Urolithin A

• Mitochondrial health
• Muscle function
• Cellular renewal

• Gut health
• Anti-inflammatory effects
• Neuroprotection
• Cardiovascular support
• Exercise recovery
• Antioxidant activity

Urolithin A (UA) exerts its diverse biological effects primarily through enhancing mitochondrial function and cellular quality control mechanisms. As a gut microbiome-derived metabolite produced from ellagitannins found in foods like pomegranates, berries, and nuts, UA represents a fascinating intersection between diet, gut microbiome, and cellular health. The most well-established mechanism of UA is its ability to stimulate mitophagy, the selective autophagy process that removes damaged or dysfunctional mitochondria. This critical quality control mechanism tends to decline with age, leading to the accumulation of damaged mitochondria that can impair cellular function and contribute to age-related decline.

UA activates mitophagy through several pathways, including the PINK1/Parkin pathway and the AMPK/ULK1 axis. By binding to specific proteins involved in these pathways, UA triggers the identification and targeting of damaged mitochondria for degradation, essentially acting as a ‘cleanup crew’ for cellular powerhouses. This enhanced mitochondrial turnover leads to a healthier, more efficient mitochondrial network. Beyond mitophagy activation, UA influences mitochondrial biogenesis—the creation of new mitochondria.

Research indicates that UA can increase the expression of PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a master regulator of mitochondrial biogenesis. This dual action of removing damaged mitochondria while stimulating the production of new ones creates a comprehensive approach to mitochondrial health, potentially explaining UA’s effects on muscle function and energy metabolism. UA also demonstrates significant anti-inflammatory properties through multiple mechanisms. It inhibits the activation of nuclear factor-kappa B (NF-κB), a key transcription factor in inflammatory responses, thereby reducing the production of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6).

Additionally, UA modulates inflammasome activity, particularly the NLRP3 inflammasome, which is implicated in various inflammatory conditions. This anti-inflammatory action may contribute to UA’s potential benefits for conditions characterized by chronic inflammation, including metabolic disorders and neurodegenerative diseases. In the gut, UA exhibits prebiotic-like effects, potentially modulating the composition and function of the gut microbiome. Interestingly, this creates a positive feedback loop, as a healthier gut microbiome may enhance the conversion of ellagitannins to UA, improving its bioavailability.

UA also appears to enhance intestinal barrier function, reducing gut permeability and the associated translocation of inflammatory bacterial components into circulation. UA’s antioxidant properties complement its mitochondrial and anti-inflammatory effects. While not a direct free radical scavenger like many traditional antioxidants, UA enhances endogenous antioxidant defenses by activating the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. This transcription factor regulates the expression of numerous antioxidant and detoxifying enzymes, providing more comprehensive and sustained protection against oxidative stress than direct antioxidants.

In muscle tissue, UA appears to enhance muscle cell metabolism and function through several mechanisms. Beyond the mitochondrial effects already described, UA may influence muscle protein synthesis and degradation pathways, potentially supporting muscle maintenance during aging or disuse. Some research suggests UA can enhance exercise capacity and recovery, possibly through improved mitochondrial function and reduced exercise-induced inflammation. In the cardiovascular system, UA demonstrates protective effects on vascular endothelial cells, the inner lining of blood vessels.

It enhances nitric oxide production and bioavailability, promoting vasodilation and healthy blood flow. UA also reduces the oxidation of low-density lipoprotein (LDL) cholesterol, a key step in atherosclerosis development. These vascular effects, combined with UA’s anti-inflammatory properties, may contribute to its potential cardiovascular benefits. In the nervous system, UA exhibits neuroprotective properties through multiple mechanisms.

It can cross the blood-brain barrier and has been shown to reduce neuroinflammation, enhance mitochondrial function in neurons, and protect against various neurotoxic insults. These effects may be particularly relevant for neurodegenerative conditions characterized by mitochondrial dysfunction and neuroinflammation. At the molecular level, UA influences various signaling pathways beyond those already mentioned. It modulates the activity of sirtuins, particularly SIRT1, which are key regulators of metabolism, stress resistance, and longevity.

UA also affects the mTOR (mammalian target of rapamycin) pathway, which integrates signals related to nutrient availability, energy status, and growth factors to regulate cellular growth and metabolism. Through these diverse and complementary mechanisms—mitophagy enhancement, mitochondrial biogenesis, anti-inflammatory effects, antioxidant activation, and modulation of key metabolic signaling pathways—Urolithin A influences numerous physiological processes, potentially explaining its wide range of observed health benefits in preclinical and emerging clinical research.

