Longevity Blog Team 2/11/22 Longevity Blog Team 2/11/22

Mitopure Review - Does this Urolithin A supplement actually work?

Reviewing Mitopure Before and After - Urolithin A Supplement Self-Experiment

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We review the Urolithin A supplement Mitopure. We review Mitopure through our favourite approach - self-experimentation to answer - does Mitopure actually work?

Urolithin A supplementation is grabbing some serious attention in the longevity technology space. With its purported benefits in mitochondrial rejuvenation, it appears to be a promising intervention into the known age-related decay of mitochondrial health over time.

Beyond its proven positive impacts on mitochondria, Urolithin A is showing promise in reducing the incidence and intensity of several types of cancer, including prostate, pancreatic and colon cancers. It also appears to have powerful effects in healing the gut barrier and may help support a healthy immune system.

Urolithin A is a by-product of the digestion of ellagitannins, which are found in certain foods, including raspberries, walnuts and pomegranate. However, only 20% of people have the right gut flora to covert ellagitannins into urolithins (more on this shortly).

This is why there are likely many benefits to Urolithin A supplementation.

In this post we’ll review:

what is the best source of Urolithin A?
who makes Mitopure and is it legit?
how can you know if Mitopure will work for you?
our Founder Nick runs a self-experiment with Mitopure

The Best Urolithin A Supplement is Mitopure

If you’re interested in self-experimenting with Urolithin A, don’t go searching for “Urolithin A supplement Amazon” hoping for an alternative to Mitopure.

Mitopure is currently the *only* and *best* Urolithin A supplement available. Putting your hard earned cash anywhere else at this stage will only lead to disappointment, as our review of the alternatives has not found anything else worth mentioning (as of late 2022).

Why is this the case? Simply put - no other supplement is actually isolating Urolithin A. What you are getting instead are pomegranate extracts. However, if you do not have the correct gut flora, pomegranate extracts will not convert to Urolithin A in your digestive tract. That’s your hard-earned money wasted!

If another source of Urolithin A supplement becomes available, we’ll be sure to share it with you.

Over the course of the next few paragraphs, we’ll explain to you in additional detail why Mitopure is your best Urolithin A supplement option (and how to know if it will work for you).

Who Makes Mitopure?

First, if you would like to understand the history behind this Urolithin A supplement and its path to becoming a consumer product, you can check out our interview with Amazentis CMO Federico Luna. He details the decade long research effort that Amazentis put into dicovering and developing a Urolithin A supplement.

Who are Amazentis? They are a Swiss pharmaceutical company that was founded by scientists, doctors and entrepreneurs who wanted to create a new class of nutrition supported by the rigor of research you typically only find in biotechs that are solely developing drugs.

To bring Urolithin A to market, they founded Timeline Nutrition, who are the makers of Mitopure.

Is Mitopure Legitimate?

Yes! Mitopure is about as legitimate as it can possibly get in the supplementation space.

Timeline Nutrition was founded by a highly respected phamarceutical company that needs to be ensure its reputation is spotless. They then branded the Urolithin A supplement used in their research studies under the brand name “Mitopure”.

Now consumers have access to the exact formulation of Urolithin A which has been producing impressive results in clinical research studies and has proven safety and efficacy.

Furthermore, Amazentis are now putting millions of additional dollars into research efforts to study and better understand the impacts of Mitopure in humans, particularly in age related decline of muscle quality and into its benefits for sport performance (for example, their collaborative relationship with the American College of Sports Medicine).

You’d be hard pressed to find another longevity supplement with such a reputable background.

How much does Mitopure cost?

Mitopure Urolithin A supplement in sachet form. It is also available as a softgel.

You won’t find a better deal on Mitopure than through our 5% discount code (‘longevityblog’) and purchasing directly from Timeline Nutrition on a subscription. That’s the most cost effective way to get your own supply for self-experimentation.

In part two of our interview with Amazentis CMO Federico Luna, we worked with him to break down the costs of Urolithin A supplementation.

