Are you looking to improve muscle performance and understand your gut microbiome more? Learn how urolithin A affects them.

Urolithin A (UA) is a biological compound created by gut bacteria from consumed ETs (ellagitannins) and EA (ellagic acid), complex polyphenols abundant in foods like berries, nuts and pomegranates. 

Individuals’ gut microbiomes are different. They vary by age, diet and genetics, among others. Because of this, various people produce urolithin at diverse ranks.

Individuals who don’t have bacteria, specifically from the Clostridiales and Ruminococcaceae families living in their gut, cannot create UA. Even those who can produce urolithin A do not make nearly enough of it. It can be said that as few as 1 in 3 people have enough urolithin A.

It was discovered 40 years ago, but it’s only recently that urolithin A’s impact on aging and disease has been looked into. UA improves cellular health by boosting mitochondrial function and mitophagy and lowering destructive inflammation. Several preclinical analyses indicate how UA protects against aging and age-related conditions affecting the brain, joints, muscle, and other organs [1]. 

The most coherent effect of UA across species is the improvement of mitochondrial health; an outcome observed in cells, mice, worms and humans [2]. This benefit is propelled by the clearing and recycling of dysfunctional mitochondria – a selective autophagy process called mitophagy. 

The process of mitophagy degrades as we grow older and in several age-related diseases [3]. Repairing correct levels of mitophagy is a promising strategy to counteract the age-related decline of organ function.

Mitophagy is a specific type of autophagy which happens within the mitochondria, recycling aging and damaged organelles making way for new, healthy mitochondria to thrive. This process is essential to antiaging and protects against numerous age-related diseases [4].

One of the most significant advantages of urolithin A is extended cellular energy in the mitochondria. These are known as “powerhouse of the cell.” Mitochondria are microscopic organelles that transform glucose and oxygen into adenosine triphosphate (ATP) for energy.

Unfortunately, as mitochondrial function declines with age, its ability to produce enough energy is impaired. Mitochondrial dysfunction is one of the known “nine hallmarks of aging” that induce cellular and molecular damage to the body, leading to age-related illness. Also regarded as an antagonistic hallmark, mitochondrial dysfunction can provoke muscle strength loss, which many people experience when they reach their 40s.

This can lead to a severe condition called sarcopenia, which affects 30 per cent of older people linked to frailty, poor mobility and fall-related afflictions. One way to combat this is through regular physical activity to sustain bone and muscle strength, with the CDC advising two strength training sessions weekly as part of the recommended 150 minutes [5].

Gut health is usually mentioned concerning health and longevity, but why? The gut’s function to masterfully digest your food is just one of its many roles [6], and there is growing proof that a healthy gut microbiome is essential for mental health and an effective immune system.

Starting from the esophagus down to the bowel, gut health is responsible for the soundness of the entire digestive system – the parts of our body accountable for breaking down food into different nutrients utilised to fuel our bodies. Each piece of the gut has a specific job, and various colonies of microorganisms break down food into more digestible forms. 

It demands commitment and mindful effort to maintain gut health. Our day-to-day decisions, even the easy ones such as deciding what to eat, can influence overall health and wellbeing. Your gut bacteria are critical for many aspects of health.

Multiple studies have shown that a disrupted microbiome can lead to numerous chronic illnesses. The most helpful way to improve and sustain a healthy microbiome is to consume a range of fresh, whole foods, particularly from plant sources like whole grains, beans, legumes, fruits and vegetables.

Rest is another critical aspect of daily bodily functions besides caring for our gut health. As we age, we get exhausted quicker and have less energy. Though it seems universally accepted, it doesn’t have to be this way.

Don’t overlook muscle recovery, whether going through daily physical activities or training for leisure or professional purposes. Aside from diet and good lifestyle practices, supplements are one way to support the body’s healing function. This way, you can also potentially do more of the physical activities you love.

In terms of cellular energy and muscle endurance, researchers are constantly trying to discover the most optimal approaches for recovery to ease the injury, fatigue and soreness from training. Yet, the flurry of information available leaves you more confused about the best way to recover than when you started.

