674 replies to this topic

[tolerant]

Depends what you mean by successful.

 

 

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.

 

In that paper mice were fed HEPPS for three months. How does that translate to human years?

[tolerant]

  Your condition similar to what people describe while having some brain inflammation.

 Look at Joe Rogan`s podcast with Dr. Mark Gordon if interested. In this case, it's from TBI but inflammation could have different causes. 

 I've kinda experienced it too when treated Lyme.

 Good thing is that decline in cognitive ability is reversible (at least for the most part).

 

Здорово! Your podcast link doesn't lead anywhere... I think this is what you mean. It's interesting he talks about GH. I have just started pinning GH. What other substances can be used for brain inflammation? I once considered the inflammation theory for my depression and anxiety, before I had any cognitive impairment, but my hs-CRP was really low, my ESR was normal, and my pro-inflammatory cytokines were normal, although the lab didn't provide figures. Also, I could not identify any therapy for inflammation. I tried NSAIDs and aspirin to no effect.

Edited by tolerant, 26 September 2018 - 09:26 AM.

[Turnbuckle]

In that paper mice were fed HEPPS for three months. How does that translate to human years?

 

No such calculation is possible. The mice were given AD symptoms with injections, whereas in humans it is a process that goes on for decades before it is noticed, and involves tau as well as Aβ, with tau acting both as an adhesive inside plaques and as tangles inside neurons. Thus no therapy that addresses either Aβ or tau alone has been successful. They are only addressing one half of the problem, or less than one half if you consider the glial cell response. That said, three months should certainly prove adequate for those who have only recently noted symptoms (and thus have a minimum of neurological damage), but there will still be the considerable plaque that is asymptomatic. Symptoms will come back much faster with that to build on, thus treatment should go on for months more even after symptoms dissipate.

 

As I said previously, I don't believe your symptoms derive from AD. I believe they may come from the use of antidepressants. One hypothesis is that many antidepressants operate by stimulating the differentiation of neural stem cells. This will surely be by asymmetric division (producing one stem cell and one new neural cell), and thus will lead ultimately to the depletion of the pool of neural stem cells and the drug's failure to work anymore. The depletion could also lead to memory problems. If one were to use antidepressants with mitochondrial fusion agents such as stearic acid, however, the stimulation of stem cells would be biased to self-renewal (symmetric division, producing two new neural stem cells). See my thread Stem cell self-renewal with C60.

Edited by Turnbuckle, 26 September 2018 - 10:19 AM.

[Andey]

Здорово! Your podcast link doesn't lead anywhere... I think this is what you mean. It's interesting he talks about GH. I have just started pinning GH. What other substances can be used for brain inflammation? I once considered the inflammation theory for my depression and anxiety, before I had any cognitive impairment, but my hs-CRP was really low, my ESR was normal, and my pro-inflammatory cytokines were normal, although the lab didn't provide figures. Also, I could not identify any therapy for inflammation. I tried NSAIDs and aspirin to no effect.

 

   If inflammatory markers are low than its probably not it. Even Alzheimer`s is associated with high hsCRP.

  Don't know what advice to give but if it's its me I would try to take active forms of B vitamins for some time.

  Do you have homocysteine results? if it's more than 8, (or  less than 5.5) it could mean that methylation is not working efficiently.

 

Another idea is some poisoning - mercury, arsenic etc.

[tolerant]

As I said previously, I don't believe your symptoms derive from AD. I believe they may come from the use of antidepressants. One hypothesis is that many antidepressants operate by stimulating the differentiation of neural stem cells. This will surely be by asymmetric division (producing one stem cell and one new neural cell), and thus will lead ultimately to the depletion of the pool of neural stem cells and the drug's failure to work anymore. The depletion could also lead to memory problems. If one were to use antidepressants with mitochondrial fusion agents such as stearic acid, however, the stimulation of stem cells would be biased to self-renewal (symmetric division, producing two new neural stem cells). See my thread Stem cell self-renewal with C60.

 

First of all, thank you for responding and for your attention to my situation. This is now getting very complicated, but also interesting and promising. My mental health was brilliantly held together from age 17 to 32 by a single drug, Zoloft. At times I was able to do fine without it, but always found myself coming back to it. At age 32, it suddenly stopped working and I have been very unwell ever since, for the past six years, with continuous deterioration over that period. During that period I have been prescribed over 20 drugs and nothing has worked. I am familiar with the hippocampal neurogenesis theory of depression. So taking into account what you just said, it could be argued that after being on Zoloft for 15 years, my neural stem cell pool was exhausted, or at any rate has not been sufficient enough to produce the amount of neurogenesis required for symptomatic relief, and therefore no other antidepressant has worked ever since the depletion. It would follow that continuing on antidepressants for the past six years has had the effect of further diminishing the pool of stem cells. So could it be that I no longer have any hippocampal stem cells? If I do still have some hippocampal stem cells and I apply your stem cell self-renewal protocol, what I would get is stem cells dividing symmetrically. But in order to address my problems with depression and cognition, I will need stem cells to mature into actual neurons. How would these two considerations be balanced?