No official Recommended Dietary Allowance (RDA) has been established for Urolithin A, as it is not considered an essential nutrient but rather a metabolite produced by gut bacteria from dietary precursors. Based on the limited clinical research available, effective doses of purified Urolithin A (such as the branded form Mitopure) typically range from 500-1,000 mg per day. The optimal dose may vary depending on the specific health goal, individual factors such as age and health status, and the form of supplementation. For synthetic Urolithin A supplements (which provide the compound directly rather than relying on gut conversion), the most studied dose in human clinical trials is 500 mg daily, which has shown benefits for muscle endurance and mitochondrial health in both older adults and middle-aged individuals.

Some studies have used higher doses (1,000 mg daily) with good safety profiles, though it’s not clear if these higher doses provide proportionally greater benefits. When consuming precursor-rich foods like pomegranates, walnuts, and berries, the conversion to Urolithin A is highly variable between individuals due to differences in gut microbiome composition. Some people (estimated at 30-40% of the population) may be ‘low converters’ or ‘non-converters’ who produce little to no Urolithin A even with high precursor consumption. For these individuals, direct supplementation with synthetic Urolithin A may be necessary to achieve potential benefits.

The bioavailability of Urolithin A (UA) presents a unique and complex scenario compared to many other supplements. When consumed as a purified compound (synthetic UA), oral bioavailability appears moderate, with studies indicating approximately 20-30% absorption of the administered dose. After oral administration of purified UA, plasma concentrations typically peak within 3-6 hours, suggesting relatively slow absorption through the gastrointestinal tract. The compound undergoes significant phase II metabolism, primarily glucuronidation in the intestinal wall and liver, forming Urolithin A glucuronide as the predominant metabolite in circulation.

However, both free UA and its glucuronide appear to have biological activity. The situation is considerably more complex when considering UA derived from dietary precursors (ellagitannins and ellagic acid found in foods like pomegranates, walnuts, and berries). In this case, bioavailability depends on a two-step process: first, the conversion of these precursors to UA by specific gut bacteria, and second, the absorption of the produced UA. Research indicates dramatic individual variation in the first step, with studies suggesting that 30-40% of individuals may be ‘low converters’ or ‘non-converters’ who produce little to no UA even after consuming substantial amounts of precursor-rich foods.

This variability is primarily attributed to differences in gut microbiome composition, specifically the presence and abundance of bacteria capable of performing the necessary metabolic conversions. For those who are efficient converters, UA can be detected in plasma within 12-24 hours after consuming precursor-rich foods, with levels typically peaking at 24-48 hours and remaining elevated for up to 72 hours. This extended timeline reflects the time required for precursors to reach the colon, undergo bacterial metabolism to form UA, and then be absorbed. Once in circulation, UA appears to distribute widely throughout the body and can cross the blood-brain barrier, though in relatively low concentrations.

The plasma half-life of UA is approximately 15-20 hours, allowing for once-daily dosing of purified UA supplements. Urinary excretion represents the primary elimination route for UA metabolites.

Direct supplementation with synthetic Urolithin A (bypasses variable gut conversion), Consuming with a small amount of fat to potentially enhance absorption, Micronized formulations for improved dissolution and absorption, Lipid-based delivery systems to enhance bioavailability, Combining precursors with specific probiotics that enhance conversion, Regular consumption of diverse polyphenol-rich foods to support a microbiome capable of UA production, Sustained-release formulations to maintain blood levels, Enteric-coated formulations to protect from stomach acid degradation, Nanoparticle delivery systems (emerging technology), Avoiding factors that negatively impact gut microbiome health (e.g., excessive alcohol, certain medications)

For purified Urolithin A supplements (such as Mitopure), consistent daily use appears more important than specific timing. Most clinical studies showing benefits have used once-daily dosing without specifying particular timing relative to meals or time of day. However, some preliminary evidence and pharmacokinetic considerations suggest taking Urolithin A with a small amount of fat may enhance absorption, making administration with a meal containing some healthy fats a reasonable approach. Morning or early afternoon administration is generally recommended based on the compound’s relatively long half-life (15-20 hours), which allows for sustained blood levels throughout the day.

