In the exploration of life sciences and health, there are always some initially niche substances that, with in-depth research, reveal astonishingly wide-ranging applications. Urolithin A is one such example. Its name may be unfamiliar to you, but it is quietly emerging in several key areas, from maintaining metabolic health to helping combat neurodegenerative diseases, and even showing promise in the beauty and skincare field, attracting the attention of researchers and industry. Let’s delve into the amazing uses of urolithin A.
The Origins of Urolithin A
The Origins of Urolithin A(I) Origin and Source
Urolithin A does not exist independently in nature, but is a natural polyphenol metabolite. Its formation process is quite remarkable, often originating from familiar foods such as pomegranates, nuts (like walnuts), strawberries, and blackberries. These foods are rich in ellagic acid and ellagitannins. After we ingest these foods, the ellagic acid and ellagitannins undergo a series of complex metabolic processes under the influence of the gut microbiota, a “mysterious processing plant,” ultimately producing urolithin A. This means that the type and quantity of gut microbiota significantly affect the efficiency and amount of urolithin A production. Due to differences in gut microbiota, even when consuming the same foods rich in ellagic acid, the level of urolithin A produced in the body will vary among individuals.
(II) Chemical and Physical Properties
From a chemical structure perspective, urolithin A has the molecular formula C13H8O4 and a molecular weight of 228.2. Its structure contains a unique dibenzopyranone skeleton with hydroxyl groups attached at positions 3 and 8. This special chemical structure endows it with many unique chemical properties; for example, its phenolic hydroxyl groups give it a certain degree of acidity, allowing it to participate in some acid-base reactions. In terms of physical properties, at room temperature and pressure, urolithin A is a white to light yellow powder, which is the most common form we see. It has a melting point of 340-345°C, within which it will transform from a solid to a liquid state. In terms of solubility, it exhibits slight solubility in water, which leads to poor dispersibility in water. However, it can dissolve well in highly polar organic solvents such as dimethyl sulfoxide and N,N-dimethylformamide, while its solubility in low-polarity petroleum ether and diethyl ether is poor.
A Versatile Agent in the Medical Field
The research achievements of Urolithin A in the medical field make it a rising star, bringing a glimmer of hope for conquering various diseases.
(I) New Hope for Cardiovascular Diseases
Cardiovascular diseases have always been the “number one killer” threatening human health. Ischemic heart diseases such as coronary heart disease and myocardial infarction cause a large number of patients to lose their lives or suffer a severe decline in their quality of life every year. Urolithin A has shown unique potential in the treatment of cardiovascular diseases. Research has found that it can promote angiogenesis, which means it can stimulate the growth of new blood vessels. For patients with coronary heart disease, the coronary arteries may become narrowed or even blocked due to atherosclerosis and other reasons, affecting myocardial blood supply. Urolithin A can promote the formation of coronary collateral circulation, just like opening up “backup channels” for myocardial blood supply, improving myocardial blood supply, and thus effectively alleviating the condition. Simultaneously, it can improve blood circulation, allowing blood to flow more smoothly in blood vessels, and reduce inflammatory responses, decreasing the damage of inflammation to the blood vessel walls. From multiple perspectives, it safeguards cardiovascular health and provides a novel strategy for the treatment of cardiovascular diseases.
(II) A Glimmer of Hope for Neurodegenerative Diseases
With the increasing global aging population, the incidence of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases continues to rise, placing a heavy burden on patients’ families and society. Advances in the research of urolithin A in this field have brought new hope to patients. Mitochondria are the “energy factories” of cells, and mitophagy is crucial for clearing damaged or excess mitochondria and maintaining normal cell function. Impairment of this function plays a key role in the occurrence and development of neurodegenerative diseases. Researchers from institutions such as the University of Copenhagen in Denmark have found through mouse experiments that urolithin A can stimulate mitophagy. Long-term treatment of experimental mice with urolithin A significantly improved their learning, memory, and olfactory functions, and reduced significant pathological features of Alzheimer’s disease such as abnormal deposition of beta-amyloid protein and hyperphosphorylation of Tau protein. This indicates that urolithin A has great potential in the prevention and treatment of neurodegenerative diseases.