[Turnbuckle]

First of all, thank you for responding and for your attention to my situation. This is now getting very complicated, but also interesting and promising. My mental health was brilliantly held together from age 17 to 32 by a single drug, Zoloft. At times I was able to do fine without it, but always found myself coming back to it. At age 32, it suddenly stopped working and I have been very unwell ever since, for the past six years, with continuous deterioration over that period. During that period I have been prescribed over 20 drugs and nothing has worked. I am familiar with the hippocampal neurogenesis theory of depression. So taking into account what you just said, it could be argued that after being on Zoloft for 15 years, my neural stem cell pool was exhausted, or at any rate has not been sufficient enough to produce the amount of neurogenesis required for symptomatic relief, and therefore no other antidepressant has worked ever since the depletion. It would follow that continuing on antidepressants for the past six years has had the effect of further diminishing the pool of stem cells. So could it be that I no longer have any hippocampal stem cells? If I do still have some hippocampal stem cells and I apply your stem cell self-renewal protocol, what I would get is stem cells dividing symmetrically. But in order to address my problems with depression and cognition, I will need stem cells to mature into actual neurons. How would these two considerations be balanced?

 

 

Likely your stem cell pool is vastly diminished but not gone altogether. By cycling an antidepressant with a mito fusion agent, you may be able to reestablish the pool to more youthful levels. It's the magic of a geometric progression. If you double stem cells each time, after 20 cycles you have a million times what you started with. It's not going to be that good, of course as the antidepressant is likely not that good a stimulant and the bias is not perfect, but it should be far better than purely asymmetric division. And after that the antidepressant would hopefully work as it did years ago.

[tolerant]

Likely your stem cell pool is vastly diminished but not gone altogether. By cycling an antidepressant with a mito fusion agent, you may be able to reestablish the pool to more youthful levels. It's the magic of a geometric progression. If you double stem cells each time, after 20 cycles you have a million times what you started with. It's not going to be that good, of course as the antidepressant is likely not that good a stimulant and the bias is not perfect, but it should be far better than purely asymmetric division. And after that the antidepressant would hopefully work as it did years ago.

 

Right. So I will ask you a few basic questions about your stem cell renewal protocol, and if I have any more questions after that, I will post them in that thread? So basically you recommend that I should follow the protocol set out in this post? Do I have to do all of A, B, and C? I've ordered stearic acid from here. Will this do? I ordered it because I was going to use it in your red light weight loss protocol. I notice there's much discussion in the stem cell thread about getting the best stearic acid. If what I ordered will not do the job, can you please provide a link to a good source? Furthermore, what's the deal with mixing it in hot chocolate or brownies? What's wrong with just putting it in your mouth and washing it down with water? Finally, when you talk about C60, is this it? If not, can you please provide me with a link? And since it's so light-sensitive, do I have to put it in a spoon and drink it quickly? Thank you very much for your time!

[tolerant]

Another thing. I had a brain MRI 12 months ago, and I was able to put the images through NeuroQuant software, and the surprising result was that my hippocampal volume was in the top 1% of the population for my age. This doesn't fit in at all with my complaints of depression and impaired cognition, and it doesn't fit in at all with the theory that my hippocampal stem cell pool has been depleted. Furthermore, in your stem cell thread I read something to the effect that stem cells won't divide if there's no room, so now I'm wondering whether this applies to me. On the other hand, if one looks at the actual image of my hippocampus, there's obvious "empty" space next to it, but from memory the empty space is not next to the areas of the hippocampus where the stem cells are supposed to be. So I don't know what to make of all that. I guess I will just try your protocol and see what happens.

[Turnbuckle]

Right. So I will ask you a few basic questions about your stem cell renewal protocol, and if I have any more questions after that, I will post them in that thread? So basically you recommend that I should follow the protocol set out in this post? Do I have to do all of A, B, and C? I've ordered stearic acid from here. Will this do? I ordered it because I was going to use it in your red light weight loss protocol. I notice there's much discussion in the stem cell thread about getting the best stearic acid. If what I ordered will not do the job, can you please provide a link to a good source? Furthermore, what's the deal with mixing it in hot chocolate or brownies? What's wrong with just putting it in your mouth and washing it down with water? Finally, when you talk about C60, is this it? If not, can you please provide me with a link? And since it's so light-sensitive, do I have to put it in a spoon and drink it quickly? Thank you very much for your time!

 

 

I post my latest protocol updates on my profile page. For stem cells the latest is here. You might try the whole thing with the antidepressant, or you might try stearic acid and the antidepressant alone. Stearic acid has a high melting point and one can't be sure how long granules will take to get digested, if ever, thus the brownies. I'm not going to get into the stearic acid debate here (suffice to say that most stearic acid is actually more palmitic acid) nor will I make any recommendations on C60 as I don't buy any commercial mixes. However, your linked product doesn't raise any red flags. And while it's not so light sensitive that you have to worry about it in a spoon, the amber bottles they sell it in are inadequate, so you should store it in the dark.

[ryukenden]

OK. I see what you mean. When I say I'm not concerned by the safety of the protocol, I mean the individual substances of the protocol. True, I've never heard of HEPPS or dihydromyricetin before, but dihydromyricetin is a flavanolol, so no issues there, while HEPPS does come across as a little concerning because it's some sort of chemical used as a buffer (whatever that means), but since people in this thread are using it, then it must be fine. Also, my cognitive symptoms are so debilitating that I would be willing to try anything, really. 

 

So by safety, I guess I mean that if I definitely don't have AD, is it safe to fix something that ain't broke, i.e. to mess around with things I have zero understanding of.

 

P.S. I would also very much like to avoid my symptoms getting worse during the first few days because it would cause great anxiety. I take it that the way to do it is to slowly build up the dose of HEPPS/taurine?

