674 replies to this topic

[Empiricus]

Thanks, Turnbuckle.  The scheduling suggestion is helpful.  Fortunately, my toleration for both taurine and vitamin C is very high. 

 

BTW, anyone having trouble tolerating taurine should experiment with different brands. There's a cheap brand of taurine that makes me run to the bathroom. Also, I have much higher toleration for NOW capsules than the bulk NOW powder (strange, I know). Swansons stocks a pharma-grade taurine product (AjiPure) that I also tolerate well, but NOW capsules, being 1,000 mg, are the ideal size.

Edited by Empiricus, 02 October 2018 - 05:34 AM.

[Turnbuckle]

 Also, I have much higher toleration for NOW capsules than the bulk NOW powder (strange, I know). 

 

 

This is likely due to the slow dissolution of capsules. You could probably achieve the same effect by taking several small doses of dissolved taurine over a period of time rather than taking it all at once.

[Empiricus]

In preparing HEPPS and oleuropein for consumption over the course of this week, I used a mortar and pestle to crush 1 gram of HEPPS and 500 mg oleuropein into an extremely fine powder which I then mixed into 50 ml of olive oil.  My idea was to take 1 teaspoon/day for 10 days, imposing a strictly lower dose of HEPPS (100mg/day).    I also started taking 3 grams of vitamin C + 5 grams of taurine + 1 gram of citrus flavonoids at 3 and now 6 hours.

 

Judging by the effect (mild headache and above average flakiness), today's preparation feels far more potent than when I took a much higher dose of HEPPS. I don't know whether it was having crushed the HEPPS, or the combination of C+taurine+flavinoids that makes the experience intense and somewhat unpleasant.  (I've taken loads of taurine and C by themselves many times, so I can rule out being either in isolation.  Also I've mega-dosed taurine hours after HEPPS, and not felt anything).  

Edited by Empiricus, 02 October 2018 - 01:17 PM.

[Turnbuckle]

HEPPS is highly soluble in water but not soluble in oil, so I wouldn't expect dispersing it in olive oil would make it stronger. Oleuropein, however, should be rather more bioavailable in oil. 

[Moumou]

I live in France and sooner in the post someone posted a French (imported from Morocco) organic Olive oil claiming x30 polyphenol (233mg/kg Hydroxytyrosol - 10 mg/kg d'oleuropéine), their first package was a transparent glass, they have now a dark glass package (https://www.naturame...vie-pharma.html). I will buy some, but don't know how to test it's x30 polyphenols claiming

 

 

 

I've found a 4% Taurine eye drops (https://www.belmedpr...d=493&lang_id=2), maybe at the same dosage I could speculate that Intranasal 4% HEPPS would be tolerated by the Olfactory system. I've found also some occular drop testing on rabbits that uses 10% Taurine.

 

Plus, Beta-alanine inhibit Taurine intake. Don't know if beta-alanyl-L-histidine (carnosine) would deplete Taurine like Beta-alanine.


o Mechanism underlying the antioxidant activity of taurine:prevention of mitochondrial oxidant production

"The taurine analogue, beta-alanine, is considered an inhibitor of taurine’s actions, as it both interferes with the actions of taurine and facilitates cellular taurine depletion. Therefore, to provide information on the mechanism of taurine’s actions, b-alanine was used to reduce taurine levels and suppress taurine action."

https://link.springe...0726-011-0962-7
 

 

o The effect of taurine and ß-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice

"Furthermore, taurine supplementation significantly increased, while ß-alanine supplementation significantly decreased, muscle taurine content in mdx and WT mice when expressed relative to wet or dry weight."

https://link.springe...0726-016-2292-2
 

 

o Interplay of histidine residues of the Alzheimer’s disease Aß peptide governs its Zn-induced oligomerization

"Taken together, the data indicate that interplay of histidine residues in the minimal zinc-binding site 6–14 of Aß upon its interactions with zinc ions underlies critical conformational changes of Aß, which in turn lead to Aß dimerization, oligomerization and aggregation."

https://www.nature.c...icles/srep21734

Edited by Moumou, 02 October 2018 - 03:20 PM.