(III) A Powerful Anti-inflammatory Weapon
In the human body, inflammation is a defense mechanism against various stimuli. However, when inflammation gets out of control, it can trigger a series of health problems, such as arthritis and enteritis. Urolithin A acts like an “anti-inflammatory guardian,” possessing significant anti-inflammatory activity. It can inhibit the production of various inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These inflammatory mediators play important roles in the inflammatory response, and their excessive release can exacerbate inflammation. By inhibiting their production, urolithin A effectively reduces the inflammatory response and has great potential in the development of anti-inflammatory drugs. Perhaps in the future, it could become an important component in the treatment of various inflammatory diseases.
(IV) Pioneer in Anti-aging and Immune Regulation
Aging is an inevitable natural process, but the emergence of urolithin A may offer a turning point in slowing down aging. Studies have shown that it can delay the process of cellular aging by inhibiting telomerase activity. Telomerase is closely related to cell lifespan, and inhibiting telomerase activity can slow down the rate of cellular aging. At the same time, urolithin A can also promote mitochondrial function. As the energy metabolism center of cells, improving the function of mitochondria helps to increase the energy metabolism level of cells and maintain normal cell function. Furthermore, urolithin A also plays a positive role in immune regulation. It can improve the body’s immunity and resistance, helping the body better resist the invasion of pathogens. Urolithin A has broad application prospects in the development of anti-aging drugs and immunomodulators.
A “Star Ingredient” in Health Supplements
In today’s pursuit of health and a high-quality life, the health supplement market is booming, with a dazzling array of ingredients. Urolithiasis A, with its remarkable efficacy, is gradually emerging as a prominent “star ingredient” in the health supplement field.
(I) An Antioxidant “Vanguard”
In our bodies, free radicals are like a group of mischievous “monsters,” constantly attacking cells and causing oxidative damage. At the cellular level, free radicals damage the structure of cell membranes, altering their permeability and affecting the normal exchange of substances between the inside and outside of cells, thus interfering with normal cellular physiological functions. They also attack intracellular proteins, altering their structure and function, causing many important enzymes to lose activity and affecting cellular metabolic processes. At the tissue level, oxidative damage damages collagen and elastin fibers, much like the steel bars and cement of a building being destroyed, leading to loss of skin elasticity, wrinkles, sagging, and other signs of aging. It also accelerates organ aging and increases the risk of chronic diseases. Urolithin A acts as a valiant “antioxidant vanguard,” possessing powerful antioxidant capabilities that effectively eliminate free radicals in the body and reduce oxidative damage. Related experiments have shown that in in vitro cell experiments, the addition of urolithin A significantly reduced intracellular free radical levels, and markedly improved cell activity and survival rate. In animal experiments, supplementing aging model animals with urolithin A for a period of time significantly improved their oxidative stress indicators, and also enhanced skin elasticity and luster, fully demonstrating the remarkable efficacy of urolithin A in antioxidation, aging prevention, and chronic disease management.
(II) Weight Management “Assistant”
Obesity not only affects physical appearance but is also a trigger for many health problems, such as cardiovascular disease and diabetes, which are closely related to obesity. Urolithin A has a unique mechanism of action in weight management. The human body contains two important types of adipose tissue: brown adipose tissue and white adipose tissue. Brown adipose tissue acts like a “heat-generating motor,” primarily functioning to produce heat by converting fat into energy, thus helping to reduce fat accumulation in the body. White adipose tissue, on the other hand, is mainly responsible for storing fat; excessive accumulation of white adipose tissue leads to obesity. Urolithin A can promote thermogenesis in brown adipose tissue by increasing the level of triiodothyronine (T3) in fat, making this “motor” run more frequently and accelerating fat burning. Simultaneously, it can induce browning in white adipose tissue, transforming white fat cells that originally stored fat into brown fat cells with thermogenic function, increasing energy expenditure. In an experiment on mice on a high-fat diet, after two weeks of urolithin A supplementation, the mice’s body weight and fat mass were 23.5% and 61.3% lower than the control group, respectively, with a body fat percentage less than one-third of the control group. This fully demonstrates the significant effects of urolithin A in weight loss and improving metabolic function.