This timing also aligns with the natural circadian rhythms of mitochondrial function and cellular repair processes, which may theoretically enhance benefits, though this specific timing advantage hasn’t been directly studied for Urolithin A. For those using Urolithin A specifically for exercise recovery or performance enhancement, taking it 1-2 hours before exercise may theoretically provide optimal timing to support mitochondrial function during the workout, though again, clinical evidence for specific timing benefits is limited. Some users report taking Urolithin A approximately 30-60 minutes before exercise. When consuming precursor-rich foods (like pomegranates, berries, or walnuts) rather than direct Urolithin A supplements, consistent daily consumption is recommended rather than occasional high-dose consumption.

This approach may better support the gut microbiome populations capable of converting these precursors to Urolithin A. For those taking multiple supplements, Urolithin A can generally be taken alongside most other supplements without significant interaction concerns. However, separating it from supplements or medications that might alter gut transit time or microbiome composition by at least 2 hours may be advisable to maintain consistent absorption patterns. For individuals using both precursor-rich foods and direct Urolithin A supplements, there’s no evidence suggesting they need to be separated in timing.

In fact, the combination may provide complementary benefits, with the supplement ensuring a consistent dose of Urolithin A while the foods provide additional polyphenols and support for a healthy gut microbiome. Consistency in daily supplementation is generally more important than specific timing for many of Urolithin A’s benefits, particularly for mitochondrial health and muscle function, which typically require several weeks of regular use to show noticeable improvements.

• Generally well-tolerated with minimal reported side effects at recommended doses
• Mild gastrointestinal discomfort (occasional)
• Nausea (rare)
• Mild headache (rare)
• Temporary changes in stool consistency (occasional)
• Mild allergic reactions in sensitive individuals (very rare)
• Fatigue (rare)
• Mild dizziness (very rare)
• Note: Most clinical trials report side effect profiles similar to placebo

• Known hypersensitivity to Urolithin A or its precursors
• Pregnancy and breastfeeding (insufficient safety data)
• Children and adolescents under 18 (insufficient safety data)
• Caution advised in patients with severe liver or kidney disease (limited research)
• Caution in patients taking immunosuppressant medications (theoretical concern based on immune-modulating properties)
• Caution in patients with bleeding disorders or on anticoagulant therapy (theoretical concern based on limited data suggesting mild antiplatelet effects)
• Scheduled surgery (consider discontinuing 2 weeks before due to theoretical concerns about bleeding risk)
• Note: These contraindications are primarily precautionary due to limited long-term human data rather than documented adverse effects

• No significant drug interactions have been definitively established in human studies
• Theoretical interaction with immunosuppressant medications due to immune-modulating effects
• Potential interaction with anticoagulant and antiplatelet drugs (theoretical mild additive effect on bleeding risk)
• Possible interaction with medications metabolized by specific cytochrome P450 enzymes (based on preliminary in vitro data, clinical significance unknown)
• Medications that significantly alter gut microbiome composition may affect conversion of precursors to Urolithin A (not relevant for direct UA supplementation)
• Potential for enhanced effects when combined with other mitochondrial-targeting compounds (not necessarily adverse)
• Note: Due to the relatively recent emergence of Urolithin A as a supplement, drug interaction studies are limited

No official Tolerable Upper Intake Level (UL) has been established for Urolithin A. Based on available research, doses up to 2,000 mg per day have been used in short-term human studies without significant adverse effects, though such high doses are not typically necessary for potential benefits. The most extensively studied dose in human clinical trials is 500 mg daily, which has demonstrated a good safety profile in studies lasting up to 4 months. For synthetic Urolithin A supplements (such as Mitopure), the manufacturer-recommended dose of 500 mg daily is based on both safety and efficacy considerations from clinical research.

For Urolithin A derived from dietary precursors (ellagitannins in foods like pomegranates), there is no established upper limit, and these foods have long histories of safe consumption. However, extremely high consumption of some precursor-rich foods might cause digestive discomfort due to their fiber and tannin content, rather than due to Urolithin A itself. As with any relatively new supplement, long-term safety data (beyond several months) is limited. The compound has received Generally Recognized as Safe (GRAS) status from the FDA for use in food and supplements at specified levels, providing some regulatory assurance of safety.

Urolithin A has also received Novel Food approval in the European Union following safety evaluations. As a naturally occurring metabolite produced by gut bacteria from dietary compounds, Urolithin A likely has a good safety profile at physiological levels. However, as with any supplement, it’s prudent to use the lowest effective dose for the intended purpose, particularly for long-term use. Those with specific health conditions, on medications, or with known sensitivities should consult healthcare providers before using Urolithin A supplements.

