It's very complex there also seems to be a massive hydrogen sulphide deficiency in Alzheimer's and a lesser one in Parkinson's but Downs Syndrome cases have too much of that.
I am currently wondering how to raise hydrogen sulphide levels in vitro before trying NGF. I'd like to know what supplements are available nasally that contain NGF without going near something that had been part of a human and I'd like to know what supplements might be precursors of hydrogen sulphide I think this might help. Hopefully there might be an overlap with supplements that could raise HDL
HONG KONG – In the hunt for ways to extend life, scientists are turning to an unlikely source: the gas that gives rotten eggs their foul smell.
Hydrogen sulfide — maligned for its toxic and explosive properties — may slow aging and block damaging chemical reactions inside cells, according to scientists in China, who reviewed studies on the malodorous gas and its effects on the cardiovascular and nervous systems.
Hydrogen sulfide activates a gene linked to longevity in a way similar to resveratrol, an antioxidant in red wine that GlaxoSmithKline PLC tried to turn into a drug, scientists found. Unlike resveratrol, hydrogen sulfide is made by the body. Pills that boost levels of the compound may one day prolong life.
“Everyone always thought of hydrogen sulfide as the bad guy — an environmental pollutant, a toxin,” said Matt Whiteman, associate professor of experimental therapeutics at England’s University of Exeter. Since the discovery that the gas is made in mammalian cells, “this research area has exploded,” he said.
and:
Hydrogen sulfide appears to slow aging and aging-related diseases in at least three ways, said Jiang Zhisheng and colleagues at the University of South China in Hengyang City, Hunan Province, in a report slated for publication next month in the journal Molecular and Cellular Biology.
It helps counter cell-damaging free radicals, encourages production of an enzyme thought to be a regulator of life span, and interacts with a gene that appears to have its own set of antiaging activities.
“Data available so far strongly suggest that hydrogen sulfide may become the next potent agent for preventing and ameliorating the symptoms of aging and age-associated diseases,” Jiang said in a statement, adding that people may one day take hydrogen sulfide-rich food or supplements to slow aging.
The gas has a role for regulating blood pressure, improving the flexibility of veins and arteries and producing a smoother flow of blood, researchers from the University of Exeter’s Peninsula Medical School and King’s College London said in study in the journal Circulation published in 2008. Whiteman and fellow University of Exeter researchers showed the following year that decreases in hydrogen sulfide may contribute to vascular complications in diabetics.
and:
“In the space of about 10 years, it’s gone from there being sessions at conferences on hydrogen sulfide to full-grown conferences where only hydrogen sulfide is talked about,” he said. “It’s made a massive leap.”
Looks like you might be on to something here.
Food sources include: onions, garlic, leek, asparagus and eggs.
And there are sulphides in MSM.
Maybe this is the reason for the rumoured effectiveness of MSM
At the top of the top of the thread The Latest Alzheimer's Research there is an abstract
Hydrogen Sulphide ameliorates Homocysteine-Induced Alzheimer's Disease like Pathology,Blood Brain Barrier and Synaptic Disorder.
It would be wonderful if cognitive decline could be treated with NGF alone but I think it is more complex and involves things like Hydrogen Sulphide,cholesterol and blood sugar levels too. Could NGF correct all those other problems. It would be wonderful if it could. Maybe for cognitive decline. Alzheimers might be something else as by the time that happens all those other things are going wrong. RG could if he wanted take NGF orally I suspect but tablets containing NGF seem to have stopped working for me. That is when other ways of getting it into the body become more important. With Alzheimer's the new growth caused by NGF when taken orally no longer merges with the brain but lines the skull instead so doesn't grow properly. There might be things that target all the above when taken with NGF ameliorate the disease I wonder what they might be
I am thinking of taking DMSO. Asparagus is seasonal. I love garlic. I might try MSM again though it didn't do much when I tried it before. The good thing about DMSO is that whatever it's mixed with gets transported past the blood brain barrier. I liked your and RG's idea about the disease being caused by a pathogen clamidia pneumonaie could well be right. DMSO is a possible treatment but what is really needed is something to stop the decline.
