Urolithin A is a powerful compound derived from foods like pomegranates and berries, known for its remarkable benefits in fitness and overall health. Recent studies highlight its ability to enhance muscle endurance, protect joints, and support mitochondrial health. In this article, we will take you to learn more about Urolithin A.
What Is Urolithin A?
Urolithin A is a compound metabolized by gut microbiota, primarily found in pomegranates and berries. It promotes the production of intestinal mucosal epithelial cells and tight junction proteins, enhancing the intestinal barrier function and inhibiting the onset and progression of inflammatory bowel disease (IBD).
Studies show that consuming pomegranates helps alleviate IBD, with urolithin A being the key component. Urolithin A regulates the expression of tight junction proteins, strengthening the connections between intestinal epithelial cells. This reduces intestinal permeability and effectively blocks harmful substances, such as bacteria and endotoxins, from crossing the intestinal mucosa into the bloodstream. Currently, no drug exists to directly stimulate the production of tight junction proteins, highlighting the unique role of urolithin A.
Extensive in vitro and in vivo experiments have confirmed the significant effect of urolithin A in repairing intestinal epithelial barriers. Previously, research primarily focused on its anti-inflammatory properties. However, recent findings reveal its primary function is repairing intestinal barrier dysfunction.
Sources of Urolithin A
1. Food Sources
The primary sources of urolithin A are foods rich in ellagitannins, such as pomegranates, raspberries, blueberries, blackberries, walnuts, pistachios, and pecans. These foods are not only important for providing urolithin A but also contain antioxidants, vitamins, and minerals, with relatively low sugar content.
Adopting a Mediterranean diet can help boost the production of urolithin A. This diet typically includes ellagitannin-rich foods such as pomegranates, walnuts, and almonds. The natural polyphenol metabolites in these foods, including urolithin A, can enhance immune function and support healthy hematopoietic and immune systems.
For older adults, regular consumption of urolithin A-rich foods may reduce the risks of declining hematopoietic function, infections, and tumors.
2. Artificial Synthesis
Urolithin A can also be industrially produced through chemical synthesis. As early as 2018, the U.S. Food and Drug Administration (FDA) classified Urolithin A as a “Generally Recognized as Safe” (GRAS) substance for consumption. It is widely used in protein shakes, meal replacement beverages, instant oatmeal, nutrition bars, and dairy drinks (up to 500 mg per serving). It is also included in Greek yogurt, high-protein yogurt, and milk protein shakes (up to 1000 mg per serving). Its safety has been confirmed through multiple toxicological studies.
In chemical synthesis, optimizing the reaction process significantly increases yield. For example, when the molar ratio of 2-bromo-5-hydroxybenzoic acid to resorcinol is 6:1, the NaOH solution concentration is 5%, and the CuSO4 solution concentration is 15%, the cyclization reaction achieves a yield of 86%. Other methods also exist. One approach involves mixing Compound I and Compound II in specific proportions, dissolving them in a solvent, and adding a base and catalyst. Refluxing the mixture completes the synthesis of Urolithin A.
These methods have effectively expanded the production and application of Urolithin A. They provide a promising future for its use in food and health-related industries.
Benefits of Urolithin A
Urolithin A delivers numerous health advantages backed by scientific research. Below are some key benefits this compound offers for gut, muscle, and mitochondrial health, as well as its anti-aging and protective properties:
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Improves Gut Health
Urolithin A is produced by the gut microbiome and promotes the tight junctions between intestinal epithelial cells. This helps to inhibit inflammatory bowel diseases. Studies have demonstrated the positive impact of Urolithin A on intestinal epithelial barriers, mainly by repairing gut barrier dysfunction.
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Enhances Muscle Endurance and Reduces Joint Cartilage Damage
A study published in JAMA shows that Urolithin A can enhance muscle endurance and reduce joint cartilage damage. In a randomized clinical trial with 66 elderly participants (aged 65 and above), the group that took Urolithin A supplements (1 gram daily) showed muscle endurance 7 to 8 times greater than the placebo group after 4 months.
