Urolithin A Supplementation for Obesity

No longer recruiting at 1 trial location

Overseen By Ana Clara da Costa Pinaffi Langley, MSc, ELS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Oklahoma

Disqualifiers: Uncontrolled hypertension, Diabetes, Cardiac disease, others

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a dietary supplement called urolithin A can improve blood flow in middle-aged individuals with obesity. Participants will take either the supplement or a placebo (a dummy treatment) daily for four weeks. Researchers aim to determine if blood flow differs between those taking the supplement and those taking the placebo. This trial suits individuals comfortable with study visits and having a BMI of 30 or higher, indicating obesity. As an unphased trial, it offers participants the chance to contribute to scientific understanding and potentially experience improved health outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Urolithin A is safe and well tolerated in humans. In studies where participants took Urolithin A for up to four months, it did not cause major side effects. One study identified 33 side effects, but only 31 were linked to the treatment, and none were serious. Participants did not report any major problems. Other research also indicates that even in larger amounts, Urolithin A remains safe. Thus, the available evidence suggests that Urolithin A is generally safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for obesity focus on diet, exercise, or medications that suppress appetite or inhibit fat absorption. But Urolithin A is different because it targets the mitochondria, the energy powerhouses in our cells, to enhance their function. Researchers are excited about Urolithin A because it is derived from natural sources, like pomegranates, and may improve cellular health and metabolism, potentially offering a new way to tackle obesity. This unique mechanism sets it apart from standard treatments, providing a promising alternative for those struggling with weight management.

What evidence suggests that urolithin A might be an effective treatment for obesity?

This trial will compare Urolithin A supplementation with a placebo. Research has shown that Urolithin A, a dietary supplement, can increase muscle strength and endurance. In one study, participants taking Urolithin A experienced about a 12% improvement in muscle strength. This supplement also supports mitochondrial health, crucial for energy production in cells. Urolithin A aids by clearing out damaged cell parts, potentially enhancing overall cell function. Although direct evidence on its effects on blood flow in individuals with obesity is limited, these findings suggest potential benefits for energy and overall health. ^{1 2 3 6 7}

Who Is on the Research Team?

Andriy Yabluchanskiy, MD, PhD

Principal Investigator

University of Oklahoma Health Science Center

Are You a Good Fit for This Trial?

This trial is for middle-aged adults (40-64 years old) with obesity, defined as having a BMI of 30 or higher. Participants must be able to understand and consent in English. It's not open to those with cognitive impairments, swallowing issues, recent heart problems, severe mental health conditions like depression or anxiety, significant GI diseases, allergies to the supplement ingredients, active cancer treatment, diabetes history or neurodegenerative disorders.

Inclusion Criteria

Competence to provide written informed consent

I am between 40 and 64 years old.

My BMI is 30 or higher.

Exclusion Criteria

You are allergic or have a bad reaction to any of the treatment ingredients.

I am currently receiving treatment for cancer.

I have difficulty swallowing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take the dietary supplement daily for 4 weeks

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Urolithin A

Trial Overview The study tests if Urolithin A supplementation can improve blood flow in large and small vessels among obese middle-aged adults. Over four weeks participants will take either this dietary supplement or a placebo daily. Their vascular health will be assessed through two visits involving vessel checks and questionnaires.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Group II: Control Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Amazentis SA

Industry Sponsor

Trials

21

Recruited

1,400+

Published Research Related to This Trial

In a study involving 94 participants with varying BMI and health statuses, specific urolithin metabolites (UMs) were found to correlate with cardiometabolic risk factors, suggesting they could serve as potential biomarkers for assessing cardiovascular health.

Urolithin-A was associated with positive lipid profiles in overweight-obese individuals, while Urolithin-B was linked to higher cholesterol levels, indicating that the type of urolithin produced may influence cardiometabolic disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome. Selma, MV., González-Sarrías, A., Salas-Salvadó, J., et al.[2019]

A new analytical method using liquid chromatography high-resolution mass spectrometry (LC-QToF-MS) was developed to detect 111 amine-based compounds in weight loss and sports supplements, revealing that two-thirds of the tested products contained undeclared active ingredients.

The study found that 44% of the supplements analyzed did not contain one or more of the ingredients listed on their labels, highlighting potential safety concerns and the need for regulatory oversight in the supplement industry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid chromatography-quadrupole time of flight mass spectrometric method for targeted analysis of 111 nitrogen-based compounds in weight loss and ergogenic supplements. Avula, B., Bae, JY., Chittiboyina, AG., et al.[2020]

A new method using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) allows for rapid and sensitive detection of β-agonists in human urine, with a detection limit as low as 0.1 ng/mL and analysis completed in just 12 minutes.

The method demonstrated high accuracy (94.5 to 109%) and precision (<5.60%) in detecting β-agonists, and it successfully identified salbutamol in the urine of one volunteer, highlighting its potential for monitoring β-agonist misuse in both human health and veterinary contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous determination of 11 β-agonists in human urine using high-performance liquid chromatography/tandem mass spectrometry with isotope dilution. Wang, X., Guo, T., Wang, S., et al.[2019]

Therapeutic use of octopamine resulted in a significant increase in urinary levels, reaching up to 142 µg/mL, indicating effective absorption and elimination from the body.