OK sorry for the long post. Just catching up here.
First of all, let me say that, next to betaNGF, oxaloacetate impresses me. So if betaNGF isn't for you, look into that instead.
@ Metagene:
Do you see anything novel and appealing about GK2 as opposed to betaNGF? In particular, is this just a case of researchers attempting to find something patentable that's "not quite" natural, or is there something more here?
@ Playground:
First of all, I think you're correct in that the effects of betaNGF will vary over time. The maximum success case would be one of periodic neuron repopulation, in the sense of what we suspect was occurring with Rita. To answer your questions:
"Have you been doing your brain trainers recently ?"
I played Cambridge Brain Sciences about a month ago in order to form a baseline, in particular on the memory tests. I will play them again in a few months, when in theory the betaNGF effects will have maxed out. I can say that, at least until late last week, there were no obvious memory improvements. That seems to be changing, however, provided of course that I obtain sufficient sleep.
"Is there any evidence of you performing better on those exercises at which you've plateaued ?"
N/A
"Do you had any experiences that might suggest enhanced learning capacity?"
Well, my sense of smell is performing very well. And apart from the dreams, I have found that I don't seem to forget as easily where I put something. I've also become better at remembering names and conversations from a few days ago. To be fair, I'm doing so much that this could well be due to something else, for example, high dose pterostilbene or my calorically restricted juice diet or LLLT or oxaloacetate or...
"What kind brain stimulation are you experiencing ?"
It was all manner of trivial thoughts while trying to sleep. This might be part of the retraining process, or something else, I don't know, but fortunately I had a good night's sleep Monday and Tuesday. I haven't taken betaNGF since Sunday night. I'll try again today, and we'll see if this problem recurs.
"Is this raw cognitive stuff ?"
"Raw" would be a good word, indeed. It's like crosstalk going on between a hundred different thought channels. Very annoying.
"Or is this emotional stuff (worries, antipathies, jealousies etc) ?"
Good question. Not at all. Just a "spray" of trivial information.
"Is this more like watching TV ... visual stuff ?"
The visual quality of the "thought spray" is low. There's no continuity of ideas -- no flow -- unlike in the dreams, which flowed as if constructed deliberately.
And yes, I continued with 300 ug of melatonin per night, but it was of no help. It just quit on its own. I dreamt normally last night (meaning: of the quality that I would have experienced regularly maybe 10 years ago), but not at the MITS level.
As to meditation, I can only agree with your recommendation. There's a mountain of science to back it up. I've been too damn lazy in this regard and need to do more.
"The beta-NGF element has a weight of 26 K daltons. Note: The beta-NGF available from RG's source, is 13.2 K daltons."
I think betaNGF is indeed 13 KDa. I checked with Sigma Aldrich, a top tier US vendor. You can see the weight on this page. To complicate matters more, Wiki insists that it's 26 KDa (27 with rounding), but provides no citation in the literature.
What I can say is that this study, which involved some form of murine NGF, succeeded in treating a 94-year-old human with macular degeneration; the molecule used was reported to be 30 KDa, which agrees with 27 KDa to one significant figure. So maybe it's all about murine vs. human. I'm trying to get clarification on this.
Wiki also says that NGF is actually known as "proNGF" because it is only after cleaving off the beta subunit that it becomes active. In other words, betaNGF is the activated form of NGF, as opposed to a precursor in its own right. Sorry I was mistaken about this before: "NGF is initially in a 7S, 130 kDa complex of 3 proteins - Alpha-NGF, Beta-NGF, and Gamma-NGF (2:1:2 ratio) when expressed. This form of NGF is also referred to as proNGF (NGF precursor). The gamma subunit of this complex acts as a serine protease, and cleaves the N-terminal of the beta subunit, thereby activating the protein into functional NGF. The term "Nerve Growth Factor" usually refers to the 2.5S, 26 kDa beta subunit of the protein. The beta subunit is the only component of the 7S NGF complex that is biologically active (i.e. acting as signaling molecules)."