We found that Mitopure costs about 50-60% of what it would cost to get an equivalent amount of Urolithin A from pomegranate juice (you’d also have to drink 1.3L of it each day).

The cost of Mitopure is between $2.50 to $4.00 per day, dropping to $2.35 to $3.80 per day with our discount code ‘longevityblog’. The lower cost options are for longer term subscriptions (up to 12 month supply), which save you progressively more as you extend your supply.

We have found that 1-2 months supply is effective for testing before and after to see if Mitopure works for you (read on for those details).

Once you have decided on your volume of supply. You’ll of course want to be able to test and see - does Mitopure actually work? This is where Longevity Blog content really starts to shine! It is self-experiment time!

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Mitopure review - is it worth it? We self-experimented to find out

In this self-experimentation, as per usual we had our Founder Nick set off on a detailed self-experiment to test Mitopure before and after.

However, in a Longevity Blog first, we have also invited members of our readership to participate in self-experimentation as well!

In an upcoming post, we’ll also share the results from both a high performing amateur cyclist (Aaron) and an ironman triathlete (Claire). Be sure to subscribe to get notified when we post their results!

Starting Point: Do your gut flora produce Urolithin A?

The answer to this question is paramount. If you are one of the 20-30% of individuals who can produce Urolithin A from the ellagitannins in foods (pomegranate, walnuts, berries, etc), then you are much less likely to have a measurable response from supplementing Urolithin A.

Nick takes the “Mitopure Challenge” to see if he produces Urolithin A from Pomegranates

Nick undertook the ‘Mitopure Challenge’ to see if he was a natural producer of Urolithin A (no need to supplement) or if he would benefit from taking a Urolithin A supplement.

In this experiment, Nick drank 300ml (11oz) of fresh pomegranate juice and then gave a few drops of blood via finger prick the next morning.

On the following day, he took 500mg of Urolithin A supplement Mitopure and repeated the blood test process. This blood was sent back to Timeline where they analysed it to see the concentration of Urolithin A Glucuronide.

The result? Nick was not a producer of Urolithin A (at left in image). His gut flora did not produce Urolithin A after drinking pomegranate juice.

However, there was a significant increase in Urolithin A in his bloodstream after taking 500mg of Mitopure.

At left (zero), Nick’s Urolithin A Glucuronide levels after drinking 300ml of pomegranate juice (11oz). At right, after 500mg of Mitopure. This result shows that Nick was not naturally producing Urolithin A through his diet and that supplementing with Urolithin A would be likely to provide him with measurable benefit.

Measuring Urolithin A Supplement Benefits

As we look at the research into Urolithin A, most of the results thus far have focused on muscle strength as the primary measure of performance improvement. However, several studies are underway to look at Urolithin A benefits and safety in athletes.

While the results from these works have not yet been published, we can expect them quite soon. Naturally, given the exceptional role of mitochondria in athletic performance and the primary mechanism for Urolithin A’s health benefits being mitophagy, we can expect that athletic performance is an excellent data point for establishing the efficacy of Mitopure.

“What we’ve shown is Urolithin A acts on the mitophagy pathway... 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 ”

— Federico Luna, CMO at Amazentis

But not just any exercise - we need to look to specific types of exercise which are repeatable, well controlled and which place significant demand on mitochondria.

Given these requirements, Nick decided to use running interval workouts as his primary before and after data point.

This type of exercise is energetically demanding, repeatable and relatively well controlled (if we use the same workout).

It entails running at a very high intensity, where mitochondria are under very high demand for energy production.

If Urolithin A really does trigger mitophagy, then Nick’s older less functional mitochondria should be recycled into new more efficient mitochondria, and this should be observable as an improvement in his athletic performance.

In addition to running data collected from Nick’s Garmin Fenix 6 and HRM Pro (Chest-strap heart-rate monitor), Additionally, a detailed blood panel was collected using the i-Screen Sport Hormone Check (self-ordered blood tests available in Australia).

Mitopure Before and After Results

Nick’s training load from mid-June to mid-July. Relatively light and recovery focused.