(III) Muscle Health “Guardian”
Muscles are the source of our body’s movement and strength. With age, reduced physical activity, and the effects of disease, muscles gradually atrophy and lose strength. Urolithin A plays a crucial role in maintaining muscle health. From a physiological perspective, it promotes muscle health through multiple pathways. As a potent antioxidant, urolithin A can scavenge free radicals in the body, reducing oxidative stress damage to muscle cells. Studies have shown that it can significantly reduce the levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the body, while increasing the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), thereby effectively reducing oxidative damage. It also exhibits significant anti-inflammatory effects, reducing the production of inflammatory factors by inhibiting the activity of nuclear factor κB (NF-κB), thereby mitigating the damage of inflammatory responses to muscle tissue. This mechanism is particularly important in the prevention and treatment of muscle diseases caused by inflammation. Urolithin A can also promote mitochondrial function and improve cellular energy metabolism. Mitochondria are the “energy factories” of cells, and their normal function is directly related to the health and vitality of muscle cells. Urolithin A maintains the energy supply and metabolic balance of muscle cells by inducing mitophagy, clearing damaged mitochondria, and promoting the generation of new mitochondria. In practical applications, a large amount of experimental data supports the positive effects of urolithin A on muscle health. For example, a study published in *Cell Reports Medicine* by Swiss scientists in 2022 showed that after four months of continuous use of urolithin A, middle-aged people experienced a significant 12% increase in muscle strength. Blood tests and skeletal muscle biopsies showed significant improvement in biomarkers of healthy mitochondrial function and reduced inflammation. This indicates that urolithin A has important value in preventing muscle atrophy, improving athletic performance, treating muscle diseases, and promoting muscle repair, making it a well-deserved “guardian” of muscle health.
A Rising Star in the Cosmetics Industry
In the cosmetics industry, consumer demand for anti-aging, repair, and moisturizing products remains consistently strong. Urolithin A, with its unique biological properties, has demonstrated remarkable efficacy in these key areas, becoming a rising star in the cosmetics industry for anti-aging.
(I) Wrinkle Eraser
As we age, the amount of collagen and elastin in our skin gradually decreases, reducing skin elasticity and firmness, and wrinkles begin to appear. Urolithin A acts like a magical wrinkle eraser, effectively combating this aging process. Its anti-wrinkle mechanism is primarily based on activating mitophagy and promoting collagen synthesis. Mitochondria are the cell’s “energy factories.” With age, mitochondrial function gradually declines, damaged mitochondria accumulate, reducing energy production efficiency and releasing large amounts of reactive oxygen species (ROS), triggering oxidative stress and accelerating cell aging. Urolithin A can activate mitophagy, a cellular self-cleaning mechanism that promotes cell recognition and removal of damaged mitochondria. Urolithin A initiates mitophagy by regulating key molecules such as PINK1 (PTEN-induced putative kinase 1) and Parkin protein. PINK1 protein typically accumulates when mitochondria are damaged and recruits Parkin protein to label damaged mitochondria, which are then encapsulated and degraded by autophagosomes. This effectively clears dysfunctional mitochondria from aging cells, providing a healthier internal environment and improving energy metabolism in skin cells.
Simultaneously, urolithin A can also increase collagen synthesis by activating the transforming growth factor-β (TGF-β)/Smad pathway, upregulating the expression of collagen genes (such as COL1A1 and COL3A1). Furthermore, it inhibits the activity of matrix metalloproteinases (MMPs), particularly MMP-1, MMP-3, and MMP-9. MMPs are enzymes that degrade collagen and other extracellular matrix components; their activity increases during skin aging, accelerating collagen degradation. Urolithin A, by inhibiting the activity of MMPs and reducing collagen degradation, combined with its effect of promoting collagen synthesis, effectively reduces skin wrinkles and restores skin elasticity and radiance.
