Metabolic Health and Longevity
“Urolithin A” Supplementation Might Improve Mitochondrial Health, Muscle Strength, and Longevity.
I provide my independent perspectives on urolithins based on a literature review and the results of recent clinical trials.
Purpose of the Article
This article introduces the potential use of urolithins as a supplement for older adults and provides key findings from scientific studies in a summary format.
My investigation into “urolithin A” supplementation for mitochondrial health in older adults has produced promising results.
The inspiration for this piece came from readers of my recent article titled Here’s How I Initiate Mitophagy and Make My Mitochondria Denser in 7 Steps. The article’s premise is that activating the mitochondria’s self-healing mechanism can produce more energy and a better mood.
Some readers wanted to learn about the benefits of “urolithin A” supplementation for mitochondrial health.
As I have been investigating the potential health benefits of urolithins and watching this specific product for a while, I decided to create a short article summarizing my findings and independent perspectives neutrally.
This article is not health advice and not a recommendation for this supplement. Instead, it is for the information and awareness of my readers.
Importance of Mitochondrial Health
I have been focusing on cellular and mitochondrial health for decades due to its importance to our healthspan and lifespan. I recently posted an article summarising my findings and perspectives about mitochondrial health titled Here’s How I Initiate Mitophagy and Make My Mitochondria Denser in 7 Steps.
Related to cellular health, I also wrote about autophagy and documented my experience in an article titled Here Is What Happened When I Experimentally Initiated Autophagy Decades Ago.
The bottom line is our cells cannot survive and thrive without energy. Thus, mitochondria play a critical role in our energy metabolism in every cell, affecting our overall health and well-being.
Despite their small sizes, these organelles play a critical role in our cellular health. For example, they can trigger metabolic reprogramming of the cell.
Mitochondria are tiny organelles converting electrons from food to ATP molecules for energy. In addition, they can turn genes on and off, making epigenetic effects, good or bad.
Due to their vital roles in the body, dysfunction of mitochondria and mitochondrial DNA cause health conditions impacting the body’s homeostasis. The critical point is that damaged mitochondria can lead to metabolic and mental health disorders.
For example, as informed in this paper, “Mitochondrial dysfunction contributes to a wide spectrum of age-related diseases, including neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease.”
There are many threats to mitochondrial health. The most critical ones are toxins, pathogens, and damaged proteins in the body. Therefore autophagy and mitophagy are self-healing mechanisms of the body that I keep highlighting in my health articles.
What are urolithins, and why might supplementation be needed for some people?
Urolithins are organic compounds. They are metabolites of ellagitannins. Ellagitannins are bioactive polyphenols found in fruits and nuts. For example, they exist in strawberries, blueberries, raspberries, pomegranates, almonds, and walnuts.
Urolithins do not exist in food as an organic compound. They are derived from gut microbial action on food with ellagitannins and ellagic acid.
They are transformed from the digestion process. More specifically, our gut microflora from foods rich in ellagitannins can produce urolithins. Specific bacteria in the gut can convert ellagitannins into urolithins.
Even though gut bacteria can create urolithins, not everyone has these specific bacteria in their gut flora. So in the absence of bacteria, even some people who consume lots of ellagitannins cannot produce urolithins and are unable to convert them.
In addition, manufacturers claim that one needs to take many glasses of juice from ellagitannin, including fruits such as pomegranate. Too much sugar in fruit is a genuine concern for metabolic health. Thus, they believe that supplementation is a better way of benefiting from urolithins for mitochondrial health.
Therefore, supplementation is seen as necessary for those who want to benefit from this organic compound, especially those who suffer from mitochondrial dysfunction. Studies show compelling benefits that I will cover in the next section.
There are various types of urolithins. The most frequently mentioned ones in the literature are “Urolithin A”, “Isourolithin A”, “Urolithin B”, and “Phase II Conjugates”. All these molecules are bioavailable. They can reach the bloodstream and can be excreted via urine.
I only focus on “urolithin A” supplementation in the following section.
Indicative Benefits of Urolithins from Literature
I came across theoretical research studies on urolithins in the early 2000s. So, research into these molecules has been intense in the last two decades. However, experimental studies just started a few years ago. And they look promising to scientists.
Recent studies show that urolithins stimulate mitochondria, especially in muscle cells. These findings were initially obtained from studies on worms and mice. Let me provide a summary of what I learned from preliminary studies.
In worms, “urolithin A” supplementation depicted around a 50% increase in their lifespan upon consumption of urolithin-containing nutrition.
Mice started running 40% faster and longer. In addition, after keeping them on urolithin containing diet, especially older and metabolically damaged mice started building new muscles.
Later, scientists tried on humans for a short period of time, observing biomarkers by taking biopsies. At the end of a few weeks, they noticed mitochondrial gene expressions.
Damaged mitochondrial clearance and renewing them with new ones during the process are frequently mentioned. During this process, our energy levels drop. But in a few days, we can get an increase in energy.
A Summary of Recent Findings from Credible Sources
In addition to many commercial papers, around 775 medical reports on urolithins are indexed on PubMed. It is not feasible to cover the details from those reports. Therefore, I introduce a few critical studies to give an idea of this specific molecule (urolithin A) and depict its progress. Most of the papers repeat the findings in the below summary.
Alzheimer’s Drug Discovery Foundation (ADDF), reviewing urolithin, reports that “the autophagy and mitophagy effects of Urolithin A make it a promising longevity molecule.”