In the United States, Urolithin A has a somewhat unique regulatory status compared to many other supplements. The branded form of Urolithin A, Mitopure (developed by Amazentis), received Generally Recognized as Safe (GRAS) status from the FDA in 2020. This GRAS designation indicates that the ingredient is considered safe for its intended use based on scientific procedures and a substantial history of consumption. The GRAS notification (GRN No.

971) specifically covers the use of Urolithin A in food and supplement products at levels up to 1,000 mg per day. This regulatory milestone is significant, as it represents a higher level of regulatory recognition than many dietary supplements receive. As a dietary supplement ingredient, Urolithin A falls under the regulatory framework of the Dietary Supplement Health and Education Act (DSHEA) of 1994. Under this classification, manufacturers are responsible for ensuring their products are safe before marketing, though they are not required to provide evidence of safety to the FDA before selling products.

Manufacturers are prohibited from making specific disease claims (such as claiming Urolithin A treats a specific disease) but can make structure/function claims (such as ‘supports mitochondrial health’ or ‘may help maintain muscle function’). All Urolithin A supplements must include a disclaimer stating that the product has not been evaluated by the FDA and is not intended to diagnose, treat, cure, or prevent any disease. The FDA does not specifically regulate the quality or purity of Urolithin A supplements, which may lead to variability in product content and quality between manufacturers. The FDA has not established a recommended daily intake for Urolithin A, as it is not considered an essential nutrient.

Eu: In the European Union, Urolithin A has received Novel Food approval from the European Food Safety Authority (EFSA). In January 2021, the European Commission implemented regulation (EU) 2021/50, authorizing the placing on the market of Urolithin A as a novel food. This approval followed a rigorous safety assessment by EFSA, which concluded that Urolithin A is safe for use in food supplements for the general adult population at doses up to 1,000 mg per day. The novel food authorization specifies certain conditions of use and labeling requirements. This regulatory approval represents a significant milestone, as the EU’s novel food process involves a comprehensive safety evaluation. The approval applies specifically to synthetic Urolithin A that meets certain specifications, rather than to all forms or sources of the compound.

Canada: In Canada, the regulatory status of Urolithin A is less clearly defined than in the US or EU. It is not currently listed in the Natural Health Products Ingredients Database (NHPID) as an approved medicinal or non-medicinal ingredient for natural health products. This means that products containing Urolithin A may face regulatory challenges in the Canadian market. Manufacturers would likely need to apply for approval through Health Canada’s Natural and Non-prescription Health Products Directorate before marketing products containing this ingredient.

Australia: In Australia, Urolithin A is not currently listed in the Therapeutic Goods Administration’s (TGA) list of permissible ingredients for use in listed complementary medicines. This means that products containing Urolithin A would likely need to go through a more comprehensive evaluation process before they could be legally marketed in Australia. The regulatory pathway would likely involve application for assessment as a new complementary medicine ingredient.

Japan: In Japan, Urolithin A does not currently have an established regulatory status within the Foods with Function Claims (FFC) system or as a pharmaceutical ingredient. Products containing Urolithin A would likely need to undergo evaluation before they could make specific health claims in the Japanese market.

Global Outlook: The regulatory landscape for Urolithin A is still evolving globally. The GRAS status in the US and Novel Food approval in the EU represent significant regulatory milestones that may influence regulatory decisions in other countries. As research on Urolithin A continues to develop and more clinical evidence emerges, its regulatory status may continue to evolve across different jurisdictions.

High

$3.00-$5.00 per day for purified Urolithin A (500 mg); $0.50-$2.00 per day for precursor-rich foods and extracts (pomegranate, etc.)

Urolithin A represents one of the more expensive supplements on the market, with costs significantly higher than many other mitochondrial and muscle support supplements. Purified Urolithin A supplements (such as Mitopure) typically cost $3.00-$5.00 per day at the clinically studied dose of 500 mg daily. This places it at the premium end of the supplement market, comparable to some of the more expensive NAD+ precursors and specialized formulations. The high cost reflects several factors: the relatively new nature of the ingredient, the complex manufacturing process for synthetic Urolithin A, patent protection on certain formulations, and the significant research and development investment behind branded products.