[Empiricus]

Plus, Beta-alanine inhibit Taurine intake. Don't know if beta-alanyl-L-histidine (carnosine) would deplete Taurine like Beta-alanine.

o Mechanism underlying the antioxidant activity of taurine:prevention of mitochondrial oxidant production ...

 

I found something about how much beta-alanine may be derived from oral carnosine:  

 

"...carnosine, when taken by mouth, is simply broken down during digestion to its components, histidine and beta-alanine. This results in only about 40% of the total dose being available as beta-alanine. Histidine as discussed before, does not need to be supplemented to increase carnosine levels."  https://www.pharmaci...ise-performance

 

The 40% figure is quoted all over the internet, but I can't find the source.  Writer might have got it backwards.  

Edited by Empiricus, 02 October 2018 - 04:25 PM.

[ryukenden]

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.

Memory problems from ECT are usually short term and very rarely long term. If you're worried about memory side effects, you can try unilateral ECT. We have treated so many severely depressed patients with ECT. Magnetic therapy may also help but not available in Uk. Possibly PEMF might help your depression. I assume you have tried Lithium augmentation as it is a mood stabiliser.

[Empiricus]

I live in France and sooner in the post someone posted a French (imported from Morocco) organic Olive oil claiming x30 polyphenol (233mg/kg Hydroxytyrosol - 10 mg/kg d'oleuropéine), their first package was a transparent glass, they have now a dark glass package (https://www.naturame...vie-pharma.html). I will buy some, but don't know how to test it's x30 polyphenols claiming

 

 

The source of the olives is Morocco, and desert conditions are associated with much higher phenol content.  Almost any Moroccan or Tunisian olive oil is probably a lot higher in phenols than the average European olive oil (which is where we get the "standard" measures for phenol content).  So I'm not sure if there's anything special about that brand.  "Tunisian varieties like Betsijina, Chétoui, and Oueslali ...showed a high content in total phenolic compound(>1000mg/kg)".  

https://www.jstage.j...3_ess13098/_pdf

 

It looks like the imported Morocco oil you found appears to come packaged in a box.  If so, this would reduce light damage better even than the brown glass. (Nowadays I don't buy any olive oils that come packaged in transparent containers).   It's just too bad their bottles are so small (250 ml).  

 

One factor contributing to higher phenol content of desert olive oils is the lack of fly infestation. "Total phenol content in olive oils is inversely related to the olive fly infestation level of the olive fruits (Tamendjari et al., 2009)."  

 

Most North African olive oils probably offer far more bang for the buck in terms of health benefits than European ones.  But an industry centered in Europe can't afford to let this secret become too well known!  

Edited by Empiricus, 03 October 2018 - 01:55 AM.

[Empiricus]

Yesterday confirmed for me that I wasn't imagining some side effects.  In addition to having commenced taurine and C every three hours, I made some additional changes today.  First, today (at least) I didn't take any HEPPS;  second, I significantly increased my oleuropein intake; third, I took D3 with curcumin; fourth, I resumed popping jujube berries. A fifth thing is the subject of this post.    

 

I found the easiest-to-tolerate olive leaf derived phenols to be a bottle of LE oleuropein that also contains celery seed extract (butylphthalide or l-3-n-butylphthalide). Might butylphthalide complement the protocol?  Here's what came up:  

• https://www.ncbi.nlm...pubmed/20554868 L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer's disease.  
• https://www.ncbi.nlm...pubmed/27439966 L-3-n-butylphthalide Rescues Hippocampal Synaptic Failure and Attenuates Neuropathology in Aged APP/PS1 Mouse Model of Alzheimer's Disease  
• https://www.ncbi.nlm...pubmed/28131710 DL-3-n-butylphthalide-Edaravone  hybrids as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases with high antioxidant potency for Alzheimer's therapy
• https://www.ncbi.nlm...pubmed/25176222 l-3-n-Butylphthalide attenuates β-amyloid-induced toxicity in neuroblastoma SH-SY5Y cells through regulating mitochondrion-mediated apoptosis and MAPK signaling.
• https://www.ncbi.nlm...pubmed/26215907 L-3-n-butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral Ischemic Rats.
• https://www.ncbi.nlm...pubmed/22233765 L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimer's transgenic mice.
• https://www.ncbi.nlm...pubmed/19214478 Long-term treatment of l-3-n-butylphthalide attenuated neurodegenerative changes in aged rats

Edited by Empiricus, 03 October 2018 - 12:48 PM.

