Natural Compound Urolithin A Found to Support Muscular and Mitochondrial Health in Older Adults
As early as our 30s, muscle mass and strength decrease progressively year after year. This gradual decline means that people can lose 50% or more of their muscles by the time they reach their 80s, affecting obvious functions like walking ability, strength, and mobility, to lesser-known things like metabolism, weight, bone health, and mood disorders.
Dysfunction in our cells’ energy production centers — the mitochondria — is a leading cause of age-related muscle loss, as muscles without adequate energy input are bound to deteriorate. However, mitochondria tend to have altered structures and functional abilities with age, leading to bodily decline and disease.
Recent research has looked at targeting dysfunctional mitochondria as a way to boost muscle health, using the compound urolithin A. Published in the journal JAMA Network Open, researchers out of the University of Washington School of Medicine report how long-term urolithin A supplementation supports markers of muscle and mitochondrial health in aging adults. As lead author and professor of radiology at the UW School of Medicine, David Marcinek, states of their study’s significance, “This is relevant both to people with chronic diseases and people who want to be more active later in life.” (In other words — just about everybody.)
Urolithin A Upgrades Mitochondrial Function
Urolithin A is a natural compound known as a metabolite, as it’s produced in the gut via the bacterial metabolism of certain foods, including pomegranates, berries, and nuts. However, consuming these foods isn’t always enough to raise urolithin A levels in the body, as its formation requires having a specific set of gut bacteria — only about 40% of people can naturally convert foods into substantial levels of urolithin A. Instead, urolithin A can be taken in supplemental form.
Previous research has found that urolithin A supports cellular health by enhancing mitochondrial function and mitophagy — a beneficial process that eliminates dysfunctional mitochondria to clear the way for new ones. In studies with humans and mice, urolithin A supplementation has supported mitophagy, muscular health, and elevated ATP (energy) production in the skeletal muscle.
One way that urolithin A bolsters these processes is by boosting levels of NAD+ (nicotinamide adenine dinucleotide), a vital molecule that supports healthy cell functioning and regulates the aging process. A recent study found that long-term urolithin A supplementation effectively elevated NAD+ in the skeletal muscle of middle-aged mice, allowing for increased mitophagy and ATP production.
Declining mitophagy is thought to play a critical role in aging and disease development, so researchers like Marcinek and colleagues speculate that boosting this process with urolithin A may help support both mitochondrial health and muscle function.
Metabolite Magnifies Muscular Endurance in Older Adults
In this study, Marcinek and colleagues recruited healthy adults between 65 and 90. This small cohort was notably undiverse, with the participants being predominantly white females. Sixty study participants were randomly chosen to take either 1,000 mg of urolithin A or a placebo for four months, with measurements of muscular and mitochondrial health assessed at two and four months.
They found that the urolithin A-supplemented group had significantly enhanced skeletal muscle endurance in both hand and leg muscles, as assessed by an increase in the number of muscle contractions until fatigue set in. However, both the urolithin A and placebo groups showed clinically meaningful improvements in how far they walked in a 6-minute walk test, but these scores were not significantly different from each other.
They also looked at maximal adenosine triphosphate (ATP) production — the energetic compound produced by mitochondria to fuel our cells. Urolithin A was not found to increase maximal ATP production in either hand or leg muscles more than the placebo. However, the urolithin A-treated group did see significant benefits to blood markers of mitochondrial health and inflammation. Urolithin A reduced levels of acylcarnitines, which elevate in circulation in cases of mitochondrial dysfunction.
Similarly, urolithin A lowered blood levels of ceramides — fatty molecules necessary for cell membrane structure, but are linked to poor metabolic and cardiovascular health when elevated. Lastly, those supplemented with urolithin A showed reduced blood C-reactive protein (CRP) levels, a protein commonly associated with whole-body and cardiovascular-related inflammation.
Marcinek isn’t discouraged by the lack of benefits to skeletal muscle ATP production and the walk test, stating, “Even though we did not observe an effect of the supplement in whole-body function (via six-minute measure and ATP production), these results are still exciting because they demonstrate that just taking a supplement for a short duration actually improved muscle endurance. Fatigue resistance got better in the absence of exercise.” The fact that urolithin A improved the endurance of two skeletal muscles that are very different in both function and anatomy — without physically training these muscles — suggests a direct benefit of the compound on muscular performance.
One Step at a Time
Despite some of their anticipated endpoints being unaffected by urolithin A supplementation, this research adds to the evidence of the mitochondria- and muscle-related benefits of this metabolite. These results are also functionally important because performing repeated muscle contractions is a key aspect of maintaining an older adult’s ability to care for oneself and remain mobile and active, thereby supporting quality of life and independence
As Marcinek states, “Just getting them over that point where exercise is possible — a walk around the block or climbing some stairs — might help a person build their own health.” Similarly, this research could set the stage for using urolithin A to support people of all ages with muscle-related diseases.
The authors conclude in their paper, “The findings from this exploratory work suggest that urolithin A is a promising approach to counteracting age-associated muscle decline. However, future work is needed to confirm the beneficial role of urolithin A supplementation in healthy aging.”
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. Published 2022 Jan 4. doi:10.1001/jamanetworkopen.2021.44279