When evaluating the value proposition of Urolithin A, it’s important to consider both the cost and the unique benefits it may provide. Unlike many supplements with overlapping mechanisms, Urolithin A’s specific action on mitophagy (the clearance of damaged mitochondria) represents a somewhat unique mechanism not directly addressed by many other supplements. This distinctive mechanism may justify the higher cost for some users, particularly those specifically seeking mitochondrial quality control support. Compared to other mitochondrial support supplements, Urolithin A is generally more expensive.

Coenzyme Q10 typically costs $0.50-$1.50 per day, while PQQ (pyrroloquinoline quinone) costs approximately $1.00-$2.00 per day. Even premium mitochondrial formulas combining multiple ingredients often cost less than purified Urolithin A supplements. For those primarily interested in the mitochondrial and muscle benefits, this cost differential raises important value considerations. An alternative approach is consuming precursor-rich foods like pomegranates, berries, and walnuts, which typically cost $0.50-$2.00 per day.

However, this approach has significant limitations due to the variable conversion of these precursors to Urolithin A in the gut. Research suggests that 30-40% of individuals may be ‘low converters’ or ‘non-converters’ who produce little to no Urolithin A even with high precursor consumption. For these individuals, direct supplementation with synthetic Urolithin A may be the only effective option, despite the higher cost. For ‘high converters’ with the right gut microbiome composition, the food-based approach may offer better value.

The cost-effectiveness calculation should also consider the emerging clinical evidence. Human studies have demonstrated benefits for muscle endurance and mitochondrial health biomarkers with Urolithin A supplementation. These benefits, particularly for muscle function in aging individuals, could potentially offset costs if they reduce other healthcare expenses or improve quality of life. However, the research is still relatively limited compared to more established supplements.

For those with specific interest in healthy aging and maintaining muscle function, particularly older adults experiencing age-related decline, the unique benefits may justify the premium price. For younger, healthy individuals without specific mitochondrial or muscle concerns, the value proposition is less clear given the high cost. As with many newer supplements, the cost of Urolithin A may decrease over time as manufacturing scales up, patents expire, and more companies enter the market. Early adopters typically pay premium prices that may not reflect long-term market positioning.

Urolithin A stability varies based on the specific formulation, storage conditions, and protective measures implemented by manufacturers. Under optimal storage conditions, purified Urolithin A in solid dosage forms (capsules, tablets) typically maintains acceptable potency for 18-24 months from the date of manufacture, as reflected in the expiration dates assigned by manufacturers. The primary degradation pathway for Urolithin A appears to be oxidation, which can be accelerated by exposure to light, heat, and oxygen. As a polyphenolic compound, UA has structural features that make it susceptible to oxidative degradation, similar to other polyphenols.

In powder form, UA may be more susceptible to degradation due to increased surface area exposure to air and moisture. Some manufacturers incorporate stabilizers or use specialized packaging to enhance shelf life. Proprietary formulations like Mitopure (a branded form of UA) may have specific stability profiles based on their unique formulation and packaging. Products containing UA precursors (ellagitannins/ellagic acid) rather than direct UA generally have good stability, with ellagitannins being relatively stable compounds in properly stored supplements.

However, once these precursors are consumed, their conversion to UA in the gut is time-limited and highly dependent on individual microbiome composition. Properly manufactured commercial products typically include stability testing to ensure that products maintain acceptable potency throughout their stated shelf life when stored according to recommendations.

Store in a cool, dry place away from direct light, preferably at temperatures between 15-25°C (59-77°F). Keep containers tightly closed to prevent moisture absorption and minimize oxygen exposure, as both can accelerate degradation of Urolithin A. Avoid storing in bathrooms or other high-humidity areas where temperature and humidity fluctuate. Light protection is important for Urolithin A stability.

Store in the original opaque container or packaging that blocks light exposure. If transferring to another container, ensure it is opaque and airtight. Refrigeration is generally not necessary for most Urolithin A supplements but may help extend shelf life, particularly in hot and humid climates. Check product-specific recommendations, as formulations vary in their sensitivity to environmental factors.

Some products include oxygen absorbers or desiccants in the packaging to protect against oxidation and moisture – these should be left in place but not consumed. For powder formulations, use the included scoop or a clean, dry utensil to prevent introducing moisture into the container. Avoid exposure to strong oxidizing agents or extreme pH conditions, which can accelerate degradation. When traveling with Urolithin A supplements, maintain appropriate storage conditions as much as possible and keep in original packaging or a suitable light-protective container.

If the supplement changes color significantly, develops an unusual odor, or shows physical changes like clumping (for powders) or softening (for capsules), it may have degraded and should be replaced.

