674 replies to this topic

[Neurocryo]

 

AD protocol update:

 

I’m going to put the previous protocol with grape juice and methylene blue on hold and revert to a simplified version of an older one. A couple of commenters worried about the HEPPS dose and its stability in grape juice, and likely they are right. The results seemed fine for a couple of months, after which symptoms began returning in one individual, and after one dose of the simplified protocol shown below, the symptoms resolved within an hour. As I noted in the above post, I have another idea for using the MB/HEPPS protocol to simultaneously treat P-tau and Aβ as well as a third AD etiology, but I’m still testing it.

 

 

Plaque cocktail (dose):

 

●   Taurine (5 g)

●   HEPPS (500 mg)

●   Nicotinamide (500 mg)

●   Sulforaphane glucosinolate (50 mg)

●   Oleuropein (100 mg)

●   Hydroxytyrosol (25 mg)

●   Vitamin C (1 g)

●   Glutathione, liposomal or phytosomal (1 g)

 

Dosed as needed — once a day to once a week.

 

 

 

Haven’t tried HEPPS yet cause I’m still pretty young and good genotype.  I have taken some head hits so focus my protocols on tau.

 

I think you may need to incorporate some additional chemicals to address the brain physiology this regiment will elicit.  When you break up a plaque, it won’t go straight from fibril to monomer.  The plaque will transiently be an oligomer and at that instant, in theory, your brain will experience a huge molar excess of toxic species compared to when they are stabilized in fibrils and dynamically forming smaller concentrations of oligomers.  
 

I would recommend a pretreatment with AHCC, lions mane, autophagy inducers before disrupting the plaques,  My theory is to prime my brain to respond to the transient extreme increase in concentration of toxic species of tau, promote neurotrophic signaling, autophagy, and immune system to chomp up the prions first.

 

From what I’ve read about tau it seems to be phosphorylated allll over the place.  One thing I am starting to take into consideration is dosing with one tau disrupted at a time.  That is, some anti tau intercalators may be more effective in an aggregate of a specific species of phosphorylations.  Theory is that if you hit it with methylene blue or anti tau compound x, you affect all the plaques in your brain differently.  I look at it like plaques developing antibiotic resistance so you can hit them with various disrupters in succession alternating, before a bad phosphorylation profile takes hold.

[lancebr]

So any opinions about the newly FDA approved Alzheimer's drug called Aduhelm/Aducanumab?

 

 

https://www.statnews...s-drug-aduhelm/

 

https://www.cnbc.com...st-4-years.html

 

 

Supposedly it is suppose to "clear away clumps of a misshapen protein called beta-amyloid".

Edited by lancebr, 07 June 2021 - 07:24 PM.

[Advocatus Diaboli]

.

 

A brand of HEPPS that can be used in protocol.

 

Another more expensive choice (per gram)

Edited by Advocatus Diaboli, 07 June 2021 - 07:58 PM.

[EliotH]

So any opinions about the newly FDA approved Alzheimer's drug called Aduhelm/Aducanumab?

 

 

https://www.statnews...s-drug-aduhelm/

 

https://www.cnbc.com...st-4-years.html

 

 

Supposedly it is suppose to "clear away clumps of a misshapen protein called beta-amyloid".

 

From a UPI article (no direct link I copied from another website). Turnbuckle's protocol is much less expensive and probably works better.

 

The drug could carry a cost somewhere between $10,000 and $50,000 per patient per year, according to Wall Street analysts, though Biogen has yet to announce a price.

 

[aribadabar]

 

Another more expensive choice (per gram)

 

That's because you haven't used the same size package.

[Advocatus Diaboli]

Re: post #632:

 

lancebr, from your first link:

 

"In two clinical trials, about 40% of clinical trial patients who got the approved dose of Aduhelm developed painful brain swelling. Symptoms included headache, dizziness, visual disturbances, nausea, and vomiting; about 17% to 18% of patients had microhemorrhages, or small bleeds in their brain. Patients will be monitored for brain swelling before their seventh and 12th infusions. If imaging shows severe swelling, treatment can continue “with caution only after a clinical evaluation and a follow-up MRI demonstrates radiographic stabilization,” the label says."