 

How is your mood like? If you still have mood symptoms, it can have impact on cognition and we call it pseudo-dementia.
 

[Moumou]

AON: anterior olfactory nucleus / OB: Olfactory bulb

 

 

o Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology

 

"Damage to the olfactory bulb (OB) in young Metropolitan Mexico City residents is early, progressive, exhibits Alzheimer and alpha-synucleinopathies hallmarks, and the damage is particularly severe in APOE 4 carriers. The neuropathology in children and teens strongly suggests the OB is an unavoidable target of pollution and nanoparticles likely play a critical role. The neurovascular unit is an early, critical target and active endothelial phagocytosis of red blood cell (RBC) fragments containing combustion-derived nanoparticles (CDNPs) is an ongoing phenomenon. The significant vascular and extensive damage to unmyelinated and myelinated axons in the olfactory tracts and the hallmarks of the most prevalent tauopathies and synucleinopathies, obligates us to consider the olfactory bulb as a sentinel for evolving neurodegenerative processes.

The Aβ pathology in the form of diffuse plaques was mostly mild and remained stable throughout the first 4 decades of life. It is important to emphasize that the AON was not involved by hTau and/or ɑ-Syn pathology in the first 4 decades; strikingly however, was the significant increase in AON corpora amylacea (CA), particularly in APOE4 carriers.

Corpora amylacea (CA) -glycoprotein-based deposition- in significant numbers is an outstanding OB finding. In the work of Pirici et al., the three-dimensional structure of CA is complex with branching exhibiting a direct correlation with the diameter of vessels, while perivascular CAs are enclosed in pockets of the basement membranes. Interestingly, endogenous astrocytic heme oxygenase-1 (HO-1)-a cytoprotective enzyme-, reported to be localized in mitochondria under stress and contributing to preserve mitochondrial function, promotes transformation of normal mitochondria to CA-like inclusions."


"A key finding was the accelerated OB pathology course relative to Braak early subcortical stages a-c, cortical lesions stages 1a, 1b, I and II and NFT stages (Braak and Del Tredeci, 2015). Thus in the first two decades when the majority of children and teens exhibited pretangle stages 1a and 1b, 84% have already OB hTau NTs, strongly suggesting olfactory deficits could be an early guide of subcortical and cortical AD pretangle hTau (Braak et al., 2011b). ɑ-Syn is a different story. We previously found LNs in the brainstem and the enteric nervous system (ENS) in children which coincided with 68% OB ɑ-Syn neurites in the first two decades. MMC children would be at Lewy pathology stages 1 and 2 according with the distribution of Lewy pathology in sporadic Parkinson's disease in Del Tredeci and Braak's work (2017). This PD staging would be critical because autonomic symptomatology occurs in > 60% of the young adult MMC population ages 20.5 ± 1.08. "

"The relationship between APOE4 status, suicide risk, depression, olfaction deficits, and cumulative PM 2.5 deserves extensive research. We found APOE4 carriers have 4.57 times higher suicide odds, and higher odds of OB AD and ɑ-Syn pathology. These findings are critical for several reasons: i. We fully expect a relationship between the OB neuropathology and olfactory deficits, a relationship that is clear in older populations with both AD and alpha-synucleinopathies. ii. There are a significant number of papers on depression, OB size, and emotions. Misiak and collaborators stated that APOE4 is a key player in olfactory impairment and along with neuroimaging, psychological tools and molecular studies, holds promise for characterization of preclinical stages in people at risk.

The key question is how many young subjects with olfaction deficits,depression and altered emotional responses are already in their way to AD, PD/DLB?"


https://www.scienced...013935118303281

Edited by Moumou, 27 September 2018 - 01:26 AM.

[tolerant]

How is your mood like? If you still have mood symptoms, it can have impact on cognition and we call it pseudo-dementia.

 

I think I have mentioned that I have severe treatment-resistant major depression and anxiety, amongst other assorted psychiatric symptoms. I actually believe that pseudodementia is the likeliest cause of my cognitive symptoms. But for me, the way to tackle pseudodementia is to rule out all other causes. 

[ryukenden]

I think I have mentioned that I have severe treatment-resistant major depression and anxiety, amongst other assorted psychiatric symptoms. I actually believe that pseudodementia is the likeliest cause of my cognitive symptoms. But for me, the way to tackle pseudodementia is to rule out all other causes. 

 

If treatment resistant depression, have you tried combination of medications such as two antidepressants (SSRI plus Mirtazapine), or Lithium augmentation or antidepressant plus antipsychotic etc. The last resource could be ECT treatment.

[Moumou]

Maybe, already and currently damaged brains with consequant accumulation of plaques (post 40's) possibly due to intensive lesion regeneration processes, would be likely to decrease intake of Taurine-like substances in the Olfactory Bulb. Maybe Intranasal inoculation would couteract the latency and impairment of Taurine intakes in the Olfactory Bulb.

 

 

 

o Taurine in the olfactory system: effects of the olfactory toxicant dichlobenil.

 

https://www.ncbi.nlm...6?dopt=Abstract

 

"In mice treated with the olfactory toxicant dichlobenil, inducing necrosis in the dorsomedial olfactory region, there was a dose-dependent decrease in the level of 14C-taurine and 3H-carnosine (derived from the precursor 3H-beta-alanine) in the olfactory bulb. The migration of 14C-taurine in the olfactory system of dichlobenil-dosed mice gradually recovered 3 - 8 weeks later although an atypical epithelium remained in the dorsomedial portion of the olfactory region. The results suggest a transient reduction of the migration of taurine in the olfactory system of mice following chemically-induced toxicity at this site."