The self-experiment begins as Nick enters the triathlon ‘off season’ where he is not running interval workouts. He travels to the United States for 6 weeks starting in mid-June 2022 and has only intermittent training opportunities; while he is consistent with training his volume/load is much lower (see image) than it was in the preceding 6 months.

Nick’s training load from mid-August to mid-September. It was gradually picking back up, but consisted mostly of ‘base training’ in August and did not train running intervals in August (leading up to the test date).

Nick begins Urolithin A supplementation at the start of July (training load remains low) at 500mg/day and returns to Australia and regular triathlon training at the start of August. At the end of August, he re-tests the VO2 max pyramid workout.

As his first proper interval workout in nearly three months his expectations were low. However, as he began the workout, he was very surprised by how he felt.

Let’s take a look at the data and let it do the talking.

Before - Interval Run

Data from Nick’s ‘Before’ running interval workout. Click to zoom. Blue is running speed and red is heart-rate.

The before and after running test are a VO2 max pyramid. This type of workout is structured such that you add one minute at your target pace for each interval.

There are 7 intervals. The first is 1-minute, the second is 2-minutes, then 3-minute, 4-minutes and then back down the pyramid (3min, 2min, 1min) each with two minutes of recovery in between.

There is also a warm-up with some 30 second ‘builds’ at the beginning where your work up to your target pace to get your body ready to perform.

In the ‘Before’ test, Nick had a target pace of 4:10-4:15/km, which he was able to hold for the first 3 intervals, but not for the fourth interval.

His heart-rate peaked at 187bpm (Nick’s maximum HR is 210bpm) on the third interval. Nick reported that he was unable to finish the full pyramid after failing to complete the fourth interval at pace. Simply put, he ran too fast and built up too much lactate and couldn’t hold the target pace.

After - Matched Interval Run

Data from Nick’s ‘After’ running workout. Click to zoom.

At the end of August, Nick completes the ‘After’ test, which is the same structure as the first.

This time he was able to complete the work out at the target pace of 4:10-4:15/km. Additionally, he did so at 5-7% lower heart-rate than in the ‘before’ test, running at 175-180bpm.

He also found he had to moderate his pace as he was running the intervals too quickly at the start (3:50/km pace).

This was due to a change in relative perceived effort (RPE) where faster speeds felt easier than they did previously.

There certainly appears to be a significant change in Nick’s performance. So let’s discuss.

Discussion: Does Mitopure Urolithin A Supplement Work?

Before we jump to any conclusions at Longevity Blog - we have a thorough discussion. Sure, the numbers appear convincing, but let’s make sure we consider the results carefully (and scientifically).

There are some potential confounding factors to consider in answering the question, did Urolithin A supplementation boost Nick’s athletic performance?

First - training. It would be expected that Nick’s ability to hold a given running pace would improve over time as he is training. Could he have simply gotten 5-7% faster from his off-season training?

As we mentioned already, Nick wasn’t running any interval workouts during the intervening period. In fact, he had much lower training load while he was travelling.

In run training, it is generally accepted that if you want to run faster, you have to train by… running faster. This is what running intervals are for, they allow you to accumulate training time at a faster pace so that you can hold that pace for longer.

Nick was not doing this. It is safe to say that training was not a factor.

Second - reduced training load; could it be a factor?

It is possible that the several weeks off provide Nick with ample recovery time and that he was able to re-engage the interval workout with ‘fresh legs’ and hence why he was able to perform so well.

However, Nick reports that his ability to run these interval workouts has been sustained as he picked back up his training load in September and October. As he has again become fatigued and picked his training load back up by 3-4x what is was in June, he can still run at this pace for his running interval workouts.

It does not appear that being ‘fresh’ and well rested is why Nick was able to run faster for longer in the ‘After’ workout.

Third - the one off nature of the analysis; Nick could have had a bad day in the ‘before’ workout and a ‘great day’ in the ‘after’. Was this the case?

Our response to the ‘second issue’ about re: training load addresses the latter. Nick’s performance gains have been sustained as he has continued with Urolithin A supplementation. In fact, he can now run 3:50/km intervals for 4-5 minutes at a time and is running a 20-minute 5km race time (that’s 4:00/km for 20 minutes).