 

That would be enough for me to say "no thanks" to Aduhelm.

 

 

Re: post #635

 

My "per gram" mention in post #633 was specifically about the "...more expensive choice (per gram)" for the two products in the given links, and was not about the price per gram for two equal quantities ("same size package") of a product.

 

In one purchase you are paying  $118.72/100 = $1.1872/gram and in the other purchase: $39.59/25 =  $1.5836/gram. So, as presented, my claim: "...more expensive choice (per gram)" is correct and your: "That's because you haven't used the same size package." has no relevance to the correctness of my claim, unless, perhaps, if you are mistakenly assuming that I'm attempting claim something that I'm not. Had I been doing a "value" comparison, then equal quantities would have been considered in coming to a "per gram" cost. But, I wasn't doing that comparison. One might question my intent, and the reasoning by which I phrased things as I did, but that's another matter. (Incidentally, I'm not saying you said my claim was incorrect.).

 

I suspect that for some, a particular purchase may come down to choices among perceived urgency of need, cash availability, and value, among others. Sometimes "value" is sacrificed by dint of availability of funds.

 

 

 

 

[Mind]

Donanemab works very well, a-beta levels remain low long after treatment.

[Mr Matsubayashi]

Damn, Donanemab sounds amazing. 

 

I stumble upon this and thought of you turnbuckle, 

 

Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD Mice

https://www.ncbi.nlm...les/PMC5074695/

Diosmetin, one major bioactive metabolite of diosmin, increased inhibitory GSK-3β phosphorylation, while selectively reducing γ-secretase activity, Aβ generation, tau hyperphosphorylaion and pro-inflammatory activation of microglia in vitro, without altering Notch processing.

 

 

Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain

https://www.ncbi.nlm...les/PMC5031820/

Hesperidin is a lipophilic compound that has shown pharmacological central actions as analgesic [26] and anxiolytic-sedative [12] suggesting that it may effectively cross the blood-brain barrier to display central effects. In fact, in the present study, the presence of hesperidin was corroborated in brain homogenates of rats treated by the systemic route of administration, where a portion of the administered hesperidin was metabolized into the flavonoid diosmin

 

 

I love Hesperidin. I take 2g in the morning with my coffee, can feel the warmth in my extremities and a good bump in mental clarity. It is also a selective Pde4 inhibitor, VEGF agonist, vasodilator. Initially it gave me a headache at 500mg but now it's just awesome. 

 

Edit: Oh, and I think it has worked wonders for my skin. 

Edited by Mr Matsubayashi, 23 September 2021 - 12:49 PM.

[Turnbuckle]

 

Damn, Donanemab sounds amazing. 

 

I stumble upon this and thought of you turnbuckle, 

 

Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD Mice

https://www.ncbi.nlm...les/PMC5074695/

Diosmetin, one major bioactive metabolite of diosmin, increased inhibitory GSK-3β phosphorylation, while selectively reducing γ-secretase activity, Aβ generation, tau hyperphosphorylaion and pro-inflammatory activation of microglia in vitro, without altering Notch processing.

 

 

It might be interesting as an add-on, as the reported effects aren't that strong. They require daily treatment, and the positive effects in mice are sex-linked.

 

Diosmin markedly decreased cerebral Aβ levels... as well as soluble Aβ1–40, 42 levels by 37% (DLO) and 51% (DHI)... Most notably, oral diosmin treatment reduced Aβ oligomer levels more in female than in male 3xTg-AD mice (26% reduction in females versus no significant difference in males)

 

[Old grandpa]

Hello all. I haven't read this thread all the way through, so don't know if this has been discussed. Have you seen the data for Viagra and Alzheimer's? Looks very promising. https://www.nih.gov/...heimers-disease

[poonja]

Would that apply to other pde5 inhibitors such as cialis.

