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1Mitochondria modificationsSystematic ReviewCited 34×n=201 · medium study2022
Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults.
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.
Moreover, approximately 10% of individuals are classified as urolithin nonproducers, independent of age, posing an additional challenge for clinical translation.
To overcome those limitations, formulation strategies such as nanoparticles and liposomes have been developed, resulting in several-fold increases in systemic bioavailability compared with unformulated UroA.
This review would provide a comprehensive overview of recent advances in the metabolism of UroA, current approaches to improve its bioavailability, safety evaluations, and elucidated the underlying mechanisms of its bioactivities.
Shao S et al. · Phytotherapy research : PTR (2025)
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.
8Muscle strength and enduranceRCTCited 13×n=20 · very small study2024
After 8 weeks of UA supplementation at 1 g/day, resistance-trained male athletes showed improvements in muscle strength and endurance.
Zhao H et al. · Journal of the International Society of Sports Nutrition (2024)
Noticeable benefit
← WorseNo effectBetter →
Likely real
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).
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.
Kaplan A et al. · The American journal of clinical nutrition (2022)
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).
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.
11Urolithin A and butyrate productionRCTCited 10×n=32 · small study2025
This is the first synbiotic to increase both UroA and butyrate.
Napier BA et al. · Nutrients (2025)
Noticeable benefit
← WorseNo effectBetter →
Likely real
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).
12Running performance and recoveryRCTCited 2×n=42 · small study2025
Our results show that 4 weeks of daily UA supplementation facilitates recovery by downregulating inflammatory pathways and indirect markers of muscle damage.
Whitfield J et al. · Sports medicine (Auckland, N.Z.) (2025)
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.
13Echocardiographic and biochemical indicesCrossoverCited 6×n=10 · very small study2024
The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF.
Jamialahmadi T et al. · Reviews on recent clinical trials (2024)
Noticeable benefit
← WorseNo effectBetter →
Likely real
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.
158-OHdG levels in prostate tissueRCTCited 51×n=33 · small study2013
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.
Freedland SJ et al. · Cancer prevention research (Philadelphia, Pa.) (2013)
Large benefit
← WorseNo effectBetter →
Borderline
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).
17Muscle enduranceRCTCited 130×n=66 · small study2022
This randomized clinical trial found that urolithin A supplementation was safe and well tolerated in the assessed population.
Liu S et al. · JAMA network open (2022)
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.
Significant improvements in FMD were observed at 2 h (1.6% (95%CI 1.2, 1.9) and 1.2% (95% CI 0.8, 1.5)) and 24 h (1.0% (95% CI 0.6, 1.2) and 0.7% (95%CI 0.2, 0.9)) post-consumption of the 200 and 4...
Istas G et al. · Archives of biochemistry and biophysics (2018)
Significant improvements in FMD were observed at 2 h (1.6% (95%CI 1.2, 1.9) and 1.2% (95% CI 0.8, 1.5)) and 24 h (1.0% (95% CI 0.6, 1.2) and 0.7% (95%CI 0.2, 0.9)) post-consumption of the 200 and 400 g raspberry drinks as compared to control, respectively.
Plasma ellagic acid, urolithin A-3-glucuronide and urolithin A-sulfate correlated with the improvements in FMD at 2 and 24 h post consumption, respectively.
Consumption of dietary achievable amounts of red raspberries acutely improves endothelial function up to 24 h and ellagitannins may be responsible for the observed effect.
20Safety and tolerability of pomegranate fruit extractRCTCited 20×2021
PFE administration for 12-month was well-tolerated and the protocol followed in an active surveillance population.
Jarrard D et al. · The Prostate (2021)
PFE administration for 12-month was well-tolerated and the protocol followed in an active surveillance population.
Analyses suggest that PFE contains bioactive compounds capable of altering biomarkers involving oxidative stress and androgen signaling in prostate tumor and normal-appearing adjacent tissue.