In contrast, administration of synephrine and dietary supplements did not show any increase in urinary octopamine levels, suggesting that synephrine does not convert to octopamine in vivo under these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of octopamine in human doping control samples. Thevis, M., Koch, A., Sigmund, G., et al.[2013]

Urolithin A and B were found to improve liver and kidney functions in normal rats without affecting body weight, indicating their potential as beneficial functional food ingredients.

Both Urolithin A and B promoted the growth of beneficial gut bacteria (Akkermansia), but Urolithin A also reduced microbial diversity and richness, suggesting it may have complex effects on gut health that need to be considered when used as a prebiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Analysis of the Impact of Urolithins on the Composition of the Gut Microbiota in Normal-Diet Fed Rats. Al Khalaf, AK., Abdulrahman, AO., Kaleem, M., et al.[2021]

In a study involving 24 male Wistar rats, both urolithin A (Uro-A) and urolithin B (Uro-B) were found to significantly reduce body weight and visceral fat accumulation in rats fed a high-fat diet for 10 weeks.

Uro-A and Uro-B improved liver health by restoring antioxidant capacity, decreasing lipid accumulation, and altering gene expressions related to fat metabolism, suggesting their potential as effective anti-obesity agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet. Abdulrahman, AO., Kuerban, A., Alshehri, ZA., et al.[2022]

The lyophilized juice (LJ) of Stellaria media significantly inhibited pancreatic amylase and lipase activity in vitro, suggesting it may help reduce fat and carbohydrate absorption in the intestines.

In an in vivo study with Swiss albino mice on a high-fat diet, LJ at a dose of 900 mg/kg effectively reduced body weight, liver weight, and harmful serum cholesterol levels, indicating its potential as an anti-obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality assessment and anti-obesity activity of Stellaria media (Linn.) Vill. Rani, N., Vasudeva, N., Sharma, SK.[2021]

Urolithin B (Uro B), derived from gut bacteria processing ellagitannins and ellagic acid found in foods like pomegranates and raspberries, has strong antioxidant and anti-inflammatory properties that may help prevent hyperlipidemia, cardiovascular disease, and tumors.

This review highlights the need for more detailed studies on Uro B's pharmacological activities and its potential as a nutritional agent, as most existing literature focuses on other related compounds like Urolithin A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances and Perspectives on the Health Benefits of Urolithin B, A Bioactive Natural Product Derived From Ellagitannins. Chen, P., Guo, Z., Chen, F., et al.[2022]

Obesity has more than doubled in the U.S. over the past 30 years, leading to increased risks for serious health issues like type 2 diabetes and certain cancers, highlighting the urgent need for effective treatment and prevention strategies.

Current treatment options for obesity include lifestyle changes, FDA-approved medications like sibutramine and orlistat, and bariatric surgery, but the review emphasizes the importance of evaluating the safety and efficacy of various weight-loss diets and over-the-counter supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A perspective on the current strategies for the treatment of obesity. Joyal, SV.[2019]

Urolithin A (UA), a metabolite from foods like pomegranates, was found to be non-genotoxic in a series of tests, indicating it does not damage genetic material.

In a 90-day study with rats, UA showed no adverse effects on health at doses up to 5% of their diet, suggesting it is safe for consumption at high levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of Urolithin A, a metabolite produced by the human gut microbiota upon dietary intake of plant derived ellagitannins and ellagic acid. Heilman, J., Andreux, P., Tran, N., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9133463/

Urolithin A improves muscle strength, exercise ... The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A. We observe clinically meaningful improvements with ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2788244

Effect of Urolithin A Supplementation on Muscle Endurance ... These findings indicate that urolithin A was safe and well tolerated as well as beneficial for muscle endurance and mitochondrial health in older adults.

3. timeline.com timeline.com/?srsltid=AfmBOope_RQDzNiXPJuaXXjk81bOkyExNFtJVCURxABnZ6wmR_CeqyR6

Timeline: Mitopure® | #1 Doctor Recommended Urolithin A Optimize your cellular health with Mitopure® by Timeline, the first and only Urolithin A supplement clinically-proven to target the root causes of aging.

4. nature.com nature.com/articles/s43587-025-00996-x

Effect of the mitophagy inducer urolithin A on age-related ... In summary, our data indicate that the mitophagy inducer UA supplementation affects mitochondria in CD8+ cells in vivo, possibly via PGC-1α- ...

5. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Urolithin_A_UPDATE_%28supplement%29.pdf

Urolithin A One study including. 100 healthy adult participants found that only 12% had detectable levels of urolithin A at baseline, and only 40% produced significant ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05921266

Urolithin A Supplementation in Middle-aged Adults With ... Data collection will occur at baseline (day 0) and endpoint (day 28). The investigators will compare outcomes between control and intervention group.

7. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1585922/full

Emerging evidence of Urolithin A in sports nutrition In conclusion, oral UA supplementation, whether administered acutely or chronically at both low and high doses, demonstrate considerable safety.