As to the romance aspects of NGF, in all seriousness, I think it's probably good science. We know that subventricular zone (SVZ) neurogenesis is driven by courtship in mammals. But alas, it has not had any such effect in my own situation
@ceridwen:
You're right. Growing neurons takes months, not weeks or days. (The recovery in the study linked above took a year.) There are different effect phases in the process, which probably explains my short term results.
Really cool article you posted about cholesterol vs. Alzheimer's. (Press release is here.) I'm not sure what to make of it at the moment, except to say that I think we should dig deeper (and maybe have some more olive oil).
As to human betaNGF, it is of E. coli origin -- not human origin.
As to raising sulpide levels, I believe you can do this with brocolli (sulphorophane), garlic, and onions, but I have no evidence on hand. In any event, do not take hydrogen sulphide directly! It can be fatal at a certain dose.
Having said that, I think Playground is onto something with the low dose or indirect administration of hydrogen sulphide. But this is one case in which I would leave it to the researchers to figure out the proper dose and route of administration.
I don't think oral NGF is the way to go. That's too much of a big hammer. For one thing, it supports the survival of pancreatic beta cells. I really wouldn't want to encourage the survival of much of anything in the pancreas, frankly.
@ Irishdude:
"Did Rita cycle it? Any notes from her regarding how to use it? I'm thinking of purchasing B-NGF if I can't get my hands on straight NGF. I remember reading Rita used to dose through her eye balls. May I ask why you arent doing the same?"
I could not obtain (pro)NGF either, which is why I'm using betaNGF. I'm not going through the eyes because one of the studies in this thread (I believe, coauthored by Rita) suggested that transocular administration would be at most 10% as efficient as intranasal, and maybe more like 1%. That could be useful in someone with no discernable cognitive impairment, but I'm making up for a lot of damage, so I need to be more aggressive.
"Also, did anyone on here use NGF for an extended period of time? I can't be arsed reading the whole thread."
To my knowledge, no, unless ceridwen has in fact been dosing orally as she seemed to suggest above. But if anyone did, please let us know!
Edited by resveratrol_guy, 16 September 2015 - 01:29 PM.
Oh by the way, a team of scientists rebuilt a damaged mouse visual cortexin vivo following acute TBI, apparently by inducing embryonic stem cells to differentiate into cells specialized for that particular brain area. Unfortunately, the article is paywalled and obviosly we're a long way from human trials, let alone FDA approval. A bit more info is found here in the abstract.
Edited by resveratrol_guy, 16 September 2015 - 01:44 PM.
Oh by the way, a team of scientists rebuilt a damaged mouse visual cortexin vivo following acute TBI, apparently by inducing embryonic stem cells to differentiate into cells specialized for that particular brain area. Unfortunately, the article is paywalled and obviosly we're a long way from human trials, let alone FDA approval. A bit more info is found here in the abstract.
I have not been dosing orally recently that was decades ago. I started on DMSO today and now feel much worse. I had great problems typing some data into some software that I could use easily a month ago. Dimethylsulphate well it must have sulphur in it. If it is making me worse then do I have too much hydrogen sulphide in my brain? In which case my death is proceeding right on schedule and this is genetic? As you can imagine I am not at all happy. Sorry about my complete lack of school science.
Your article gives me hope that bodies will all be repairable to the extent that it will be possible to wake up from an otherwise endless sleep. Where then is brain death?
I have not been dosing orally recently that was decades ago. I started on DMSO today and now feel much worse. I had great problems typing some data into some software that I could use easily a month ago. Dimethylsulphate well it must have sulphur in it. If it is making me worse then do I have too much hydrogen sulphide in my brain? In which case my death is proceeding right on schedule and this is genetic? As you can imagine I am not at all happy.
Sorry about my complete lack of school science.
Hi ceridwen,
I recommend you stop taking DMSO.
If you want to increase the sulphides in your body,
I suggest you prefer to use onions, garlic, asparagus, etc.
It's the 'natural' way our bodies receive sulphide compounds.
