614 replies to this topic

[dz93]

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.

I should have a quote on a price within the week.

[playground]

For those of you who are interested, there is a a new thread on HGH and neurogenesis.

http://www.longecity...ealth/?p=745139

[resveratrol_guy]

Sorry for the brain dump, but there's a lot to cover here...

 

So I've started noticing something odd the past few days. Time and again, I'll be lying in bed, and for whatever reason, I'll get uncomfortable and decide to flip over. When I do so, of course, I end up seeing the ceiling, and then finally the furniture on the other side of the room. Only, I realize after the fact that I still have my sleep blinders on, so I can't actually see anything through my eyes at all. It's all being rendered in real time in crystal clear detail, to the extent that it fools me in my twilight level of consciousness. Maybe this happened when I was younger, but I don't remember it.

Then yesterday afternoon, having settled down for a nap, it went absolutely bananas. I was sitting there, looking at a small plastic aquarium, in particular, one of the corners at the top. I could see 3 images of the same fish, due to the diffraction of light through the water. I could see the air bubbles coming out of the filter, the imperfections in the plastic walls, the scales on the fish, and the distortions in the water surface due to his yawning mouth searching for food. But it was all fake. I just sat there, staring into my mind's eye, wondering where this was all coming from. This definitely wasn't a memory, as I had never owned such a setup. It was clearly a synthesis of many separate memories, unified into a realistic whole. Even the sound of the air pump was getting annoying. I would put this on the MITS level of realism, despite its mundane lack of cinematic appeal.

The only unusual thing I did yesterday was to have some magnolia bark (Swanson's 400 mg) in the morning, as opposed to the evening, when I took it on the few times I took it before. (This was the honokiol that I've referred to elsewhere. I thought it was 90% standardized but it turns out that's a different supplement sold by the same company. Nevertheless it certainly contains honokiol.) Maybe honokiol or magnolol enhances visual memory acutely, but I haven't found any data to support this. I also had 3 eggs in the morning, instead of my usual one, which no doubt helped.

It's either that, or betaNGF. I can't think of anything else that was out of my ordinary dietary pattern yesterday. For that matter, I actually skipped my shiitake-maitake pill yesterday.

I don't know where this is occurring in the brain. I'm tempted to run to the neurologist's office and say that I'm having strange visualizations just so I can get an fMRI and determine its spatial locale. In paricular, is it prefrontal, near the betaNGF insufflation site, or elsewhere? Visual processing is usually in the back of the brain, but apparently visual simulation occurs at the junction between the left parietal lobe and the left temporal lobe, if I remember correctly. But I'm no neuroanatomist. Does anyone know?
 

I should be clear that I don't think this is visual memory enhancement; it's visual synthesis enhancement. Not that I'm complaining, but it's all rather mysterious to me.

 

Now, here are some other questions that I have been asked privately, but I think the answers are publicly relevant, so I'll post them here:

So how are you feeling these days?

Quite good, apart from a few minor injuries sustained by not looking where I was going. The worst thing I can say is that I'm having a bit more difficulty containing my hunger, now that I'm 70 kg and probably a bit too thin. I'm upping my protein intake a bit in order to arrest the catabolism. At least, pterostilbene still helps quell the food obsession.

Are you still experiencing the brain chatter?

Not at all. It stopped several days ago. Sorry I have no clue as to what that was all about, unless perhaps it was betaNGF causing my neurons to figure out how to rewire their peer connections.

Is your sleeping still negatively affected?

My sleep quality is OK, but not the greatest. At least, it's better now in the absence of the brain chatter.

Are you nasal passages still a little sensitive?

Nope. That cleared up within a day. Again, a nasal humidifier is highly recommended.

Are you experiencing something like 'tinnitus of the sinuses'?

Not all all. My sinuses, while not completely clear, are not a source of annoyance. OTOH, my auditory tinnitus has been quite annoying lately, which sort of flies in the face of the other positive changes which have occurred, but I can tolerate it.

And how's your imagination and creativity, .. still notably inventive?

It's hard to quantify this, except to say that the visualization improvement has been immensely useful because I can see how my work will look before I actually do it. For example, I'm working a new website. I can see myself using it before I've actually written any of the code. This isn't new to me, except that it's so clear. I can change the layout, font size, colors, etc. and it just happens before my "eyes", somewhere in the wetware.

And how's your focus now?

This is also quite good. I've started to attempt multitasking, which I've never been good at, especially since my stroke-or-whatever 2 years ago. I'm still no good at it, but I will keep trying.

Has your focus declined now that it's been some days since your last dose?

No. I can pay rapt attention to conversations, videos, textual information, etc. The only thing is that I can't work for hours on end. I need to take breaks every half hour or so.

Do you feel like your emotional state is 'coming down'... or do you think there's been no change ?

This is hard to pinpoint, except to say that I feel my best after drinking green juice (especially with kale and ginger, it seems). When in doubt, load up on vegetable juice! My only regret in this department is the hunger, but when I look at what caloric restriction and juicing have given me, it's very hard to feel depressed about the results.

As the saying goes, you can always have more food on a calorically restricted diet... tomorrow!
 

[ceridwen]

It sounds to me like you're dreaming while you are still awake either that or you're becoming schizophrenic there are links between that and creativity. Might be worth thinking about. I've never heard of NGF doing that

[resveratrol_guy]

It sounds to me like you're dreaming while you are still awake either that or you're becoming schizophrenic there are links between that and creativity. Might be worth thinking about. I've never heard of NGF doing that

 

Not exactly. The key difference here is that, as long as I'm fully awake, I'm aware of when I'm visualizing something; I don't mistake it for reality. When I hear music or smell something odd, I tend to ask people around me if they perceive them as well. So far, it seems that they do.