The ADDF report mentioned that “In a phase 1 study in elderly adults, 28-day consumption of Urolithin A (250–2000mg/day) upregulated autophagy, improved mitochondrial function, and improved fatty acid oxidation in human skeletal muscles (from Amazentis conference presentation).”
However, ADDF reports highlight that “long-term safety for supplementation of Urolithin A and pomegranate is not known, though short-term treatment with pomegranate extract is safe.”
As Nature is a credible resource, I’d like to reflect on the findings from a 2021 paper titled “Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population.”
The study investigated the prevalence of urolithin producers in a healthy population and the ability of direct urolithin supplementation to overcome both microbiome and dietary variability. Researchers used a glass of pomegranate juice for assessment. Their goal was to “characterize differences in gut microbiome between Urolithin A producers from non-producers.”
So the study published in Nature concluded that “Differences in gut microbiome and diet that dictate natural exposure to urolithin can be overcome via direct dietary urolithin supplementation.”
The first clinical trial I read about was in 2019. As reported in this source, a private company (Amazentis) developed the supplement for clinical trials. The trial indicated that administration of “Urolithin A” leads to improved mitochondrial function by stimulating mitophagy.
Earlier this year, I came across a report of a randomized clinical trial using 66 participants on JAMA Network’s Nutrition, Obesity, and Exercise. The paper is titled “Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.”
This randomized clinical trial found that:
“Urolithin supplementation was safe and well tolerated in the assessed population. Although the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not significant in the urolithin group vs. the placebo group, long-term urolithin supplementation was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin may counteract age-associated muscle decline; however, future work is needed to confirm this finding.”
Last May, I came across a paper on Cell reporting another clinical study. The paper is titled” Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.”
The Cell paper reports the following four benefits:
“1 — Oral supplementation with Urolithin A increases muscle strength
2 — High dose of Urolithin A positively impacts exercise performance measures
3 — An increase in mitophagy proteins in human skeletal muscle observed in parallel
4 — Supplementation is safe and increases circulating levels of Urolithin A.”
The paper is publicly available as a PDF document at this link.
Apart from counteracting age-associated muscle decline, urolithins are also being investigated for potential contribution to nitric oxide production (an important molecule for cardiovascular health), as I introduced in an article titled Three Tips to Boost Nitric Oxide and Lower Heart Disease/Stroke Risks.
Interested readers might check this 2016 paper on MDPI titled “Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells.”
I also found research into the benefits of urolithins in handling diabetes. My favorite review paper citing 143 reports published on MDPI titled “Urolithins: Diet-Derived Bioavailable Metabolites to Tackle Diabetes” can be freely accessed via PubMed.
Conclusions and Takeaways.
I am an open-minded and optimistic scientist. However, I am also a diligent consumer who is extremely cautious about using supplements for health improvement or performance.
For example, I don’t use supplements without long-term investigation supported by multiple clinical studies proving efficacy and safety. In addition, I always triangulate my findings with other users and get guidance from qualified/trusted healthcare professionals.
I do not use this specific supplement yet. However, some biohacker friends took the plunge and used it in powder format ordering from overseas, mainly in European countries like Switzerland. My friends mentioned that capsules are not available yet, so they need to use powder supplements.
So far, their anecdotal feedback is also positive. The key points are an increase in their energy, improvement in stamina, and better muscular profile.
However, some scientists are extra cautious about supplements related to gut flora as the science knows very little about it. Besides, research into the microbiome is highly murky. As an avid researcher, I cannot even make sense of microbiome research with conflicting results depending on the worldview of scientists.
The second caution is that plant molecules such as from pomegranate fruit, including intense polyphenols, might pose risks if used excessively.
Even though I admire the progress and am inspired by the findings so far, I don’t personally consider supplementing with urolithins yet. I am satisfied with numerous proven supplements such as CoQ10, N-Acetyl-Cysteine, and Acetyl-L-Carnitine for cellular and mitochondrial health. I plan to write about my experience with PQQ soon.
However, my opinions and personal choices should not influence readers’ desires and informed choices after reviewing research and discussing the implications with their qualified healthcare professionals.
My focus is on health improvement, not on supplements. I see supplements as only tools for nutrients that we cannot get from foods. There are, of course, use cases for proven supplements.
Furthermore, it is essential to note that any supplement we ingest into our body will have a good, neutral, or harmful effect. There are many variables, from genetics to lifestyle choices. Without consideration of all factors, we might face risky situations.
Therefore, we need to make a systematic risk assessment based on findings from credible sources and guiding help from professionals who have access to our medical history. Some supplements might interfere with some health conditions and medication.
Thank you for reading my perspectives. I wish you a healthy and happy life.
As a new reader, please check my holistic health and well-being stories reflecting my reviews, observations, and decades of experiments optimizing my hormones and neurotransmitters. I write about health as it matters. I believe health is all about homeostasis.
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Lutein/Zeaxanthin, Phosphatidylserine, Boron, Urolithin, taurine, citrulline malate, biotin, lithium orotate, alpha-lipoic acid, n-acetyl-cysteine, acetyl-l-carnitine, CoQ10, PQQ, NADH, TMG, creatine, choline, digestive enzymes, magnesium, zinc, hydrolyzed collagen, nootropics, pure nicotine, activated charcoal, Vitamin B12, Vitamin B1, Vitamin D, Vitamin K2, Omega-3 Fatty Acids, N-Acetyl L-Tyrosine, and other nutrients.
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