674 replies to this topic

[ceridwen]

DHEA might help and really get to the root of the problem. Life extension says some very interesting things about it.

[Turnbuckle]

If you can't get HEPPS, ceridwen, try it with just taurine. You might also add tauroursodeoxycholic acid (TUDCA), which is available in the UK. This is a bile acid that is like HEPPS and taurine in having a sulfonic acid group at one end, and has been demonstrated to lower Amyloid-β.

 

TUDCA treatment significantly attenuated Aβ deposition in the brain, with a concomitant decrease in Aβ₁₋₄₀ and Aβ₁₋₄₂ levels. The amyloidogenic processing of amyloid precursor protein was also reduced, indicating that TUDCA interferes with Aβ production. In addition, TUDCA abrogated GSK3β hyperactivity, which is highly implicated in tau hyperphosphorylation and glial activation. This effect was likely dependent on the specific activation of the upstream kinase, Akt. Finally, TUDCA treatment decreased glial activation and reduced proinflammatory cytokine messenger RNA expression, while partially rescuing synaptic loss. Overall, our results suggest that TUDCA is a promising therapeutic strategy not only for prevention but also for treatment of AD after disease onset.

https://www.ncbi.nlm...pubmed/25443293

 

 

As for DHEA and lifestyle changes and all the other approaches to AD, these are better discussed on another thread. My intention with this one is a quick fix to Aβ/tau using easily available supplements.

[Mind]

I think you misunderstood my point turnbuckle. There are several "big pharma" drugs that were tested in humans and DID dissolve a-beta.

 

The reason the drugs were reported as "failures" is because they did not improve cognitive functioning of people with dementia and Alzheimer's.

 

If your primary motivation is to dissolve a-beta, then these would work, and I have considered taking them myself to prevent the build up of a-beta in my brain as I age. It doesn't matter if the drugs show some cognitive improvement. I just want to clear out the a-beta.

[Turnbuckle]

I think you misunderstood my point turnbuckle. There are several "big pharma" drugs that were tested in humans and DID dissolve a-beta.

 

The reason the drugs were reported as "failures" is because they did not improve cognitive functioning of people with dementia and Alzheimer's.

 

If your primary motivation is to dissolve a-beta, then these would work, and I have considered taking them myself to prevent the build up of a-beta in my brain as I age. It doesn't matter if the drugs show some cognitive improvement. I just want to clear out the a-beta.

 

 

Can you recommend one that is available?

[ceridwen]

Thanks Turnbuckle I am trying Taurine now. I think I might also have found a tick at the back of my head but that is a more recent thing I think having been ill for 4 years. I think the Taurine is making some changes but not sure which way it's going as yet. Seems to be lessening my tinnitus I hope

[Daniel Cooper]

 

 

 

 

No anti-Aβ drugs have proven successful in trials. Part of the problem is that big pharma has been looking for a single patentable silver-bullet drug that can make them billions. But for the great majority that is not going to work, because few of these groups are looking at both Aβ and tau.

 

 

 

I thought aducanumab was successful.  Looks like they are going forward w/ Stage 3 clinicals.

 

 

Depends what you mean by successful.

 

Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating-Sum of Boxes and Mini Mental State Examination scores. 

https://www.ncbi.nlm...pubmed/27582220

 

 

 

Though this failure to reverse the clinical decline may have more to do with their attacking only the Aβ aspect and not the tau. Still, after one year? The removal of Aβ with HEPPS, while with mice, went much faster than that. See Fig. 4 in this paper.

 

 

 

Turnbuckle -

 

As I'm certain you're aware, the Korean group that did that paper on HEPPS also studied Taurine, in fact they studied it first.  Were you able to get a handle on how effective HEPPS was versus Taurine were at removing Aβ plaque?

[Turnbuckle]

 

 

 

 

Turnbuckle -

 

As I'm certain you're aware, the Korean group that did that paper on HEPPS also studied Taurine, in fact they studied it first.  Were you able to get a handle on how effective HEPPS was versus Taurine were at removing Aβ plaque?

 

 

See my post #11 for a rationale of including both. Without knowing what the actual efficiencies are, they will likely be quite different due to their half lives when taken once a day rather than continuously in drinking water. Taurine has a short half life of an hour, HEPPS a longer one, and TUDCA is likely longer still, though I haven't been able to find a half life for it. 

