Urolithin A Supplement - Benefits, side effects, healthy Mitochondria
Urolithin A supplement benefits
In this post we’ll cover:
The top benefits of Urolithin A supplementation
What is Urolithin A and is it safe?
Urolithin A supplement Mitopure
Interview with topic expert Federico Luna of Amazentis, including
Urolithin A clinical trials
Mitophagy and improved mitochondrial function
Urolithin A in the body
Urolithin A is certainly turning some heads in the longevity & wellness biohacking community, owing to an unusually wide array of purported benefits. Chief amongst them - improving mitochondrial health.
Urolithin A (UA) is a new longevity supplement with excellent results in placebo controlled human clinical trials. In this post, we’ll learn about what it is, its benefits, side effects and where to get it + save 5% off the best available option. we’ll also hear from an expert on the latest science.
Urolithin A benefits
Urolithin A supplement benefits video with our Founder Nick.
UA and gut health
UA has shown remarkable benefits in the digestive track, with an apparent ability to heal the all-important and notably fragile, gut-barrier.
Currently being explored in non-human studies, Urolithin A appears to offer notable levels of improvement for irritable bowel syndrome and Crohn’s disease. These benefits also appear to extend to colon cancer.
Improvement to the gut microbiome and gut bacteria requires a strong gut-barrier and is linked to many positive health benefits. Therefore, it seems UA is clearly quite good for your gut!
Read the Nature Communications article on Urolithin A benefits in the gut here
UA cleans up metabolism
Urolithin A (and B) appear to possess anti-glycative properties, meaning they can help prevent the accumulation of advanced glycation end-products or AGEs which leading to age-related complications such as the loss of flexibility in tissues with age.
Similar mechanisms may also link Urolithin A benefits to neurodegenerative disease, currently being researched in the (Julie) Anderson lab at the Buck Institute.
UA and muscle strength
Perhaps the most interesting benefits are observed in mitochondrial health and skeletal muscle, which have recently been discovered in randomized double blind placebo controlled clinical trials through research led by Amazentis (2019 to present).
In our upcoming interview, we’ll focusing specifically on the ability of Urolithin A to improve mitochondrial function and restore healthy mitochondria in the skeletal muscle.
But first, what is Urolithin A exactly?
What is Urolithin A?
Given Urolithin A is demonstrating extraordinary promise in a few key areas of age-related disease, it’s natural to be curious about what it is and where it comes from.
Urolithins are a by-product of the digestion of ellagitannins, which are found in certain foods, including raspberries, walnuts and pomegranate, which also include the polyphenol ellagic acid.
Before you jump toward filling up the shopping trolley with pomegranate juice, note that urolithins are only produced by certain types of gut flora, who participate in the digestion of ellagitannins.
Only 20-30% of people are thought to have the right gut microbiome to complete this conversion, and the ability to produce urolithins in the bloodstream. They naturally have UA levels several times higher than those who do not have these gut flora (who may have no UA in their bloodstream at all!).
 |
We’ve completed a thorough Urolithin A supplement review, including a self-experiment guide to see if Urolithin A supplementation will work for you! Read it here.
Is Urolithin A safe? Urolithin A side effects?
The inability of most people to produce Urolithin A has given rise to the first Urolithin A supplementation options.
Notably, using Urolithin A as a dietary supplement has achieved GRAS status from the US FDA (2018), meaning it is ‘Generally Recognised as Safe’ for human consumption in the proscribed range of 250 mg to 1000mg per dose.
Urolithin A does not have any documented adverse side effects - provided you choose from a high quality provider. As per usual, many imposters exist on eBay and Amazon - buyer beware! (We write more about this issue here)
The best Urolithin A supplement
‘Mitopure’ is a Urolithin A supplement, and the focus of our interview content in this post.
Studying the effectiveness and safety of Urolithin A in human subjects, is what leads us into our interview subject - Swiss bioscience company Amazentis and their recently launched (2019) “Timeline” nutrition brand.
Their mainstay product “Mitopure”, is a Urolithin A supplement, brought to market in the culmination of more than ten years of scientific work, including capstone clinical trials in human subjects.
The Timeline brand’s ‘Mitopure’ is a high purity form of Urolithin A with excellent bioavailability (proven in clinical trials which we will discuss shortly), demonstrated to show up in the blood supply after supplementation.
Urolithin A in humans
Amazentis’ growing number of clinical trials in humans has demonstrated Urolithin A to function as a catalyst for mitophagy, which is the orderly death of dysfunctional mitochondria.
This has been demonstrated to be specifically helpful in skeletal muscle, which accumulates an increased number of dysfunctional mitochondria as we age.
These benefits look to be a welcome ally in the struggle against loss of muscle mass and power with age, and there is early evidence Urolithin A supplementation is particularly effective for this purpose in leg muscle.
To dive deeper into these fascinating and promising results we completed a detailed interview with Amazentis Chief Marketing Officer Federico Luna, to get into the nitty gritty details and enable our readers to make an informed decision on whether or not to self-experiment with Urolithin A.
This interview was conducted on 30 March 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.
A Longer Life (LB):
Federico, thank you for joining us today. To start out, let’s discuss the central values of your venture. Timeline refers to itself as a “science-first nutrition brand”, explain what this means, and how it might differentiate you from other companies which sell dietary supplements?
Federico Luna (FL):
Our interview guest, Federico Luna, Chief Marketing Officer at Amazentis + our subject matter pomegranate!
Great question. There's a lot of brands out there that call themselves science driven. We thought hard about how we are different to that.
It's difficult in a world where perception is everything, and anyone can put a couple of words on a website, and consumers interpret that as sort of very high science.
‘Science first’ means a couple of very concrete things.
