Rejuvenate muscle health without working out? New studies show a postbiotic derived from pomegranates and other foods boosts muscle energy.

When it comes to muscle strength and performance, you likely think of exercise routines and protein intake. However, emerging research is identifying new nutrients that may play a role in muscle health. Urolithin A (UA) is one of these nutrients, with some exciting research backing its credibility.

What is muscle health and why is it important?

Whether you are an elite athlete, weekend warrior, or don’t engage in physical activity at all, health experts agree that muscle strength should be a focus for living a long and healthy life. Most athletes and exercise enthusiasts know that strong muscles will help them to perform better in their favorite activities, but many of us are not aware that muscle strength is a key determinant in the aging process.

As we age, we naturally experience a decline in muscle mass and strength. This decline can start in our 30s or 40s,¹ which is much earlier than most people think. Sarcopenia, the term that defines significant muscle loss, is associated with frailty and increased mortality in older adults.²

As far back as 2002, the World Health Organization identified the preservation of muscle mass and the prevention of frailty as key indicators of healthy aging.² Currently, the two main interventions to prevent sarcopenia and its adverse outcomes are nutrition and exercise,³ but adhering to a lifestyle change is a challenge for many.

What if there was a way to preserve muscular strength, or even improve it, without diet or exercise? That’s what researchers studying Urolithin A are set to find out.

What is UA?

Before we jump into the science behind Urolithin A (UA) and muscle strength, let’s explore this novel compound and its role in cellular health.

UA is a natural substance that is produced in our bodies by our gut microbiome. Specific plant compounds called polyphenols, found in pomegranates, berries, and some nuts, can be converted into UA by bacteria in our gut, where it is then absorbed into our bloodstream, travels to the cells, and gets to work.

Once inside a cell, Urolithin A targets the mitochondria. These cellular “organelles” are responsible for creating most of the energy we need to live. As we age, our mitochondria become damaged and dysfunctional, and their ability to generate energy declines. This dysfunction may be a contributor to age-related disease.

Since our mitochondria are so crucial for life, our bodies have created a biological system where older, damaged mitochondria can be recycled into healthier, more efficient ones. This process is called mitophagy⁴, and it’s here that Urolithin A works its magic.

Urolithin A upregulates mitophagy, and in doing so may be able to play a role in ameliorating age-related chronic conditions.⁵

Mitochondrial health and muscle health

Since the mitochondria generate energy, it should come as no surprise that energy-dependent tissue such as muscles have a high concentration of these organelles. Studies have shown that the decline in mitochondrial function associated with age may be a key contributor to muscle health and performance.⁶

Finding solutions to prevent or, better yet, reverse age-related muscle decline would be a huge win for helping people to live a longer and healthier life. And the recent research behind Urolithin A suggests that a solution may not be so far off.

Urolithin A supplements

As previously mentioned, Urolithin A can be made by our gut microbiome, so theoretically eating a diet rich in pomegranates, berries, and nuts would be able to supply us with the precursor molecules we need to make enough. Unfortunately, the research indicates otherwise.

A clinical trial compared the blood levels of UA after direct supplementation versus drinking pomegranate juice. What the researchers discovered was that only 40% of the people who drank the pomegranate juice were able to convert these precursors into UA.

While diet is usually the best way to get important nutrients, an argument can be made that for many of us, a UA supplement may offer a more consistent and efficacious way to get adequate amounts.

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Urolithin A supports muscle health

Since we know that muscle tissue has a high concentration of mitochondria, researchers hypothesized that targeting mitochondrial health could support muscle health. Two recent studies are beginning to shed some light on this connection.

The Energize Trial

The Energize Trial, published in JAMA in January 2022, was a randomized, double-blind, placebo-controlled study that looked at the effects of 1000mg of Urolithin A in older adults compared to placebo. The investigators measured tests of muscle fatigue and endurance, and biomarkers of mitochondrial health at baseline, 2 months, and 4 months.

Skeletal muscle endurance was measured with an isometric exercise performed in the hand. By the end of the four months, significant improvements were seen in the Urolithin A group compared to the placebo group.⁷

Plasma biomarkers also improved in this trial. C-reactive protein, a marker of inflammation, significantly decreased compared to placebo. Acylcarnites and ceramides, which are markers of mitochondrial health significantly improved.⁷

What’s particularly surprising about the results is that improvement occurred in the absence of changes to activity level or diet.

