Urolithin A to boost mitochondrial function

Urolithin A is the end product created when bacteria in the gut break down ellagitannins, the polyphenols found in fruits such as pomegranates, strawberries, walnuts, and raspberries. The substance does not appear naturally in its end form, so we normally rely on the beneficial bacteria in the microbiome, our internal ecology of gut bacteria, to convert the polyphenols into urolithin A.

Because this compound needs a particular bacterium to create it, the bioavailability of urolithin A could vary considerably from person to person, having a greater or lesser effect depending on individual gut bacteria diversity.

Urolithin A has been a subject of interest to researchers for a while, as there have been promising early results in mice and flatworms, in which the compound increased lifespan. It appears to be geroprotective, meaning that is has age-delaying, properties.

The geroprotective effect of urolithin A appears to be focused on improving the function of the mitochondria, the power plants of our cells, which are responsible for turning nutrient-derived molecules into a form of cellular energy called adenosine triphosphate (ATP).

In a small, recent human trial, this naturally occurring compound has yielded positive results and appears to slow down part of the aging process that is related to the production of energy in our cells [1].

In 2020, the researchers launched their first urolithin A product, Timeline, via their company Amazentis, and have initiated further human clinical trials. Their hope is that urolithin A may be able to slow down the loss of skeletal muscle that happens with age and reduces mobility and independence.

A randomized, double-blind, placebo-controlled clinical trial (NCT03464500) in healthy middle-aged participants (40 to 65 years old) showed that 4 months of daily consumption of 500mg Mitopure™ (highly pure Urolithin A) led to a significant improvement in leg muscle strength.

A separate randomized clinical trial (NCT04160312) conducted in healthy adults (18-80 years old) in the USA compared Urolithin A levels following consumption of Mitopure™ and pomegranate juice. It showed that 500mg of Mitopure™ delivers greater than 6X more Urolithin A compared to 8oz (240ml) of 100% pomegranate juice.

December 6, 2022 Amazentis  updated clinical trial NCT04783207  Clinicaltrials.gov indicates all data on primary outcomes from its study “Effects of Mitopure (Urolithin A) on Skeletal Muscle Function, Iron Metabolism and Endurance Performance (ENDURO)” have been collected.   Collected primary outcomes measures were change in plasma levels over time of creatine kinase (CK) [ Time Frame: 4 weeks ] and change in race performance time during a 3000 m track race in elite runners [ Time Frame: 4-weeks ]. Results have not been released.  Secondary measures including changes in aerobic capacity, lean body mass, body fat, resting metabolic rate,  maximal muscle strength, and others appears to be ongoing.

Reference

[1] Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., … & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 1(6), 595.

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