[Turnbuckle]

3nB (3-n-butylphthalide) looks interesting, and is reasonably cheap. It also has anti-hypertensive properties, which quite a few users have noted on Amazon.

Edited by Turnbuckle, 04 October 2018 - 10:19 AM.

[Empiricus]

 

Yesterday confirmed for me that I wasn't imagining some side effects.  In addition to having commenced taurine and C every three hours, I made some additional changes today.  First, today (at least) I didn't take any HEPPS;  second, I significantly increased my oleuropein intake; third, I took D3 with curcumin; fourth, I resumed popping jujube berries. A fifth thing is the subject of this post...    

 

That all went fairly well. I took 120 mg of oleuropein and didn't seem much the worse for it.  And -- welcome change from the previous day -- nothing alarming to report.

 

Today I resumed the HEPPS (300 mg), along with the above noted additions (including taurine & C every 3 hours, 80 mg of oleuropein). I dropped carnosine and added back TUDCA.  The result is a return of side effects (increased typos, etc). And that's despite consuming a comparable amount of oleuropein to Turnbuckle's protocol (oleuropein dose high relative to HEPPS dose).  To rule out quality issues with HEPPS, I will order a batch from a different supplier. 

Edited by Empiricus, 05 October 2018 - 12:31 PM.

[Turnbuckle]

 To rule out quality issues with HEPPS, I will order a batch from a different supplier. 

 

Check the pH.

[Empiricus]

Check the pH.

 

How?  

[Moumou]

>>> To improve Curcumin absorbtion we could use Tumeric (curcuma) essential oil with tumerones, which also promotes neurogenesis.


o Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo

"In this study, we investigated the effects of ar-turmerone on neural stem cells in vitro and in vivo. Ar-turmerone increased the number of neural stem cells both in cell culture and in the adult rat brain in vivo. This increase resulted from enhanced neural stem cells proliferation and led to promoted neurogenesis during differentiation. In vivo, ar-turmerone mobilized endogenous neural stem cells from both neurogenic niches, the  subventricular zone and the hippocampus. We propose that ar-turmerone constitutes a promising future drug candidate to support regeneration in neurologic disorders."

  https://www.ncbi.nlm...les/PMC4180255/


o The Role of Turmerones on Curcumin Transportation and P-Glycoprotein Activities in Intestinal Caco-2 Cells

 "Unlike other studies in which the changes in gene expression induced by Curcuma extracts or curcumin were observed after a 72-hour exposure, the changes were observed at a much earlier time in our study because the cells were exposed to curcumin or turmerones for 24 hours only."

"Our in vitro results demonstrated that the presence of turmerones increased the accumulation of curcumin inside intestinal epithelial cells. Our results agree with a recent clinical study in which curcumin with the noncurcuminoid components of turmeric was taken by human volunteers; the bioavailability of curcuma was sixfold higher than that of normal curcumin. Nonetheless, our study also demonstrated the roles of individual turmerones in curcumin transport. As previous studies suggested that most of the oral curcumin was excreted in the feces, it is possible that curcumin could reach the colon without being metabolized and that more curcumin could be absorbed into the cells with turmerones."


  https://www.ncbi.nlm...les/PMC3282471/

 

 

>>>  For those who are using Methyleneblue, MSM increase MB intestinal permeability.

 

 

o Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy

 

"Higher concentrations of methylenesulfonylmethane increased the rate of transport of methylene blue  1 mg/ml across a porcine intestinal membrane as measured with a spectrometer set at 668 nm over a 2-h time period."

 

"Study determined if the porcine intestinal membrane impermeability recovered after exposure and removal of MSM. Membrane soaked in MSM for 24 h then washed was no more permeable to methylene blue than control solution of methylene blue without MSM. Concurrent MSM increased the permeability of methylene blue through the membrane."

 

https://www.tandfonl...717540902896362

 

 

 

 

Edited by Moumou, 06 October 2018 - 01:12 AM.

[Phoebus]

here is something to consider - iron. 

 

levels of brain iron is the difference between those with amyloid with NO dementia symptoms and those with dementia symptoms. 

