May 2025 Issue
Ask the Expert: Urolithin A
By Toby Amidor, MS, RD, CDN, FAND
Today’s Dietitian
Vol. 27 No. 5 P. 6
Does It Support Healthy Aging?
Q: I have clients asking about taking a Urolithin A supplement for healthy aging and inflammation. Could you discuss if there’s any scientific evidence behind it for these health issues?
A: Urolithin A (UA) is a postbiotic that some research suggests may help support healthy aging and improve mitochondrial health, muscle function, neurodegenerative disorders, and inflammatory bowel disease. This article will discuss how UA is produced in the gut and provide an overview of the research.
About Urolithin A
UA is a postbiotic, meaning you do not get it directly from food but rather need a healthy gut microbiome to make it. Melissa Mitri, MS, RD, nutrition writer and owner of Melissa Mitri Nutrition, says the production of UA is a “digestive byproduct of the fermentation process. Upon digestion of certain foods, probiotics in the gut break down prebiotics to produce UA.” Ellagitannins such as polyphenols in pomegranates, berries, and nuts are metabolized by bacteria in the gut and converted to UA.1
Mitri points to a 2021 study published in the European Journal of Clinical Nutrition, which revealed that about 40% of people have the right gut bacteria to convert ellagic acid to UA from food sources.1 As such, some may wonder if there’s a need for the rest of the population to take a direct dose of UA to receive its benefits for mitochondrial health. This study suggests that differences in gut microbiome and diet that dictate natural exposure to UA may be overcome via direct dietary UA supplementation.
At this time, it’s unknown what specific strains of gut bacteria can achieve the conversion of foods high in polyphenols and ellagitannins to UA. Although some research has shown that a diverse gut microbiome may correlate with higher natural production, the research findings are conflicting at this time and more research is needed.
Healthy Aging
UA targets three of the hallmarks of healthy aging, including mitochondrial decline, the decline in macroautophagy (including mitophagy2), and chronic inflammation.3 In 2024, a published systematic review looked at the effect of direct supplementation with UA on aging and age-related diseases in humans in five studies that were intention-to-treat studies conducted among healthy adults in the United States, Canada, France, and Japan.4
The sample sizes ranged from 36 to 88 individuals, with a total of 250 participants, and an intervention duration range from 28 days to four months. From the data reviewed, researchers determined that in humans, evidence did not support the beneficial effects of UA on physical function in healthy individuals. However, UA may potentially decrease inflammation and enhance muscle strength and endurance. There were numerous limitations in this study, including a small sample size, short intervention duration, and a wide participant age range of 45 to 85 years of age. As such, the impact of UA on human health span and lifespan requires further exploration.
Muscle Support
Human clinical data suggests UA may “improve muscular strength and endurance in older- and middle-aged adults,5 as well as resistance-trained athletes,”6 says Emily N. Werner, PhD, RD, CSSD, IFNCP, team dietitian for the Philadelphia 76ers and owner of Eat Elite Performance Nutrition. In addition, some studies have shown that supplementing with UA may reduce inflammatory markers in the blood5,7 and may even reduce the overall amount of protein breakdown in the muscle.8 These are all results that can be beneficial for athletes as they train and recover from workouts.
Additional clinical trials demonstrating muscle benefits in humans include a 2019 published study that found that both 500 and 1,000 mg of UA significantly improved skeletal mitochondrial turnover in sedentary older adults after one month,9 while a 2022 study found that 1,000 mg of UA significantly improved muscle endurance in older adults.10 Furthermore, a 2024 study found that 1,000 mg of UA improved muscle strength and endurance in strength-conditioned young athletes.11
Contraindications
UA is available in powder, soft gels, and capsules. According to Werner, UA “has achieved GRAS [generally recognized as safe] status by the FDA for its use as an ingredient in supplements, and there have been no documented adverse effects or medication interactions seen in adults 18 years and older taking UA at the recommended dose of up to 1,000 mg/day.16 However, Werner points out that it’s still possible that UA may interact with medications or supplements that have not yet been tested in studies. In addition, its safety has not yet been evaluated in pregnant or nursing women or in those less than 18 years of age.
Recommendations for RDs
The research is still evolving for UA with current evidence coming mainly from short-term studies with no follow-up. In addition, research suggests that there is a dose-dependent response for markers of autophagy, which only increased at lower—not higher—doses. Plus, some studies showing initial improvements during shorter-term interventions failed to show significant results after longer (beyond four months) interventions.10 As such, it is important to present all the evidence to the client to enable them to make an informed decision regarding the use of UA supplementation.
If a client chooses to take UA, Mitri and Werner suggest the following best practices for RDs:
1. Always advise clients to consult their doctor before starting UA.
2. Advise clients to consume a diet rich in polyphenols (eg, pomegranates) and adequate protein, to participate in regular cardiovascular and strength training regimen, and to strive for optimal sleep and stress management.
3. Emphasize the importance of purchasing from reputable, trusted, and transparent brands regarding their ingredients, research, and effectiveness. Specifically, encourage clients to look for brands that are third-party tested.
4. Advise clients take UA at the same time daily. The half-life of UA is ~24 hours.
5. Recommend taking UA with a fat source to increase bioavailability.
— Toby Amidor, MS, RD, CDN, FAND, is founder of Toby Amidor Nutrition (tobyamidornutrition.com) and a Wall Street Journal bestselling author. She’s written 10 cookbooks, including Up Your Veggies: Flexitarian Recipes for the Entire Family, Diabetes Create Your Plate Meal Prep Cookbook: 100 Delicious Plate Method Recipes, and The Family Immunity Cookbook: 101 Easy Recipes to Boost Health. She’s also a nutrition expert for FoodNetwork.com and a contributor to U.S. News and other national outlets.
References
1. Singh A, D’Amico D, Andreux PA, et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2022;76(2):297-308.
2. Picca A, Faitg J, Auwerx J, Ferrucci L, D'Amico D. Mitophagy in human health, ageing and disease. Nat Metab. 2023;5(12):2047-2061.
3. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243-278.
4. Kuerec AH, Lim XK, Khoo AL, et al. Targeting aging with Urolithin A in humans: a systematic review. Ageing Res Rev. 2024;100:102406.
5. Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633.
6. Zhao H, Zhu H, Yun H, et al. Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study. J Int Soc Sports Nutr. 2024;21(1):2419388.
7. Karim S, Madani B, Burzangi AS, et al. Urolithin A's antioxidative, anti-inflammatory, and antiapoptotic activities mitigate doxorubicin-induced liver injury in wistar rats. Biomedicines. 2023;11(4):1125.
8. Zhao H, Song G, Zhu H, et al. Pharmacological effects of Urolithin A and its role in muscle health and performance: current knowledge and prospects. Nutrients. 2023;15(20):4441.
9. Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator Urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1(6):595-603.
10. Liu S, D’Amico D, Shankland E, et al. Effect of Urolithin A supplementation on muscle endurance and mitochondrial health in older adults: a randomized clinical trial. JAMA Netw Open. 2022;5(1):e2144279.
11. Zhao H, Zhu H, Yun H, et al. Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study. J Int Soc of Sports Nutr. 2024;21(1):2419388.
12. Kothe B, Klein S, Petrosky SN. Urolithin A as a potential agent for prevention of age-related disease: a scoping review. Cureus. 2023;15(7):e42550.