Oxidation (primary degradation pathway for polyphenolic compounds like UA), Light exposure (particularly UV light, can accelerate oxidation reactions), Heat (accelerates degradation reactions; significant degradation likely occurs above 40°C/104°F), Moisture (can promote hydrolysis and other degradation reactions), Oxygen exposure (contributes to oxidative degradation), pH extremes (UA stability is likely pH-dependent, with optimal stability in slightly acidic to neutral conditions), Metal ions (particularly iron and copper, can catalyze oxidation reactions), Microbial contamination (if moisture is introduced), Enzymatic degradation (primarily relevant for precursors rather than synthetic UA), Prolonged exposure to very high humidity

Synthesis Methods

Natural Sources

Quality Considerations

Urolithin A represents a fascinating case in the supplement world, as it has virtually no traditional historical usage as a direct compound, yet its precursors have been consumed for millennia. Unlike herbs with centuries of documented medicinal use, Urolithin A was only discovered and characterized in the late 20th century, with its biological significance becoming clear only in the past decade. The story of Urolithin A begins not with the compound itself, but with its dietary precursors – ellagitannins and ellagic acid found in foods like pomegranates, berries, and walnuts. These foods have rich historical usage across multiple cultures.

Pomegranates, the richest known source of Urolithin A precursors, have been cultivated since ancient times, with evidence of their cultivation dating back to 3000 BCE in the Mediterranean region, Middle East, and India. They appear in numerous ancient texts, including the Bible, the Quran, and ancient Egyptian papyri, often symbolizing fertility, abundance, and health. In traditional Ayurvedic medicine of India, pomegranates were used for numerous health conditions, including digestive disorders, heart problems, and as a general tonic. Similarly, in Traditional Chinese Medicine, pomegranates were prescribed for conditions including dysentery, diarrhea, and parasitic infections.

Ancient Greek and Roman physicians, including Hippocrates and Dioscorides, documented medicinal uses of pomegranates for ailments ranging from inflammation to digestive disorders. Other Urolithin A precursor-rich foods like walnuts and berries also have long histories of traditional use for health purposes across various cultures. However, none of these traditional uses specifically recognized or targeted Urolithin A, as the compound was unknown until modern scientific investigation. The scientific discovery of urolithins began in the 1980s, when researchers first identified these compounds as metabolites in human urine.

Initially, they were primarily studied as biomarkers rather than bioactive compounds. The name ‘urolithin’ derives from the fact that these compounds were first isolated from urine and beaver castoreum (from the genus Castor). The specific compound Urolithin A was characterized as part of this family of metabolites. The pivotal moment in Urolithin A’s journey from obscure metabolite to promising supplement came in 2016, when researchers at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland published a groundbreaking study in Nature Medicine.

This research demonstrated that Urolithin A could induce mitophagy (the selective removal of damaged mitochondria), extend lifespan in C. elegans worms, and improve muscle function in rodents. This study revealed for the first time that Urolithin A was not merely a metabolic byproduct but a bioactive compound with significant potential health benefits. Following this discovery, research on Urolithin A accelerated rapidly.

In 2019, the first human clinical trial of Urolithin A was published, demonstrating its safety and effects on mitochondrial gene expression in elderly individuals. This was followed by additional clinical studies showing benefits for muscle endurance and mitochondrial health in both elderly and middle-aged adults. The commercial development of Urolithin A as a supplement began shortly after the 2016 breakthrough study. Amazentis, a company co-founded by researchers involved in the original discovery, developed a proprietary synthetic Urolithin A product called Mitopure.

This product received Generally Recognized as Safe (GRAS) status from the FDA in 2020 and Novel Food approval in the European Union in 2021, allowing its commercial use in supplements and foods. Unlike many traditional supplements with centuries of human use before scientific validation, Urolithin A represents a reverse trajectory – scientific discovery leading to supplement development, with no traditional usage history of the compound itself. This modern approach to supplement development, based on molecular understanding and clinical research rather than traditional usage, represents an emerging paradigm in the supplement industry. Today, Urolithin A supplements are increasingly available, though still relatively new to the market compared to many other supplements.

The scientific understanding of Urolithin A continues to evolve, with ongoing research exploring its potential benefits for various aspects of health beyond muscle function, including gut health, neuroprotection, and cardiovascular health. While Urolithin A itself has no traditional usage history, the long history of consuming its precursor-rich foods across cultures and their association with health and longevity provides an interesting historical context for this thoroughly modern supplement.

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