Urolithin A & muscle strength: Science builds for compound’s healthy aging potential

By Stephen Daniells contact

- Last updated on GMT

Urolithin A is a compound generated by gut microflora from ellagitannins found in food such as pomegranate.  Image © shorrocks / Getty Images
Urolithin A is a compound generated by gut microflora from ellagitannins found in food such as pomegranate. Image © shorrocks / Getty Images

Related tags: Urolithin A, cellular aging, mitochondrial function, healthy aging, Pomegranate, Amazentis

Supplementation with urolithin A, a pomegranate metabolite, may boost exercise endurance and physical performance, according to findings from a randomized clinical trial with 88 healthy people.

Four months of supplementation with the Mitopure-branded urolithin A from Amazentis also led to 12% improvements in muscle strength, reported scientists from Amazentis SA, KGK Science, and the Ecole Polytechnique Fédérale de Lausanne in Cell Reports Medicine.

“These findings build on previous clinical evidence with [urolithin A] and its use as a nutritional intervention to support muscle health and promote healthy aging,” ​they wrote.

The ingredient

Urolithin A is a compound generated by gut microflora from ellagitannins found in food such as pomegranate. The compounds are hydrolyzed in the stomach into ellagic acid, which is subsequently converted by the gut microflora into urolithin A. However, not everyone has the right microflora to be able to make the metabolite.

As reported previously by NutraIngredients-USA,​  Amazentis​ has developed a method to deliver finely calibrated doses of urolithin A. Preliminary data published in Nature Medicine​ indicated that urolithin A may improve mitochondrial function by stimulating mitophagy, a process by which damaged mitochondria are recycled to permit a renewal with healthy mitochondria.

These potent beneficial effects were observed in different organisms, including C. elegans​, mammalian cells, rodents, and several human clinical trials.

The new study was funded by Switzerland-based Amazentis SA.

Study details

The new study included almost 90 healthy, overweight, middle-aged adults who were randomly assigned to one of three groups: 500 mg of Mitopure, 1,000 mg of Mitopure, or placebo for four months.

Both doses of urolithin A were associated with significant increases in leg strength, but the lower dose produced better results (+12% in the 500 mg group and +10% in the 1,000 mg group).

No significant improvements were observed for either urolithin A group compared to placebo for peak power output, said the researchers.

And while no significant improvements compared to placebo were observed for VO2max, total cycling distance, and results of the 6-minute walking test, statistically significant improvements were observed in the high dose group compared to baseline levels. Specifically, the researchers noted that the cycling distance increased by 15% when compared to levels at the start of the study, while walking distance increased by an average of 33.4 meters.

“This is noteworthy, as such distance exceeds current estimates for clinically important differences in older adults (greater than 30 m),” ​wrote the researchers.

Analysis of muscle biopsies and revealed that the lower dose urolithin A was linked to increases in mitophagy proteins in human skeletal muscle.

Urolithin A supplementation was also found to impact markers of inflammation, notably CRP (C-reactive protein).  

“The reduction of the CRP by [urolithin A] is particularly relevant, as circulating CRP concentration is positively associated with an increased risk of age-related diseases and with poorer immune health,” ​they stated. “Of note, plasma CRP levels are also inversely correlated with muscle mitochondrial oxidative capacity. These biomarker data indicate how [urolithin A] supplementation offers a potential dual benefit for muscle health, by improving mitochondrial function, while also acting to reduce age-related chronic inflammation, or inflamm-aging.”

“Future confirmatory studies will focus on functional endpoints that had an impact with [urolithin A] supplementation, in particular on muscle strength and aerobic endurance, and will be powered based on the findings of this proof-of-concept study,” ​concluded the researchers.

Source: Cell Reports Medicine
Volume 3, Issue 5, 100633, doi: 10.1016/j.xcrm.2022.100633
“Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults”
Authors: A. Singh et al.

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