 

TUDCA is not the best option compared to HEPPS, especially for drinkers. It is protective of the liver if taken after alcohol, but it should be avoided before. See this paper--Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid. Otherwise it looks interesting--

 

There also appears to be some scope to apply bile acids as potential AD therapeutics [11,12]. One line of inquiry is based upon the strong modulatory effect of some bile acids on apoptosis and the observation that tauroursodeoxcholic acid (TUDCA) can inhibit neuronal apoptosis in a number of experimental models of neurodegenerative disease. TUDCA appears to be neuroprotective in AD, Huntington’s disease (HD), and Parkinson’s disease (PD) [11]. In models of AD pathology TUDCA reduces p53-mediated apoptosis in AD mutant neuroblastoma cells [11]. Systemic administration of TUDCA significantly reduces striatal neuropathology in the R6/2 transgenic HD mouse [12]. TUDCA improves the survival and function of nigral transplants in a rat model of Parkinson’s disease [13]. Furthermore, in an animal model of acute neuro-inflammation TUDCA has a ‘triple anti-inflammatory’ effect on the glial cells [14]. It reportedly reduces glial cell activation, reduces microglial cell migratory capacity, and lowers expression of chemoattractants and vascular adhesion proteins [14].

https://www.ncbi.nlm...les/PMC5487999/

 

[Daniel Cooper]

Ah, I did not appreciate that the half life for Taurine was so short.

 

I remember someone was trying to cook up their own "delayed/extended release" capsule a while back. Anyone remember if there was any success with that?  It would be interesting on other compounds as well.

 

 

 

 

[Turnbuckle]

Ah, I did not appreciate that the half life for Taurine was so short.

 

I remember someone was trying to cook up their own "delayed/extended release" capsule a while back. Anyone remember if there was any success with that?  It would be interesting on other compounds as well.

 

 

Redeposition of Aβ would seem to be a problem if you don't take it continuously, and that's why I included the oleuropein. Otherwise you could take it as the mice did, mixing it into everything you drink. I haven't seen any ER taurine.

[ceridwen]

If Taurine only lasts for 1 hour should the dose be increased and taken every hour?

[ceridwen]

Today I took Taurine every 2 hours. I don't know if this is being successful. How soon should I notice results?

[tunt01]

 

Redeposition of Aβ would seem to be a problem if you don't take it continuously, and that's why I included the oleuropein. Otherwise you could take it as the mice did, mixing it into everything you drink. I haven't seen any ER taurine.

 

 

I still fail to see how EPPS isn't effectively ER taurine.  I realize I don't have the chemistry background that others have here, but the Kim papers seem to argue that EPPS, its longer half-life and its taurine mimick status, was the reason they choose it.

[tunt01]

Today I took Taurine every 2 hours. I don't know if this is being successful. How soon should I notice results?

 

The Kim papers were done over 6 weeks w/ Taurine (1000 mg/kg in mice) and 3.5 months for EPPS (30 mg/kg in mice).  And that is in mice subjects (i.e. mouse lifespan).  I would think at least a couple weeks, ideally a couple months.

[Turnbuckle]

The mice had only Aβ, so how much you see and how soon will be dependent on how much tau you have. But it will certainly take a while. I noticed a difference after a couple of days with taurine/HEPPS/oleuropein, but I didn't have much tau and I'd only had obvious symptoms for a few months. If you've had it for years, then you'll also have a problem with glial cells migrating over to the plaques. Hopefully they will retreat on their own once the plaques are gone.

Edited by Turnbuckle, 18 January 2018 - 11:16 PM.

[ceridwen]

I don't know if it's going to make a difference. I have been taking loads of different supplements for years with no success. I will also take Metformin as I believe AD to be diabetes of the brain. Carbohydrates and sugar seem to cause the worst symptoms. I shall try your protocol as well though.
There are many different kinds of AD what works for 1 kind might not work for another! But worth a try anyway.

[ceridwen]

Discovered the olive oil I have in the house right now is the wrong sort. So ordered some from Google (40% oleupurin). My brain is failing me massively at the moment or maybe I've just become "moderate"

[Daniel Cooper]

BTW - it seems that some of the  pathogenesis of Alzheimer's may be the brain losing the ability to effectively metabolize glucose.  That may explain why simply clearing Aβ plaque doesn't seem to reverse the disease in human test subjects so far.

 

So, we might consider adding things that increase insulin sensitivity.  Perhaps inositol?  

 

 

 

[Mind]

 

I think you misunderstood my point turnbuckle. There are several "big pharma" drugs that were tested in humans and DID dissolve a-beta.

 

The reason the drugs were reported as "failures" is because they did not improve cognitive functioning of people with dementia and Alzheimer's.

