Urolithin A (UA) One of 4 Promising Agents 2024 by Brian Kennedy of NSU

I’ve seen the argument goes that if you don’t have the microbiome to produce Urolithin A you won’t create it, however I think the microbiome adapts to what you feed it.

Mitopure doesn’t seem that impressive to me if pomella extract or pomegranate juice can beat it in sufficient quantities. Reasonably someone will raise it with pomella.

1 Like

True. Does anyone know the numbers?

2 Likes

The other interesting thing has been the concern about Pomegranate constituents impairing rapamycin metabolism. I’m aware it isn’t exactly the same comparison, but I’ve found a couple of articles looking a this issue and it may not be that big of a worry. This article showed Grapefruit much more active.
https://cardiacos.net/wp-content/uploads/ArticulosMedicos/2007/2007-POMEGRANATE-JUICE-AND-CLEARANCE-OF-ORAL-OR-INTRAVENOUS-MIDAZOLAM.pdf

However other articles indicate area for concern with other drugs (in rats)
https://pubmed.ncbi.nlm.nih.gov/15673597/

Rapamycin is primarily metabolized by cytochrome P450 CYP3A4 - a recent article raises a bit of concern on this, likely with repetitive doses … https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003857/

So I’m wondering if anyone has monitored their sirolimus levels with and without supplementation with pomegranate? It seems less active than grapefruit juice - but would seem likely to have some impact? Especially as one gets into bigger doses with pomegranate extract.

2 Likes

It doesn’t seem so impressive at first glance. But they were elevated at 48 h later, does it continue to increase with repeated dosing? Plasma half-life at ~24h.

Development of a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for characterizing pomegranate extract pharmacokinetics in humans, 2023

image

image

1-s2.0-S0731708523002467-main.pdf (1.9 MB)

3 Likes

What brand and dose did you take?

Pomegranate extract has many advantages beyond its Urolithin A content.
One is its punicic acid content.

“Punicic acid, the main bioactive component of pomegranate (Punica granatum) seed oil, is an omega-5 isomer of conjugated α-linoleic acid that has shown strong anti-oxidative and anti-inflammatory effects that contributes towards its positive effect against a wide arrange of diseases.”

“Different studies conducted on animal and human models have revealed that punicic acid is very effective against various chronic diseases”

https://sci-hub.se/10.1186/s12944-017-0489-3

3 Likes

From a hedonistic perspective I like to eat Pomegranates. However, I am not sure my example is that good. I type as someone who has decided that today is a drinking day and have already drunk 3 pints of cider/beer and started on a bottle of red wine (rioja). (I have, however, taken 2g of pantethine, 1g of DHM and will take a melatonin hectodose within the next 24 hours - at a good time for the circadian cycle).

AIUI Pomegranate juice has an acidic effect and I think we should avoid driving the metabolism in the direction of lots of free protons.

The UA supplement I tried did what we should expect
a) Made me quite fatigued
b) Disrupted sleep

On a micro basis that seems wrong, but on a macro basis that is really quite good.

I have another blood test tomorrow (my weekly test).

2 Likes

Pardon my ignorance guys but if UA is causing everyone to be fatigued and it disrupts sleep then why is everyone taking it or even talking about it. I mean what other side effect would it need to have (death) for people to say it should not be taken, LOL dudes. Don’t take the damn thing, it is dangerous. Haven’t tried it myself, but would never try something that i know it makes me tired and disrupts sleep. What am I missing?

@John_Hemming your experience with UA is similar to my experience with Rapa. It’s probably the same reason…boosted autophagy of some sort or another.

2 Likes

My experience with Rapa is complete opposite. I really look forward to the day that I take it. More energy, lighter on my feet, no pains, and NEVER I feel tired. It does give me a bit of sleep issue but that because I feel more energy.

3 Likes

Nootropics Depot’s Pomegranate extract, which is Pomella, a standardized extract. You can buy pomella from other vendors too. I took 200mg a day and have so for almost two years now. It also helps firm up stools if that is an issue you experience like I did.

1 Like

N=1 I take a medication that is metabolized by CYP3A4 and haven’t noticed feeling any different taking it or not taking it. I have felt a difference with other things like D Limonene and Apigenin though.

What you are missing is that if you wish to live a healthy life then your cells need to function at a high level. One issue is how well the mitochondria function. If you want them to function well you need to take the cellular equivalent of a machine gun and kill off the badly functioning mitonchondria.

This will have both a short term negative effect on the soma (you) and a long term beneficial effect.

