#9

Amylyx Pharmaceuticals the company behind the Sodium phenylbutyrate + TUDCA combo for ALS sponsored this recent trial in AD: Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer’s disease 2024

Led by researchers from Harvard and Oxford. Short (24 weeks) and small (95 participants). No improvement in cognition or total hippocampal volume on MRI but: “exploratory CSF biomarker results provided preliminary evidence that PB and TURSO engages AD pathology and pathways of neurodegeneration, synaptic function, gliosis, and oxidative stress. Along with those from preclinical studies showing a biological effect of PB and TURSO in AD models, the findings of our analysis provide support for further clinical development of PB and TURSO for AD and may be used to inform the design of subsequent trials.”

They used 3 g PB + 1 g TUDCA per day.

Outcomes not statistically significant but the combo is always on the “bad” side (lower is better for all except MoCa and hippocampal volume):

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#10

Be aware, if you are considering TUDCA, there are reports of low quality or fake supplements. Not sure if ConsumerLab or others have tested TUDCA, but I would be wary of most brands on Amazon.

#11

Yes a lof of TUDCA brands on Amazon seem terrible. I found that one that looks good: https://vitality-pro.com/product/tudca/ (I tend to trust Vitality Pro)

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#12

I went for Nutricost, it seems like the consensus on reddit is that it’s an okay brand, and it’s selling high volumes on iHerb:
https://www.iherb.com/c/tudca?sr=2

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#13

TUDCA had been on my radar for a while because of this interview.

Pretty interesting discussion on Alzheimer’s and dementia and when asked about one supplement with a ton of potential that no one is likely to have heard of, the neurologist says, very knowingly and without batting an eye, “TUDCA.” It caught my attention because nothing he says in the hour long conversation mentions TUDCA so it was a bit of an open loop. So I researched it and it did seem pretty interesting. Clearly just the tip of the iceberg can be made out so I do wish it had ITP or wormbot data.

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#14

After reading @ActivePassenger’s comment, I avoided Nutricost: Scientists Discover That Taurine Promotes Anti-Aging - #383 by ActivePassenger

Let us know how it goes. How much do you plan to take?

1 Like
#15

FYI “quack” is the first suggestion after his name on Google :grimacing:

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But I still think TUDCA is interesting. After all, Amylyx Pharmaceuticals has a $400m market cap and is primarily trying to repurpose TUDCA for neurodegenerative diseases (without success so far).

@DrFraser: what are your thoughts on UDCA or TUDCA for:

  • Liver health
  • Overall healthspan and lifespan
  • Neuroprotection
    ?

Other good data point, in this paper (Association of cardiovascular disease management drugs with Lewy body dementia: a case–control study 2023), ursodiol use was associated with a lower risk of LBD (0.69, CI: [0.56–0.82]).

On the other hand, nothing significant in Epiterna’s study: First report from Epiterna on the search for drugs that can extend human lifespan. HR for males: 1.2, CI: [0.6–2.5], p=0.7.

#16

This is a topic with scant evidence and not nearly enough information to act on. Vera-Health on this topic says (and couldn’t find any relevant articles in pub-med). Also I see both DoubleWood and Bulk Supplements have cost effective TUDCA) and are third party tested and reliable brands.

The question regarding the use of Tauroursodeoxycholic Acid (TUDCA) or Ursodeoxycholic Acid (UDCA) for liver health, neuroprotection, and longevity is indeed medically relevant. Both TUDCA and UDCA are bile acids with distinct therapeutic roles.

UDCA is primarily used for liver health, particularly in the treatment of primary biliary cholangitis. It works by reducing the concentration of toxic bile acids, thereby protecting liver cells and improving liver function. UDCA has been shown to improve liver enzyme levels and delay disease progression in certain liver conditions.

TUDCA, a derivative of UDCA, has gained attention for its potential neuroprotective effects. It is believed to reduce endoplasmic reticulum stress and apoptosis, which are implicated in neurodegenerative diseases. Some studies suggest that TUDCA may have benefits in conditions like amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, although more research is needed to confirm these effects.