(II) A Skin Repair Expert
In daily life, skin inevitably suffers from various injuries, such as sunburn, allergies, and inflammation. At these times, a powerful skin repair expert is needed, and urolithin A is precisely such an agent. It has significant anti-inflammatory effects, inhibiting the production of various inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). When the skin is stimulated by external factors and an inflammatory response occurs, these inflammatory mediators are released in large quantities, leading to symptoms such as redness, swelling, itching, and pain. Urolithin A effectively reduces the inflammatory response and alleviates skin discomfort by inhibiting the production of inflammatory mediators.
In skin damage repair models, urolithin A can promote wound healing and reduce scar formation. It can stimulate the proliferation and differentiation of keratinocytes, upregulate the expression of cyclin proteins (such as cyclin D1) by activating the mitogen-activated protein kinase (MAPK) pathway, and promote the transition of keratinocytes from the quiescent phase to the proliferative phase, accelerating skin cell renewal. Simultaneously, urolithin A regulates the expression of genes related to keratinocyte differentiation, such as keratin genes, making the stratum corneum structure more compact and orderly, enhancing the skin’s barrier function, helping damaged skin cells repair and regenerate more quickly, and restoring the skin to a healthy state.
(III) Moisturizing “Little Guardian”
The skin’s ability to moisturize is crucial for maintaining skin health and beauty. Dry skin is prone to problems such as roughness, flaking, and fine lines. Urolithin A acts like a dutiful moisturizing “little guardian,” enhancing the skin’s barrier function, improving its moisturizing ability, and preventing moisture loss. The skin’s barrier function is mainly composed of the stratum corneum and skin lipids; the natural moisturizing factors in the stratum corneum and skin lipids work together to maintain the skin’s moisture balance. As we age or are affected by external environmental factors, the skin’s barrier function weakens, leading to faster moisture loss. Urolithin A can regulate the expression of genes related to keratinocyte differentiation, making the stratum corneum structure more compact and orderly, and enhancing the skin’s barrier function. Simultaneously, it can promote the synthesis of natural moisturizing factors within skin cells, such as hyaluronic acid. These natural moisturizing factors have powerful moisturizing capabilities, absorbing large amounts of water and keeping the skin hydrated.
A Potential Star in the Food Industry
With increasing health awareness, people’s demands for food are no longer limited to simply filling their stomachs, but rather focus on nutrition and health. The application of urolithin A in the food industry perfectly aligns with this trend, bringing new development opportunities to the industry.
(I) A New Selling Point for Functional Foods
In the pursuit of a healthy lifestyle, consumer demand for functional foods is growing. Urolithin A, with its multiple health benefits such as anti-oxidation, anti-inflammation, and improved energy metabolism, has become a new favorite in the functional food sector. In the beverage industry, some companies have launched functional drinks with added urolithin A. These drinks not only replenish water like regular beverages but also help consumers resist free radical damage, reduce inflammatory responses, and improve energy metabolism. For health-conscious consumers, enjoying delicious drinks while also gaining additional health benefits is undoubtedly very attractive. Besides beverages, yogurt, energy bars, and other foods have also incorporated urolithin A as a “health element.” Adding urolithin A to yogurt does not affect its original sweet and sour taste or rich nutrition, but also gives it antioxidant and anti-inflammatory effects. For those who like to eat yogurt after exercise or during leisure time, this urolithin A-rich yogurt better meets their dual pursuit of health and deliciousness. Adding urolithin A to energy bars allows them to provide consumers with a quick energy boost while promoting metabolism and reducing fatigue, making them particularly suitable for people who frequently engage in outdoor activities or high-intensity work. According to market research data, the market size of functional foods containing urolithin A is expanding year by year, and its growth rate is expected to remain above [X]% in the next few years, fully demonstrating the huge potential of urolithin A in the functional food field.
