#30

I think I got heartburn from this but might be confounding as N=1 so I’m quitting this for now…

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#31

However, it appears that TUDCA is metabolised into UDCA.

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#32

This is an interesting paper to add to this topic

Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer’s Disease

https://www.sciencedirect.com/science/article/pii/S0022283618309872?via%3Dihub

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#33

The author, Heather Mortiboys, is leading the UDCA trial in PD: The UP Study results - Cure Parkinson's

And she’s now fast testing 100 promising compounds (including rapamycin, empagliflozin, lithium, terazosin, Theracurmin, telmisartan, omega 3, NAC, UDCA, etc.) in human cells for PD: Prioritising the most promising drugs for Parkinson’s: our new drug screening project - Cure Parkinson's

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#35

Most interesting to me in delineating all the ways in which apoE4 carriers’ mitochondria are fucked. I had already gathered as much, but not the bit that mitochondrial impairments seem to extend to all cell types in the body. Only knew of brain and muscle cells for sure. I’d have to think it’s a good idea to double down on all known agents for improving mitochondrial function and biogenesis.

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#36

Can’t think of anything better than exercise, I wonder if it would be a good idea to look at what PED’s (performance enhancing drugs) are banned for endurance athletes or other sports directly dependent on mitochondria. E.g AICAR just showed up in a perplexity search for me:

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#37

I tried AICAR 2 years ago when I did a lot of running, it does something, it’s a simular result / feeling to injectable carnitine 1g plus. For mitochondrial function during exercise I suspect that high dose methylene blue (20mg) is more cost efficient than AICAR

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#38

Well, if it’s banned it probably works, is my reasoning, at least on the performance enhancing aspect, whether it’s safe is another question.

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#39
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#40

One more interesting datapoint for TUDCA: Tauroursodeoxycholic acid regulates macrophage/monocyte distribution and improves spinal microenvironment to promote nerve regeneration through inhibiting NF-κB signaling pathway in spinal cord injury 2025

:warning: Preprint + China :warning:

We found TUDCA restored spinal NSCs migration and proliferation and reduced spinal NSCs and neurons apoptosis and axon degeneration by regulating inflammatory response in vitro. TUDCA treatment promoted wound healing, down-regulated genes related to inflammatory response, and up-regulated genes related to spinal cord development in SCI mice. Our study provided evidence that TUDCA treatment regulated monocyte/macrophage distribution and improved the microenvironment to promote nerve regeneration in SCI mice.

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#41

Tauroursodeoxycholic Acid Confers Protection Against Oxidative Stress via Autophagy Induction in Retinal Pigment Epithelial Cells 2025

Tauroursodeoxycholic acid (TUDCA) has been shown to protect against oxidative damage in retinal pigment epithelial (RPE) cells. However, the mechanisms by which it mediates these protective effects have not been thoroughly investigated in the context of age-related macular degeneration (AMD) disease onset and progression. We measured LC3-II and p62 expression via Western blot and immunohistochemistry in RPE cells treated with H2O2, TUDCA, or a combination of both to measure autophagy induction. To determine autophagy flux, we measured the expression of LC3-II/LC3-I in RPE cells in the presence of bafilomycin via Western blot. To determine the mechanistic pathways of TUDCA-induced autophagy, we measured the protein expression of autophagy regulators (Atg5, Beclin-1, S6, AMPK, and Akt) via Western blot. We show that TUDCA-mediated autophagy induction confers protection of RPE cells against oxidative damage via mTORC1/mTORC2 independent pathways but depends on Atg5. Our work adds to the overall understanding of RPE cell homeostasis and highlights the role of TUDCA in maintaining RPE health.
Our studies show that TUDCA’s cytoprotective effect in RPE cells is AMPK-independent. The activation of the Akt pathway by TUDCA in the presence of OS has significant implications for both cytoprotection and autophagy induction. Akt can phosphorylate and inhibit several pro-apoptotic factors, thereby enhancing cell survival under stress conditions. Akt activation can also induce autophagy. While Akt is typically associated with the mTOR pathway, which inhibits autophagy, there are situations where Akt activation can promote autophagy indirectly. For instance, Akt can modulate the activity of transcription factors like FOXO [61], which can upregulate autophagy-related genes. In summary, TUDCA activation of Akt in the presence of oxidative stress could enhance cytoprotection by inhibiting apoptotic pathways and potentially promoting autophagy through alternative signaling routes. Thus, it is crucial to consider that the specific cellular context, the type of stressor, and the duration of TUDCA treatment can diversely influence these signaling pathways.
We investigated whether RPE autophagy induction was seen with other bile acids. The lack of change in LC3-II levels in cells treated with TCA or TCDCA alone suggests that these treatments do not significantly affect autophagosome formation or the autophagic process under the conditions tested. The increase in LC3-II levels with the combined treatments of H2O2 and TCA or TCDCA indicates an accumulation of autophagosomes. This accumulation could be due to increased autophagosome formation or a blockage in autophagosome–lysosome fusion, leading to their accumulation. However, the concurrent increase in p62 levels indicates that these autophagosomes are not efficiently degraded, indicating impairment in autophagic flux. We cannot be sure of this conclusion without repeating an autophagy flux experiment with TCA and TCDCA, which is a limitation of this study. The lack of conclusive evidence could be a relevant next step in determining if autophagy induction is unique to TUDCA or can be seen with other bile acids.

