Promotional Features
Why high-quality Urolithin A is the future health longevity essential
Urolithin A has gained huge attention from the public because of its unique health benefits and scientific potential.
This interest was highlighted at both Natural Products Expo West 2024 in the US and the recent NUHS Center for Health Longevity scientific summit in Singapore. With emerging research and a deeper understanding of this compound, the market demand for Urolithin A is on the rise, gaining recognition among longevity enthusiasts.
Urolithin A is a metabolite produced by the gut microbiota from ellagitannin ingested from fruits (such as pomegranates) and nuts. As the unique health benefits of Urolithin A are gradually becoming apparent, an increasing number of people are being drawn to it. Extensive studies have demonstrated that Urolithin A's primary function lies in mitophagy, the process by which cells recycle damaged mitochondria, crucial for sustaining cellular vitality and warding off age-related ailments.1
Urolithin A: The fuel of cell powerhouse and health
Mitochondria are the powerhouse of cells, generating adenosine triphosphate (ATP) through the electron transport chain. However, the reactive oxygen species (ROS) generated during this process can damage proteins, fatty acids, and nucleic acids, triggering a chain reaction of oxidation. Therefore, clearing damaged mitochondria is needed to avoid underway damage to cells. Urolithin A, a potent mitophagy inducer, activates mitophagy through multiple pathways, selectively clearing damaged mitochondria to protect cells from injury.
Urolithin A activates mitophagy through the PINK/Parkin-dependent pathway by activating parkin protein, triggering ubiquitination of damaged mitochondrial proteins, recognized by the P62 protein, and subsequently binding with the LC3 protein family on the autophagosome, initiating mitophagy. Moreover, Urolithin A can also promote the binding of proteins such as BNIP3, NIX, and FUNDC1 to LC3 that are independent to PINK/Parkin pathway.
Figure 1: Mitophagy Mechanism of Urolithin A.2
Urolithin A not only helps reduce ROS production, hence preventing mitochondrial DNA damage and mutations, it also effectively clears dysfunctional mitochondria. Subsequently, it plays a protective role in various pathological processes such as cell aging and neurological diseases.
Several studies have revealed the potential efficacy of Urolithin A in various health areas:
- Help with longevity Several animal studies show that Urolithin A can extend the lifespan of animals. It prolongs the lifespan of roundworm (Caenorhabditis elegans) by over 45%, with a significant dose-response relationship, while the same concentration of ellagic acid does not have this effect.3
Figure 2: The effect of different longevity components in extending the lifespan on Roundworm.
- Enhance muscle endurance Clinical trials have shown that daily supplementation of Urolithin A can improve strength, aerobic endurance, and exercise performance in middle-aged and elderly individuals.4,5
- Improved immunity Urolithin A can promote hematopoietic stem cell (HSC) differentiation, and it activates the immune system lymphatic zone in mice, enhancing the overall performance of HSCs.6 Studies have shown that daily administration of 50 mg/kg Urolithin A for four months restores hematopoietic capacity in aging mice to youthful levels, promotes lymphocyte generation, and enhances the proliferation and efficiency of aging CD8+ T cells.
- Mitigate neurodegeneration Urolithin A can significantly improve cognitive function, alleviate neuroinflammation, and prevent neuronal apoptosis. This is achieved by including the inhibition of microglia and astrocyte activation, scavenging of free radicals, inhibition of oxidative enzymes, activation of AMPK, blocking the p38/MAPK and p65/NF-κB inflammatory signaling pathways and reducing pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α.7,9
- Help with weight loss Studies show that Urolithin A can prevent diet-induced obesity and metabolic dysfunction without adverse effects. It increases the level of triiodothyronine (T3) in adipose tissue, promotes thermogenesis in brown adipose tissue, and induces browning of white adipose tissue to increase energy expenditure, reduce fat cells, and fat mass.10,11
- Regulation of gut microbiota Urolithin A can improve gut microbiota, reduce inflammation markers, and restore colonic barrier function by increasing the expression of tight junction proteins, alleviating colonic inflammation. Additionally, Urolithin A and its analog UAS03 can activate the AhR and Nrf2 pathways, further enhancing intestinal barrier function, which is essential for maintaining gut health.12-15
Investigating the quality of Urolithin A
According to the World Health Organization, globally 1 in 6 people will be aged 60 years or over by 2030.16 This stimulates a huge demand for healthy longevity products. Urolithin A's unique and promising health benefits are compelling consumers to opt for it as a supplement for anti-aging purposes. However, amidst the surge in the market, concerns arise regarding the quality of Urolithin A products, which may not be as positive as its health effects.