FTP or Functional Threshold Power is the highest average power you can sustain for roughly an hour, calculated in watts but unlike it, recovery can’t be precisely quantified.

In an attempt to do so, research involving 66 older people with an average age of 72 years and casually assigned them to take either 1,000 milligrams of urolithin A per day for 4 months or a placebo [7].

The scientists employed specially created lab equipment to measure the maximum number of times participants could contract a specific muscle in their hand, and another in their leg, before exhaustion set in. They also instructed participants to walk as far as they could on an indoor track for six minutes [8].

Moreover, the scientists gauged the ability of the participants’ muscles to create adenosine triphosphate (ATP), also known as the molecular fuel generated by mitochondria that powers all the cell’s activities.

Ultimately, they took blood samples to measure biomarkers of mitochondrial function and inflammation in the participants’ bodies, as inflammation is associated with several age-related diseases. After four months, there were minor improvements in walking endurance in participants who had taken the supplement than those on the placebo, but the discrepancies were not statistically substantial.

There were also no notable changes in ATP production. Yet, people who had taken the supplement performed remarkably better in the lab trials of muscle endurance. The blood tests also suggested decreased inflammation and enhanced mitochondrial health.

The trial suggests that urolithin A may be a promising strategy to offset age-associated muscle decline. Although, it’s important to note that there was no disparity in the figure of adverse events from those on the supplement and those on a placebo.

One of the study’s restrictions was that 76% of participants were females and all the participants were white. The findings may, therefore, not apply to broader populations. In addition, the study did not observe participants’ daily physical activity.

Involvement in the study may have encouraged them to increase their exercise levels, making it more challenging to notice any statistically significant effects of urolithin A with a small sample size of 66 subjects.

On this note, scientists at Swiss company, Amazentis took on this challenge. Research indicates that exposing nematodes (roundworms) to urolithin A prolongs their lifespan and mitophagy. 

The worms’ mobility also improved with age and lengthened activity. In addition, urolithin A enhanced exercise capability in mice with age-related muscle decline [9].

Recent research indicates that urolithin A can play an integral role in enhancing muscles and extending activity – particularly important as muscles degenerate with age, exposing us to the risks of frailty.

Using urolithin A in human trials implies that a precise dose is mandatory. Amazentis presented Mitopure, a proprietary urolithin A supplement, including powder and soft-gel forms. Urolithin A improves mitochondrial and muscle function – while a metabolite, indicating that the body makes it from raw materials from fruits (mainly pomegranates). Yet, not everyone can create sufficient quantities of this antiaging molecule, and that’s where the supplement comes in. 

Much analysis into urolithin A has been done on the general population, but a recent study, specifically regarding aging, could also translate to elite athletes. A study on urolithin A presented at a sports medicine conference registered advancements in muscle function and VO2 max. Any endurance progress is the first to show beneficial outcomes in a healthy middle-aged population.

By bypassing the need for the correct microbiome flora, an easy and sufficient way to boost muscle recovery is available to everyone. A daily dose of Mitopure is comparable to drinking six glasses of pomegranate juice, all without worrying that you can convert it and the excess sugar.

Aside from being a supplement assisting elite athletes, aging is another factor that Mitopure is known to address. As aging is linked to associated decline in mitochondrial function, Mitopure can be applied in older populations.

An additional study in JAMA Network Open uncovered that the urolithin A supplement can aid with the improvement or prolonging of muscle activity in older people or those with conditions that make exercise difficult [10]. 

The study’s main objective was to determine if taking urolithin A orally improved the muscle endurance in hand and leg muscles during the six-minute walk distance, as well as biomarkers linked with mitochondrial and cellular health. The trials succeeded statistically, with two measures of enhanced muscle steadiness in the supplemented group, compared with a placebo group. 

Exercises concerning the hand and leg estimated muscle endurance, with researchers calculating the gain in the number of muscle contractions until fatigue settles in, between a baseline and the final test after four months. The main endpoint was a difference from baseline in the six-minute walk distance and a change from baseline to four months in maximal ATP production in the hand skeletal muscle.