 

 

 

 

o β-Amyloid precursor protein-like immunoreactivity is upregulated during olfactory nerve regeneration in adult rats

 

https://www.scienced...006899397011876

 

"Levels of APP-like immunoreactivity substantially increased over normal levels at six weeks when fibers of theolfactory nerve are presumably reforming normal connections. Membrane associated ‘full-length’ APP-like proteinsincreased over four-fold at six weeks post-lesion and mitral cell dendrites and perikarya displayed greater immunoreactivity than did control cases. These observations suggest that APP-like proteins increased during regeneration and recovery of the olfactory bulb neuropil and support previous speculations that APP-like proteins may be involved in neural regeneration."

 

 

 

 

o Apolipoprotein E Is Upregulated in Olfactory Bulb Glia Following Peripheral Receptor Lesion in Mice

 

https://www.scienced...014488601977623

 

"In our hands, apoE immunoreactivity in the normal mouse olfactory bulb was diffuse, and visible apoE-immunoreactive perikarya were rare. Procedures to increase the intensity of perikaryal staining (nickel intensification) also raised  the  “background”  similarly, suggesting that apoE immunoreactivity was primarily present either in small processes or in the extracellular matrix. These data suggest that initially glia produce apoE immediately following lesion (hence a perikaryal localization), but then apoE is rapidly translocated to peripheral processes or an extracellular compartment or is internalized by neurons and rapidly degraded. Neurons apparently  are  not  a  major  source  of  apoE  production. The mitral neurons are found in single laminae in the bulb and it is highly unlikely that we would not have seen a labeled neuron. This suggests that intraneuronal apoE concentration in vivo is below the threshold ofdetectability by immunocytochemical techniques."

 

"Translocation occurs in the peripheral nervous system. Resident macrophages and monocyte-derived macrophages, at the site of injury, are reported to be the  primary  sources  of  the  large  quantities  of  apoE-containing lipoproteins. These lipoprotein particles probably scavenge cholesterol released from degenerating  myelin.  Scavenged  cholesterol  is  subsequently used  in  membrane  biosynthesis  by  growth  cones  of sprouting axons by LDL receptor-mediated endocytosis. Reactive gliosis in the CNS may be the equivalent of macrophage activity in the PNS."

 "Furthermore  astroglial  markers  are elevated  in  the  olfactory  bulb  for  at  least  2– 4  weeks following  lesion.  There  are  no  data  on  microglial  response in an acute olfactory bulb lesion. Our observation fits well with previous descriptions of “exuberant” and probably aberrant olfactory nerve sprouting into the olfactory bulb following a reversible olfactory nerve lesion. These data suggest that processes related to degeneration could continue for several weeks following nerve lesion. A previous study suggested that apoE might be involved in regeneration because hippocampal elevation of apoE mRNA trails that of GFAP following a perforant path lesion. These data are not  contradictory. If astroglia and microglia  must  be activated before they produce apoE, this temporal relationship is logical.

 

The double-labeling immunocytochemical  studies confirmed that both reactive astroglia and reactive microglia produced detectable amounts of apoE following a lesion. It is fairly safe to further suggest that apoE is produced by activated microglia. In vitro studies have shown apoE production by microglia, but in vivo studies have been equivocal. This difference may represent a detection problem perhaps related to the “activated” status of astro- and microglia. We were unable to unequivocally colocalize apoE and the microglial  marker  in  nonlesioned  mice,  although  we  did identify  occasional  GFAP–apoE  colocalization  in  the same  mice.  Only  at  3  and  7  days  following  olfactory nerve  lesion  was  the  cellular  concentration  of  apoE high enough to detect when combined with glial labeling.

In vivo detection of apoE in microglia may require both upregulation of a microglial antigen (F4/80) that occurs after lesion and increased cellular concentration  of  apoE.  Both  microglia  and  astroglia  produce apoE in the olfactory bulb but activation of glia might be required for colocalization. Injury-induced  apoE  production  may  explain  variable morphological effects observed in the absence of the apoE gene. In vitro, apoE, in combination with a source  of  lipids,  facilitates  process  growth .  We  propose  that in  vivo apoE  is  transiently  increased to scavenge lipids released from degenerating processes.  Much  of  this  lipid  is  posited  to  come  from degenerating axons and associated processes. This postulate is consistent with a previous study that reported   impaired   clearance   of   axonal   degeneration products following injury in apoE-deficient mice. ApoE  then  provides  those  lipids  to  regenerating  processes. In the intact CNS, inefficient recovery may be cryptic or perhaps could be compensated for by other less efficient apolipoproteins. Alternatively, only a small subset of axons may show modification, as has been reported in the PNS. Only if a lesion challenges  the  experimental  animal  will  less  efficient  lipoprotein recycling become significant. A  hypothesis  of  apoE  participation  in  lipoprotein recycling is also compatible with previous observations of the effects of apoE alleles in both AD and recovery from head injury. The apoE4 allele predisposes to AD and  increases  the  risk  of  developing  AD  after  head trauma. Patients with the apoE4 allele manifest a poorer outcome following traumatic brain injury, and  boxers  with  the  apoE4  allele  were  at  a  much greater  risk  of  developing  chronic  neurologic  deficits than those not having the apoE4 allele. Recently, it was suggested that bloodflow (measured by fMRI) in individuals with the apoE4 allele was greater than in apoE3  homozygotes  when  performing  the  same  task, suggesting some level of inefficiency in earning. If apoE is involved in efficient recycling or redistribution of  lipoproteins  during  brain  function  or  following  injury,  a  lifetime  of  inefficient  functioning  associated with the apoE4 allele may result in an accentuation of mild dysfunction and an increased risk for dementia. (https://www.nejm.org...cbi.nlm.nih.gov) "

