LONGECITY

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.

 

I think that whatever market analysis Nestle did into this produce is simply wrong if it's telling them that ~$1k/year is the optimal price point.  Unless their production costs for this compound are indeed very high. 

 

I think at $500/year they'd certainly get more than double the number of takers as they would at the current price point.

 

As I said, if UL-A does everything that it's proponents claim it will (and I think that it will), chances are you're not going to subjectively feel any improvement.  You're just going to have to take it on faith that you're getting the benefits that the research says you should.  That requires a lot of faith at that sort of annual cost.

Edited by Daniel Cooper, 25 September 2020 - 09:27 PM.

Anyone order straight urolithin A from chemical supplier such as sigma aldrich?

 

https://www.sigmaald...ng=en&region=US

 

 

I won't be able to attend the webinar. 

I would still like an answer to my post #37 https://www.longecit...e-2#entry898122

And, my post #22  https://www.longecit...pure-released/#entry897717

Also, motorcitykid's post #33, has questions I'd like answers to  https://www.longecit...e-2#entry898103

I have a bit more to report. When the product first came out, I convinced both of my parents, both of whom are well into their 70’s, to order it. My father ended up never trying it, but my mother called me a few days ago and told me that after a few days on it she was so tired she couldn’t function through the day and had to stop.

So there you go. Two cases out of two. We obviously share similar biochemistry, but there will clearly be a portion of people who try this and become exhausted. I waited two weeks to try it again and once again it forced me to lay down for several hours and sleep. I will likely be giving away an entire unopened box I have.

I would be interested to hear from the user Urolithin A if any of the participants in their study complained of fatigue?

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

 

Will this webinar be available somewhere after the fact so that those of us that can't attend the live presentation watch it?

@Decimus - why not take a dose once a week or once a month?  Or cut your dosage in half?

 

DHEA is another product where dosing is all over the place and people experience negative side effects, probably just due to over dosing.

 

 

I added 500mg of pomegranite from Bulk Supplements to my collagen shake this morning, no discernable taste difference.  Just need the bacteria now...

Edited by Gal220, 29 September 2020 - 03:06 PM.

Important question for Urolithin A: If your product promotes mitophagy, how can you be certain that it’s clearing out damaged mitochondria only and not healthy ones, as well? I would point out the following study:


Not surprisingly, mitophagy is closely coupled to mitochondrial biogenesis. Studies have demonstrated that mitophagy has the capacity to clear most of the mitochondria in cells. In fact, cells overexpressing PINK1 or Parkin can degrade all their mitochondria within 24-96 h in response to treatment with mitochondrial uncouplers 86, 92. It is therefore important for the cell to quickly replace the mitochondria that have been removed by mitophagy. Mitochondria have a significant reserve capacity that can be utilized upon demand 122. In response to modest mitophagy, myocytes can utilize their mitochondrial reserve to maintain energy production without affecting contractility. However, excessive mitophagy in the absence of mitochondrial biogenesis will result in the depletion of the bioenergetic reserve in the remaining mitochondria and subsequent cell death.

https://www.ncbi.nlm...38875/#S13title


This is concerning. It’s interesting that it took about 3 days for the extreme fatigue to set in for both me and my mother, which is inline with the 24-96 hours noted in this study.

Do you know which pathway/s urolithin a works through? Would you agree that it might be overstimulating PINK1 and causing an excessive purge of mitochondria from the cells? That seems to be the most sensical explanation.

I want to clarify, this isn’t slight fatigue. This is “I need to find the nearest place to lie down and go to sleep immediately” fatigue. Until I am convinced otherwise, I am going to assume that, at least in my body, urolithin a is causing mitochondria, both healthy and unhealthy, to be expelled from my cells at such a high rate that mitochondria biogenesis can’t keep up and thus causes extreme fatigue.

I have a bit more to report. When the product first came out, I convinced both of my parents, both of whom are well into their 70’s, to order it. My father ended up never trying it, but my mother called me a few days ago and told me that after a few days on it she was so tired she couldn’t function through the day and had to stop.

So there you go. Two cases out of two. We obviously share similar biochemistry, but there will clearly be a portion of people who try this and become exhausted. I waited two weeks to try it again and once again it forced me to lay down for several hours and sleep. I will likely be giving away an entire unopened box I have.

I would be interested to hear from the user Urolithin A if any of the participants in their study complained of fatigue?