[Old grandpa]

I have no idea since it seems to have a couple of different modes of action. This study https://www.ncbi.nlm...les/PMC3828881/ indicates it is involved in revascularization in the heart, in addition to its improving blood flow. It would seem to do little good to supplement if the supplements can't reach the intended target due to poor circulation or vascularization. I would assume the entire class of pde5 inhibitors increase blood flow but the angiogenesis aspect is unknown to me.

[rarefried]

My 86 year old mother is approaching three months into her first cycle of the protocol -- the one outlined in post 179, second I believe to the current one.   She's noticed good results, apparent in the last month or so to family members who see her regularly.  Mainly, events from the recent past, say a few weeks, which in some cases she might have had to put her mind to to recall (or might have forgotten) she's mostly recalling immediately.  She's dropping things (eg cutlery, pot lids while preparing meals) much less frequently than she has in the past few years.  Probably for the first 4 or 5 weeks of the protocol, she reported some unpleasant effects -- slight headache (she rarely gets headaches) and she reported feeling 'wingy.'  We suggested she back off a bit on the Hepps.  She didn't take the advice because she looked at the negative effects in the positive light that it was doing something.

 

Update to this post from a few years back.  This protocol is remaining effective for my mother.  She stopped taking it for about six weeks in 2020 when we had to find an alternate source of HEPPs that would ship to Canada.  About three to four weeks into that interval she reported some cognitive difficulties, in memory and concentration.  These disappeared probably a week or two after she resumed the protocol.  The other obvious effect of the protocol has remained since she began taking it:  she no longer drops objects during her breakfast routine (which she had been doing daily before commencing the protocol; perhaps she was dropping them on other occasions as well but the early AM is when a family member is consistently around to take note of these things).  She's currently taking the most recent iteration, on alternate days.  A phenomenon that might or might not be related to the protocol.  Probably eight months in, she resumed quoting verse/songs relevant to her day-to-day experience.  The return of this ability seems related to the protocol, because apparently no other changes in the conditions of her life would explain it.

[Danniel]

 

I have another idea for using the MB/HEPPS protocol to simultaneously treat P-tau and Aβ as well as a third AD etiology, but I’m still testing it.

 

 

 

Any news about these updates to the AD protocol?

[Turnbuckle]

Any news about these updates to the AD protocol?

 

No. I'm no longer a fan of MB. 

 

Adverse Effects of Methylene Blue on the Central Nervous System

 

To investigate whether systemic administration of MB induces cell death in the CNS, brains of vehicle- as well as MB-treated animals were assessed 24 h after drug exposure. At this time point, Fluoro-Jade B staining revealed an important increase in the number of degenerating neurons in the brains from animals receiving bolus injections of both 5 and 50 mg/kg MB but not in control groups where saline injections were applied

 

To further extend our investigations on the potentially neurotoxic effects of MB, we investigated whether low concentrations of this drug that did not induce cell death could still impair important morphofunctional parameters of neurons, such as dendritic arbor architecture...Therefore, in a series of experiments, we exposed cultures at the sixth day in vitro  to MB for 2 h and assessed the survival and dendritic arbor architecture of these cells 48 h ... At this time point, we found a significant loss of differentiated neurons after a 2-h-long exposure to MB at concentrations of 10 μm and greater (fig. 5B). Most importantly, analysis of neuronal dendritic architecture revealed a significant remodeling of dendritic arbor, including retraction of dendrites as well as elimination of branching points at MB concentrations of 1 μm and greater .... These in vitro  results thus suggest that MB at non–cell-death-inducing concentrations can still induce persistent changes of dendritic arbor architecture.

https://pubs.asahq.o...-on-the-Central

 

[William Sterog]

Have being saying it for years:

 

 

 

Evidence from in vitro and in vivo studies demonstrates that Aβ oligomers have potent, broad-spectrum antimicrobial properties by forming fibrils that entrap pathogens and disrupt cell membranes. Importantly, overexpression of Aβ confers increased resistance to infection from both bacteria and viruses. The antimicrobial role of Aβ may explain why increased rates of infection have been observed in some of the AD clinical trials that depleted Aβ. 

https://pubmed.ncbi....h.gov/29504537/

 

You are making your brain more vulnerable to the disease if you deplete amyloid. 