 

BONUS

 

o Are noise and air pollution related to the incidence of dementia? A cohort study in London, England

 

https://bmjopen.bmj....ock-system-main

 

"We repeated the analysis, now subclassifying dementia diagnoses   recorded   as   Alzheimer’s   disease,   vascular dementia  or  non-specific  where  no  further  information was available. The positive associations with NO2 and  PM2.5   were  more  consistent  for  Alzheimer’s  disease and non-specific diagnoses. For example, patients in the top fifth exposure category of NO2  (>41.5μg/m3) were at ahigher risk of receiving an Alzheimer’s diseasediagnosis than patients inthe bottom fifth (HR=1.50, 95%CI 1.08 to 2.08). For vascular dementia, there was less evidence of consistent effects with air or noise pollution."

"Our results suggest both  regional  and  urban  background  pollutants  may  be  as important as near-traffic pollutants. Future large-scale studies  will  need  to  rely  on  improved  recording  and  linkage of dementia diagnoses across electronic systems, particularly  Alzheimer’s  disease,  where  multiple  sources  can improve diagnostic accuracy.  Since exposure is life-long, and most cases are diagnosed in later life, historical data  are  also  ideally  required  to  better  estimate  cumulative  exposure  over  preceding  decades.  In  conclusion,  our  findings  add  to  a  growing  evidence  base  linking  air  pollution and neurodegeneration and should encourage further research in this area."

 

Edited by Moumou, 28 September 2018 - 04:42 PM.

[Empiricus]

I've carried out my version of the protocol for about 10 days over past 3 weeks.  Four days of HEPPS at 350 mg, increasing to 600 mg for 2 days, and then 1000 mg for 2 days. I would consume about 2-4 tablespoons of fresh olive oil, rest of the protocol similar to Turnbuckle's, except I added a number of other things from the studies.  My reaction to 1 drop of M Blue wasn't pleasant, so I reduced dosage to 1/4 drop per day for 4 days.  Results have been mixed.  I can't decide if the symptoms (mainly typos in writing) are worse or better. You can tell it's doing something, because you can literally feel some unusual sensations.  My suspicion is that getting sufficient olive phenols may be essential for this to work, and I may not be getting a sufficient amount relative to the above doses of HEPPS. 

 

Over the past 2 days I have reduced the HEPPS to about 200 mg, and added about 50 mg of olive leaf extract to the olive oil.  I'm keeping the taurine dose high and dropping the TUDCA for awhile.   

 

FWIW, here are some things I have added to my protocol, with references....

 

An update.  Three more days at 200-300 mg HEPPS/day, meanwhile consuming 50 ml olive oil, plus 1/7th of a 100 mg hydroxytyrosol capsule having 25% (25mg) Hydroxytyrosol and 1/7 of a Life Extension capsule of containing 500mg of Benolea Olive extract having 16% oleuropein (80 mg).  So let's call it 3 mg oleuropein/day.   My tolerance of this level of leaf extract and olive oil seems good enough.  I also took 1/5 of one drop of the Blue Brain brand MB, which I think works out to 1 mg/day.  I am taking the same amount of the carnosine and taurine as Turnbuckle recommends and 1000 mg niacinamide.  Plus all the other stuff I listed in the previous posting.   

 

I think what I am seeing is temporary improvements in typos, some improved fluency, and temporary periods where I make quite frequent typos and other undesirable things happen. To be classed with latter, I dropped my iPhone about 5-6 times in a 2 hour period. All told, negative observations outnumber the positive ones by about 2 to 1. 

 

Even just 1 mg/day MB seems to give me mild body aches.  I also think MB is associated with negative events, but I'm not sure. And have been taking it with 500 mg of niacinamide. (I think all negative observations can't be explained by MB, however, since I began it later, and negative symptoms were frequent in the first few days).

 

So the question is whether this is normal to see some things get worse in the first few weeks, or it's an indication that something needs adjustment here.  The first thing that occurs to me is the oleuropein matters, and I'm still not getting enough relative to the HEPPS. But I'm already close to my tolerable limit for olive leaf extract.  So to remain proportional to Turnbuckle's protocol, if someone's only taking 3 mg/day of oleuropein, maybe they shouldn't exceed 100 mg of HEPPS. The second possibility, relates to the fact I've been taking a lot of other stuff in attempt to compensate for being able to tolerate olive leaf extract less well, and it's possible one of those things contradicts something in Turnbuckle's protocol.  The third thing that comes to mind is maybe the HEPPS I ordered is not pure, or worse case, it's that other stuff.  I think that unlikely, but not sure how to rule it out without ordering more from a different supplier.  

 

So my thinking now is to further lower HEPPS to 100 mg and eliminate MB for a while.  I also plan to eliminate hydroxytyrosol because I seem to tolerate that formulation less well than the Life Extension capsule containing oleuropein. One concern I have though, is having started the process, that it's possibly not a good idea to discontinue aspects of it when it's evident things are unsettled but not yet in the clear.   