As for the ‘before’ data having been a ‘bad day’ as a one off, we searched through the Strava and Garmin case files. We found two matched workout runs of Nick’s from before Mitopure supplementation. In each, we observed the same inability to hold the target pace across the whole workout.

Nick at the Byron Bay triathlon in May 2022. He loves the run leg… is Mitopure helping him improve his times? Evidence suggests - Yes!

Mitopure Review - Conclusion: Nick is running faster after Urolithin A supplementation

In our view, the data support a significant improvement in Nick’s interval run times after supplementing 500mg of Mitopure Urolithin A.

This improvement has not only been sustained, but Nick’s running times continue to quicken as he continues supplementing with Urolithin A.

Anecdotally, Nick reports lower heart-rate at equal pace on his easier runs as well. He has also seen a 20% improvement in his cycling FTP (functional threshold power), but none of these results have been well controlled or directly verified.

His fellow triathlon club teammates have also noted his rapid improvement!

Will Mitopure Work For You?

So, will Mitopure work for you? We can’t tell you the answer. There is only one way to find out! Run your own-self experiment!

Price Check Mitopure

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We have two Longevity Blog readers who are trying their own Mitopure self-experiment (Aaron and Claire). Will you join them? Let us know, you just might be featured in the next Longevity Blog post!

Until then, Live Long!

Urolithin A, Endurance, Muscle Strength and the Longevity Future - An Interview with Amazentis CMO Federico Luna (Pt 2)

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Urolithin A Supplement Benefits: Endurance and Muscle Strength

Studying the effectiveness and safety of Urolithin A in human subjects has led to some exciting results in muscular endurance, strength and power.

To date, the research efforts into these benefits have been led by Swiss bioscience company Amazentis, who now sell a Urolithin A supplement under their “Timeline” nutrition brand.

This product “Mitopure” is a high purity form of Urolithin A, which as we discussed in the previous post, has been shown to have excellent bioavailability a in clinical trial setting.

Amazentis has run three clinical trials (in humans) on Mitopure as of this interview (Q1 2021).

Perhaps the most notable findings in their clinical trials so far have been the impressive benefits in skeletal muscle.

These results are notable because they are potentially important one with respect to your longevity.

Aging is known to be associated with loss of muscle mass and power, which is driven by a multitude of factors - including confusion in important signalling pathways within the skeletal muscle due to dysfunctional mitochondria.

Urolithin A acts upon the dysfunctional mitochondria in skeletal muscle by triggering mitophagy - which is the process by which these dysfunctional mitochondria die off, and are replaced by new, healthy mitochondria.

For more on this, we’ll let Federico add to the details. Without further delay, we continue our interview with Amazentis CMO Federico Luna.

[If you’ve not read part one of this interview, you can find it here]

This interview was conducted on 30 March 2021, over Zoom and is an audio transcript with minor edits for clarity, brevity and correctness.

This is part two of a two part interview. Part one of this interview is available here.

Urolithin A and Muscular Endurance

Longevity Blog (LB):

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. Clearly. you haven't studied that yet, but surely you've been asked about it?

Federico Luna:

We're getting a lot of interest from the elite athlete population, as you can imagine. The fact that this is a natural molecule, the fact that it's safe, the fact that there's a growing body of scientific and clinical evidence - that's very exciting. Sports is an area that we're very interested in for sure.

Today we don't have any clinical studies in this specific population, but we do have some very interesting pre-clinical data in younger mice and also anecdotal feedback from athletes who have been taking Mitopure.

That's purely anecdotal at this stage. But we're very excited about the sports nutrition opportunity and athlete population, for sure.

LB: That really piqued our interest. 40%+ a quite a large improvement in endurance running from a supplement alone.

Thank you for commenting on that. We understand it's anecdotal at this stage, but it could make for some excellent self experimentation in athletes who are curious about the product.