 

 

 

We present in vivo data showing that Aβ expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. We show that Aβ oligomerization, a behavior traditionally viewed as intrinsically pathological, may be necessary for the antimicrobial activities of the peptide. Collectively, our data are consistent with a model in which soluble Aβ oligomers first bind to microbial cell wall carbohydrates via a heparin-binding domain. Developing protofibrils inhibited pathogen adhesion to host cells. Propagating β-amyloid fibrils mediate agglutination and eventual entrapment of unatttached microbes. 

https://pubmed.ncbi....h.gov/27225182/

[Turnbuckle]

Have being saying it for years:

 

https://pubmed.ncbi....h.gov/29504537/

 

You are making your brain more vulnerable to the disease if you deplete amyloid. 

 

 

The paper you referenced comes to a more nuanced conclusion. They suggest that an infection may be involved in the etiology of AD in some cases, and suggest that the first step in treatment is to treat any underlying bacterial infections with antibiotics. 

 

The antibiotics rifampicin and doxycycline have also shown promise for preventing memory decline in animal models of AD [113, 114], although human trials indicate they have little effect after the onset of symptoms [115]. These results suggest that resolution of the primary infection may be a necessary first step prior to anti-A therapy, or even as a preventative measure.

 

 

[Learner056]

I don't well understand Alzheimer vs Parkinson.  They use so many words for same things so noob does not follow what is what.  Can this dissolve/detoxify Lewy bodies (as in parkinson)?

 

AD has Plaques (called: Amyloid aka alpha-beta) and Tangles (called: p-tau)?

Parkinson has: sticky proteins: Lewy bodies (called: alpha-synuclein protein)?. 

 

[tired]

With respect to the protocol are there any items on the list that can be taken on a daily basis for Brain Health and should be paired together on days not doing the protocol.  Keeping in mind remove and detoxify.  For example below is the current protocol I believe.  On days or weeks we are not doing the protocol I would like to take Sulforaphan, Oleuropein, Hydroxytyrosol and maybe more on a daily basis as I read outstanding things about them but should I also be pairing them with other things on the list. I don't want to be making things worse by dissolving and not detoxifying on days not using the protocol or vice versa. I understand without HEPPS there is no protocol so talking about the time when not doing the protocol and not using HEPPS.  For example I have given my Dad Taurine in the past (I suspected his Glutamate was high, Glutamate/GABA issues).  I noticed when I give it to him his memory is a mess and he gets restless and about 1.5 days later returns to baseline and maybe a little above baseline.  It could be a million things (neurotransmitter imbalance etc) I don't know why and just using this as an example but possibly if things are getting removed but not detoxified causing issues.  I noticed Milk Thistle seems to help some of this, need to test more to see.  Over simplifying it just trying to use as an example, I want to make sure there is balance on days not using the protocol. I want to take items on the list that both remove and detoxify as to not do more harm.  Also could someone point me to a page where each item below is shown what it does (just a simple remove vs detoxify, or neither, protection) , might help on my first question.  I put below what I have read on the thread but not sure the rest I might have missed it.

 

Finally I want to thank Turnbuckle for this thread and his help.  It's people like you that the world needs helping complete strangers in something so serious and willing to share the information and for letting someone decide whether it is right for them and also without any regard for monetary reward.  Thank you, sincerely.

 

 

Plaque cocktail (dose):

 

 

 

●   Taurine (5 g) REMOVE?

 

●   HEPPS (500 mg)-REMOVE?