Elbows leaning on my desk as I typed I used to get quite large electric shocks when leaning on my elbows too hard and for too long I got 1 today too but so soft that I barely felt it. I was wondering about the mechanism here and what this implies and if there is anything that I can do this was my physical electrical energy really weak
Elbows leaning on my desk as I typed I used to get quite large electric shocks when leaning on my elbows too hard and for too long I got 1 today too but so soft that I barely felt it. I was wondering about the mechanism here and what this implies and if there is anything that I can do this was my physical electrical energy really weak
Hi ceridwen,
don't worry about it, it sounds like you're trapping a nerve in your elbow.
It happens to everyone from time to time... It happened to me yesterday.
The size of the shock, is related to how much weight you put your elbow
I don't think it's about reduced electrical energy in your body.
You could try using a fluffy towel (or something similar)
to rest your elbows on.. it will disperse the pressure more.
playground. :-)
Edited by playground, 16 September 2015 - 11:21 PM.
Point A And yes, I continued with 300 ug of melatonin per night, but it was of no help. It just quit on its own. I dreamt normally last night (meaning: of the quality that I would have experienced regularly maybe 10 years ago), but not at the MITS level.
As to meditation, I can only agree with your recommendation. There's a mountain of science to back it up. I've been too damn lazy in this regard and need to do more.
//-----
Point B
What I can say is that this study, which involved some form of murine NGF, succeeded in treating a 94-year-old human with macular degeneration; the molecule used was reported to be 30 KDa, which agrees with 27 KDa to one significant figure. So maybe it's all about murine vs. human. I'm trying to get clarification on this.
//----- Point C As to the romance aspects of NGF, in all seriousness, I think it's probably good science. We know that subventricular zone (SVZ) neurogenesis is driven by courtship in mammals. But alas, it has not had any such effect in my own situation
About Point A:
300ug is way less than 1mg. I'm sure i've read that the 'sleep inducing' effect of melatonin is dose dependent.
Perhaps if you took 1mg you'd get better results. Just a suggestion.
About Point B:
You're right. The wikipedia statements might be misinfo based on maurine NGF.
I double checked the sigma aldrich page.
About Point C:
Not wishing to seem intrusive.
Are you single right now or .. how long have you been with your current partner ?
Any uptick in sexual interest ?
How do you feel emotionally, generally ?
There's some evidence (as i know you know) that even tiny dosages of NGF can have
an anti-depressant effect. Have you noticed this ?
Has your sleeping pattern settled down?
What quantities are you currently dosing ?
Has the experience changed qualitatively ?
Have you noticed the _expected_ benefits ?
Have you noticed _unexpected_ benefits ?
Do you find it as easy to focus on one thing at time ?
It always seemed to me that part of being able to focus
was being able to _shut_out_ distracting thoughts or ideas.
Conversely, i always felt that being creative was being able
to _allow_in_ random (distracting) thoughts or ideas.
Do you feel that you've been more creative in recent days/weeks ?
Any other side effects ?
I'm eager to learn of your experiences and opinions.
best wishes
PG
Edited by playground, 19 September 2015 - 07:43 PM.
Article in the Daily Mail Alzheimer's breakthrough discovery that dementia is caused by deformed blood vessals in the brain pave the way for new treatment.
This says that amyloid can be cleared very very quickly Article in the Daily Mail Alzheimer's breakthrough discovery that dementia is caused by deformed blood vessals in the brain pave the way for new treatment.
This says that amyloid can be cleared very very quickly
First off, here is the article to which ceridwen referred above. It reminds me very much of nilvadipine.
Playground, I've been very busy lately, but I continue to use betaNGF.
"About Point A:
300ug is way less than 1mg. I'm sure i've read that the 'sleep inducing' effect of melatonin is dose dependent.
Perhaps if you took 1mg you'd get better results. Just a suggestion."
I didn't know that. Thanks for the tip.
"About Point B:
You're right. The wikipedia statements might be misinfo based on maurine NGF.
I double checked the sigma aldrich page."
...or Sigma Aldrich is wrong on the weight, and Sino Biological copied their error. This is on my list to investigate. I see no good reason for the discrepency.
"About Point C:
Not wishing to seem intrusive.