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Improves Mitochondrial Health and Reduces Inflammation
Research in Cell indicates that Urolithin A improves mitochondrial health and reduces inflammation. Urolithin A (Mitopure®) has been shown to reduce joint cartilage damage and alleviate osteoarthritis pain. In a laboratory model for osteoarthritis, supplementation with Mitopure for 8 weeks improved mitochondrial health. It prevented the progression of the disease by inducing the recycling of damaged mitochondria (mitophagy). The process enhanced mitochondrial activity.
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Anti-Aging Effects
Urolithin A has been proven to have anti-aging effects across various species and organ systems. It induces mitophagy of dysfunctional mitochondria and regulates mitochondrial biogenesis, thus inhibiting the proliferation of aged mitochondria and extending their lifespan. It has shown anti-aging benefits in organs like hematopoietic stem cells, skin tissue, brain, immune system, and overall lifespan in various organisms including C. elegans, Drosophila melanogaster, mice, and humans.
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Anti-Inflammatory, Antioxidant, and Anti-Cancer Properties
Urolithin A inhibits mitochondrial apoptosis pathways and regulates the p-38 MAPK signaling pathway to suppress oxidative stress-induced cell apoptosis. It significantly inhibits various typical inflammatory factors and has been shown to play a role in inflammation treatments. In human cell models, it has been confirmed to induce apoptosis and block the cell cycle, exhibiting anti-cancer effects. Urolithin A also improves the survival rate of neurons under oxidative stress and offers neuroprotective functions. It plays a role in inflammation treatment across various tissues, including brain, fat, heart, gut, and liver, with notable effects on colon and prostate cancer by inducing apoptosis and blocking the cell cycle.
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Protection of the Nervous, Gastrointestinal, and Cardiovascular Systems
Urolithin A provides excellent protection for the nervous, gastrointestinal, and cardiovascular systems. Studies have shown that it can activate the SIRT1 signaling pathway, downregulate the mTOR pathway, and activate autophagy, preventing brain aging induced by d-galactose and improving cognitive impairment in aging mice.
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Improves Obesity and Regulates Gut Microbiome
Urolithin A has remarkable effects on improving obesity and regulating the gut microbiome. It reduces triglyceride accumulation, fatty acid oxidation, and the expression of genes related to fat generation. It induces the activation of brown adipose tissue and the browning of white adipose tissue, while preventing fat accumulation caused by diet.
Suitable Populations for Urolithin A
Urolithin A offers numerous benefits across various groups. Below are the specific populations who may find it particularly beneficial:
1. Fitness and Sports Enthusiasts
Enhancing Muscle Endurance
For those engaging in strength training or endurance sports (such as marathons or triathlons), Urolithin A can be a potential performance booster. Studies show it can enhance muscle endurance, improve energy utilization in muscles, and reduce fatigue during exercise. In long-duration endurance activities, Urolithin A helps maintain mitochondrial function in muscle cells. Mitochondria, the “energy factories” of cells, need to function properly to ensure a continuous energy supply.
Joint Protection
High-intensity sports or those that place stress on joints (like basketball or tennis) can lead to cartilage damage. Urolithin A helps reduce damage by regulating intracellular signaling pathways. It promotes cartilage cell health and enhances the elasticity and resilience of cartilage. This provides better protection for joints.
2. People Focused on Gut Health
Patients with Inflammatory Bowel Disease (IBD)
For individuals with inflammatory bowel diseases like ulcerative colitis or Crohn’s disease, Urolithin A may have a supportive role in treatment. It enhances the tight junctions between intestinal epithelial cells, acting as a protective barrier against harmful substances. By improving gut barrier function, Urolithin A can help alleviate symptoms such as abdominal pain and diarrhea, and improve overall gut health.
