Urolithin A Supplementation for Obesity

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

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if a dietary supplement called urolithin A can improve blood flow in middle-aged adults with obesity. Participants will take the supplement daily for a few weeks, and researchers will compare their blood flow to see if urolithin A helps blood vessels work better and improves overall blood flow. Urolithin A is a metabolite produced in the gut from foods rich in ellagitannins and ellagic acid, such as pomegranates, nuts, and certain berries, and has shown potential benefits for mitochondrial health and muscle performance.

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 Urolithin A safe for human consumption?

Research shows that Urolithin A, a compound derived from foods like pomegranates and nuts, is generally safe. Studies in rats found no harmful effects even at high doses, and it did not cause genetic damage or affect blood chemistry. ^{1 2 3 4 5}

How is Urolithin A different from other obesity treatments?

Urolithin A is unique because it is a natural compound derived from pomegranates and other fruits, and it is being studied for its potential to improve mitochondrial function, which may help with weight management. Unlike traditional obesity drugs that often focus on appetite suppression or fat absorption, Urolithin A targets cellular health, making it a novel approach in obesity treatment. ^{6 7 8 9 10}

Research Team

Andriy Yabluchanskiy, MD, PhD

Principal Investigator

University of Oklahoma Health Science Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Advances and Perspectives on the Health Benefits of Urolithin B, A Bioactive Natural Product Derived From Ellagitannins. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Analysis of the Impact of Urolithins on the Composition of the Gut Microbiota in Normal-Diet Fed Rats. [2021]

4. England 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. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet. [2022]

6. England 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Quality assessment and anti-obesity activity of Stellaria media (Linn.) Vill. [2021]

8. England 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. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Analysis of octopamine in human doping control samples. [2013]