Urolithin-A - has anyone looked into this to trigger mitophagy (and thereby generate new mitochondria)?

[JAS9]

I've been looking into Urolithin A, which is very (possibly very very) interesting due to its ability to encourage cells to recycle their damaged mitochondria so they can be replaced by new ones. Consuming pomegranates in an attempt to provide the precursor for Urolithin A is one way to go, but a recent study indicates that older people don't have the right gut bacteria to make Urolithin A from their food (only 40% of the general population does). So I'm looking into MitoPure, a company that makes a "high-quality, bioavailable Urolithin A supplement". They also sell it to other companies so they can use it in their supplements. It's expensive and they seem to be behind most of the studies so I'm a bit skeptical.

Still, it's tempting. For over 13 years I've lived with PD and my meds don't do as good a job as they used to, even though I've pushed the exercising about as hard as I could. When I'm having one of my more and more frequent "OFF" periods, my least favorite feeling is the total lack of energy in both body and mind. (And, yes, based on earlier mouse trials and biopsies, it does get into the *mouse* brain.) Increasing my mitochondrial output seems like a really good thing right now. Also, the old, damaged mitochondria that should get recycled are apparently spewing damaging molecules like an old car spews smoke.

Any thoughts about this, or have you run across anything else that might give me an energy increase?

[faridaro]

Lately, I also have been thinking about Urolithin A which sounds promising however is very pricey. To keep mitochondria in decent shape I would look into a "low hanging fruit" - homocysteine which have tendency to be elevated in PD cases and especially as a result of C/L treatment.

sciencedirect.com/science/a...

onlinelibrary.wiley.com/doi...

Available studies show that the high concentrations of Hcy may drive PD development and progression through multiple pathways involving apoptosis, oxidative stress, mitochondrial dysfunction, and DNA damage in nerve cells.

[park_bear]

mistaken comment deleted

[parkie13 in reply to park_bear]

I love pomegranates. I eat some of them when they are available. Wonder how much pomegranate contains? Thanks for your dosage explanation.

[park_bear in reply to parkie13]

I will defer to Bolt_Upright who took up the question below.

[Feargaire in reply to parkie13]

Be aware that if you lack particular gut bacterial strains your gut may not produce Urolitin A from pomegranate

[faridaro in reply to park_bear]

Looked up the mitopure supplement facts and they state that 2 softgels provide 500mg of urolithin a :timelinenutrition.com/shop/...

But strangely enough the mitopure powder nutrition facts doesn't provide amount of urolithin which is listed 2nd place among other of ingredients:

timelinenutrition.com/shop/...

[park_bear in reply to faridaro]

inaccurate comment deleted

[faridaro in reply to park_bear]

You're right! Would not trust a company with such deceptive tactics...

[Hidden in reply to park_bear]

Because Dave Asprey has a lot at stake and he is expressing his enthusiasm for this product, I think asking him (or his team) directly would be interesting. I understand where you are getting your numbers but then the misrepresentation is so blatant and obvious and they’ve invested likely millions to bring this to market, I do wonder if we are missing information

[Bolt_Upright]

Fix the gut!

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population 2021 nature.com/articles/s41430-...

"Abstract

Background

Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA an appealing strategy.

Objective

This is the first detailed investigation of the prevalence of UA producers in a healthy population and the ability of direct UA supplementation to overcome both microbiome and dietary variability. Dietary intake of a glass of pomegranate juice (PJ) was used to assess UA producer status (n = 100 participants) and to characterize differences in gut microbiome between UA producers from non-producers.

Methods

Subjects were randomized (1:1) to either PJ or a food product containing UA (500 mg). Prevalence of UA producers and non-producers were determined in the PJ group. Diet questionnaires and fecal samples were collected to compare differences between UA producers and non-producers along with plasma samples at different time points to assess levels of UA and its conjugates between the interventions.

Results

Only 12% of subjects had detectable levels of UA at baseline. Following PJ intake ~40% of the subjects converted significantly the precursor compounds into UA. UA producers were distinguished by a significantly higher gut microbiome diversity and ratio of Firmicutes to Bacteroides. Direct supplementation with UA significantly increased plasma levels and provided a >6-fold exposure to UA vs. PJ (p < 0.0001).

Conclusions

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

[Bolt_Upright in reply to Bolt_Upright]

So the PJ gets you from 12% creating UA to a 40% chance of creating UA. That's a chance right there.

[jetejp in reply to Bolt_Upright]

Unfortunately the gut microbiome seems to be much altered in PD patients (cause of PD or PD causing such a state?), so guaranteeing you have the species of biota able to produce UA would be unknown. It would be easier to take a supplement UA directly.

[Bolt_Upright]

5 glasses of PJ gets you 500 mg UA (if you can produce it)

youtu.be/ZrJatcXXcIM(Not working as expected?)

[JAS9 in reply to Bolt_Upright]

It's all about your gut biome, so it's not as simple as a yes/no; it's a range depending on what you've been eating. If you've been eating a diet of many different types of fruit, nuts, and veggies, (and especially pomegranates) you're more likely to already have the right gut bugs than someone with a poor diet (e.g. SAD). Once they've determined exactly what gut bugs perform this magic, they can make a probiotic with them in it. But you can begin improving your chances by eating those things that are on the list of foods that have the precursors of Urolithin A. By eating these you're giving your gut a chance to build these bacteria up. It's almost like taking a free probiotic before the probiotic is available.

[Bolt_Upright in reply to JAS9]

Great point! I believe when you move to a foreign country EVENTUALLY your microbiome adjusts. Of course, PD folks may not adjust.