 

●   Nicotinamide (500 mg)

 

●   Sulforaphane glucosinolate (50 mg) DETOXIFY?

 

●   Oleuropein (100 mg)-DETOXIFY?

 

●   Hydroxytyrosol (25 mg)-DETOXIFY?

 

●   Vitamin C (1 g)

 

●   Glutathione, liposomal or phytosomal (1 g)

[tired]

Whomever put its "pointless time wasting" to you it might be but for me it isn't.  I have a family member who has a serious Brain issue (yes we have a neurologist etc) and its pretty insensitive to put that.  We are trying to give our family members the best chance, whether it is from a neurologist or a message board. big pharma has no answer so we look elsewhere.  If none of the protocol applies to what I said fine then make a comment but a little couth would go a long way.  This post should be marked pointless time wasting.

[mag1]

Turnbuckle, the latest news concerning MB (as leuco-MB) from taurx appears extremely promising. The topline from the Lucidity phase 3 trials was a 3.7 point benefit on ADAS-cog.

The treatment was so powerful that even the 4 mg twice per week "placebo" was thought to be active and spoiled the as specified statistical plan.

 

I am very interested in hearing your comments about the potential use of leuco-MB as a treatment/preventative of AD. 

Perhaps the dosing of ~15 mg per day would below that of the concerns you expressed about neuron outgrowth.

[Turnbuckle]

The findings from the mild-to-moderate group represented a reduction in decline of about 75% relative to a published meta-analysis of publicly available placebo decline data from historical trials. -- https://www.neurolog...eimer-treatment

 

 

I'm not interested in minimizing declines, only in substantial improvements.

[Turnbuckle]

An updated Alzheimer’s (AD) protocol that oscillates mito fusion with fission. The goal is to detoxify and remove AD plaques (made of β-amyloid and p-tau) in a safe manner.

 

The previous protocol can be found here. My latest protocols for AD and other diseases of aging can be found on my profile page (click on my picture).

 

AD Protocol

 

Day 1:

 

●   Taurine (5 g)

●   HEPPS (500 mg)

●   Dihydromyricetin (2 g)

●   Oleuropein (100 mg)

●   Hydroxytyrosol (25 mg)

●   Vitamin C (1 g)

●   Glutathione, reduced (1 g)

 

 

Day 2 (next day):

●   Nicotinamide (500 mg)

●   Oleuropein (100 mg)

 

One to two treatments a week for two months, then once a month. Since β-amyloid has prion like properties (self-perpetuating), it will come back.

 

Notes:

 

Try it once and see how it goes. If no problem, you can increase the two day cycle to twice a week. For the first dose you might cut the HEPPS dose in half. While HEPPS disaggregates plaques, the debris are very toxic, and are only slowly removed via the circulation of cerebrospinal fluid (CSF), with a half-life of several hours.

 

If everything goes fine, you can increase the HEPPS dose in steps up to about 1 gram, but back off if it creates a headache — a sign of Aβ toxicity. Note also the spelling of HEPPS. The very similar (both in name and structure) HEEPS makes things worse..  

 

Buying HEPPS can present challenges for an individual. It can be bought from industrial supply companies in the US, but none nowadays ship to residential addresses or PO Boxes. You’ll need a corporate address. You can also get it from China. All HEPPS is made in China and then marked up at least 7 times for sale in the US. I’ve never gone that route, however, so I can’t say what problems you might encounter. Should Biden go to war with China, it may become impossible to get HEPPS at all.

 

Nicotinamide reduces the stickiness of p-tau, which joins with Aβ to form the plaques. However, nicotinamide will reduce mitochondrial fusion and thus I’ve moved it to the second day. Oscillating mito fusion with fission removes the mtDNA of defective mitochondria.

 

Overview of the ingredients:

 

Taurine reduces the neurotoxicity of β-amyloid.

HEPPS disaggregates plaques. This is the most critical ingredient.

Dihydromyricetin is an antioxidant that crosses the BBB and produces a state of mito fusion, which is protective.