 

We have dosed >300 healthy adult participants across all ages (b/w 20-90 years) in multiple clinical trials and have not seen any significant differences on reported fatigue b/w placebo and active intervention so far. The low % of reported cases of fatigue are evenly spread out between the placebo and active interventions. We would be happy to learn more about your experience and can facilitate a call with our scientific and medical experts. 

Did anyone attend the Webinar? 

Urolithin A activate mitophagy and autophagy. This new study shows autophagy dysfunction actually reduce NAD+. Probably by up regulating PARPs. Increasing NAD+ ameliate the autophagy dysfunction.

https://www.biorxiv.....01.31.928424v2

Will this webinar be available somewhere after the fact so that those of us that can't attend the live presentation watch it?

 

You can watch the presentation here: 

https://www.timeline...n=webinar_20_09

From the webinar

 

They recommend 4 months to see full benefit(muscle strength), 500mg daily.  They suggest those over 40 have damaged mitochrondia.

 

500mg is 6x what 8oz of pomegranite juice would provide assuming you have the right bacteria.

Edited by Gal220, 05 October 2020 - 03:32 PM.

You can watch the presentation here: 

https://www.timeline...n=webinar_20_09

 

Nice. Thank you. Sorry if I am overlooking but how could you estimate that only 30-40% of people have the right microbiome to produce Urolithin A?
 

Nice. Thank you. Sorry if I am overlooking but how could you estimate that only 30-40% of people have the right microbiome to produce Urolithin A?
 

 

I would just like to know how to test if I am one of those people ! 

 

No info was given on how to get this bacteria either.

Edited by Gal220, 05 October 2020 - 04:30 PM.

My correspondence with Timeline Nutrition:

 

Q:Would taking 1000 mg (two packs) per day exert a significantly greater effect than taking recommended dose of 500 mg  or do the positive health effects top out at 500mg?
 

Timeline: On average, in our double-blind RCT’s we’ve seen that 500mg daily is sufficient to boost mitochondrial function and improve leg muscle strength. That said, nutrition is very personal, and we do observe higher blood steady state levels with increasing doses of Mitopure. In some study participants this has translated into better results upon intake of a 1000mg dose.

Qa: Would taking sirtuin targeted supplements too close in time to Mitopure dosing negate Mitopure’s ability to induce mitophagy?
Qb:  What about Mito Q, NR? Milk thistle?
 

Timeline: One of the exclusion criteria commonly used in our clinical studies is avoiding intake of concomitant supplements that are known to impact mitochondrial function to observe the direct effect of Mitopure in clinical trial settings. We have not studied the impact of combining Mitopure with other supplements and can only speak to evidence we have on Mitopure’s ability to induce mitophagy and promote biogenesis. We recommend taking Mitopure in the morning, as was done during our efficacy clinical studies, and to test it first alone in order to observe its direct benefits.

Q: Can you make a distinction between berberine, an alkaloid that significantly induces mitophagy and Mitopure? Does Mitopure induce it to a greater degree? Might it be good to dose both close together in time?
 

Timeline: Berberine promotes mitophagy by inhibiting mitochondrial respiration. Such an effect can be toxic if it is too strong (this is the case for example of Rotenone, a pesticide that is now forbidden). But it can be beneficial when the inhibition of respiration is mild. The mild insult to mitochondria triggers the repair mechanism of mitophagy, that results in improvement in mitochondrial function.
Mitopure does not interfere with mitochondrial respiration. It triggers mitophagy via a novel mechanism that is independent of mitochondrial respiration.

Q: Why not offer a Mitopure capsule? I don't need the extra 2g of sugar
since I keep my daily sugar intake under 25g.
 

Timeline: For perspective, the 2g of sugar are coming from the natural whole fruit berries and pomegranate in the Timeline product but we hear you. We are working on a range of new exciting products to cater to different consumer preferences and will keep you posted on our progress.
 

 

You mentioned a “novel mechanism” through which Mitopure induces mitophagy.
Q:Can you reveal what the novel mechanism is or is it proprietary info? It would be very helpful to know. I will be able to research the different modalities of herbs and supplements included in my health regimen that might interfere or possibly support Mitopure’s mechanism of action.
 

Timeline: Unfortunately, this is information that we cannot share at the moment.
 
Q:Also, wondering if there is any info as to how the process of mitophagy via Mitopure might be influenced under Near Infrared LED light therapy wherein light photons are absorbed by the mitochondria to produce  ATP?
Near Infrared LED light therapy acts directly on the electron acceptors of mitochondrial respiratory chain, and may have an effect on the production of reactive oxygen species.