On the topic of performance, let’s discuss the second clinical trial in more detaily. This trial looked at some very specific exercise tolerance metrics - cycling ergometer, handgrip strength, gait speed, lower body muscle strength - to name a few.

Urolithin A Benefits in Leg Muscle

What were the outcomes here? On the website that you refer specifically to hamstring strength as one area of improvement. Patrick Aebischer also mentioned there were some improvements in walking speed on the LLAMA podcast. Could you comment anymore on the outcomes for that clinical trial? How comprehensive were the improvements?

FL: I can only give you a ‘top line overview’. We’re seeing remarkable results on leg muscle strength, the hamstring, as you mentioned. We're seeing significant improvements, both vs baseline and also versus placebo. So, yeah, more to come on that study once it's published.

Leg muscle strength and power are crucial for maintaining independence in aged cohorts. Urolithin A benefits to leg strength are notable to longevity enthusiasts for this very reason.

LB: We'll plan to follow up with your team once that publication comes out. In a follow-up blog entry, so we can explore the details. Let’s talk about that third clinical trial you discussed. What is it exploring?

FL: You know, one of the big questions we often get from people as they start looking into reading about Urolithin A is - where do I get Urolithin A? How many pomegranates do I need to eat?

Up until the launch of Mitopure, there was no consumer product that offered people a pure form of the active.

Urolithin A Pomegranate Power

Sure, you could buy products containing pre-cursors like ellagic acid, pomegranate extract, or even pomegranate juice but you’ll never know how much Urolithin A you’re actually going to get.

What's remarkable about Urolithin A, is that it is an unusual molecule, it’s a metabolite, which means its not in the foods we eat but is produced by our gut after eating certain foods.

When you eat a pomegranate, it has a precursor compound, a family of compounds known as ellagitannins. After you eat the pomegranate, if you've got the right gut microflora , that bacteria then helps metabolize and create the bioactive Urolithin A.

The challenge, unfortunately, is that a lot of people don't have the right gut bacteria. And even if you do have the right bacteria, it's guesswork to figure out how much Urolithin A and whether you’re getting the right dose to reap the health benefits.

“if you’ve got the right gut microflora , that bacteria then helps metabolize and create the bioactive Urolithin A.

The challenge, unfortunately, is that a lot of people don’t have the right gut bacteria. ”

That's where Mitopure is really a breakthrough. There's a decade of work that's behind this - we've found a way to create and bypass the complexity of diet and the microbiome, by providing you a precise dose of the active.

LB: A decade of work but still easier than opening a pomegranate [joking]

FL: [Laughs]. Yeah. We've got a few tips we can share on how to open pomegranates, we've done a fair amount of pomegranate opening over the years.

Mitopure vs Pomegranate Juice for Urolithin A

Pomegranate juice can provide the building blocks of Urolithin A, but the correct gut bacteria are necessary to produce Urolithin A.

LB: The first clinical trial and publication had some excellent graphics exploring various Mitopure dosing strategies, and the resultant blood serum levels.

Have you explored Mitopure versus pomegranate juice in individuals with the correct gut bacteria?

FL: In our next [third] clinical study that we're going to be publishing, it really dives deep into the microbiome and that side-by-side comparison.

It compares the pure form of Urolithin A that Mitopure delivers into the bloodstream versus natural dietary sources, in this case a glass of pomegranate juice.

We took 100% pomegranate juice and did a crossover study with 100 people in Chicago. We compared over a 24 hour period the area under the curve to see total exposure to Urolithin A from natural dietary sources versus Mitopure. The comparison is remarkable.

There's really interesting data coming out in terms of how many people at baseline have Urolithin A in their system, as you can imagine, that's very low. The second data point is - how many people can actually naturally produce Urolithin A from pomegranate juice? That's also low.

The last question is, okay, even of those who can produce Urolithin A, what is the difference? How much do you get from Mitopure, versus how much do you get from a glass of pomegranate juice. We see a six fold higher levels of Urolithin A with Mitopure over a 24 hour period versus pomegranate juice.

LB: So this third clinical trial - it sounds like you're in the data analysis stage, it is completed and you're preparing results?