Oleuropein is an olive oil polyphenol that counteracts amyloid aggregation.

Hydroxytyrosol is an olive oil polyphenol that improves cognition in AD models.

Vitamin C is an antioxidant associated with better cognitive function and lower risk of cognitive decline in AD patients.

Glutathione is the master antioxidant. Depleted Glutathione is associated with AD.

Nicotinamide reverses cognitive deficits associated with AD pathology in mice, and reduces p-tau — a hyperphosphorylated form of tau that is especially sticky and joins with Aβ to form plaques.

 

Edited by Turnbuckle, 01 November 2022 - 03:31 PM.

[C0rt3x]

Just been in contact with a research lab to see if I can buy some HEPPS, it looks doubtful but I will await their reply.

 

Just had a reply, they want to know how I would be using the product, not sure what to tell them?

[Turnbuckle]

You're using it as a buffer in a research project, I assume. Some common uses:

 

From Wikipedia: HEPPS (EPPS) is a buffering agent used in biology and biochemistry. The pKa of HEPPS is 8.00. It is ones of Good's buffers.

 

Also from Wikipedia: Good's buffers (also Good buffers) are twenty buffering agents for biochemical and biological research selected and described by Norman Good and colleagues during 1966–1980.[1][2][3] Most of the buffers were new zwitterionic compounds prepared and tested by Good and coworkers for the first time, though some (MES, ADA, BES, Bicine) were known compounds previously overlooked by biologists. Before Good's work, few hydrogen ion buffers between pH 6 and 8 had been accessible to biologists, and very inappropriate, toxic, reactive and inefficient buffers had often been used. Many Good's buffers became and remain crucial tools in modern biological laboratories.

 

From a Chinese manufacturer: HEPPS Usage

 

1.Biological buffer

 

2.Physiological pH buffer

 

3.Used as a separating agent in ultra-thin isoelectric focusing gels to enhance glucose phosphate mutase

 

 

Use are not using it on people or animals. Just a corporate research project.

 

 

Edited by Turnbuckle, 01 November 2022 - 06:15 PM.

[C0rt3x]

Thanks.

 

I have told them that I want to use it as a buffering agent in a personal project, so fingers crossed. Otherwise I will have to go the China route

[Turnbuckle]

Thanks.

 

I have told them that I want to use it as a buffering agent in a personal project, so fingers crossed. Otherwise I will have to go the China route

 

Don't use the word personal.

[C0rt3x]

Good news, they are allowing me to purchase some HEPPS.

 

Now I can start searching for the other ingredients.

 

Would 25g or 100g be better?

Edited by C0rt3x, 02 November 2022 - 10:33 PM.

[Turnbuckle]

Good news, they are allowing me to purchase some HEPPS.

 

Now I can start searching for the other ingredients.

 

Would 25g or 100g be better?

 

Given how dicey the availability may be in the future as it's made in China, and given the constantly increasing resistance of corporations selling chemicals to non-corporate clients, I'd say 100 g. This would supply one person's needs for a very long time. However, I'd break out the bulk of it into a separate container, seal it tightly with a desiccant pack and store it in a ziplock in the freezer. It is moisture and heat sensitive and will degrade with time if precautions are not taken.

 

All of the other ingredients can be obtained from Amazon. 

 

CORRECTION: In the above protocol I made a mistake, which happily does not impact any of the ingredients listed. The mistake is in saying that "HEEPS" is to be avoided. But there is no HEEPS. I meant to write HEPES. Taurine, HEPPS and HEPES are all sulfonic acids. Taurine is a weak disaggregator, HEPPS is a very strong one, while HEPES, while almost identical to HEPPS structurally, consolidates plaques rather than breaking them up. 

[EliotH]

Is this the same as Turnbuckle's link to HEPPS above?

 

https://www.amazon.c...e/dp/B01N5LTPCF

 

Also, doesn't Longecity have some buyer's groups for purchasing supplements?