[Bolt_Upright]

Impact of the Natural Compound Urolithin A on Health, Disease, and Aging 2021 pubmed.ncbi.nlm.nih.gov/340...

Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer’s Disease 2021 ncbi.nlm.nih.gov/labs/pmc/a...

Effects of Urolithin A on Mitochondrial Parameters in a Cellular Model of Early Alzheimer Disease 2021 ncbi.nlm.nih.gov/labs/pmc/a...

[Bolt_Upright]

The package says it has 500 mg of Urolithin A (as Mitopure) celltrient.com/strength-cap...

$50 for a 14 day supply.

This is not an endorsement. Too steep for me.

[park_bear in reply to Bolt_Upright]

mistaken comment deleted

[Hidden in reply to park_bear]

I wonder how the powder (which is yummy) compares to the juice in its Ellagitannin content. And, if it is heated when being made, would that reduce the benefits?

pubmed.ncbi.nlm.nih.gov/185...

[park_bear in reply to Hidden]

You may have intended this reply to a different comment.

[Hidden in reply to park_bear]

Actually, I thought you might find it interesting. Ooops! ☺️ My thoughts are, if the supplement doesn’t contain enough , and 5 cups of juice (with the precursor) is ridiculous, what about using the powder as a means of getting the Egallitannin? 😊

[park_bear in reply to Hidden]

I looked and found several studies of urolithin in Parkinson's models:

scholar.google.com/scholar?...

Every single one of them applied urolithin either at the same time or before treatment with a toxic compound. Show me a study where urolithin is applied, and demonstrated helpful, after establishment of a Parkinson's like condition and I will be interested.

[Hidden in reply to park_bear]

😡. PB why do they even bother with such studies! Dr. Singh’s studies are done that way too? He seemed so credible. This is 🤬! (Ladies don’t talk like that until they are really frustrated!)

Seriously, it’s nonsense.

Thank you for waking me up to this!

This is the doctor I was referring to.

youtu.be/4FUUzyRKvbU(Not working as expected?)

[park_bear in reply to Hidden]

I have been pondering this question also. Here is a possible scenario:

These animal trials typically have several arms, consisting of some or all of the following:

• The control arm of toxicant only

• Test substance plus toxicant, possibly more than one arm with different dosages, with simultaneous application or pretreatment with test substance

• Negative control of toxicant vehicle only

• Test substance only

With some or all of these arms going already, the cost of adding an additional arm of test substance applied after toxicant, rather than before, is insignificant. Why do they not do that? Maybe they do!

Let us suppose that they do, and the posttreatment arm fails but the pretreatment arm succeeds. If this happens and they disclose the failure of the posttreatment arm, no one is going to be very interested in publishing a study with the only success being the pretreatment arm. What to do? Deep six the failed posttreatment arm and publish the success story. I do not know that this is happening but I wonder.

[Hidden in reply to park_bear]

The lack of quality in testing is literally infuriating. I’m just going to leave it at that. There are very few truly altruistic researchers, scientists or doctors.

this makes job of patient researchers all the more important.

I am immensely grateful to the dedicated patient researchers and the Parkinson’s advocate researchers! That is what makes this forum special and very important!

We need you! ❤️

On a lighter note, I hope the pomegranate powder is beneficial like pomegranate juice but maybe it’s ruined in the process of freeze drying it. Likewise with dried versus fresh herbs and nutrients.

Getting Urolithin A via precursors seems to be the best course for now. So, where are the most bio available and abundant precursors?

[JAS9 in reply to Hidden]

This is a podcast I came across interviewing Dr. Julie Andersen from the Buck Institute (a well-known and respected organization). She talks about many issues that are being brought up here, including bacteria and prebiotics.

youtu.be/VeKLXjaXWlI(Not working as expected?)

At about 16:00 she talks about PD.

[Hidden in reply to JAS9]

Link not working for me. Attaching another interview with the doctor who specializes in it but not for the brain specifically

youtu.be/BljmvKd20oo(Not working as expected?)

[Hidden]

I use pomegranate powder. Based on the required dosage, I don’t know if it is efficacious.

Pomegranate

[Gcf51]

Dang.... Swanson's site is down can't check what they offer or price.

[JAS9]

Here's another option. This online store caters mostly to those who supplement in order to increase their athletic performance, so I feel that the feedback is possibly more reliable; if something doesn't boost their performance and/or grow their muscles, they'll rate it harshly. I've ordered from them before and have been satisfied with their products. Of course, I'm not in any way endorsing them; just relaying my limited experience with them.

bulksupplements.com/product...

[jetejp]

I agree. Looks harmless and another tool in improving mitochondrial health for the diseased state mitochondrial condition of PD.

[AlanJza]

This could be extremely beneficial. If is works in a few works coudl well be worth a short trial to judge how effective it is for an individual

[Gioc]

Here is recent research on Urolilithin-A. Although it is about middle-aged people, it is not about PD, even if it refers to PARKIN.

I find the research on this type of mithophagy-inducing supplements interesting, but in my opinion we need to be very careful in their use because we PwPs probably have mithochondria in a precarious condition and their elimination through mithophagy in a sudden way may not be supported from an effective quick replacement. Perhaps a gradual approach over time with exercise, a varied diet such as the "Mediterranean" and proportionate comprehensive vitamin and mineral supplementation could potentially promote replacement and augmentation of mithochondria,… in theory.

I hope specific research on PD will be published soon.

cell.com/cell-reports-medic...