106 replies to this topic

[Harkijn]

Urolithin A said: 

 

 As you know, Mitopure acts on an essential anti-aging pathway called mitophagy which promotes the selective recycling of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. This further promotes replenishing the cell with healthy mitochondria through a process known as mitochondrial biogenesis. This is different to many other mitochondrial supplements, such as CoQ10, which is as a co-factor in the electron-transport chain, or Nicotinamide Riboside (NR), which is primarily acting on mitochondrial biogenesis via the NAD pathway (https://www.nature.c...2255-019-0161-5).  

 

 

 

Understandably Mitopure is very careful about what they claim. However in the podcast linked above (thanks for that , Albedo!) dr. Auwerx briefly hypothesizes (not more than that) about taking a stint of Mitopure to clear up dysfunctional mitochondria and then following up with NR to boost mitochondrial biogenesis. Once Mitopure becomes available/affordable in EU I will try an approach based on his idea.

 

 

 

[motorcitykid]

Thank you for your follow up request and concerns. I am sorry that our response was not what you are looking for. As a company founded and run by scientists and doctors, we value scientific responsibility and can only provide recommendations that are evidence backed. We cannot take a “stab at it” and provide informal hypotheses on what interactions may or may not happen when taking Mitopure with other mitochondrial targeted supplements as we have not conducted those types of interventional trials in humans. Our focus has been on understanding the isolated effects that Mitopure has on essential biomarkers of mitochondrial health and physiological endpoints such as muscle strength. As you know, Mitopure acts on an essential anti-aging pathway called mitophagy which promotes the selective recycling of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. This further promotes replenishing the cell with healthy mitochondria through a process known as mitochondrial biogenesis. This is different to many other mitochondrial supplements, such as CoQ10, which is as a co-factor in the electron-transport chain, or Nicotinamide Riboside (NR), which is primarily acting on mitochondrial biogenesis via the NAD pathway (https://www.nature.c...2255-019-0161-5).  

 

Taking a supplement can have different effects from one person to another, let alone taking multiple supplements. In regards to the other supplements that you have mentioned and currently take, we are well aware of them but have not studied them with Mitopure in clinical trial settings. In fact, one of the commonly used exclusion criteria in our studies is that participants do not take these any other supplements similar to ones that you mentioned that could possibly impact study endpoints focused on muscle and mitochondrial health that are used in our studies. Since we do not have any studies or data on combinations, we cannot provide the specific answer you are looking for with regards to co-administering with other supplements. The science around Mitopure is rigorous but still emerging. We know that the absorption of Mitopure is similar when taken with or without food (for e.g. in a high-protein matrix) and that the levels peak in circulation within the first 6 hours from intake and is eliminated in approximately a day (Nat. Metab 2019).

 

We proactively engage in forums like Longecity to gather insights on how our clinical trials translate into the real world and welcome your questions and feedback. We work diligently to provide as much insight and guidance so that you get the most out of Mitopure based on the research we have. N=1 experiments have many pitfalls but if you would like to isolate the effect of the different supplements you are taking we are open to hearing about your experience and learning from it.

Thank you for pointing out that Mitopure's "levels peak in circulation within the first 6 hours from intake and is eliminated in approximately a day (Nat. Metab 2019)". I missed this detail when looking through the papers. In the context of my question, it is helpful to consider the half life of Mitopure when mixing and matching other potentially incompatible substances.

 

So in your overall response, you essentially did begin to "take a stab at", or scratch the surface of my question. The clean layout of criteria and data points is somewhat helpful in formulating a way forward to gathering more info on dosing. I do appreciate whatever effort is offered.. and that is what I think was missing in the initial attempts at a meaningful correspondence(see my post on my initial correspondence).

 

Thank you for bringing a great product to market. Hopefully there will soon be more pertinent  information on Mitopure's compatibility with other mitochondrial targeted supplements. Most people who take these high end supplements(such as Mitopure) aren't using just one supplement in a vacuum, the supplements are usually part of a regimen (as you are most likely aware).  Always hoping to get the most out of each supplement, taken together or apart in a time frame that will maximize efficacy and reduce any potentially negative crossover effects.

[motorcitykid]

 

Urolithin A said: 

 

 As you know, Mitopure acts on an essential anti-aging pathway called mitophagy which promotes the selective recycling of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. This further promotes replenishing the cell with healthy mitochondria through a process known as mitochondrial biogenesis. This is different to many other mitochondrial supplements, such as CoQ10, which is as a co-factor in the electron-transport chain, or Nicotinamide Riboside (NR), which is primarily acting on mitochondrial biogenesis via the NAD pathway (https://www.nature.c...2255-019-0161-5).  