Timeline: Our research has shown that Mitopure acts independently of reactive oxygen species, and does not impair mitochondrial respiration.
Therefore in theory, the two approaches should be compatible. However, this has never been tested and requires further validation.
 
 

 

No evidence that this product produces urolithin, other than their claim, but they are offering a free trial on many of their products atm, including this one.

 

https://www.wtrawlei.../ultrapome.html

 

Formulated by Harvard, supposedly.

 

Amazon description shows they understand the process.

 

Also mentioned briefly in this article

 

 

Longevity Tips with Dr. David Katz

We’re offering our inner circle a complimentary webinar led by our Chief Medical Officer, Anurag Singh MD, PhD, and leading preventative medicine physician, Dr. David Katz MD, MPH, FACPM, FACP, FACLM, on the relationship between cellular health and longevity.

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

 

 

Webinar: Cellular Health & Longevity

Date: Wednesday, November 18th, 2020

Time: 7 am PST/10 am EST

REGISTER NOW ➔

 

 

About Dr. Katz:

David L. Katz, MD, MPH, FACPM, FACP, FACLM earned his BA at Dartmouth College (1984); his MD at the Albert Einstein College of Medicine (1988); and his MPH from the Yale University School of Public Health (1993). He completed sequential residency training and board certification in Internal Medicine (1991) and Preventive Medicine/Public Health (1993).

Katz is the founder and former director of Yale University’s Yale-Griffin Prevention Research Center (1998-2019); Past President of the American College of Lifestyle Medicine; President and Founder of the non-profit True Health Initiative; and Founder and CEO of Diet ID, Inc. He is a Fellow of the American College of Preventive Medicine; the American College of Physicians; the American College of Lifestyle Medicine; and Morse College, Yale University.

The recipient of numerous awards for teaching, writing, and contributions to public health, Katz was a 2019 nominee for a James Beard Foundation Award in health journalism, has been a widely supported nominee for the position of U.S. Surgeon General, and has received three honorary doctorates.

He holds multiple US patents; has over 200 peer-reviewed publications; has published many hundreds of on-line and newspaper columns; and has authored/co-authored 19 books to date including multiple editions of leading textbooks in nutrition, preventive medicine, and epidemiology.

 

 

 

Mitopure's only reported mechanism of action is mitophagy, induced via the active indgredient Urolithin A.

 

I still can't help but wonder if other substances that induce mitophagy might be just as beneficial to one's health as Urolithin A. The people at Timeline Nutrition say it works through "a novel mechanism"to induce mitophagy. But seriously, is this novel mechanism more effective then the mechanisms of berberine, resveratrol, spermidine and others -they all induce mitophagy . If in-depth, well financed studies were to be conducted, might these other substances prove to be just as beneficial to a person's health as UA? 

I'm not bashing Mitopure, it's a good product. I use it and I would recommend it. It is costly, and that's why the thought still kicks around in my head about these other less expensive mitophagic substances (w the exception of spermidine):

 

https://www.mdpi.com...21/9/10/932/htm

 

4.1.1. Curcumin

4.1.2. Astaxanthin 4.1.3. Resveratrol 4.1.4. Olive Oil 4.1.5. Spermidine  

 

 

 

 

I wonder if Urolithin A's novel mitophagic mechanism of action supports eye health.

 

 

Spermidine for eye support (not sure if mitophagy plays a role here).

 

https://www.ncbi.nlm...les/PMC4650557/

Edited by motorcitykid, 27 November 2020 - 02:46 AM.

I want to clarify, this isn’t slight fatigue. This is “I need to find the nearest place to lie down and go to sleep immediately” fatigue. Until I am convinced otherwise, I am going to assume that, at least in my body, urolithin a is causing mitochondria, both healthy and unhealthy, to be expelled from my cells at such a high rate that mitochondria biogenesis can’t keep up and thus causes extreme fatigue.

 

That sounds like a low potassium attack.  I do not have experience with MitoPure, but I have over a decade of experience with "need to find the nearest place to lie down and go to sleep immediately".  I would have that "must lie down and blank out" feeling accompanied by nonstop yawning during exercise, at different times of the day, and on walks, one to three times a day.  The episodes would last 1 to 3 hours and made my life difficult. 