(II) A New Treasure Trove for Food Preservation
Food preservation has always been a key focus of the food industry, as it directly relates to the quality, taste, and safety of food. Urolithin A, with its excellent antioxidant properties, provides a new solution for food preservation, becoming a “new magic weapon” for food preservation. During food processing and storage, oils are easily oxidized and rancid, leading to off-flavors, spoilage, and a significant reduction in nutritional value. Urolithin A can effectively inhibit the oxidative rancidity process of oils. In an experiment on edible oils, under the same storage conditions, the peroxide value of edible oils with added urolithin A increased at a significantly lower rate than that of edible oils without added urolithin A. This indicates that urolithin A can slow down the oxidation rate of oils and extend their shelf life. For some oil-rich foods, such as nuts and fried foods, adding urolithin A can effectively maintain the flavor and nutritional value of the food. Nuts are prone to developing a rancid taste during storage due to oil oxidation, affecting their taste and quality. However, nuts with added urolithin A can still maintain their crisp texture and rich nutrients even after long-term storage. This not only reduces food waste caused by oxidation and spoilage, but also provides consumers with safer, healthier, and tastier food, which is of great significance to the sustainable development of the food industry.
A “Booster” for Tissue Repair and Regeneration
Rapid angiogenesis is crucial for tissue repair and regeneration after tissue injury or organ transplantation. Urolithin A plays a vital role in this process, accelerating tissue repair and regeneration by promoting angiogenesis and cell proliferation, and has potential applications in burn and wound healing.
In burn treatment, severely burned patients face challenges such as extensive skin damage, high infection risk, and slow healing. Urolithin A can promote angiogenesis at the burn site, providing sufficient oxygen and nutrients to damaged tissue, accelerating skin cell proliferation and migration, and promoting wound healing. Related studies have shown that in animal models of burns, intervention with urolithin A significantly shortens wound healing time and reduces scar tissue formation. In wound repair, for tissue trauma caused by accidents, surgery, etc., urolithin A can stimulate fibroblast proliferation and collagen synthesis, promoting wound contraction and epithelialization, helping damaged tissue quickly restore normal structure and function. In the treatment of some chronic wounds, such as diabetic foot ulcers, urolithin A holds promise for providing new treatment options for these difficult-to-heal wounds by improving local blood circulation and promoting cell proliferation.
Summary and Outlook
Urolithin A, as a natural polyphenol metabolite with unique biological characteristics, has demonstrated remarkable application value in multiple fields, including medicine, health products, cosmetics, food, and tissue repair and regeneration. In the pharmaceutical field, it brings new hope for the treatment of cardiovascular diseases and neurodegenerative diseases, while also possessing powerful anti-inflammatory, anti-aging, and immunomodulatory capabilities. In health products, it performs excellently in anti-oxidation, weight management, and muscle health maintenance. In the cosmetics industry, its anti-wrinkle, repair, and moisturizing effects make it a new favorite in anti-aging. In the food industry, it provides new selling points for functional foods and serves as a new method for food preservation. In tissue repair and regeneration, it also plays an important role in promoting angiogenesis and cell proliferation.
However, the research and application of urolithin A are still in the developmental stage. Future research will focus on exploring its mechanism of action, which will help us to more precisely target its efficacy. For example, in the treatment of neurodegenerative diseases, further clarifying the specific molecular signaling pathways by which urolithin A stimulates mitophagy, and how it synergizes with other neuroprotective mechanisms, will enable the development of more effective treatment strategies. Simultaneously, optimizing the preparation process of urolithin A to increase its yield and purity while reducing production costs will lay a solid foundation for its large-scale application. With ongoing research and technological advancements, it is believed that urolithin A will demonstrate greater potential in more fields, making a greater contribution to improving human health and quality of life.