 

 

Previous research has long linked Alzheimer’s to a build-up in amyloid protein fragments in the brain that are normally broken down in healthy brains. But efforts to treat Alzheimer’s by using drugs that reduce amyloid levels have so far failed, leading to speculation that something else is driving the disease.

 

New research from the Florey Institute of Neuroscience and Mental Health and the University of Melbourne has found that iron might be the culprit. Iron has a special property that allows it to exchange electrons, which is crucial in allowing our bodies to generate energy from oxygen and fuels such as sugars. But it can also damage neurons in the same way that iron metal rusts in the presence of oxygen.

The researchers used cutting edge magnetic resonance imaging techniques to measure iron levels in the brain. They found that people with high levels of iron in combination with high levels of amyloid were suffering rapid cognitive decline, but that people with high levels of amyloid but low levels of iron in the brain, were stable.

They are now going to carry out a five year trial to test whether an anti-iron drug can slow the progress of Alzheimer’s, in what would be a major breakthrough in finding a treatment.

https://pursuit.unim...-to-alzheimer-s

 

 

in fact an iron chelator reduced leves of both tau and amyloid in rabbits with AD 

 

 

 

Deferiprone reduces amyloid-β and tau phosphorylation levels but not reactive oxygen species generation in hippocampus of rabbits fed a cholesterol-enriched diet.

Accumulation of amyloid-β (Aβ) peptide and the hyperphosphorylation of tau protein are major hallmarks of Alzheimer's disease (AD). The causes of AD are not well known but a number of environmental and dietary factors are suggested to increase the risk of developing AD. Additionally, altered metabolism of iron may have a role in the pathogenesis of AD. We have previously demonstrated that cholesterol-enriched diet causes AD-like pathology with iron deposition in rabbit brain. However, the extent to which chelation of iron protects against this pathology has not been determined. In this study, we administered the iron chelator deferiprone in drinking water to rabbits fed with a 2% cholesterol diet for 12 weeks. We found that deferiprone (both at 10 and 50 mg/kg/day) significantly decreased levels of Aβ40 and Aβ42 as well as BACE1, the enzyme that initiates cleavage of amyloid-β protein precursor to yield Aβ. Deferiprone also reduced the cholesterol diet-induced increase in phosphorylation of tau but failed to reduce reactive oxygen species generation. While deferiprone treatment was not associated with any change in brain iron levels, it was associated with a significant reduction in plasma iron and cholesterol levels. These results demonstrate that deferiprone confers important protection against hypercholesterolemia-induced AD pathology but the mechanism(s) may involve reduction in plasma iron and cholesterol levels rather than chelation of brain iron. We propose that adding an antioxidant therapy to deferiprone may be necessary to fully protect against cholesterol-enriched diet-induced AD-like pathology.

 

https://www.ncbi.nlm...pubmed/22406440

 

 

 

barring getting a prescription for an iron chelator you can use a fat soluble version of quercetin 

 

 

 

 Quercetin was found to bind Fe2+ more strongly than the well-known Fe2+ chelator ferrozine. Quercetin can also bind Fe3+, Ga3+ and Zn2+. Interestingly, quercetin completely suppressed iron-promoted Fenton chemistry at micromolar levels, even in the presence of the major cellular iron chelators ATP or citrate. Data from this study indicate that the radical scavenging activity of quercetin provides only partial protection against Fenton chemistry-mediated damage. On the other hand, iron chelation by quercetin can completely inhibit the Fenton chemistry. Thus, quercetin’s antioxidant activity may be attributed to its iron-chelation activity [191]. Furthermore, superoxide radical-scavenging activity of flavonoid iron complexes was found to be more effective than the uncomplexed parent flavonoid [195]. Quercetin was found to bind Fe2+ more strongly than the well-known Fe2+ chelator ferrozine. Quercetin can also bind Fe3+, Ga3+ and Zn2+. 95].               https://www.ncbi.nlm...les/PMC3821171/

 

Plain Q is not going to get into the brain much, but Q in fat might. There is an excellent Q prodcut that is Q bound to a phospholipid, which will make it more likely to cross the BBB and chelate brain iron 

 

https://www.amazon.c...e?ie=UTF8&psc=1

 

something to consider 

[William Sterog]

What do you people think about NT-020 for repairing the brain?