At the NUHS Center for Health Longevity summit in March 2024, Bonerge had the invaluable opportunity to talk with leading longevity scientists and experts. They expressed their worries regarding a critical gap in the supplement market concerning potent nutraceutical ingredients – like Urolithin A and Fisetin – backed by scientific validation yet lacking high-quality products to meet consumer demand. Understanding that quality forms the foundation of all supplements, Bonerge felt compelled to investigate the quality of Urolithin A.
As expected, the findings revealed the inconsistency of Urolithin A quality across various tests, and the product quantity can be seen from its appearance. Allen Ge, product manager at Bonerge, shared his team's insight: "After investigating Urolithin A products on the market, we noticed that dark yellow or even blackish Urolithin A is often indicative of potential organic impurities. Whereas high-purity Urolithin A exhibits a light yellow hue.”
Following extensive consultations with experts, Bonerge reached a consensus that premium products demand high-quality raw materials. Bonerge team poured significant efforts into research and development (R&D) and successfully developed the high-purity Urolithin A, UroAce. UroAce has a delightful yellow color that shows ultra-pure quality and minimal impurities. UroAce is the new addition to Bonerge’s top-notch Branded ingredient, along with Fisetin (BeFisetin) and more.
Figure 3: Color comparison of Urolithin A from different factories.
Despite the proven health advantages of Urolithin A, challenges persist in its product applications. Poor absorption, limited water solubility, and low lipid solubility hinder its efficacy. To overcome these hurdles, enhancing Urolithin A's bioavailability is imperative. Through novel derivative development and formulation, its solubility and absorption can be effectively improved, unlocking its full potential in delivering health benefits.
The future of health management
Looking ahead, Bonerge anticipates that Urolithin A will play a pivotal role in health management and longevity, driven by continuous R&D and product improvement. Consumers eagerly await the assurance of high-quality Urolithin A, verified by extensive clinical trials. As an innovative manufacturer specialized in longevity ingredients, Bonerge also offers array of outstanding products, like Fisetin and Dihydroberberine, with enormous market potential.
Figure 4a: Key health benefits of Fisetin.
Figure 4b: Key health benefits of Dihydroberberine.
Fisetin is a potent senolytic that reduces senescence-associated secretory phenotype (SASP) driven chronic inflammation and promotes cell health. Dihydroberberine is a natural GLP-1 agonist with improved bioavailability, absorption, safety and efficacy than Berberine. Bonerge is looking forward to collaborating with global brands to develop anti-aging products available for everyone.
References
1. Tolkovsky A. M. (2009). Mitophagy. Biochimica et biophysica acta, 1793(9), 1508–1515.
2. Palikaras, K.; Lionaki, E.; & Tavernarakis, N. (2018). Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nature cell biology, 20(9), 1013–1022.
3. Ryu, D.; Mouchiroud, L.; Andreux, P. A.; et al. (2016). Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature medicine, 22(8), 879–888.
4. Singh, A.; D'Amico, D.; Andreux, P. A.; et al. 2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell reports. Medicine, 3(5), 100633.
5. Liu, S.; D'Amico, D.; Shankland, E.; et al. (2022). Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial. JAMA network open, 5(1), e2144279.
6. Girotra, M.; Chiang, Y. H.; Charmoy, M.; et al. (2023). Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems. Nature aging, 3(9), 1057–1066.
7. Niranjan R. (2018). Recent advances in the mechanisms of neuroinflammation and their roles in neurodegeneration. Neurochemistry international, 120, 13–20.
8. Cásedas, G.; Les, F.; Choya-Foces, C.; et al. (2020). The Metabolite Urolithin-A Ameliorates Oxidative Stress in Neuro-2a Cells, Becoming a Potential Neuroprotective Agent. Antioxidants (Basel, Switzerland), 9(2), 177.
9. Gong, Z.; Huang, J.; Xu, B. et al. (2019). Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice. J Neuroinflammation 16, 62.
10. Toney, A. M.; Fan, R.; Xian, Y.; et al. 2019). Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis. Obesity (Silver Spring, Md.), 27(4), 612–620.
11. Xia, B.; Shi, X. C.; Xie, B. C.; et al. (2020). Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice. PLoS biology, 18(3), e3000688.
12. Larrosa, M.; González-Sarrías, A.; Yáñez-Gascón, M. J.; et al. (2010). Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. The Journal of nutritional biochemistry, 21(8), 717–725.
13. Kujawska, M.; & Jodynis-Liebert, J. (2020). Potential of the ellagic acid-derived gut microbiota metabolite - Urolithin A in gastrointestinal protection. World journal of gastroenterology, 26(23), 3170–3181.
14. Zhao, R.; Long, X.; Yang, J.; et al. (2019). Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet. Food Funct, 10: 8273-85
15. Singh, R.; Chandrashekharappa, S.; Bodduluri, S.R.; et al. (2019). Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun 10, 89.
16. World Health Organization. Aging and health.