Regarding longevity, the evidence is less clear. While both TUDCA and UDCA may contribute to improved health outcomes by supporting liver function and potentially offering neuroprotection, direct evidence linking these compounds to increased lifespan in humans is limited. Most longevity studies are conducted in animal models, and their applicability to humans remains uncertain.

In summary, UDCA is well-established for liver health, while TUDCA shows promise for neuroprotection. Both may contribute to overall health, but their direct impact on longevity requires further investigation. Always consider consulting with a healthcare professional before starting any new treatment.

1 Like
#17

There are few larger companies that provide CoA’s when asked. I think I prefer a larger supplement company with higher volume compared to a smaller one since if there is any problem it will be detected quicker. Seems like a good heuristic for most things.

I think 500 mg.

#18

In terms of liver health I think there’s enough evidence, no?

For Covid-19 prevention and recovery, the evidence looks good to me as well.

#19

I’m not sure what this term “liver health” means. I know what liver diseases are.
Folks who have no evidence of any liver dysfunction, e.g. INR normal, Ammonia normal, Albumin normal, Transaminases optimal, Alk Phos normal. MRI liver without steatosis. That probably makes up the vast majority of folks on this board.

Taking something for “Liver Health” when there is no issue probably is unnecessary, but there could be other benefits, if the neurocognition component ends up being real.

On the topic just of “Liver Health” here is what Vera-Health says
Tauroursodeoxycholic acid (TUDCA) is a bile acid derivative that has been studied for its potential benefits in liver health. TUDCA is known for its ability to protect liver cells from damage and improve liver function. It works by reducing endoplasmic reticulum (ER) stress, which is a condition that can lead to cell death and is implicated in various liver diseases. By alleviating ER stress, TUDCA helps in maintaining cellular homeostasis and preventing apoptosis (programmed cell death) in liver cells.

Additionally, TUDCA has been shown to have anti-inflammatory and antioxidant properties, which further contribute to its protective effects on the liver. These properties help in reducing liver inflammation and oxidative stress, both of which are common in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and cholestatic liver diseases.

Clinical studies have suggested that TUDCA may improve liver enzyme levels and histological features in patients with liver diseases, indicating its potential as a therapeutic agent. However, while the current data is promising, more extensive clinical trials are needed to fully establish the efficacy and safety of TUDCA in various liver conditions
1
.

In summary, TUDCA benefits liver health primarily through its ability to reduce ER stress, inflammation, and oxidative damage, thereby protecting liver cells and improving liver function.

References

  1. UDCA, NorUDCA, and TUDCA in Liver Diseases: A Review of Their Mechanisms of Action and Clinical Applications.
    Handbook of Experimental Pharmacology
    Cabrera et al.
1 Like
#20

OK sorry, I meant elevated AST, ALP, ALT or GGT as UDCA lowers these by 30–50% apparently.

#21

So … if those are elevated, addressing the cause is the primary focus.

For most of us, we have normal levels, so the liver health part of this isn’t the benefit - the question is on the neurocognitive component, which I wish we had more evidence for.

Now for @John_Hemming who enjoys his ethanol … might be another mitigating action in addition to the citrate.

On UDCA seems like Vera-Health has much more to say, and many more references
Ursodeoxycholic acid (UDCA) has shown potential in addressing neurodegeneration through various mechanisms. UDCA is a bile acid that has been studied for its neuroprotective properties in several neurodegenerative diseases. It is known to cross the blood-brain barrier, making it a promising candidate for treating central nervous system disorders.

In Parkinson’s disease (PD), UDCA has been investigated for its ability to rescue mitochondrial function, a key factor in neurodegeneration. A study demonstrated that high-dose UDCA was safe and well-tolerated in early PD, with evidence of improved ATP hydrolysis in the midbrain, suggesting potential neuroprotective effects
7
.

UDCA has also been studied in the context of GM2 gangliosidosis, a neurodegenerative disorder. It was found to diminish neurite atrophy and decrease pro-apoptotic signaling, indicating its role in alleviating endoplasmic reticulum stress and promoting neuronal survival
8
.

Furthermore, UDCA and its derivative, tauroursodeoxycholic acid (TUDCA), have been shown to reduce prion protein conversion and neuronal loss in prion disease models. These compounds demonstrated neuroprotective effects by reducing astrocytosis and prolonging survival in prion-infected mice, highlighting their potential in treating protein misfolding diseases
1
.