Edited by Empiricus, 30 September 2018 - 10:01 PM.

[tolerant]

Patience, tolerant. Try it for two weeks. [emphasis mine] As for your other questions, answer these: Are you past sixty? Do you have at least one APOE4 gene? If no to both and you don't feel anything after a couple of weeks, then maybe it is something else. Though I expect everyone of a certain age has some Aβ, even if asymptomatic. You can actually have quite a bit--

 

 

The global incidence of APOE4 is about 14%, which means that roughly half of those with high levels of Aβ don't carry the allele.

 

As for tau, several ingredients impact tau, including nicotinamide, which acts against hyperphosphorylation, and those derived from olive oil--

 

 

I stopped using MB as its use is so problematical, staining anything it touches.

 

ALCAR is another supplement that goes after tau, and might make a good addition--

 

 

The damage wrought in AD proliferates glial cells and those themselves can cause symptoms. It may take longer for that to be reversed by natural processes. While I'm not aware of any treatments to reverse that faster, removing the stimulus (plaques) should reverse the response (glial cells).

 

 

No such calculation is possible. The mice were given AD symptoms with injections, whereas in humans it is a process that goes on for decades before it is noticed, and involves tau as well as Aβ, with tau acting both as an adhesive inside plaques and as tangles inside neurons. Thus no therapy that addresses either Aβ or tau alone has been successful. They are only addressing one half of the problem, or less than one half if you consider the glial cell response. That said, three months should certainly prove adequate for those who have only recently noted symptoms (and thus have a minimum of neurological damage), but there will still be the considerable plaque that is asymptomatic. Symptoms will come back much faster with that to build on, thus treatment should go on for months more even after symptoms dissipate.

 

As I said previously, I don't believe your symptoms derive from AD. I believe they may come from the use of antidepressants. One hypothesis is that many antidepressants operate by stimulating the differentiation of neural stem cells. This will surely be by asymmetric division (producing one stem cell and one new neural cell), and thus will lead ultimately to the depletion of the pool of neural stem cells and the drug's failure to work anymore. The depletion could also lead to memory problems. If one were to use antidepressants with mitochondrial fusion agents such as stearic acid, however, the stimulation of stem cells would be biased to self-renewal (symmetric division, producing two new neural stem cells). See my thread Stem cell self-renewal with C60.

 

So your advice of following the protocol for two weeks before concluding that I don't have AD is based on commons sense?

[tolerant]

I have followed the latest incarnation of the protocol for the past two days. I do not feel any different. If I continue to feel that the protocol doesn't make a difference to my cognitive impairment, for how long should it be continued? And will continuing it with no change in cognition for that period of time mean that I do not have amyloid beta plaques and tau?

 

Alternatively, can I use the substances from the protocol differently to establish whether I have amyloid beta plaques and tau in a shorter period of time? For example, use a high dose of HEPPS with no oleuropein and see whether it increases my cognitive impairment, and if it doesn't, conclude that I do not have amyloid beta plaques and following the protocol will not result in improvement in cognition. Similarly with tau, can I use the "dissolve" portion of the protocol without nicotinamide for diagnostic purposes? If so, which substances in the latest protocol constitute the "dissolve" part in relation to tau? Initially, it was methylene blue, but it's not clear to me which substance or substances have replaced methylene blue in the latest protocol.

 

An update. As far as I can remember I took the third day off, not taking anything in the protocol. On the fourth day, I lowered my dosage of HEPPS to 200 mg, in part because I was copying Empiricus and in part because 200 mg is roughly the HED based on one of Kim's papers, where the most effective dose for mice was 30 mg/kg. I still felt nothing, so on the fifth day I took 2 g of HEPPS and 15 g of taurine without any other substances (i.e. the "dissolve" part without the "detoxify" part). I don't recommend anyone else try it, but I did it to "force" a diagnosis. I still felt no different, so considering the very long half-life of HEPPS and that it was still in my system, on the sixth day I took no HEPPS or taurine, but double doses of oleuropein and hydroxytyrosol and Vitamin C, and 2 g of nicotinamide (i.e. the "detoxify" part without the "dissolve" part). I don't know where carnosine, dihydromyricetin and magnesium threonate fit in, so I didn't take them.

 

I still can't say that I feel any different, so I may continue with the protocol for another week and may try methylene blue, because a number of people (i.e. Turnbuckle and Empiricus) have reported bad experiences with it, which means that there is something there that needs correcting. 

[tolerant]

My reaction to 1 drop of M Blue wasn't pleasant, so I reduced dosage to 1/4 drop per day for 4 days.  

 

 

I also took 1/5 of one drop of the Blue Brain brand MB, which I think works out to 1 mg/day. 

...

 

Even just 1 mg/day MB seems to give me mild body aches.  I also think MB is associated with negative events, but I'm not sure. And have been taking it with 500 mg of niacinamide. (I think all negative observations can't be explained by MB, however, since I began it later, and negative symptoms were frequent in the first few days).

 

The second possibility, relates to the fact I've been taking a lot of other stuff in attempt to compensate for being able to tolerate olive leaf extract less well, and it's possible one of those things contradicts something in Turnbuckle's protocol.  The third thing that comes to mind is maybe the HEPPS I ordered is not pure, or worse case, it's that other stuff.  I think that unlikely, but not sure how to rule it out without ordering more from a different supplier.   