Are you single right now or .. how long have you been with your current partner ?
Any uptick in sexual interest ?"
Unfortunately, this data point is uninformative because I'm down to 71 kg on caloric restriction. My ribs are showing and my shorts are very loose. So in this state, reproductive networks are severely down-regulated.
I continue on my juice diet, and I've plateaued at 1400 calories per day. Although, I would say that only half those calories are from juice on a typical day, with the rest being normal healthy food.
How do you feel emotionally, generally?
Well, it's very mixed. But there's no noticeable change in this regard since I started betaNGF.
There's some evidence (as i know you know) that even tiny dosages of NGF can have
an anti-depressant effect. Have you noticed this ?
No.
Has your sleeping pattern settled down?
Yes. It's the best it's been in a long time.
What quantities are you currently dosing ?
Well, I've been so busy lately that I've only managed 30 or 40 drops to each nostril every other day, at a concentration of 100 ug per 22 mL. To my surprise, I would have to say that the 20 ug dose was more effective. This might be confirmation of an effect plateau, or frankly just more heat damage during transport to the 100 ug vial. I'm in the process of planning my next therapy phase and will post about that in a few weeks.
Has the experience changed qualitatively ?
See below.
Have you noticed the _expected_ benefits ?
I would have expected more in the way of memory benefits. But at least I tend to have better recollection of where I put my tea, my keys, etc.
Have you noticed _unexpected_ benefits ?
My verbal fluidity has improved considerably, subsequently to ehanced olfactory perception. The dreams, of course, were entirely unexpected. I continue to dream, but not currently at the MITS level.
Do you find it as easy to focus on one thing at time ?
Yes, definitely.
Do you feel that you've been more creative in recent days/weeks ?
Strange you should ask -- very much so, to the point that I'm considering filing a patent application on a new invention created this past week, which would be my first for many years.
Any other side effects ?
I do have some irritation and lingering taste from the nasal spray; it mitigates after a day or two. Headaches have occurred on occasion as well, although the reason is unclear.
I'm in pain. I just took normal my double dose (about 8 sets of 10 drops per nostril, as opposed to 4 each last night, and maybe 3 each on average). The area behind my nostrils where it drains into my throat feels like a sun burn. It's bad enough that I've had to turn off my aircon so that it won't hurt as much to inhale through my nose.
I'm salivating excessively, just as one would pursuant to an excessive dose of chili peppers, although I'm not crying.
Perhaps nociceptor activation is a contributing factor. I've done 5 rounds before, but it was never debilitating like this. It's half an hour later, and I can hardly hold my head up straight. Shit this hurts.
I'm jusy saying. Watch your dose. Give your nasal passages time to recover. Get a nasal humidifier.
Otherwise, my body feels light as air. Perhaps this is the same light feeling, maybe due to my deep painful breathing, which I suppose would leave plasma CO2 a bit out of whack.
Did anyone catch this? There appears to be a dipeptide mimetic of NGF.
Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer’s Disease http://www.ncbi.nlm....les/PMC3848070/
I'm wondering if we might be able to have this synthesized for us a cheaper cost than straight NGF. If I remember correctly, GK-2 is a mimetic of the beta turn of NGF. I'm just reciting this from memory. But it should be very similar to bNGF. I think its worth looking into.
Edit: GK-2 has also been shown to lack the side effects typical of NGF. I'm surprised that no one here has taken an interest to this substance. Perhaps I've just missed the section on here where you discussed it but if there's something wrong with gk-2 or some reason why we wouldn't be able to use, please let me know. Otherwise I'm going to continue digging up information on it.
I don't have any thoughts on the NGF part yet, but I have been using saline internasally the past month dosing Epitalon. I use 0.1ml of saline+ethanol mix per day, the alcohol at 8.6% by volume. Only spray it in my left nostril, there is no pain involved spraying it into my nose. Asked my mother who is a doctor to have a quick look in my nose with her ear-nose-throught kit, to compare left to right and she didn't see anything significant. I will repeat it in a month or 2, but so far I don't see daily saline use as an issue.
