LONGECITY

 

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.

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".

.

A brand of HEPPS that can be used in protocol.

Another more expensive choice (per gram)

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.

 

 

Another more expensive choice (per gram)

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

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

 

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)

 

Would that apply to other pde5 inhibitors such as cialis.

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.

 

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?

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

 

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/

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. 

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)?. 

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.

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.

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.

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.

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?

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.

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

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

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.

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?

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. 

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?