 

What kind of "unpleasant" reactions to methylene blue are you experiencing? Is it just the body aches? Or cognitive stuff as well? And how can you measure 1/4 or 1/5 of a drop? I would have thought a drop of something is the smallest amount you can measure. Unless you dilute it in something and drink 1/4 or 1/5 of the solution.

 

You got your HEPPS from China, right? Are you able to order HEPPS from Amazon. You can use Shipito if Amazon doesn't ship to your country. That's what I did. If you can't do that for whatever reason, I can send you 20 g or so. This is the HEPPS I got, and it is actually yellowish if anybody is wondering.

[tolerant]

   If inflammatory markers are low than its probably not it. Even Alzheimer`s is associated with high hsCRP.

  Don't know what advice to give but if it's its me I would try to take active forms of B vitamins for some time.

  Do you have homocysteine results? if it's more than 8, (or  less than 5.5) it could mean that methylation is not working efficiently.

 

Another idea is some poisoning - mercury, arsenic etc.

 

The inflammatory markers were low, but the tests were done when I already had serious mental health issues before I developed any cognitive symptoms. I tested all the B vitamins that could be tested (again, before the onset of cognitive symptoms), and they were all normal or high. I supplement with a regular complex B formula. Do you think I should switch to active forms? I don't remember whether I ever had a test for homocysteine. Can you explain what methylation is? With regards to mercury, I had my blood levels checked. I think I also had lead checked, but I don't think I ever checked arsenic. Is it more meaningful to check metals with a blood test or a hair sample?

 

Помоги соотечественнику!

[tolerant]

If treatment resistant depression, have you tried combination of medications such as two antidepressants (SSRI plus Mirtazapine), or Lithium augmentation or antidepressant plus antipsychotic etc. The last resource could be ECT treatment.

 

Yes, I tried various combinations, including two antidepressants, as well as augmentation with various antipsychotics, mood stabilizers... and I think one other type of drug... I forget what it's called. All in all, I have been prescribed over 20 drugs by doctors and tried many others on my own, e.g. drugs only available in Russia or Europe, as well as drugs that are under development and were available through group buys or on the Darkweb. I have also tried TMS. Also tried about 100 over-the-counter substances, such as vitamins, minerals, herbs, etc. I think I've tried 5-10 types of magnesium alone. I can't try ECT until I quit clonazepam, which will take at least another six months. And I am very afraid of trying ECT, because, as is well-known, it negatively impacts memory in a big way, and I'm on this thread precisely because I've already got horrendous memory problems. There's a new type of stimulation that works like ECT but is not associated with memory problems. It's called MST -- magnetic seizure therapy. It was undergoing trials in Australia, who knows when it will be available. There is also Brainsway, which is a kind of deep TMS that can reach the limbic system. There are a few other types of stimulation, like vagus nerve stimulation, deep brain stimulation and transcranial direct-current stimulation, but I don't know much about them.

Edited by tolerant, 01 October 2018 - 12:18 AM.

[tolerant]

 Who is voting down all my posts as pointless and timewasting? Would you mind coming out and explaining why?

Edited by tolerant, 01 October 2018 - 01:30 AM.

[tolerant]

I couldn't get HEPPS. I ordered some but it never arrived.

 

Would you like me to send you some? I can spare 10 g, maybe 20 g, depending on whether Empiricus needs some too.

[tolerant]

Discovery could explain failed clinical trials for Alzheimer's, and provide a solution

 

Is this relevant to this thread? I think there's been discussion here of a number of drugs proven to dissolve Aβ but are not yet available. The drug discussed in the article, fasudil, is already available in China and Japan, so should be easier to get.

[Empiricus]

An update.  Three more days at 200-300 mg HEPPS/day, meanwhile consuming 50 ml olive oil, plus 1/7th of a 100 mg hydroxytyrosol capsule having 25% (25mg) Hydroxytyrosol and 1/7 of a Life Extension capsule of containing 500mg of Benolea Olive extract having 16% oleuropein (80 mg).  So let's call it 3 mg oleuropein/day.   

 

Correction: For the past 5 days I was taking at least 11.5 mg oleuropein per day (not 3 mg/day as I stated). ProHealth hydroxytyrosol capules and the 50 ml of olive oil probably contains some too.  

 

To take less than a drop of something, simply dissolve it in a measuring flask. 

Edited by Empiricus, 01 October 2018 - 03:20 AM.

[Empiricus]

An update. As far as I can remember I took the third day off, not taking anything in the protocol. On the fourth day, I lowered my dosage of HEPPS to 200 mg, in part because I was copying Empiricus and in part because 200 mg is roughly the HED based on one of Kim's papers, where the most effective dose for mice was 30 mg/kg. I still felt nothing, so on the fifth day I took 2 g of HEPPS and 15 g of taurine without any other substances (i.e. the "dissolve" part without the "detoxify" part). I don't recommend anyone else try it, but I did it to "force" a diagnosis. I still felt no different, so considering the very long half-life of HEPPS and that it was still in my system....

 

Taking HEPPS in the beginning, during first 3-4 days (350-650 mg), I observed: ringing in the ears within 5 minutes of taking it. It was like the ring when a gong or bell is hit, fading quickly; every time I have taken HEPPS I get a runny nose within 10 minutes; also I get sensations over my skin. Throughout the day, I experienced mental fatigue, it's if I am doing many hours of meditation or spreadsheets.  Around the night of the third dose, I had a dream where I had trouble finishing sentences; two other nights I experienced dreams briefly carrying into the waking state. 