 

If your primary motivation is to dissolve a-beta, then these would work, and I have considered taking them myself to prevent the build up of a-beta in my brain as I age. It doesn't matter if the drugs show some cognitive improvement. I just want to clear out the a-beta.

 

 

Can you recommend one that is available?

 

 

No clue on that question. Sorry. I just know that there are some drugs out there that have been tested in humans.

 

I suspect it would be expensive to attempt to get a third party to synthesize it.

[Daniel Cooper]

 

No clue on that question. Sorry. I just know that there are some drugs out there that have been tested in humans.

 

I suspect it would be expensive to attempt to get a third party to synthesize it.

 

 

 

My rather obvious conclusion is that there is some sort of upstream pathology that causes Aβ plaques rather than Aβ plaques being a root cause itself.  Whatever that cause is, it seems to be also responsible for a majority of the cognitive decline that Alzheimer's patients experience, although I don't doubt that excess Aβ plaques and tau tangles are pathological in their own right and can cause cognitive decline. 

 

We have various mouse models for Alzheimer's, but whatever route is being used in those models to induce Aβ plaque formation (in many cases that is the direct inject of human Aβ) does not seem to be the operative route in human patients.  But, you certainly do see that clearing these plaques in mice improves their cognitive measures so reducing them in humans seems like a worthy goal in any case.

 

I do think that glucose metabolism in the brain is likely involved in the disease process.  Restoring that to normal would seem like a good idea.

[Heisok]

Thank you for  sharing research, and self trials !!!

 

If you have more thoughts about the whole glial process, please post.

 

I posted a thread about an article from Brain A Journal of Neurology about Tauopathy, and many other issues.. Likely very informative.

 

The mice had only Aβ, so how much you see and how soon will be dependent on how much tau you have. But it will certainly take a while. I noticed a difference after a couple of days with taurine/HEPPS/oleuropein, but I didn't have much tau and I'd only had obvious symptoms for a few months. If you've had it for years, then you'll also have a problem with glial cells migrating over to the plaques. Hopefully they will retreat on their own once the plaques are gone.

 

Edited by Heisok, 20 January 2018 - 12:01 AM.

[ceridwen]

I thought Inositol was harmful but I can't remember why

[ceridwen]

Perhaps Glucosamine might be added to the stack?

[ceridwen]

Taurine has beneficial effects on glucose levels though

[ceridwen]

I started taking Taurine and Nicotinamide. Problem is I have started feeling very sick and found that these supplements exacerbated this. I was sick yesterday. Should I continue to try? but maybe at a reduced level because I feel I can't take a lot of supplements at present?

[Turnbuckle]

I started taking Taurine and Nicotinamide. Problem is I have started feeling very sick and found that these supplements exacerbated this. I was sick yesterday. Should I continue to try? but maybe at a reduced level because I feel I can't take a lot of supplements at present?

 

I always go to amazon for these questions and look under the one star reviews. Out of more than one thousand reviews for taurine, I found one that said it gave them an acid stomach and they were up all night. For nicotinamide, a few one star reviews said it gave them stomach discomfort or burning. So the answer is to try just one at a time at first, to take them with food and/or with antacids, and not to take them at the same time or when you are otherwise sick.

Edited by Turnbuckle, 21 January 2018 - 11:36 AM.

[Blueflash]

HEPPS [aka, EPPS] — 1g (1/4 level teaspoon)

Taurine — 8g (2 level teaspoons)

Oleuropein — 200 mg

Vitamin C — 2g

 

May be a dumb question, but is all this taken at once?

[Turnbuckle]

Yes. You can dissolve the taurine and HEPPS in water or fruit juice, and since taurine has a short half life, you'll want to take the oleuropein and C and the same time. Ester C might be best due to its long half life.

[Blueflash]

Thank you so much, Turnbuckle. I really appreciate what you've done for the community. I think some of these protocols will be game changers for many.

[ceridwen]

I couldn't get HEPPS. I ordered some but it never arrived. I have to come to terms with the fact that I'm dying. I will continue to take the rest of the stack but I'm in great pain. Thanks for telling us about it though

[aribadabar]

Yes. You can dissolve the taurine and HEPPS in water or fruit juice, and since taurine has a short half life, you'll want to take the oleuropein and C and the same time. Ester C might be best due to its long half life.

 

What is the suggested duration of this protocol for prevention purposes (i.e. if there is no apparent manifestation of symptoms)?

 

Thanks!