The secondary endpoints were changes in muscle endurance of two skeletal muscles (tibialis anterior in the leg and first dorsal interosseus in the hand). Cellular health biomarkers were also studied through plasma metabolomics. Adverse events were documented and compared between the two groups during the intervention.

This randomised clinical trial saw that urolithin A supplementation was safe and well tolerated in the assessed population. Although the improvements in the six-minute walk distance and maximum ATP output in the hand muscle were not revealing in the urolithin A group vs the placebo group. Long-term urolithin A supplementation was restorative for muscle endurance and plasma biomarkers, proposing that urolithin A may prevent age-associated muscle decline. Even so, future work is needed to confirm this finding.

Considering that the gut microbiome naturally produces urolithin A, it is deemed safe to take every day for better cellular function and muscle strength. Mitopure has been considerably evaluated both pre-clinically and clinically to back its usage as a nutritional supplement. Furthermore, Mitopure has been agreeably reviewed by the FDA (US Food and Drug Administration) and considered safe, following a GRAS (generally recognised as safe) filing [11].

Are there any side effects? Urolithin A does not have any documantary adverse side effects – provided you choose from a high quality provider. There are many imposters selling supplements online, so be vigilant [12].

The Mitopure supplements hold 500mg of highly pure urolithin A, delivering six times the amount of urolithin A available from diet alone [13].

It is specifically effective as the exactly calculated dosage of Mitopure provides urolithin A and triggers mitophagy in the body whether or not considering individuals’ diet or microbiome. Designed to be taken daily, the supplement from Timeline Nutrition is available in powder and soft-gel forms, which can be mixed in your yogurt or smoothie of choice.

While the supplement is not meant to substitute a healthy diet or regular exercise, urolithin A supplements like Mitopure are a handy and reasonable way to boost mitochondrial health, muscular strength and energy in older people.

Previous work by the same scientists uncovered that urolithin A enhances muscle function mainly by increasing the activity of mitochondrial genes and stimulating mitophagy.

Although, there remains a potential that other modifications directed the improvements observed in the current study. Other biochemical aspects of the muscle and mitophagy were not measured in this study, so it can’t be plainly said that this is the mechanism driving the changes.

Asked why there was no revealing breakthrough in walking ability than with a placebo, the researchers noted a considerable placebo effect on this measure. This could make it challenging to detect a significant improvement.

“One potential reason we did not observe a significant effect of the treatment on the six-minute walk was that the placebo group also increased significantly above baseline”.

This increase in the placebo group could have been because of raised participant activity that was motivated by study inclusion.

In addition and looking into including other bodily functions, Lorrie Kirshenbaum, PhD, a professor from the Institute of Cardiovascular Sciences at the University of Manitoba in Canada, who studies the role of mitophagy in heart aging, mentioned that urolithin A could possibly protect the heart in addition to skeletal muscle [14]. “The article is interesting, and it does support a potential cardioprotective effect of urolithin A although the mechanism is not provided”.

The information included in this article is for informational purposes only. The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.

[1] https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00118-0 [2] https://www.sciencedirect.com/science/article/pii/S1471491421001180 [3] https://www.sciencedirect.com/science/article/pii/S1471491421001180#bb0065 [4] http://pdf.amazentis.com/pdf/Amazentis_Timeline_Launch_PR_7.27.2020_v9_Final.pdf [5] https://www.cdc.gov/physicalactivity/basics/adults/index.htm [6] https://www.livescience.com/what-is-gut-health-and-why-is-it-important [7] http://www.medicalnewstoday.com/articles/306437 [8] https://bit.ly/3Cu2Iry [9] https://www.nature.com/articles/nm.4132 [10] https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788244 [11] https://rb.gy/8hiump [12] https://www.nickengerer.org/longevity-and-wellness/urolithin-a-supplement-benefits-mitophagy-interview [13] http://pdf.amazentis.com/pdf/Amazentis_Timeline_Launch_PR_7.27.2020_v9_Final.pdf|[14] https://umanitoba.ca/faculties/health_sciences/medicine/research/mb_epigenetic/l_kirshenbaum.html