 

Thanks tolerant for offering to send me some of your HEPPS. Also, it's also good to know about shipitto works.  Probably I will just order more from another Chinese supplier, as I will eventually run out and need to do that anyway.  

Edited by Empiricus, 01 October 2018 - 06:36 AM.

[Turnbuckle]

Correction: For the past 5 days I was taking at least 11.5 mg oleuropein per day (not 3 mg/day as I stated). ProHealth hydroxytyrosol capules and the 50 ml of olive oil probably contains some too.  

 

To take less than a drop of something, simply dissolve it in a measuring flask. 

 

 

3mg or 10mg, it doesn't matter. For this purpose you are essentially taking nothing.

[Empiricus]

3mg or 10mg, it doesn't matter. For this purpose you are essentially taking nothing.

 

In your protocol of 13 Sept (#239) you decided to reduce your oleuropein intake from 200 mg to 100 mg oleuropein, so 10 mg didn't seem quite negligible compared to 100 mg, although compared to 200 mg, the one you know works, it starts to look that way.

 

If I add 50 ml olive oil to 10 mg of oleuropein, I get an extra 10 mg phenols (1), though basically none of that is oleuropein (2). A study shows that just olive oil given to mice fed a human equivalent of 50 ml, get "clearance" just by that (3), which leads me to suspect that oleuropein only obtainable from leaf-derived extracts, and the higher doses you took, may not be necessary, particularly when taken in conjunction with other things that do the heavy lifting.  The study of olive-oil drinking mice showed olive oil in older mice achieved clearance of AB, but not much else (but thanks to HEPPS and taurine, we don't need it to do much else). 

 

(1) "A daily consumption of 50 g olive oil with a concentration of 180 mg/kg of phenols would result in an estimated intake of about 9 mg of olive oil phenols per day." Boskou, 2000

(2) Effects of the Olive-Derived Polyphenol Oleuropein on Human Health https://www.ncbi.nlm...s/PMC4227229/).   

(3) "The EVOO-enriched diet was prepared by mixing EVOO with powdered diet to produce a dose of 0.7 g/day that is equivalent to dietary intake of EVOO in Greek population (50 g/day)"... "although feeding mice with EVOO-enriched diet for 3 months, beginning at an age after Aβ accumulation starts, showed improved clearance across the BBB and significant reduction in Aβ levels, it did not affect tau levels or improve cognitive functions of TgSwDI mouse."  Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice. https://www.ncbi.nlm...ubmed/26344778 

 

I would be interested to hear any thoughts you might have had since I last asked you about it, what your approach would be, in terms of adjusting your protocol, were the amount of oleuropein one could tolerate negligible.  

Edited by Empiricus, 01 October 2018 - 01:41 PM.

[Turnbuckle]

In your protocol of 13 Sept (#239) you decided to reduce your oleuropein intake from 200 mg to 100 mg oleuropein, so 10 mg didn't seem quite negligible compared to 100 mg, although compared to 200 mg, the one you know works, it starts to look that way.

 

 

 

 

I reduced the oleuropein and added HT and dihydromyricetin . You are taking those two, right? So if you're getting toxic results from HEPPS (actually from Aβ and p-tau released into the CSF, which might redeposit elsewhere), you might want to up those. See also my post #166.

Edited by Turnbuckle, 01 October 2018 - 02:08 PM.

[Empiricus]

I reduced the oleuropein and added HT and dihydromyricetin . You are taking those two, right? So if you're getting toxic results from HEPPS (actually from Aβ and p-tau released into the CSF, which might redeposit elsewhere), you might want to up those. See also my post #166.

 

Post #166 is helpful, thanks for reminding me of that. I decided to stop HT (hydroxytyrosol) and only take oleuropein, because HT seems to be the olive phenol that disagrees with me most.   Come to think of it, I probably could increase the oleuropein since I dropped the HT.

 

I have been taking dihydromyricetin since the beginning, but I had been thinking of stopping everythign that wasn't in your original protocol to avoid contradictions.  Maybe I should try dihydromyricetin at a higher dose (go from 350 mg to 1gram)...   

 

To keep the stuff from depositing, I wonder if it would also make sense to take more frequent taurine like the rats.   

Edited by Empiricus, 01 October 2018 - 02:50 PM.

[Turnbuckle]

Post #166 is helpful, thanks for reminding me of that. I decided to stop HT (hydroxytyrosol) and only take oleuropein, because HT seems to be the olive phenol that disagrees with me most.   Come to think of it, I probably could increase the oleuropein since I dropped the HT.

 

I have been taking dihydromyricetin since the beginning, but I had been thinking of stopping everythign that wasn't in your original protocol to avoid contradictions.  Maybe I should try dihydromyricetin at a higher dose (go from 350 mg to 1gram)...   

 

To keep the stuff from depositing, I wonder if it would also make sense to take more frequent taurine like the rats.   

 

 

Taurine reaches a max plasma concentration at 1.5 hours with a subsequent half life of one hour. CSF volume is up to 150 ml with a production rate of 20 ml/hr, so I'd expect materials suspended in it to have a half-life of around 7 hours. Thus you might consider taking subsequent doses of taurine at 3 hours, 6 hours, and 9 hours. After the first week you will probably have a much reduced problem, having cleared out the most loosely bound deposits by that point. High doses of Vitamin C may also be helpful, and C is available in time release form.

Edited by Turnbuckle, 01 October 2018 - 07:45 PM.