 

 

 

Understandably Mitopure is very careful about what they claim. However in the podcast linked above (thanks for that , Albedo!) dr. Auwerx briefly hypothesizes (not more than that) about taking a stint of Mitopure to clear up dysfunctional mitochondria and then following up with NR to boost mitochondrial biogenesis. Once Mitopure becomes available/affordable in EU I will try an approach based on his idea.

 

 

 

Nice find and it's in the direction I was thinking (and probably many others here).

Considering Mitopure's plasma peak at the 6 hour point, how long to wait before NR? Wait the full 6 hours to get the most out of the two supplements. Will taking them too close together in time (lets say 2 hours apart) reduce the effectiveness of Mitopure? 

Edited by motorcitykid, 11 September 2020 - 05:39 PM.

[Daniel Cooper]

I’ve noticed a massive increase in exercise endurance. I usually do 30 minutes on a stationary bike every day and by the end of it I’m spent. On the first day I took UA I reached the 30 minute mark and I felt like I had basically just started. So I did another 30 minutes. I got to the one hour mark and I was definitely tired but I felt like I could do another 30 minutes, however, I stopped myself because I didn’t want to shock my system. The following days I had similar results, but not quite as pronounced, perhaps because I did strain my body on day one.

Nonetheless, it is clearly a performance enhancer. Here’s a reference to a study that showed a 42% increase in the endurance of mice running on urolithin a.

https://www.lifeexte...arkers-of-aging

Who knows if any of this translates into longevity. Taking too many antioxidants takes away some of the benefits of exercise, so I’m on the fence about it’s affect on exercise, however, it definitely demonstrates that it’s doing something of interest in my body.

 

I'd be absolutely shocked if you felt a benefit so quickly.

 

The MOA for Urolithin A is improved mitophagy.  That's something that would probably take a least a month or more to notice, if you noticed anything at all.

 

I think you're looking a placebo effect here.

 

 

[Decimus]

I'd be absolutely shocked if you felt a benefit so quickly.

The MOA for Urolithin A is improved mitophagy. That's something that would probably take a least a month or more to notice, if you noticed anything at all.

I think you're looking a placebo effect here.

Possibly. Then again I wasn’t aware that UA increased endurance until after I noticed the effect and began looking for items in literature around endurance. My goal with all supplementation is longevity, not benefits to my health or short-term effects.

By that logic though then the other effect I had, extreme fatigue after a few days of taking it, would also have to be placebo, because it wouldn’t affect my energy production before a month. I guess when a person wakes up at 8am takes the supplement and has to fall asleep by 10am for a few hours on the days he took the supplement it might be a huge coincidence even though that’s never happened to that person before.

Bottomline, more people need to try it and post their experiences.

[Decimus]

Btw, if anyone is in Philadelphia and wants a few packets for free they can swing by my place and pick some up. Like I said, I’m not going to use it more than twice a month so I have plenty. Preferably it would go to someone that exercises and you can test it to see if you notice a short-term gain.

Just PM me.

[APBT]

Would member Urolithin A, be able to offer a possible mechanistic explanation for Decimus' acute experiences in posts 9, 23, 25 and 36?

In the Mitopure trials and studies, did any participants experience anything similar to what Decimus did?  

[aribadabar]

Would member Urolithin A, be able to offer a possible mechanistic explanation for Decimus' acute experiences in posts 9, 23, 25 and 36?

In the Mitopure trials and studies, did any participants experience anything similar to what Decimus did?  

 

 

I will take a stab at it - the proposed mechanism of action of UA is mitophagy i.e. destroying ( a large number of) mitochondria. It worked exactly at it is supposed to.

Losing a ton of mitochondria at once will make anyone fatigued.

 

I am more surprised by the surge of energy followed its intake. Perhaps the body reacted to the massive loss of mitochondria and turned the mitochondrial biogenesis in overdrive thus resulting in improved mitochondrial ( and therefore endurance) capacity 6h later?

Edited by aribadabar, 12 September 2020 - 02:16 AM.

[motorcitykid]

Mitophagy is Mitopure's primary mechanism of action. Berberine, a relatively inexpensive supplement has also been shown to induce mitophagy. Would it be plausible to think that a relatively inexpensive supplement such as berberine could exhibit similar health benefits and possibly be considered as a viable replacement to urolathin a? 

 

 

https://www.frontier...2018.01121/full

 

Results: Berberine dramatically alleviated hypertrophy of H9C2 cell line and significantly ameliorated mitochondrial function by rectifying the imbalance of fusion and fission in mitochondrial dynamics. Furthermore, berberine further promoted mitogenesis and cleared the damaged mitochondria via mitophagy. In addition, berberine also restored autophagic flux in high glucose-induced cardiomyocyte injury via AMPK signaling pathway activation

[APBT]

Urolithin A:

Are there any commercially available blood tests that would indicate positive or negative effects from using Mitopure?

