#61

Nothing specific behind the “basics” (A1c, lipids, etc.) I guess. Unless there’s a way to easily measure UA’s impact?

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#62

Another thing I haven’t researched yet.

@John_Hemming do you have any tests that are relevant for triangulating mitochondrial health?

One thing you could do is do some form of zone 2 output measure before and then after again (without changing you exercise regime).

From the papers you’ve been reading are their any of the assessments they were doing that we could do?

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#63

Sorry, but I don’t really have any good macro measure of mitochondrial health. I have tended to follow an increase in heart rate and blood pressure, but that only lasts a few days. Even that is not certain.

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#64

I wanted to look at that from a “qualitative” way. I’ll have a planned VO2max test but the last one was in mid 2023 so the differences, if any, might not be due to Mitopure.

In the papers, they looked at strength and Vo2 max: Urolithin A (UA) One of 4 Promising Agents 2024 by Brian Kennedy of NSU - #50 by adssx

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#65

I now have 30g of UA powder in my “substances to test” box. The week just gone was a rapamycin week (every 21 days at the moment) so I may go for this. I am pleased that my BP seems to have come back to good territory. (116/68-57 notwithstanding around 10g of sodium supplementation today)

It strikes me UA is a sort of spring cleaning substance. Is there an agreed dosing and or timing system?

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#66

I booked a free 15min call with a Mitopure “nutrition expert”. It might be useless but it was offered after I purchased :man_shrugging: If you have questions: let me know, I’ll ask her.

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#67

Question for Mito pure: how can I tell if it is working? What blood markers would indicate mitophagy and, later, improved mitochondrial function?

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#68

Do they still offer the blood test to check your Urolithin A levels? Any way to get it still? Or is there a third party that can provide it?

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#69

Thanks, I’ll try to ask all your questions on Friday. You can also email them at care@timelinenutrition.com to ask them directly.

By the way, their FAQ says:

  • Can I take more than one dose at a time?
    • “Our clinical studies have tested doses at 250mg-500mg and 1000mg. We have observed a positive impact on cellular and muscle function starting at the 500mg dose, but have noticed even more robust effects with the highest dose. In real life, we’ve received very positive feedback from customers taking 500mg per day with some customers saying that they felt further improvements when they doubled their dose.”
  • How long should I take it for and what is the recommend dosage?
    • “For optimal benefits, based on our clinical trials, we recommend 500mg of Mitopure® per day for a minimum of 4 months to support mitochondrial function and muscular health.”
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#70

I assume you’re referring to the lifespan sudy in WT mice in this paper in Geroscience. Note that this was 25 mg/kg food: they had the good form to measure their actual food consumption, and it worked out to 5 mg/kg of mouse body weight. “mice were fed regular chow or chow supplemented with 25 mg/kg of UA in alternate weeks (1 week on, 1 week off). Estimated oral consumption of UA is 5 mg kg day−1.”

So the implied human dose is even lower.

There’s a very important caveat to this paper: they only had 5 mice per arm in the survival study, which is about a tenth of what you need for a decent well-powered result.

OTOH, in this paper in AD mice they used 200 mg/kg,

Thanks for these!

That may be a better journal (I am not expressing a view), but it’s in vitro work, so the animal data is more likely to mean something.

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#71

My bad, thanks for catching that.

Hopefully UA will be tested in the ITP to give us some clarity…

@RapAdmin: when is the new ITP cohort usually announced? (hopefully we might get the FOIA before…)

#72

I’ve not followed the ITP announcements that closely. They take submissions at the end of February, and I’m assuming a few months after that they make a decision after meeting and discussing. I’ll see if I can go through some of my past email conversations with the ITP team and see if I can find anything with details.

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#73

This study is worth a read. It gives some functional tests for urolithin a impact.

Here are the functional tests:

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#74

This study is exactly on point. Thanks. However it just confirms my lack of confidence in Urolithin A as something that can help me beyond a tiny bit.

These study subjects were strange creatures: heathy BP despite being overweight, middle aged and very unfit (<30 vo2max). In 4 mos the UA subjects had great improvement in many strength markers while the placebo got worse in nearly everything. Why worse? What can explain worse? I think it’s small sample sizes and a measurement error that’s hard to detect.

When I am lifting weight, the most important factor in how much I can lift or how many reps I can get is motivation and willingness to suffer. I have it more on some days than others, and if I had a coach encouraging me, that would make a big difference. So, does UA affect motivation?

Another possibly is pain. Joint pain would limit the amount of weight lifted. Does UA impact joint pain?

And these are untrained people who would get big effects from small amounts of training. With such small groups (6-8), it would not take much training to overwhelm the effect of a supplement.

My conclusion so far is UA has a small positive effect. No magic here. I’ll keep watching.

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#75

Yes I was particularly interested in the impact of Urolithin a on grip strength (only 5% after 4 months) and realised the futility of self experimentation with such a small impact. And very interesting that the placebos had such a deterioration!
I think you’re right to treat this as a wait-and-see, but I suspect I’ll crack and chug down some 5000mcg capsules at some point.

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#76

Yes, but we would have to have data on people who had been assayed at least decades ago, when no one was looking: you need a baseline, ideally repeat measurements, and a decade or more of followup just to get all-cause mortality, let alone something that would hint at maximum lifespan.

And, in any case, having the bacteria would do nothing for you unless you were getting enough urolithin-A precursor. That would entail e.g. 200 g (almost half a pound) of pomegranates daily to match Timeline’s clinical dose. Not happening.

If the rodent data on the ITP’s four winners translated, that’s exactly what they would do (for those who were already destined to live over 100: life extension is relative to one’s non-intervened lifespan potential, of course).

MR wouldn’t help you: the relevant genes are in your gut microbiome, not your somatic cells.

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#77

Yes, there are people who will live close to or above 120 who are alive today without any interventions from ITP. So you can perhaps even say that smoking can help get some people above 120yrs.

Good point re the MR in this context - but there could still be genetic instruments that correlate with having a microbiome that is favorable to UA and that could be used for an MR analysis.

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#78

So I have something that is claimed to by Urolithin A from Aeturnum (which seems to be an australian limited company that looks to be inactive on the Australian companies records).

It is a greyish yellowish powder. Looking at a manufacturer online it perhaps should be yellow.

It wasn’t cheap so it might be a reliable substance. Aeturnum claim on their site to have third party certification, but I have not seen the certificates.

Any thoughts on this?

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#79

I am also taking that one, bought off Amazon UK. As you say, it isn’t cheap and you would think the regulatory environment of the UK would dissuade bad actors. :crossed_fingers:

#80

The “regulatory environment” is not particularly strong for something like this. The main constraint is whether or not Amazon get complaints. In any event I have now taken 0.5g of the substance and I can still type so it is not that lethal.

I am not drinking today so I might spot if autophagy is kicked off (it would potentially cause sleep problems.) My next scheduled Rapamycin dose is 20th Feb.

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