 8 weeks of UA supplementation, the UA group showed a significant decrease in 3-methylhistidine (3-MH) compared to baseline measurement (Δ=-2.38 ± 1.96 μmol/L, p = 0.049).
Additionally, the UA group exhibited a significant increase in C-reactive protein (CRP) compared to baseline (Δ = 0.71 ± 0.21 mg/L, p = 0.001).
Furthermore, the UA group showed a significant decrease in SOD compared to the placebo group (Δ=-4.32 ± 0.90 U/mL, p = 0.041).

RCTn=20

DOI

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS)

Kaplan A et al. • The American journal of clinical nutrition (2022)

A Green-MED (high-polyphenol) diet, rich in Mankai, green tea, and walnuts and low in red/processed meat, is potentially neuroprotective for age-related brain atrophy.This trial was registered at clinicaltrials.gov as NCT03020186.

Among 284 participants (88% men; mean age: 51 y; BMI: 31.2 kg/m2; APOE-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs.
The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes.
Compared with younger participants, atrophy was accelerated among those ≥50 y old (HOC change: -1.0% ± 1.4% compared with -0.06% ± 1.1%; 95% CI: 0.6%, 1.3%; P < 0.001; LVV change: 3.2% ± 4.5% compared with 1.3% ± 4.1%; 95% CI: -3.1%, -0.8%; P = 0.001).

RCTn=284

DOI

Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial

Denk D et al. • Nature aging (2025)

This rct examined the effects of Urolithin A.

Exploratory single-cell RNA sequencing demonstrated UA-driven transcriptional shifts across immune populations, modulating pathways linked to inflammation and metabolism.
These findings indicate that short-term UA supplementation modulates human immune cell composition and function, supporting its potential to counteract age-related immune decline and inflammaging.
ClinicalTrials.gov registration number: NCT05735886 .

RCTn=50

DOI

Multi-Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo-Controlled Trial

Napier BA et al. • Nutrients (2025)

This is the first synbiotic to increase both UroA and butyrate.

Results: The synbiotic significantly increased alpha-diversity of Bifidobacterium and Lactobacillus spp. at all timepoints, including at end-of-study (Day 91, p < 0.0001) and increased native beneficial microbes.
UroA production was significantly increased in the synbiotic arm at short-term (Day 7, 12-fold, p < 0.02) and long-term (Day 91, 49-fold, p < 0.001) timepoints.
A higher proportion of synbiotic participants were capable of converting polyphenols into UroA (Day 91, 100% vs. 44.4%; p < 0.01).

RCTn=32

DOI

The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial

Yaskolka Meir A et al. • BMC medicine (2023)

This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging.

This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging.
To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging.
Further research warranted to confirm findings

RCTn=256

DOI

The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial

Zelicha H et al. • BMC medicine (2022)

A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.

Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs.
A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.
Further research warranted to confirm findings

RCTn=294

DOI

Evaluating the Impact of Urolithin A Supplementation on Running Performance, Recovery, and Mitochondrial Biomarkers in Highly Trained Male Distance Runners

Whitfield J et al. • Sports medicine (Auckland, N.Z.) (2025)

Our results show that 4 weeks of daily UA supplementation facilitates recovery by downregulating inflammatory pathways and indirect markers of muscle damage.

While not statistically significant, UA led to a medium effect for increased markers of mitophagy (d = - 0.74), without changes in mitochondrial function.
Our results show that 4 weeks of daily UA supplementation facilitates recovery by downregulating inflammatory pathways and indirect markers of muscle damage.
However, despite a reduction in rating of exertion and increased aerobic capacity, UA supplementation did not further enhance performance in highly trained male endurance athletes.

RCTn=42

DOI

Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial

Jamialahmadi T et al. • Reviews on recent clinical trials (2024)

The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF.

Serum HDL-C levels were increased with UA compared with placebo (+6.46 ± 2.33 mg/dL, p =0.026), whereas other lipid indices (LDL-C, triglycerides, total cholesterol, and VLDL-C) remained unchanged (p >0.05).
The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF.
Further studies with higher doses of UA and longer supplementation duration are encouraged to be conducted.

Crossovern=10

DOI

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population

Singh A et al. • European journal of clinical nutrition (2022)

Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.

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.
Direct supplementation with UA significantly increased plasma levels and provided a >6-fold exposure to UA vs.

RCTn=100

DOI

A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy

Freedland SJ et al. • Cancer prevention research (Philadelphia, Pa.) (2013)

Future larger longer studies are needed to more definitively test whether POMx reduces prostate oxidative stress, as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology.

Primary endpoint was differences in 8-OHdG, and the study was powered to detect 35% reduction.
POMx was associated with 16% lower benign tissue 8-OHdG (P = 0.095), which was not statistically significant.
Urolithin A was detected in 21 of the 33 patients in the POMx group versus 12 of the 35 in the placebo group (P = 0.031).

RCTn=33

DOI

Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial

Liu S et al. • JAMA network open (2022)

This randomized clinical trial found that urolithin A supplementation was safe and well tolerated in the assessed population.

These participants had a mean (SD) age of 71.7 (4.94) years, were predominantly women (50 [75.8%]), and were all White individuals.
Urolithin A, compared with placebo, significantly improved muscle endurance (ie, increase in the number of muscle contractions until fatigue from baseline) in the FDI and TA at 2 months (urolithin A: FDI, 95.3 [115.5] and TA, 41.4 [65.5]; placebo: FDI, 11.6 [147.4] and TA, 5.7 [127.1]).
These results showed no significant improvement with urolithin A supplementation compared with placebo.

RCTn=66

DOI

Urolithin A improves muscle strength in middle-aged adults

Singh A et al. • Cell Reports Medicine (2022)

Urolithin A significantly improved muscle endurance and strength.

Improved leg muscle endurance
Increased muscle strength
Benefits in 4 months

RCTn=88

DOI

Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients

Ávila-Gálvez MÁ et al. • Molecular nutrition & food research (2019)

This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively.

This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively.
Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.
Further research warranted to confirm findings

RCTn=101

DOI

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