The Energize Trial was an important first step in demonstrating the efficacy of Urolithin A for older adults, and it supports the need for continued studies.

The Atlas Trial

Soon after the Energize Trial was published, the results of the Atlas Trial were released. Published in the May 2022 issue of Cell Reports Medicine, this study built on the strong foundation the Energize Trial laid out.

The Atlas Trial looked at the effect of Urolithin A on muscle strength and performance in healthy middle-aged adults. Eighty-eight adults aged 40–64 were randomized to receive either 500mg UA, 1000mg UA, or a placebo. The investigators selected people who were overweight and had low physical endurance so they could get a good measure of the impact of the intervention.

Just like the Energize Trial, this study showed significant improvements in muscular strength, endurance, and serum biomarkers of health. Muscular strength was measured using average peak torque, and both the 500mg and 1000mg UA group saw significant improvements compared to their baseline measurements. Interestingly, the placebo group saw a significant decline in this measure.

Exercise performance was evaluated with a measure of VO₂ max with a stationary cycle ergometer and a six-minute walking test. The 1000mg group saw a significant change with these measures as well.

Positive biomarkers were observed, with both treatment groups demonstrating improvements in measures of mitophagy and C-reactive protein.

Again, these findings are impressive considering the absence of exercise and dietary intervention during the trial.

What’s next?

These two studies are only the first chapter in the story of Urolithin A and muscle health. While they build a case for using UA in untrained adults, the question remains how UA will impact highly trained athletes. That’s where Professor Louise Burke and her research team come in.

Dr. Burke is a sports dietitian and researcher at Australian Catholic University. She’s in the midst of conducting a trial to investigate the use of Mitopure, a Urolithin A supplement, in trained endurance runners. This randomized, double-blind, placebo-controlled trial will look at biomarkers of muscle damage and recovery such as creatine kinase. She’ll also assess changes in performance in a 3000m track race.

Another muscle health study is currently underway at Nestlé Health Science Labs. Researchers in this trial are looking at how Urolithin A impacts muscle health in a rehabilitation center, to see if it can prevent muscle wasting due to injuries such as fractures.

Verdict / Summary

While diet and exercise will always be the foundational support for muscle health and performance, it is clear that other options are needed for people who have trouble maintaining lifestyle changes, or for athletes looking to level up their performance. The science behind Urolithin A suggests it could be an emerging tool to support muscle health, and continued research will help build out this story.

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References:

1.   Keller K, Engelhardt M. Strength and muscle mass loss with aging process. Age and strength loss. Muscles Ligaments Tendons J. 2014;3(4):346-350.

2.   Chang SF, Lin PL. Systematic Literature Review and Meta-Analysis of the Association of Sarcopenia With Mortality. Worldviews on Evidence-Based Nursing. 2016;13(2):153-162. doi:10.1111/wvn.12147

3.   Naseeb MA, Volpe SL. Protein and exercise in the prevention of sarcopenia and aging. Nutrition Research. 2017;40:1-20. doi:10.1016/j.nutres.2017.01.001

4.   Chen G, Kroemer G, Kepp O. Mitophagy: An Emerging Role in Aging and Age-Associated Diseases. Frontiers in Cell and Developmental Biology. 2020;8:200. doi:10.3389/fcell.2020.00200

5.   D’Amico D, Andreux PA, Valdés P, Singh A, Rinsch C, Auwerx J. Impact of the Natural Compound Urolithin A on Health, Disease, and Aging. Trends in Molecular Medicine. 2021;27(7):687-699. doi:10.1016/j.molmed.2021.04.009

6.   Zane AC, Reiter DA, Shardell M, et al. Muscle strength mediates the relationship between mitochondrial energetics and walking performance. Aging Cell. 2017;16(3):461-468. doi:10.1111/acel.12568

7.   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. doi:10.1001/jamanetworkopen.2021.44279

*This article is provided by an advertiser. Statements made are not meant to offer medical advice nor to diagnose any condition. Any studies cited here may be preliminary, and may or may not be peer reviewed, and may or may not have sufficient participants to be statistically relevant. Anecdotal accounts should not be taken as scientific results. Products discussed in this article are not designed to diagnose, treat, prevent, or cure any disease. The FDA does not evaluate dietary supplements. Consult your doctor about possible interactions, allergies, and if you are considering using a natural and/or dietary supplements for any condition. Individual results will vary.