FL: Correct. We're preparing to publish them.

LB: Do you have an indication on when the preprints for those publications might be showing up? Is that something we could expect in 2021?

FL: Hopefully. The target is to get these published in 2021.

Is Urolithin A from Mitopure Too Expensive?

LB: Great, we’ll be sure to follow up on that. Let’s talk about the Mitopure product. One of the most common objections we’ve read, in our background research for this interview is cost.

People often balk at the price. That is understandable, as it's a relatively expensive supplement at $100 a month. Help us understand that price point.

There's 10 years of work that have gone into this. Amazentis has pioneered this work, but let’s go a bit further into why that number is something that's defensible. Why should a reader invest their budget in Mitopure?

FL: Coming back to the comparison I gave you around pomegranate juice - you know, one glass of pomegranate juice, [Mitopure] is not priced anywhere near to 6x the price of a pomegranate juice. In fact, we're very reasonably priced, if you make that comparison.

Comparing Mitopure vs Pomegranate Juice Cost

We did the comparison, based on Australian prices. $4 for a pomegranate or $6 for 1L of 100% pomegranate juice (from concentrate).

One pomegranate will yield about 150ml of juice. That's 6.6 pomegranates for a 1L at a price of $26.

$26 for 1L of juice is a significant premium ($20) on buying a ‘from concentrate’ source, but likely to be more potent, and is what the ‘6x more effective’ figure is based on, so we need to use ‘fresh’ for a like-for-like comparison.

Our base unit is the 500mg dose of of Urolithin A (the standard Mitopure dosage) versus drinking 8 ounces of pomegranate juice (225ml).

225ml of fresh pomegranate juice would cost $5.85AUD. Multiply that by 6 for a whopping $35 worth of fresh pomegranate juice, not to mention the 1.3L you’d have to drink to get the same Urolithin A benefits (with the right gut flora, of course).

Even with the discount on the ‘'from concentrate’ option at 1.3L, you’d still be paying $7.80AUD.

Mitopure 500mg sachet works out to be $4.30AUD without the subscription discounts.

The takeaway: Federico is right on the maths. if you’re after Urolithin A benefits, Mitopure is a good deal and you’ll have fewer trips to the restroom each day ;)

Is Mitopure too expensive? Not according to the math

FL (cont.): The $100, for some people, we can understand that that's a sticker shock. On the other hand, if you break it down per dose, you're looking at a price of $3.33[USD] per dose. We do actually offer an [annual] plan, which is selling extremely well, where people get a discount - a per dose price of $2.87[USD].

Make the math even better - use the code ‘longevityblog’ to save 5%!

Save 5% on Mitopure

When compared to your alternative, which is, I would say at best a blind gamble with pomegranate juice - here you have a product that can deliver six times more at a relatively small premium.

Obviously, we're hoping over time, as more and more people start benefiting from Mitopure, that as our volumes increase - we'll be able to reduce cost and offer people an even better price.

LB: We will do that calculation to pomegranate juice, for the benefit of the readers just check that out.

One of the things that is often valuable in this case, are customer testimonials. You earlier mentioned you're getting some positive feedback. How does someone know that their investment in Mitopure is working for them? What feedback do you hear?

Urolithin A Benefits: What customers are saying about Mitopure

FL: I can't share details just yet what those testimonials are. What I can tell you is - we're getting great feedback. Biology is very personal, there is no average patient in a clinical study, as they say.

As you’d expect a few people are saying it's either too early to tell or some people don't necessarily feel a measurable difference. The majority however are giving us remarkable feedback.

We’re hearing from a variety of age groups - people as young as 30, all the way to people in their 80s talking about benefits in terms of energy and strength. Those are sort of the two primary areas where we're getting positive feedback.

We're working on taking all these great testimonials and making them available - because we do get that question a lot.

LB: Thanks for sharing that. We understand that individual biology is complicated. Everybody is their own self experiment. That's actually one of the things that Longevity Blog focuses on - helping people learn to take one thing at a time and measure meaningfully whether or not it's benefiting them.

Urolithin A and Mitopure: What’s Next?