[Turnbuckle]

What do you people think about NT-020 for repairing the brain?

 

 

There are rat studies on it, conducted by the researchers/marketers of the product. The ingredients--mostly blueberry extract, vitamin D3, green tea extract, and carnosine--are cheap and readily available, while the reports on Amazon aren't exactly stellar. The previous work by the researchers suggests that it will promote stem cells in various parts of the body, but this seems rather marginal in the brain (see Figs. 2-3). There is an improvement, but well short of youthful levels. And while they previously showed that blueberry extract might be helpful in AD, their remarks weren't exactly enthusiastic--

 

Thus, taking previous these previous studies and current findings into account, we suggest that BB extract supplementation might prevent cognitive deficits most likely through an antimicroglial activation mechanism, which results in the protection of neurons and synapses from toxic inflammatory mediators, without a necessary reduction in parenchymal Aβ.

https://www.ncbi.nlm...les/PMC2751806/

 

[Moumou]

Pointing out the multifaceted effects of AD neurodegeneration at early stages, when the first areas affected by runaway proteins seem to be the olfactory bulb, the auditory cortex, the retina, the optic nerves, the spinal neurons and also the enteric nervous system. All following a life-long accumulated cycle of damages and repairs, imbalancing negentropy homeostasis to an entropic cascade of neurodegenerations from periphery to the center.

Early AD stages found Beta-A and TAU accumulation into:

. the Olfactory bulb: causes: particulate matter, chemical substances, biological contaminants (virus, bacterias & parasites / ex: HSV, P.acnes or T.gondii)

. the Auditory cortex: causes: loud noises, chemical substances (some antibiotics), biological contaminants

. the Optical nerves & retina: causes: solar damages, chemicals substances, biological contaminants

. Enteric nervous system: causes: chemical substances, metal overload, biological contaminants & disturbed microbiome

. Spinal neurons : causes: chemicals substances, metal overload, biological contaminants & disturbed microbiome


I would add cognitive and sensorial understimulations with age and isolation, inducing less neuroplastogenesis which would be as well an aggravating factor to AD. Deficiencies are also a factor of neurodegeneration (ex: B12 for the auditory cortex, taurine for the retina & optic nerves).

Edited by Moumou, 06 October 2018 - 06:32 PM.

[tolerant]

That all went fairly well. I took 120 mg of oleuropein and didn't seem much the worse for it.  And -- welcome change from the previous day -- nothing alarming to report.

 

Today I resumed the HEPPS (300 mg), along with the above noted additions (including taurine & C every 3 hours, 80 mg of oleuropein). I dropped carnosine and added back TUDCA.  The result is a return of side effects (increased typos, etc). And that's despite consuming a comparable amount of oleuropein to Turnbuckle's protocol (oleuropein dose high relative to HEPPS dose).  To rule out quality issues with HEPPS, I will order a batch from a different supplier. 

 

Empiricus, would you mind setting out your protocol, especially where it deviates from Turnbuckle's? Which elements do you think produced the cognitive "side effects"? I would welcome experiencing temporary cognitive "side effects" because if you can unmask the problem, you can then fix it. I used Turnbuckle's protocol about 10 times and never felt any different. The only thing I tried adjusting was HEPPS: on one occasion I took 2 g and on another occasion I didn't take any.

Edited by tolerant, 13 October 2018 - 09:30 AM.

[Empiricus]

Empiricus, would you mind setting out your protocol, especially where it deviates from Turnbuckle's? Which elements do you think produced the cognitive "side effects"? I would welcome experiencing temporary cognitive "side effects" because if you can unmask the problem, you can then fix it. I used Turnbuckle's protocol about 10 times and never felt any different. The only thing I tried adjusting was HEPPS: on one occasion I took 2 g and on another occasion I didn't take any.

 

My protocol has consisted of Turnbuckle's protocol (August version), but without any oleuropein until last week. Additionally, I took various other supplements listed in previous posts. I attribute all the side effect to HEPPS, which amount to more frequent and more outrageous typos.  The symptoms are consistent with debris being released, and not cleaned up -- possibly on account of lack of oleuropein which Turnbuckle included in his protocol for that purpose.