Unlike many nutrition companies, Amazentis was founded by leading scientists, doctors and entrepreneurs in the life sciences who wanted to create a new class of nutrition supported by the rigor of research you typically only find in biotechs that are developing drugs.
The company invested over a decade into research before commercializing its first product, Mitopure (the first clinically tested pure form of Urolithin A). Our primary focus for all these years has been to pioneer the pre-clinical and clinical trials with this novel molecule, Urolithin A.
We started with preclinical trials, using tiny little worms called C. elegans, and showed that these worms were living close to 40-45% longer after taking your Urolithin-A compared to placebo. We then took it into mice, and started learning more about the running endurance and muscle health potential benefits.
And now we’re translating this science into humans. In the last five years, we've run multiple human clinical trials. This approach is what we mean when we say ‘science first’. You do the rigorous science first, and only then go to market.
Amazentis - Pioneers and experts on Urolithin A
ALL: It sounds like what we are hearing from you, is that Amazentis has been leading in this research area, since the beginning. We might have to consider Amazentis to really be the authority on Urolithin A? Would you agree with that statement?
FL: Many researchers around the world are doing interesting studies with Urolithin A. And in the last 10 years alone, if you go to pubmed.org, you'll find over 100, preclinical studies, exploring the benefits of Urolithin A.
Not only for muscle, but also for brain and other very important organs. But Amazentis is the first and only company that has taken Urolithin A into the clinic with very rigorous double blind placebo controlled trials.
Urolithin A clinical trials
ALL: To date there have been two clinical trials in humans, is that correct?
FL: There's actually been three. One with published results in Nature Metabolism.
The purpose of this first trial was a couple of things. First and foremost, was to establish safety. So that was the primary endpoint. But what was fascinating and remarkable is we also started looking at the impact of Urolithin A on mitochondrial function, and more specifically on gene expression.
ALL: Let's talk a little bit about that first trial and follow-up publication. One of the most notable things about the study was the proof of the bioavailability of Mitopure. It demonstrated that Urolithin A is getting into the bloodstream and spreading throughout the rest of the body.
Help our readers understand - why is this such an important and significant finding? Can you walk us through what that means in terms of the downstream effects?
Mitopure supplementation at 250mg, 500mg and 1000mg in human subjects, with the concentrations of Urolithin A and its metabolites (UA glucuronide, UA sulphate) in the blood.
FL: One of the key outcomes of this study was a characterization of the pharmacokinetic profile of Urolithin A in humans. We wanted to understand the absorption, bioavailability, distribution and excretion of different doses of UA.
We found that UA was bioavailable in plasma at all doses tested, which is indicative of its potential to have a systemic impact and it also gave us insight into the right dosing to take into subsequent clinical trials.
If you think about mitochondria, these little energy factories inside of most of our cells – in the brain, in our muscle, our eyes, our liver, in a number of key organs - by looking at the bloodstream, we're gaining more insight on how Urolithin A could act on the mitochondria, across all these other potential organs.
“We found that Urolithin A was bioavailable in plasma at all doses (of Mitopure) tested, which is indicative of its potential to have a systemic impact”
The second thing we did is look at the muscle specifically. We wanted to understand if the molecule can actually make it into specific muscle tissues. That's very important for the molecule to have a local effect.
ALL: One interesting aspect about that publication was in the concluding remarks, where the effects were described to ‘resemble a regular exercise regimen’. While we don't quite have that elusive ‘exercise in the pill’ solution yet, it does seem that Mitopure may be conveying many of the benefits of exercise.
How can your Urolithin A supplement benefit sedentary folks and folks who are perhaps a bit older and losing muscle strength and power?
Urolithin A restores healthy mitochondrial function
FL: If you think about the mechanism of action here, what we've shown is Urolithin A acts on the mitochondria. Even more specifically, it acts on the mitophagy pathway. In short, mitophagy is a natural cleansing and renewal process whereby damaged and inefficient mitochondria are identified and cleared away.
This makes room for new healthy mitochondria, a process known as [mitochondrial] biogenesis to kick in and help create and rejuvenate the mitochondria.
This mitophagy pathway is really a breakthrough scientific discovery. A lot of that work was led by Professor Johan Auwerx, here at [Laboratory for Integrated and Systems Physiology at École Polytechnique Fédérale].
Love podcasts? Live Long and Master Aging is one of the best in the longevity field. Listen to an interview about Urolithin A with Chairman of Amazentis’ Scientific Advisory Board Patrick Aebischer.
As you look at mitophagy and inducers of mitophagy, exercise is a one, another key one is caloric restriction.
We don't see Mitopure as a substitute or replacement, but as complimentary to physical exercise and caloric restriction.
ALL: Patrick Aebischer (Chairman of the Amazentis Scientific Advisory Board) said previously on a podcast in 2020, that Mitopure was the only known compound capable of simulating mitophagy. Do you still know if that's still believed to be the case?
Mitopure: The best Urolithin A supplement?
FL: This is a rapidly evolving space and there's a lot of ongoing scientific research. So I can't comment in absolute terms. What we do know is Mitopure is the only mitophagy inducer that has been taken into the clinic and has been shown to improve mitochondrial function and muscle strength in humans.
ALL: On the topic of mitophagy and muscle tissue, let’s come back around to this 40%+ improvement in running endurance in mice, as compared to untreated peers of the same age.
It naturally starts a conversation around whether Mitopure could improve athletic performance…
Want to learn more? Read Part 2 of our Interview Here
You can also check-out our Urolithin A supplement review and self-experiment guide here
FDA & TGA DISCLAIMER
This information is intended for educational purposes only and is not meant to substitute for medical care or to prescribe treatment for any specific health condition. These blog posts are not intended to diagnose, treat, cure or prevent any disease, and only may become actionable through consultation with a medical professional.