The modulation of apoptosis through the p53 pathway is another mechanism by which UDCA exerts its effects. It has been suggested that UDCA can modulate p53-triggered apoptosis, which is relevant in various neurodegenerative conditions
1
.

Overall, UDCA shows promise as a therapeutic agent in neurodegenerative diseases due to its ability to modulate mitochondrial function, reduce protein misfolding, and influence apoptotic pathways. However, further research and larger clinical trials are needed to fully establish its efficacy and safety in these conditions.

References

  1. Solving neurodegeneration: common mechanisms and strategies for new treatments
    Molecular Neurodegeneration
    Wareham et al.
    121 citations
    2022
    Major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions are discussed.

Open Access
Highly Influential Journal
Show more
2. The Q/R editing site of AMPA receptor GluA2 subunit acts as an epigenetic switch regulating dendritic spines, neurodegeneration and cognitive deficits in Alzheimer’s disease
Molecular Neurodegeneration
Wright et al.
9 citations
2023
Eliminating unedited GluA2(Q) expression in AD mice prevented dendritic spine loss and hippocampal CA1 neurodegeneration as well as improved working and reference memory in the radial arm maze and revealed increased spine density in non-AD mice with exonically encoded Glu a2(R) as compared to their wild-type littermates, suggesting an unexpected and previously unknown role for un edited GLUA2 (Q) in regulating dendrites.

Open Access
Highly Influential Journal
Show more
3. BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia
Molecular Neurodegeneration
Sudwarts et al.
39 citations
2022
The consensus from in vitro and in vivo findings showed that loss of Bin1 impaired the ability of microglia to mount type 1 interferon responses to proinflammatory challenge, particularly the upregulation of a critical type 1 immune response gene, Ifitm3 .

Open Access
Highly Influential Journal
Show more
4. Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Molecular Neurodegeneration
Querfurth et al.
131 citations
2021
Beyond rapamycin; an mTOR inhibitor, there are rapalogs having greater tolerability and micro delivery modes, that hold promise in arresting these age dependent conditions.

Open Access
Highly Influential Journal
Show more
5. cGAS-STING triggers inflammaging-associated neurodegeneration
Molecular Neurodegeneration
Izquierdo et al.
0 citations
2023
Open Access
Highly Influential Journal
6. Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
Translational Neurodegeneration
Verma et al.
169 citations
2022
Evidence for sublethal excitatory injuries in relation to neurodegeneration associated with Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and Huntington’s disease is reviewed and strategies for normalizing the flux of calcium into and out of the mitochondrial matrix are discussed, thereby preventing excitotoxic dendritic loss.

Open Access
Influential Journal
Show more
7. A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson’s Disease.
Movement Disorders
Payne et al.
14 citations
2023
High-dose UDCA is safe and well tolerated in early PD and midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis.

Open Access
Influential Journal
Show more
8. Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis
International Journal of Molecular Sciences
Morales et al.
2 citations
2023
It is found that UDCA significantly diminished the neurite atrophy induced by GM2 accumulation in primary neuron cultures, suggesting a direct interaction between UDCA and the cytosolic domain of PERK, which promotes kinase phosphorylation and dimerization.

Open Access
Influential Journal
Show more
9. Glycoursodeoxycholic Acid Reduces Matrix Metalloproteinase-9 and Caspase-9 Activation in a Cellular Model of Superoxide Dismutase-1 Neurodegeneration
Molecular Neurobiology
Vaz et al.
53 citations
2014
Data highlight caspase-9 and MMP-9 activation as key pathomechanisms in ALS and GUDCA as a promising therapeutic strategy for slowing disease onset and progression.

Show more
10. The role of p53 in apoptosis.
Discover medicine
Amaral et al.
347 citations
2010
It is suggested that the finely tuned, complex control of p53 by Mdm-2 (mouse double minute-2, an oncoprotein) is a key step in UDCA modulation of p52-triggered apoptosis, with particular emphasis on potential benefits of UDCA.