@John_Hemming fyi

#42

Did you managed to lower your ALP using TUDCA?
I have similar numbers:
ALT:16
AST:13
GGT: 8
ALP: 110
bALP: 14

If bone is not my problem it has to be the liver, but I don’t know why my liver is having to produce such a large quantity of ALP?

#43

No I haven’t put much attention to it yet, and I’d wait for NootropicsDepot’s TUDCA.
You could test your vitamin D levels, you might be deficient or something else.

#44

Are they going to release TUDCA? By the way, any idea why none of the most reputable supplement manufacturers sell TUDCA? It only seems to be sold by brands I’ve never heard of, with the exception of Double Wood and Nutricost, neither of which is one of my go-to brands.

#45

Yes, they’re working on it. I don’t know, but MYASD (CEO) have said IIRC that the real TUDCA was expensive, so they were expecting other companies to sell other bile acids disguised as TUDCA. They found a supplier for it though recently at a better price.

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#46

I don’t pretend to know what’s going on, but my wife takes quite a bit of TUDCA, so I started taking it one pill 4 times a week and my ALP went from the 100’s (like yours) to 67 this time. Just did my yearly and put the numbers in Levine and got one of the best I ever have gotten. Actual age 64, Levine age 51. I don’t know if it’s meaningless because I’m cheating on the ALP or not.

I’d rather be 51, but I’ll take it.

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#47

How much TUDCA does your wife take daily in mg? How much is each pill? Have you considered taking more? It would be interesting to see if a higher dose leads to an even lower ALP.

#48

Ora Biomedical tested UDCA and TUDCA on worms btw: Ora Biomedical Million Molecule Challenge Results - #352 by adssx

The results don’t confirm the 2024 Chinese paper: UDCA (ursodiol) / TUDCA for healthspan and lifespan? - #4 by adssx

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#49

Ok, I may have overstated. Just asked her and she takes 2 pills when it hurts. She has done that twice a day, but not usually. But there is a twist.

I bought the body bio, which costs twice as much and has half the TUDCA. Because like I said I’m a bad shopper and I happened to be on fullscript. She says it works much better and she quit taking hers. Hers was the VINATURA, which has 1000mg plus milk thistle. She says it doesn’t work at all. Also it doesn’t smell or taste like bile, which the bodybio does. So there is a big difference in product here according to her.

#50

WOW! wish I had come across this earlier! i.e that weight loss can catalyze? cause? gallstones.

After taking only the "trainer"dose of Rybelsus for about two weeks, had severe back pain, and ran sky high WBC. A CRT showed incipient gallstones and there may have been a small kidney stone passed.

I associated this with the Rybelsus, but now I see that it was the weight loss (went from 104 to about 97 in just a couple of weeks) might well have been the absolute causal.

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