After years of experimentation, I discovered that one glass of water with 1 teaspoon NOW brand Potassium Gluconate powder (equivalent to 350mg K) plus one 500mg capsule of Ecological Formulas Allithiamine would reverse my symptoms quickly.  It was like a switch being flipped.  Later I found that B12 shots mostly prevented the slowdowns.  The Bs and potassium interact somehow, and it's complicated.   Both my serum K and B12 were in range; there's no obvious answer for why they stopped the slowdowns, since on paper they were fine.  Other people have noticed this interaction too... see "the deadlock quartet" discussions on the PhoenixRising.me forums.

It would be interesting to see if your MitoPure symptoms were caused by low potassium.  You could take 350 or 400mg of potassium (in liquid form) and see if it reverses your symptoms.  Low-sodium V8 juice is high in potassium, as is coconut water.

Edited by genereader, 18 January 2021 - 11:20 AM.

Urolithin A is unlikely to target mitophagy specifically. It is highly likely that mitophagy enhancement is just a result of other actions such as mTORC1 inhibition.

https://mct.aacrjour...ontent/18/2/301

No evidence that this product produces urolithin, other than their claim, but they are offering a free trial on many of their products atm, including this one.

 

https://www.wtrawlei.../ultrapome.html

 

Formulated by Harvard, supposedly.

 

Amazon description shows they understand the process.

 

Also mentioned briefly in this article

 

I tried the UltraPome, because it was free. Sorry, no before and after biomarker testing, mainly because I didn't expect much biological change from such short-term small dosing. Didn't notice too much different, but didn't mind taking it because of the known health benefits of pomegranates.

I am thinking that 500mg of mito pure is too much. This mice study got good results with only 10mg/kg dose. That translate into 0.83mg/kg for humans. For a 75kg human, the dose is only 62.5mg. The recommended dose maybe 10 times more than required and causes sides effects.

https://www.nature.c...598-020-76564-7
Edited by MikeDC, 22 May 2021 - 10:55 PM.

"Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation."

 

Singh, A., D’Amico, D., Andreux, P.A. et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr (2021). https://doi.org/10.1...430-021-00950-1

"Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation."

 

Singh, A., D’Amico, D., Andreux, P.A. et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr (2021). https://doi.org/10.1...430-021-00950-1

So 60% percent of this group did not form significant UA after drinking PJ. That is more than I expected. I think we can assume that this part of the population also does not react to berries and walnut consumption as far as UA is concerned.

Though I would have preferred a longer research period everything seems to point to  pricy supplementation...

Nice recent review from the team at the origin of the work on UA:

 

https://www.cell.com...80?showall=true

 

Urolithin A (UA) is a natural compound produced by gut bacteria from ingested
ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in
foods such as pomegranate, berries, and nuts. UA was discovered 40 years
ago, but only recently has its impact on aging and disease been explored. UA
enhances cellular health by increasing mitophagy and mitochondrial function
and reducing detrimental inflammation. Several preclinical studies show how
UA protects against aging and age-related conditions affecting muscle, brain,
joints, and other organs. In humans, benefits of UA supplementation in the
muscle are supported by recent clinical trials in elderly people. Here, we review
the state of the art of UA’s biology and its translational potential as a nutritional
intervention in humans.

I just came across a product from Pure Encapsulations with Mitopure on Amazon: https://www.amazon.c.../dp/B08VDB31YY/ .  60 capsules, 250mg Mitopure along with some Resveratrol and CoQ10.  The cost per g of Mitopure is well below what Timeline Nutrition charges.  Has anyone tried it?

Edited by timedilation, 24 July 2021 - 07:48 PM.

Interesting find but:

 

Pure Encapsulations at 250 mg per serving and 30 servings per bottle (= 7.5 grams) at $62.20 = $8.29 per gram.

 

Timeline at 500 mg per serving and 60 serving per 2 month subscription (= 30 grams) at $200 = $6.67 per gram.

 

Timeline at 1 year subscription = (180 grams) at $1020 = 5.67 per gram.

 

I'll stick with Timeline.  And Timeline occasionally offers 10% off.

Hah, whoops!  I read through it too quickly and didn't notice that the 250mg corresponds to 2 capsules instead of 1.  Thanks for the correction.

.

 

 

 

Celltrient from Nestle, 14 grms. of Mitopure (56 capsules, 250 mgr. each, 2 capsules per day) for 95$. In other words, 6,78$/gr. for 28 days.

 

Unfortunately and inexplicably, shipping to USA only, not Europe yet, while Timeline ships to Switzerland also.

 

 

Edited by Engadin, 05 August 2021 - 09:08 PM.