People with Constipation or Gut Dysfunction
Urolithin A also benefits those suffering from constipation or gut disorders like irritable bowel syndrome. It improves the gut microbiome, promoting the growth of beneficial bacteria and restoring the balance of gut flora. This balance is essential for normal digestion and bowel function. Urolithin A helps restore gut motility, alleviating constipation and improving overall gut function.
3. Older Adults
Anti-Aging Seekers
As people age, bodily functions gradually decline, and older adults are increasingly focused on anti-aging. Urolithin A shows great promise in this regard. It induces autophagy in dysfunctional mitochondria, removing damaged or aged mitochondria while promoting the production of healthy new mitochondria. This cellular-level process helps slow the aging process and improves skin elasticity, vitality, and other signs of aging.
Chronic Disease Prevention
Older adults are more susceptible to chronic diseases like cardiovascular diseases and neurodegenerative disorders. Urolithin A’s anti-inflammatory and antioxidant properties are crucial in preventing these conditions. It suppresses inflammation and reduces oxidative stress, protecting cells from damage. Urolithin A also helps improve blood lipid levels and blood pressure, and it can protect nerve cells, preventing or delaying the onset of neurodegenerative diseases like Alzheimer’s.
4. Obese Individuals
Weight Management Aid
For obese individuals or those engaged in weight management, Urolithin A is a helpful supplement. It improves obesity by modulating the gut microbiome. The gut microbiome plays a key role in energy metabolism and fat storage, and Urolithin A optimizes the composition and function of this microbiome, promoting fat breakdown and energy expenditure. This helps individuals control their weight more effectively and reduces the risk of metabolic syndrome associated with obesity, further improving overall health.
How to Supplement Urolithin A
To ensure optimal supplementation of Urolithin A, consider these approaches:
1. Directly Take Urolithin A Supplements
One way to obtain Urolithin A is by taking supplements like Mitopure®, a product from Amazentis. Promoted by Maye Musk, it has gained significant popularity in recent years.
Mitopure® is a high-purity Urolithin A derived from a bioactive dietary metabolite produced by gut bacteria. Since most people find it difficult to obtain sufficient Urolithin A from regular food, Mitopure® provides an efficient alternative. Research indicates that Mitopure® stimulates mitochondrial autophagy, improving mitochondrial function. It clears aged and damaged mitochondria while promoting the generation of healthy mitochondria, thereby enhancing cellular energy metabolism.
Mitopure® has received GRAS (Generally Recognized as Safe) certification from the U.S. Food and Drug Administration (FDA) and has undergone comprehensive preclinical and clinical evaluations. Its safety and effectiveness have been validated, making it an ideal choice for human nutritional supplementation.
2. Supplement Through Food and Its Precursor, Ellagic Acid
Another way to obtain Urolithin A is by consuming foods that contain its precursor, ellagic acid. Foods rich in ellagic acid include pomegranates, raspberries, blueberries, blackberries, walnuts, pistachios, and hickory nuts. However, whether ellagic acid can be converted into Urolithin A in the body depends on an individual’s gut microbiome. Only about 40% of people can successfully complete this conversion.
These foods are not only sources of Urolithin A but also rich in antioxidants, vitamins, and minerals, with relatively low sugar content. Adopting a Mediterranean diet, which includes many foods rich in ellagic acid, can also promote the production of Urolithin A. Foods like pomegranates and nuts are common in this diet.
Studies have shown that the natural polyphenol metabolites in these foods, such as Urolithin A, enhance immune function. Regular consumption of these foods helps maintain hematopoietic and immune system function. For older adults, this can reduce the risk of hematopoietic dysfunction, infections, and tumors. Additionally, Urolithin A has mitochondrial-regulating properties and can reverse the aging process. It rejuvenates hematopoietic stem cells by restoring mitochondrial function, thereby enhancing their vitality.
A diet rich in Urolithin A can also improve hematopoietic system characteristics associated with aging, boost lymphocyte function, and restore balance between lymphocytes and bone marrow immune cells that tends to deteriorate with age. This increases the body’s immune response to viral infections, making Urolithin A an essential nutrient in a healthy diet.