4 Likes

The objective of this study was to determine the effects of supplementation with a standardized punicalagin-enriched pomegranate extract, Pomella® (250 mg), on the gut microbiome, circulating short-chain fatty acids, and gut microbial-derived ellagitannin metabolite urolithins. A randomized, double-blind, placebo-controlled study was conducted over 4 weeks on healthy volunteers aged 25–55 years.

There was no significant change in the gut microbial diversity in both cohorts after 4 weeks of intervention, but there was a significantly increased relative abundance of Coprococcus eutectus, Roseburia faecis, Roseburia inullnivorans, Ruminococcus bicirculans, Ruminococcus calidus, and Faecalibacterium prausnitzii. Pomegranate extract (PE) supplementation led to the augmentation of circulating propionate levels (p = 0.02) and an increasing trend for acetate levels (p = 0.12). The pomegranate extract (PE) supplementation group had an increased level of circulating urolithins compared to the placebo group (6.6% vs. 1.1%, p = 0.13).

Not the best journal, and I don’t understand why they compared percent increase of circulating urolithins rather than saying the absolute number. Is it because it is very low?

That makes me very skeptical if anything.

But one dose of 1g Pomella should increase serum Urolithin A to 77.8 ng/mL it seems.

What I don’t understand is Pomella has a lot of punicalagins, standardized to 30%, but it doesn’t seem to increase Urolithin A much more than pomegranate juice. 300 mg punicalagins is only 77.8 ng/mL Urolithin A it seems…

FDA link for GRAS for pomella:
https://www.fda.gov/media/171773/download

The equivalence in direct terms to
pomegranate juice shows that, based on these values, a 50 mg serving of Pomella® is roughly equivalent
to 10 ml, or about one third of an ounce, of commercial pomegranate juice wi th regard to the provision
of punicalagins and other polyphenolics.

Lol so 1 gram of Pomella = 200 mL of pomegranate juice…? Well then it does make sense.

I buy some supplements from Hansen Supplements; they do third-party testing on their products. Their NMN supplement was tested by NUS, National University of Singapore, and came out as the top brand. Se YouTube at around 8 min 15 sec. Presented at ARDD 2023.

Where do they get the supplements from? Probably China. But I prefer to buy from a company like this that has rigorous quality control, than from a western company that lacks it.

They also sell Urolithin A. (I don’t use it myself.)

2 Likes

@SNK The rapa effect is quite variable based on what I read here. Perhaps it relates to what each of us needs from rapa. I need more autophagy I assume. I wonder what rapa does for you and others who feel energized by a rapa dose?

3 Likes

That is pretty expensive. I’m not sure we gain much if anything from it, if already on Rapamycin - which is way cheaper!

1 Like

This is confusing, since this study showed 71 mg in 240 mL punicalagins in pomegranate juice, which increased to 110 ng/mL UA glucoronide levels?

In all, 100% PJ was selected as the comparator as it showed a batch-to-batch consistency of the two-precursor compounds (71 mg punicalagins and 36 mg EA/8 fl. oz).

In the PJ intervention, the baseline (T0) mean UA glucuronide levels were 5.48 ± 19.97 ng/mL, slightly increasing to 12.84 ± 36.34 ng/mL at the 6 h time point and rising to 110.47 ± 131.6 ng/mL 24 h following PJ intake.

What is going on? 71 mg punicalagins in juice in this study had a larger increase than 300 mg punicalagins in the pomella study of 1 g pomella?

Why is the FDA gras saying 50 mg pomella is equivalent to 10 ml juice, when there is only 71 mg in 240 mL juice?

Based on the findings of the current study, to achieve the equivalent dosing of 500 mg supplementation of UA from dietary exposure via PJ, on average, an individual would need to drink six glasses (approx.1.5 L) of PJ that contained the necessary dietary precursors.

6 glasses if standardized to punicalagins would be 400 mg punicalagins… yet 300 mg does not come near even 1 glass.

1 Like

My energy is not like a jolt of energy, it is more of a sense of alertness, but definitely I do not feel tired. The thing though is, I can feel a difference (for better) than the day before I take Rapa, and that I am 100% sure, so clearly it is doing something good. It is subtle though, but it is noticeable enough that there is no way in hell I’ll forget to take it, because I am looking forward to it. And that in itself shows that it is really good for me. There is literally so many times that I forget to take something. for example I take a baby aspirin each day and there is so many times that I realize after couple days that I had forgotten, and then just take it. why is that? well because aspirin is doing nothing that I can notice (good or bad) and obviously it’s easy to miss/forget to take it. But as I said it is Imposible for me to forget to take Rapa. Clearly that says more than I can explain with words.

3 Likes

Ok. Thats a good point on which to agree to disagree.

I think that something that is bad now can be good in the long term. Exercise is a good example of this.

2 Likes