 

I got my HEPPS from a Chinese supplier.  It's possible it's not of good quality, but I won't know until I try some from a different supplier.  I can't rule out "defective HEPPS" because I don't see the improvements described by Turnbuckle, rather more of what Turnbuckle described experiencing prior to beginning the protocol. 

 

I took no protocol-related supplements this past week, but plan to resume taurine and oleuropein.  

Edited by Empiricus, 13 October 2018 - 03:51 PM.

[Turnbuckle]

My protocol has consisted of Turnbuckle's protocol (August version), but without any oleuropein until last week. Additionally, I took various other supplements listed in previous posts. I attribute all the side effect to HEPPS, which amount to more frequent and more outrageous typos.  The symptoms are consistent with debris being released, and not cleaned up -- possibly on account of lack of oleuropein which Turnbuckle included in his protocol for that purpose.

 

I got my HEPPS from a Chinese supplier.  It's possible it's not of good quality, but I won't know until I try some from a different supplier.  I can't rule out "defective HEPPS" because I don't see the improvements described by Turnbuckle, rather more of what Turnbuckle described experiencing prior to beginning the protocol. 

 

I took no protocol-related supplements this past week, but plan to resume taurine and oleuropein.  

 

Taste the crystals. HEPPS should have a mild chemical taste. If it has almost no taste, then it may be HEPES. HEPES makes plaques worse.

[Empiricus]

Taste the crystals. HEPPS should have a mild chemical taste. If it has almost no taste, then it may be HEPES. HEPES makes plaques worse.

 

The main thing I notice is the crystals melting on my tongue. The melt-in-your-mouth sensation is stronger than the taste. It's close to having no taste. But I'm saying this based on rather tiny amount I put on my tongue just now (and not swallowing).  I would have a better answer if not for the fact most times I poured it into gelatin capsules before taking. I used the capsules in order to measure sub-gram doses.  I have some HEPPS on order from USA.  

 

By any chance is HEPES oil-soluble?  That could explain the stronger side-effects observed when taken crushed into olive oil. 

 

I was thinking it would be most helpful if we could identify a chemical reaction that works differently with HEPES and HEPPS.  With this in mind, I just dropped a few dozen crystals into a glass of MCT oil.  First the oil became a little foamy.  Then the crystals disappeared. In place of crystals, not floating, but resting at the bottom of the glass are bubbles. When shaken, the MCT oil becomes filled thousands of these bubbles.  Does the same thing happen when genuine HEPPS is placed in MCT oil?  

Edited by Empiricus, 14 October 2018 - 05:26 AM.

[Turnbuckle]

By any chance is HEPES oil-soluble?  That could explain the stronger side-effects observed when taken crushed into olive oil. 

 

I was thinking it would be most helpful if we could identify a chemical reaction that works differently with HEPES and HEPPS.  With this in mind, I just dropped a few dozen crystals into a glass of MCT oil.  First the oil became a little foamy.  Then the crystals disappeared. In place of crystals, not floating, but resting at the bottom of the glass are bubbles. When shaken, the MCT oil becomes filled thousands of these bubbles.  Does the same thing happen when genuine HEPPS is placed in MCT oil?  

 

 

Good's buffers were chosen for low reactivity, as well as low solubility in nonpolar solvents, and that includes HEPPS and HEPES. They are not oil soluble. They do not produce any bubbles when added to MCT oil, though my sample of HEPES is a much finer powder and will suspend for a while if you shake it up, then settle out. In any case, I would not use the product you got from China, Wait on your purchase from the US.

Edited by Turnbuckle, 14 October 2018 - 10:31 AM.

[tolerant]

FWIW, this is what ACTGene HEPPS looks like. I know the quality is not good. I also took a picture with a proper camera, but can't find the USB cord to it. If I find it, or get a new one, I'll upload it if it's still relevant. 

Attached Files

•  HEPPS_ACTGene.jpg   52.72KB   1 downloads

[tolerant]

Pointing out the multifaceted effects of AD neurodegeneration at early stages, when the first areas affected by runaway proteins seem to be the olfactory bulb, the auditory cortex, the retina, the optic nerves, the spinal neurons and also the enteric nervous system. All following a life-long accumulated cycle of damages and repairs, imbalancing negentropy homeostasis to an entropic cascade of neurodegenerations from periphery to the center.