[Gal220]

Mitophagy is Mitopure's primary mechanism of action. Berberine, a relatively inexpensive supplement has also been shown to induce mitophagy. Would it be plausible to think that a relatively inexpensive supplement such as berberine could exhibit similar health benefits and possibly be considered as a viable replacement to urolathin a? 

 

Nootropic expert recommends taking it with milk thistle to prevent DNA damage.

 

 

One theory is it works through malabsorbtion , so it could possibly stop other nutrients besides sugar from being absorbed.

[motorcitykid]

I've been taking berberine about 8 months w/ Milk Thistle and artichoke extract. I like to keep in mind that every herb or supplement will not affect everyone the same Ex. Honokial is great for most but spikes the liver enzymes terribly for a handful. 

 

I dose berberine twice per day( instead of recommended 3 x per day) because of some conflicting studies on berberine potentially impairing muscle gains. I take it around 3 hours apart from my workout (there's just not enough time in the day to dose all supplements at the perfect hour).

 

I fell sharper when I take it (berberine also functions as a Noot through several mechanisms of action). 

 

Periodic blood test show normal liver enzymes.

 

Malabsorbtion is a concern (wish there was more info on this). 

 

I also take Mitopure about two hours apart from berberine and take Mito q and Broccomax approx two hours after Mitopure. I fit NR here and there along w/ resveratrol early morning. 

 

 

Edited by motorcitykid, 16 September 2020 - 06:09 PM.

[Urolithin A]

Great question. Not yet, but stay tuned because we're working on some exciting new solutions. 

 

Urolithin A:

Are there any commercially available blood tests that would indicate positive or negative effects from using Mitopure?

 

[MikeDC]

One of the benefits of increasing NAD+ is to restore mitophagy and autophagy. Is there a need to take Urolithins A if you are taking NAD+ supplements already?

https://www.nature.c...467-019-13172-8

[APBT]

I received this email for anyone interested:

 

 

An exclusive invitation

We’re offering our inner circle (that’s you) a FREE webinar led by our Chief Medical Officer, Anurag Singh MD, Ph.D. to break down the science behind mitochondria and muscle.

For those of you who are already taking Timeline, you’ll have an opportunity to share your experience and ask questions.

 

The science and clinical evidence behind Mitopure

Date: Wednesday, September 30th, 2020

Time: 7 am PST/10 am EST

REGISTER NOW ➔

 

 

 

 

 

Follow us on social

 

 

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First product in the world with Mitopure Urolithin A

 

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100+ published studies about the benefits of Urolithin A

 

 

 

 

 

 

 

[Urolithin A]

I received this email for anyone interested:

 
We're looking forward to having members from this forum participate in our first webinar. You can register here: 
 
https://us02web.zoom...VSpOpYII3GWXodg

[motorcitykid]

I was unable to attend the Mitopure webinar. Any new relevant info to share from Longecity peeps who may have attended?

[Daniel Cooper]

I was unable to attend the Mitopure webinar. Any new relevant info to share from Longecity peeps who may have attended?

 
 
Surely it was recorded and is available somewhere?

When I click on the link above it says the Webinar is September 30th, so a week from today.

Edited by Daniel Cooper, 23 September 2020 - 06:43 PM.

[Guest]

 

Urolithin A said: 

 

 As you know, Mitopure acts on an essential anti-aging pathway called mitophagy which promotes the selective recycling of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. This further promotes replenishing the cell with healthy mitochondria through a process known as mitochondrial biogenesis. This is different to many other mitochondrial supplements, such as CoQ10, which is as a co-factor in the electron-transport chain, or Nicotinamide Riboside (NR), which is primarily acting on mitochondrial biogenesis via the NAD pathway (https://www.nature.c...2255-019-0161-5).  

 

 

 

Understandably Mitopure is very careful about what they claim. However in the podcast linked above (thanks for that , Albedo!) dr. Auwerx briefly hypothesizes (not more than that) about taking a stint of Mitopure to clear up dysfunctional mitochondria and then following up with NR to boost mitochondrial biogenesis. Once Mitopure becomes available/affordable in EU I will try an approach based on his idea.

 

 

 

 

 

why not try Glucosamine as a complement to UA? In the study that showed life-extension of Glucosamine in c.elegans and old mice they noticed a notable uptick in mitochondrial biogenesis in both species (they speculate that glucosamine switches the metabolism to mitochondrial oxidation and thus the need for more mitochondrial capacity in the cells):

 

https://www.ncbi.nlm...les/PMC3988823/

[motorcitykid]

 
 
Surely it was recorded and is available somewhere?

When I click on the link above it says the Webinar is September 30th, so a week from today.

Thanks Daniel!

