An oral supplement intended to stimulate a natural bodily process appears to support muscle endurance and mitochondrial health in humans. New research suggests that the supplement, urolithin A, may help improve or prolong muscle activity in people who age or have conditions that make exercise difficult.
The paper was published in JAMA network open.
“This applies both to people with chronic conditions and to people who want to be more active later in life,” said lead author David Marcinek, professor of radiology at the University of Washington. His research focuses on the role of mitochondria in aging and chronic disease.
Urolithin A is a byproduct of a person’s gut bacteria and a diet that includes polyphenols found in pomegranates, berries, and nuts. Because diet, age, genetics, and disease affect the composition of the gut microbiome, people produce urolithin A at varying rates. The compound is also produced and sold by dietary supplement companies.
Supplemental urolithin A has been shown in animal tests and molecular studies on humans to stimulate mitophagy, a process Marcinek explained as “mitochondrial quality control.”
“Mitochondria are like batteries that power your body’s cells,” he said. “But over time, they break down. The process of mitophagy recognizes this failure and proactively destroys mitochondria, reducing them to building blocks that a cell can reuse. But with aging, mitophagy becomes less efficient and your body accumulates this pool of failing mitochondria. It’s a way for muscles to become less functional as we age.”
The researchers studied a small cohort of people over the age of 65 who were randomly assigned to receive a placebo or a daily supplement of 1000 mg of urolithin A for four months. Each of the 66 subjects was initially confirmed to have an average or lower ability to produce adenosine triphosphate (ATP), which mitochondria produce to help cells perform a myriad of functions.
The researchers hypothesized that if the urolithin A supplement did indeed increase mitophagy, the test cohort would experience improved muscle function and greater ATP production.
In both cohorts, two comparisons of muscle function were found to support the thesis, but two others did not:
- Two measures of muscle endurance were improved in the supplemented group compared to the placebo group. Endurance was measured with exercises involving the hand (first dorsal interosseus, between the thumb and index finger) and the leg (tibialis anterior, along the tibia). The researchers measured the increase in the number of muscle contractions until fatigue between a baseline test and the final test four months later.
- Measures of distance walked during a six-minute walk improved markedly between testing at baseline and four months in the supplement and placebo groups. However, the researchers saw no significant effect of the supplement compared to the placebo.
- Measurements (via magnetic resonance spectroscopy) of enhancement of peak ATP production did not change significantly from baseline to four months in either group.
“Even though we did not observe an effect of the supplement on whole-body function (via a six-minute measurement and ATP production),” Marcinek said, “these results are still exciting because they demonstrate that simply taking a supplement for a short time actually improved muscle endurance Resistance to fatigue improved in the absence of exercise.
Plasma samples were also collected from study participants at baseline, two months, and four months. The aim was to assess the potential effect of the supplement on the bioavailability of urolithin A and on biomarkers of mitochondrial health and inflammation. In the test cohort, urolithin A was associated with a significant reduction in several acylcarnitines and ceramides implicated for their role in metabolic disorders involving mitochondria, the researchers reported.
“I think these changes suggest that the treatment is affecting people’s metabolic state. Although it didn’t affect peak ATP production, it did improve test subjects’ overall metabolism,” Marcinek said.
He added that urolithin A supplements could have the potential to benefit people who can’t get the exercise they want due to poor muscle health or disease.
“Just getting them past that point where exercise is possible — going around the block or climbing stairs — can help a person develop their own health.”
The study funder, Amazentis, of Lausanne, Switzerland, manufactures the urolithin A supplement used in the trial.