Amazentis CMO Federico Luna - with a pomegranate, of course!

So energy and strength - that feedback matches with the research. There's also been other complimentary research on Urolithin A. Particularly around helping the gut barrier heal in cases of ulcerative colitis or irritable bowel syndrome.

Others have focused on neurodegenerative disease and also found a role for Urolithin A in triggering of autophagy. That work by Julie Anderson's group at the Buck Institute.

How do you feel the work of Amazentis has helped to ‘move the needle’, so to speak, in terms of the interest in Urolithin A more broadly?

Do you expect that the research in this area will be maturing quite quickly over the next few years?

Urolithin A science is moving quickly

FL: We've seen tremendous excitement from the scientific community. Again, if you look at PubMed as a source, typing ‘Urolithin A’ into PubMed - you'll see there's been an explosion of preclinical research over the past 10 years.

You mentioned the Buck. Its a remarkable research institution and Julie Anderson's lab is doing groundbreaking work on Urolithin A and Alzheimer's. There are a number of other leading researchers around the world pioneering new potential applications for Urolithin A. Interest is really growing.

The fact that Amazentis’ pioneered the first translation of the science into humans - I think that gives researchers the confidence. It’s been shown to do something in worms, it's something that's been shown to do something in mice.

Now there's very promising data in humans. We think that will catapult Urolithin A research over the next few years. We like to think of Urolithin A as sort of the ‘next omega 3’ and while there is a strong body of evidence already today, there’s much more to come.

LB: That's a fascinating answer. We're coming up on the end of our time here. So let's try to draw it to a close, by thinking about where this particular supplement (Mitopure) and the Timeline Nutrition brand are going to fit in the personal longevity strategies for people moving forward.

This particularly supplement seems to be filling a niche around loss of muscle mass and power as we age, as well a loss of energy as we age. Coming back to your company mission, your ‘science first’ approach, at Amazentis - where do you see Amazentis contributing to improving our healthspans over time?

The Amazentis & Timeline Mission

“It’s a really exciting time for longevity. It’s a really exciting time for muscle health. And we’re just at the beginning”

— Federico Luna, Amazentis CMO

FL: Our mission is to optimize cellular health and help people live healthier lives for longer. As we talk to people, and take them through the science, particularly around muscle, people are surprised at how early our muscle health actually peaks.

There isn't an exact number, it varies from person to person, but we've seen studies that show muscle starts to peak in our 30s or 40s.

One of the big challenges in health is getting people to invest in prevention, because while we all like the sound of prevention, when it comes down to it - are you willing to invest in your health?

What's really exciting is we're seeing more and more people say - “Yes, I want to invest in my health, and I want to invest now”. So that I don't have to try to cure later on in life. That growing buy into prevention coupled with the data we have that shows that Mitopure can have in impact on your muscle health in 2-4 months is a great match.

It's a really exciting time for longevity. It's a really exciting time for muscle health. And we're just at the beginning. And, the fact that we've got the first and only clinically tested, pure form of Urolithin A, and we're offering that direct to consumers, through the Timeline brand and also through a great partnership with Nestle Health Science - arguably one of the leading global players in science driven nutrition is the perfect combo. We think this is just the beginning of a really exciting portfolio of products and innovations and things to come on Urolithin A.

LB: Fantastic. We look forward to staying in touch with you on that future vision, Federico. Particularly we look forward to those upcoming clinical trial results, as well as how you'll be expanding your partnerships and improving access to the forthcoming healthspan boosting technologies in the pipeline. It's exciting stuff. Thanks for speaking with us today.

FL: A pleasure! Thank you.

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Urolithin A Supplement - Benefits, Side Effects, Healthy Mitochondria

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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.

Longevity Blog (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

LB: 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

LB: 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.

LB: 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.

LB: 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. — 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.

LB: 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.

LB: 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

We’ve negotiated a discount on Timeline Nutrition’s Urolithin A supplement “Mitopure” for our readers.

Use the code ‘longevityblog’ at the Timeline Nutrition website to save 5% on any order

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