[Urolithin A]

You may also want to check out the Cold Spring Harbor Laboratory virtual meeting on Mechanisms of Aging #cshlaging that is happening this week. CSHL is one of the world's leading research organizations and is home to eight Nobel Prize winners. For this 10th edition there’s a fantastic speaker line up and some exciting workshops including one from Amazentis: Translating the positive impact of Urolithin A on muscle health in aging and disease. From molecular mechanisms to clinical trials, Thursday 24, 12:30pm-13:30pm EDT. Registration link here: https://lnkd.in/dE-ExUk

Edited by Urolithin A, 23 September 2020 - 07:19 PM.

[MikeDC]

Urolithin A said:



As you know, Mitopure acts on an essential anti-aging pathway called mitophagy which promotes the selective recycling of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. This further promotes replenishing the cell with healthy mitochondria through a process known as mitochondrial biogenesis. This is different to many other mitochondrial supplements, such as CoQ10, which is as a co-factor in the electron-transport chain, or Nicotinamide Riboside (NR), which is primarily acting on mitochondrial biogenesis via the NAD pathway (https://www.nature.c...2255-019-0161-5).



Understandably Mitopure is very careful about what they claim. However in the podcast linked above (thanks for that , Albedo!) dr. Auwerx briefly hypothesizes (not more than that) about taking a stint of Mitopure to clear up dysfunctional mitochondria and then following up with NR to boost mitochondrial biogenesis. Once Mitopure becomes available/affordable in EU I will try an approach based on his idea.

NR also restore mitophagy and autophagy In addition to biogenesis and other benefits.

[Daniel Cooper]

NR also restore mitophagy and autophagy In addition to biogenesis and other benefits.

 

You'd hope that NR and Urolithin A would have some synergy.  But it would be nice to know at least that the most expensive supplement I might take (Urolithin A) did not in some way counteract what would be the 2nd most expensive supplement I currently take (NR), with Urolithin A costing about 3x what NR costs.

[MikeDC]

You'd hope that NR and Urolithin A would have some synergy. But it would be nice to know at least that the most expensive supplement I might take (Urolithin A) did not in some way counteract what would be the 2nd most expensive supplement I currently take (NR), with Urolithin A costing about 3x what NR costs.

If you take NR, you probably don’t need Urolithin A until you are over 70.

[Gal220]

@MikeDC, what happens at 70?

[MikeDC]

@MikeDC, what happens at 70?

Just an arbitrary number. My thinking is NR supplementation May not be enough when you are really old. Urolithin A or Rapamycin might provide additional benefit.

[Daniel Cooper]

Well, the thing about Urolithin is it is the proposed active agent in pomegranate juice and extract's ability to seemingly reverse atherosclerosis.  NR also seems to do positive things for the arteries and might work as well as UL for this application, we just don't know. I don't think NR and atherosclerosis have been specifically studied.

 

There's just way less research on all these compounds than we'd like.  That is the quandary with UL - there's some limited research that shows some benefits, some hints at other benefits.  The problem is at this price point is this limited evidence something you're willing to take a gamble on given that you likely aren't going to feel much benefit.  You're basically looking at mitigating some of the problems brought about by aging. So take it for a decade and maybe you'll be able to tell us if it worked for you.  But at $1,000 per year, are you willing to lay out that sort of cash for something that may or may not work?  

 

NR is something I'm more willing to gamble on simply because it's about a third the cost.  I wonder how many takers Nestle is going to get at this price?  After all, I'm the guy that started the "Anyone considering supplementing with Urolithin A?" thread and at $1k per year I've not yet decided to take the plunge.  When Nestle announced that they would be releasing this product my hope was that it would come to market at about half of where Nestle is right now.

 

 

 

[Gal220]

 at $1k per year I've not yet decided to take the plunge.  

 

If you get the bacteria(surely this will available soon) and feed them a daily dose of pomegranite, seems the way to go to me.

 

I wonder how this price point came about, I think NR is way over priced as well(imagine if there was no patent the cost), but still at a number that gives it a large audience.

[Harkijn]

Perhaps you should give Mitopure  some time to get settled in the market place. Then price might come down. After all, a number of clinical trials will have to be organized and payed. 

NR is a small decade older and Chromadex has given  away NR to research projects free of charge in their CERP project.( A number of human clinical trials have confirmed positive effects.) I am a bit proud to say that in the past six years or so I have contributed to science by buying NR at a price which I too would like to see lower.

[Gal220]

Perhaps you should give Mitopure  some time to get settled in the market place. Then price might come down. After all, a number of clinical trials will have to be organized and payed. 

 

No doubt it was expensive getting this product tested and approved, but it is still surprising to me that their analytics pointed to the current price point as the most profitable.

 

Anyone can charge more for their product, but at some point you start to lose money by charging more.