Show more
11. Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease
Journal of Virology
Cortez et al.
49 citations
2015
It is demonstrated that TUDCA and UDCA substantially reduced PrP conversion in cell-free aggregation assays, as well as in chronically and acutely infected cell cultures, and this effect occurs in prion disease, with an added mechanistic target of upstream prion seeding.

Open Access
Show more
12. Targeting the p53 pathway of apoptosis.
Current pharmaceutical design
Amaral et al.
62 citations
2010
Recent developments of p53-induced apoptosis in human diseases are highlighted, and controversies arising from the double-edge sword of targeting p53 in disease are discussed.

Show more
13. Role of neuroinflammation in neurodegeneration development
Signal Transduction and Targeted Therapy
Zhang et al.
259 citations
2023
The factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis are reviewed.

Open Access
Show more

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#22

Rapamycin definitely pushes up GGT.

These are all my GGT figures since 2021 (only started weekly part into 2022) you can see the high dose Rapamycin pushing it up at the and it is only slowly coming down. One reason I may hold back on Rapamycin after 8th December is to see what happens with GGT.

43		37		32		28		34		34		28		29		30		30		31.89		26		34.94		28		36.71		37.6		30		24.68		27.96				29		35		30		28						30.2				31.15				23.7				23.5		23.99		27		22.73		24		23		22.12				26		27		23		28		29		32				27		28		30		30		27.9		27		27				23		25		24.7				25		26.1				22		33.4		25		25.5				25		38.8				36.9				29.9		28		32.3		32.16		25		24		28		32		27.7					26		29.8		28		27.8		28		32.6		32		26		33.1		28		28		32.5		33		26		28		32		31		31		30				29.2		28		35.7		30		32.4		32		32.5		31		41		32		27.2		34		33.1		36.8		33		27.4						35				35		43.3		37				40		39.4				48		43.8		46		38.9		39		44		16.8		50.6		56.3		55.8		58		56.3		57.4		49.8		49		51		56		58		59		56

GGT is just at the top end of the normal range, but it was a lot lower.

2 Likes
#23

The man is convinced C. Diff. is what causes Alzheimer’s so that sounds a bit cooky on the surface but he presents his clinical evidence which suggests to me that infections of all sorts can cause Alzheimer’s if they make it into the brain. It’s probably a subset of causes.

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#24

Vaccines of all kinds seem to be associated with reduction in neurodegenerative disease. Assuming that this is due to a reduction in infections and not some other effect of vaccines would seem to imply that infection burden is possibly a causal factor for neurodegenerative disease. If we take that assumption, CDiff could very well be contributing to neurodegenerative disease.

Search vaccines on this forum for more info, eg Shingles vaccine had a significantly lower risk of developing dementia within 6 years of vaccination

3 Likes
#25

Low level infection increases inflammation, which is a known neuro problem.

Plus many bacterial and viral infections leave a mark on the immune system as a way to avoid complete clearance. Once you get a staph infection you become more susceptible due to the way staph modifies your immune system to hide.

These hidden reservoirs of past infections are quite the thing and cause a variety of seemingly unrelated illnesses.

Covid is a significant modifier of the immune system.

#26

I’m interested in this concept. Broadly speaking it seems like a mental safety barrier that people could use to avoid marketing driven wishful thinking.

The whole concept of “marginal gains” whereby lots of little benefits could add up to big improvements seems foolish when talking about a biological system we don’t understand. In addition, the wishful thinking associated with taking stuff that is “good for you” can remove the motivation to make real lifestyle change that would really drive improvement in healthspan outcomes. Taking a pill is so easy to do… it’s an attractive nuisance I’m fighting to avoid.

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#27

Just checked the half-life: 4 days for UDCA but 3 hours for TUDCA!

#28

I’m starting ~400 mg TUDCA and 10 mg Ezetimibe. Not taking any other medication right now. Hoping to lower ALP and ApoB. ALP already decreased a bit from 108 U/L with I think vitamin D supplementation. I took a few other blood tests. We’ll see…

ALT 26 U/L
AST 20 U/L
ALP 102 U/L
GGT 14 U/L
Bilirubin 0.9 mg/dL
ApoB 60 mg/dL
Triglycerides 64 mg/dL
CRP 0.7 mg/L

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