Early AD stages found Beta-A and TAU accumulation into:

. the Olfactory bulb: causes: particulate matter, chemical substances, biological contaminants (virus, bacterias & parasites / ex: HSV, P.acnes or T.gondii)

. the Auditory cortex: causes: loud noises, chemical substances (some antibiotics), biological contaminants

. the Optical nerves & retina: causes: solar damages, chemicals substances, biological contaminants

. Enteric nervous system: causes: chemical substances, metal overload, biological contaminants & disturbed microbiome

. Spinal neurons : causes: chemicals substances, metal overload, biological contaminants & disturbed microbiome


I would add cognitive and sensorial understimulations with age and isolation, inducing less neuroplastogenesis which would be as well an aggravating factor to AD. Deficiencies are also a factor of neurodegeneration (ex: B12 for the auditory cortex, taurine for the retina & optic nerves).

 

Hi moumou,

 

Are you saying that in AD, all the sensory and motor functions that you listed are the first to show signs of the disease? Isn't it things that memory, problem-solving, decision-making, inability to complete tasks which were very easy before that are signs of AD? All these apply to me, yet I have no problems with vision, hearing, etc. Or you saying that stresses to these parts of the CNS is what causes memory, thinking and other issuers? If not, then how "cognitive and sensorial understimulation ... and isolation" fit in within this taxonomy? That does apply to me, I've been relatively isolated for the past six years because of depression. But your bullet points list parts of the CNS, while isolation is something else entirely. Please educate me. 

[tolerant]

Is J147 worth a try?

[Turnbuckle]

I should be more specific about how to taste HEPPS. You need to add a small amount of water and then swish it around to detect the chemical taste, as taste buds are distributed around the tongue in a pattern.

[Turnbuckle]

Is J147 worth a try?

 

J147 is a cucurmin derivitive that has been tested in mice and has been shown to be increase ATP synthase activity. I expect it will show short term promise but will fail rather badly in the long term for two reason: first, it does not address the underlying cause of AD, and second, it will interfere with the cellular QC program for getting rid of dysfunctional mitochondria. It also reduces inflammation, but other drugs do that as well.

[tunt01]

J147 is a cucurmin derivitive that has been tested in mice and has been shown to be increase ATP synthase activity.

 

J147 inhibits ATP Synthase activity.

 

https://onlinelibrar...1111/acel.12715

 

 

 

We have previously demonstrated the therapeutic efficacy of J147 in several mouse models of AD. Here, we identify the mitochondrial α‐F1‐ATP synthase (ATP5A) as a target for J147. By targeting ATP synthase, J147 causes an increase in intracellular calcium leading to sustained calcium/calmodulin‐dependent protein kinase kinase β (CAMKK2)‐dependent activation of the AMPK/mTOR pathway, a canonical longevity mechanism. Accordingly, modulation of mitochondrial processes by J147 prevents age‐associated drift of the hippocampal transcriptome and plasma metabolome in mice and extends lifespan in drosophila. Our results link aging and age‐associated dementia through ATP synthase, a molecular drug target that can potentially be exploited for the suppression of both.

 

 

 

Changes in ATP synthase activity occur concomitantly with the production of reactive oxygen species (ROS) (Laura Formentini, Sánchez-Aragó, Sánchez-Cenizo, & Cuezva, 2012). Although traditionally thought of as being detrimental, new evidence suggests that inhibition of ATP synthase can elicit a retrograde, ROS-mediated prosurvival response (Laura Formentini et al., 2012). Both J147 treatment and ATP5A knockdown caused a significant increase in superoxide levels within the mitochondria (Figure 2f,g).

[tunt01]

Additionally, there is another derivative called CAD-031, which has the same mechanistic behavior and some of the data here on how it altered inflammation and lipid metabolism was pretty interesting to me, because it is effectively the metabolic signature of longevity inducing phenotype (i.e. fasted state).

 

 

 

Daugherty, D., Goldberg, J., Fischer, W., Dargusch, R., Maher, P., & Schubert, D. (2017). A novel Alzheimer’s disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimer's Research & Therapy, 9(1). doi:10.1186/s13195-017-0277-3