Saline sprays are typically non medicated. A mist of saline solution containing sodium chloride is delivered to help moisturize dry or irritated nostrils. This is a form of nasal irrigation. They can also relieve nasal congestion and remove airborne irritants such as pollen and dust thereby providing sinus allergy relief.
Three types of nasal sprays preparations of sodium chloride are available including hypertonic (3% sodium chloride or sea water), isotonic (0.9% sodium chloride) and hypotonic (0.65% sodium chloride). Isotonic solutions have the same salt concentration as the human body, whereas hypertonic solutions have a higher salt content and hypotonic solutions have a lower salt content. Isotonic saline nasal sprays are commonly used in infants and children to wash out the thick mucus from the nose in case of allergic rhinitis. Hypertonic solutions may be more useful at drawing moisture from the mucous membrane and relieving nasal congestion.
I don't have any thoughts on the NGF part yet, but I have been using saline internasally the past month dosing Epitalon. I use 0.1ml of saline+ethanol mix per day, the alcohol at 8.6% by volume. Only spray it in my left nostril, there is no pain involved spraying it into my nose. Asked my mother who is a doctor to have a quick look in my nose with her ear-nose-throught kit, to compare left to right and she didn't see anything significant. I will repeat it in a month or 2, but so far I don't see daily saline use as an issue.
betaNGF dosing is fundamentally different because it involves retaining the insufflated fluid in the upper regions of the nostrils for about a minute at a time. Spraying would be useful in order to accelerate plasma uptake, but in this case, we're attempting to enhance olfactory nerve uptake. I definitely would not use alcohol with betaNGF because of this distinction.
Playground, I think you raised a number of important issues regarding the pros and cons of nasal saline use, and its sustainable limits. First of all, fortunately, most of the pain had dissipated as of this morning. Sleeping with my CPAP humidifier maxed out certainly helped. So too did opening Curcubrain capsules and swishing them around my mouth.
"OCEAN Saline Nasal Spray contains sodium chloride 0.65% in purified water (USP), made isotonic with sodium phosphate/sodium hydroxide, with phenylcarbinol and benzalkonium chloride as preservatives"
I'm actually done with my 100 ug, so fortunately I'm forced to break for a while anyway. I have some novel approaches to solving the saline issues, but let me get things together first. I'll post when I have a compelling strategy. Meanwhile, your explorations of other methods would be valuable. The only thing we absolutely must ensure is sanitation, on account of the mortal hazards of certain nasal infections. But this could in principle be done with boiling, UV, ozone, or other methods not involving salt and preservatives.
On the topic of nasal irrigation, I might suggest doing that afterwards in order to mitigate the pain, say, an hour later, after most of the betaNGF has been absorbed.
As to the pain, for the reasons you stated, it's very difficult to determine the extent to which nociceptor activation was responsible. My nasal passages were already somewhat parched, and certainly saline by itself could cause such an effect at a sufficiently long exposure. There is clearly room to optimize pH and salinity, within the constraints of sterilization.
On the plus side, neurologically speaking, this was definitely a good day. Perhaps the increased dose gave me another "ping" of early-phase mental enhancement. Or maybe it was just the avocado meat I had this morning.
Edited by resveratrol_guy, 22 September 2015 - 04:04 AM.
Did anyone catch this? There appears to be a dipeptide mimetic of NGF.
Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer’s Disease http://www.ncbi.nlm....les/PMC3848070/
I'm wondering if we might be able to have this synthesized for us a cheaper cost than straight NGF. If I remember correctly, GK-2 is a mimetic of the beta turn of NGF. I'm just reciting this from memory. But it should be very similar to bNGF. I think its worth looking into.
Edit: GK-2 has also been shown to lack the side effects typical of NGF. I'm surprised that no one here has taken an interest to this substance. Perhaps I've just missed the section on here where you discussed it but if there's something wrong with gk-2 or some reason why we wouldn't be able to use, please let me know. Otherwise I'm going to continue digging up information on it.
If anyone can actually synthesize this and supply it economically, I'm all ears. Otherwise, sadly, it belongs to the FDA black hole.
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