SCIENCE  |  SUPPLEMENTS

Urolithin A

Urolithin A is a compound derived from the transformation of ellagitannins, found in foods like pomegranates, berries, and nuts, by gut bacteria. It has garnered attention for its potential to improve mitochondrial health, support cellular energy production, and promote healthy aging. Research suggests that it may enhance muscle function and exhibit anti-inflammatory and antioxidant properties.

Urolithin

PUBLICATIONS

  1. 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 Dec;21(1):2419388.
          • Design: 8-week randomized, double-blind, placebo-controlled study on resistance-trained male athletes.
          • Summary: Urolithin A (UA) supplementation at 1g/day showed improvements in muscle strength and endurance, with significant gains in Maximum Voluntary Isometric Contraction (MVIC) and repetitions to failure (RTF) compared to baseline and the placebo group. UA also led to a significant reduction in oxidative stress markers (3-MH) and a decrease in inflammation markers (CRP) compared to the placebo group, though not all inflammatory markers showed significant change.
  2. Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial.
          • Rev Recent Clin Trials. 2024;19(3):221-228.
          • Design: Randomized, double-blind, placebo-controlled 2×2 crossover trial on heart failure patients.
          • Summary: Urolithin A did not significantly improve echocardiographic or biochemical indices but increased HDL-C levels.
  3. Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review.
          • Cureus. 2023 Jul 27;15(7):e42550.
          • Design: Scoping review of studies on Urolithin A’s potential in preventing age-related diseases.
          • Summary: UA shows promise as a dietary intervention to prevent aging-related pathology by supporting mitochondrial health and reducing inflammation.
  4. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.
          • Cell Rep Med. 2022 May 17;3(5):100633.
          • Design: Randomized, placebo-controlled trial in middle-aged adults, testing Urolithin A at two doses over 4 months.
          • Summary: Urolithin A (UA), a known mitophagy activator, was administered to middle-aged adults in this 4-month trial. Results showed a significant 12% improvement in muscle strength with UA compared to placebo. Aerobic endurance, measured by peak oxygen consumption (VO2) and the 6-minute walk test, also improved significantly. Plasma biomarkers indicated better mitochondrial efficiency, as seen by reduced acylcarnitines and C-reactive protein levels. However, the primary endpoint of peak power output did not show a significant difference. Additionally, UA increased the expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle, further supporting its role in enhancing mitochondrial health and physical performance.
  5. 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 Feb;76(2):297-308.
          • Design: Randomized trial comparing dietary exposure and direct supplementation of UA in healthy adults.
          • Summary: Direct UA supplementation significantly increased plasma levels compared to natural dietary intake, overcoming microbiome variability.
  6. Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
          • JAMA Netw Open. 2022 Jan 4;5(1):e2144279.
          • Design: Double-blind, placebo-controlled randomized clinical trial in older adults.
          • Summary: UA improved muscle endurance and reduced inflammation markers, although no significant difference was found in maximal ATP production compared to placebo.
  7. Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions.
          • Eur J Nutr. 2021 Jun;60(4):1957-1972.
          • Design: In vitro studies comparing the effects of urolithins and their metabolites on macrophage and neutrophil activity.
          • Summary: Urolithin A was the most effective in modulating inflammatory response, while phase II metabolites showed reduced pharmacological activity.
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