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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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