[Sasha_]

It sounds to me like you're dreaming while you are still awake either that or you're becoming schizophrenic there are links between that and creativity. Might be worth thinking about. I've never heard of NGF doing that

 

Sounds more to me like a transient autistic-like ability to visualize or "think in pictures".

I wonder, is there a pertinent link between ngf levels and autistic brains ?

[playground]

 

It sounds to me like you're dreaming while you are still awake either that or you're becoming schizophrenic there are links between that and creativity. Might be worth thinking about. I've never heard of NGF doing that

 

Sounds more to me like a transient autistic-like ability to visualize or "think in pictures".

I wonder, is there a pertinent link between ngf levels and autistic brains ?

 

 

Everyone can think in pictures, can't they ?

Perhaps some women are less spatially/visually adept than average men.

 

I remember reading recently that autistic children's brains have _less_ NGF than

'normal' children's brains.  

 

Maybe you could treat autism with NGF.

(But i suspect that this is a symptom, not a cause of the autism)
 

[Sasha_]

Of course everyone can do it to a certain extant, but not with the same clarity and vividness as some Aspergers can.

I believe  Temple Grandin gave a good account of what it is in one of her books or conference, can't remember.

And well, if you ever tried microdosing on certain psychedelic substances, then you would probably realize how limited your baseline abilities are.

Although to be fair some neurotypicals do have above average visualizing abilities and I wouldn't be surprise if it was the case amidst some longecity members since there are quite a few brainy people out there.

 

EDIT: That being said, my first assumption linking autism and ngf was probably misled.

Edited by Sasha_, 30 September 2015 - 03:44 PM.

[ceridwen]

I think there's a big difference between visualization and actually thinking you saw something

[resveratrol_guy]

On the topic of visualization, I would have to say that my experience has not been particularly autistic. I say this mainly on account of the unified nature of the visions and events. For instance, in the MITS dream, there was a cohesive storyline and visual reality. In other words, it wasn't just a massive amount of disconnected minutiae, as one might expect of a more autistic experience. I could see the forest, the trees, and the leaves on the trees, so to speak. And yes, ceridwen is right that visualization is not the same as hallucination.

Secondly, I promised to post once I had everything set up for my next phase of NGF boosting. I've managed to obtain a large quantity of ashitaba extract, both chalcone liquid and chalcone-rich stem powder. In theory, the xanthohumol in the chalcone mixture should upregulate intracranial NGF by something like 20%, if the rat studies are any clue and I ingest enough. I just took a couple tablespoons of the yellow liquid a while ago. It tasted like celery juice mixed with medicine -- yuck! Anyway, I wouldn't really expect anything for days if not weeks. I'll crank up the dose and see if anything interesting happens. So far, I feel fine, but nothing out of the ordinary.
 

[ceridwen]

I am taking 4 teaspoons of sulphur a day. I hope this will lower my homocystine. Correct me if I'm wrong please. I am also taking Noopept up the nose a couple of squirts a day. I still think I'm dying though. I have tried almost everything now unless I can get some Salsalate but that probably only works on mice like everything else. The tinnitus feels toxic oxidative stress that I don't know how to stop

[Debonaire_Death]

 

 

does your memory continu to improve?

 

 

 I'm currently using LLLT directly aimed through the eyes in an attempt to do exactly that. I started doing so shortly before the first vivid dream, so perhaps this was the reason, but I doubt it because I don't recall such reports. If I notice any further improvements I'll report them, although I don't expect much more from such a small NGF dose. Granted, I'm doing so much therapy that it's hard to say what, in fact, is responsible. Caloric restriction is no doubt a huge factor, as well.

 

What I have noticed is that I seem to more alert and responsive, despite having much the same memory performance as when I first took betaNGF.

 

 

What do you mean by aiming your LLLT directly through the eyes? Do you mean you look into the IR LED?
 

[tunt01]

I am taking 4 teaspoons of sulphur a day. I hope this will lower my homocystine. Correct me if I'm wrong please. I am also taking Noopept up the nose a couple of squirts a day. I still think I'm dying though. I have tried almost everything now unless I can get some Salsalate but that probably only works on mice like everything else. The tinnitus feels toxic oxidative stress that I don't know how to stop

 

Salsalate might make sense if you have coindicating symptoms of osteoarthritis rheumatoid arthritis.  Have you looked at Dale Bredesen's protocol about lowering homocysteine and treating alzheimer's?  

[ceridwen]

Thanks
I was thinking of that as a last resort as I can't kick the sugar habit.
The sulphur actually made me a lot worse caused so much pain I stopped taking it. Now the pain is back

[playground]

 

 

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.

I should have a quote on a price within the week.

 

 

HI dz93,

 

Looking at the paper you cite, it seems that GK-2 has a weaker effect than Memantine (or a comparable effect to Memantine).

But that's no recommendation.  Since Memantine is basically ineffective.

 

See here (wikipedia)

 

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA receptors. It was first synthesized by Eli Lilly and Company in 1968. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Mimetix by Abbott in Latin America, as well as in various generic formulations. Memantine has been shown to have a modest effect in moderate-to-severe Alzheimer's disease^[1] and in dementia with Lewy bodies.^[2][3] Despite years of research, there is little evidence of effect on mild Alzheimer's disease.^[4]

 

Surely, NGF would be better.

 

Playground.

 

 

[Debonaire_Death]

 

 

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.

I should have a quote on a price within the week.

 

 

Did you ever get a quote for the GK-2? I'm looking at some more research on the stuff and from the looks of it there are so many potential side effects with NGF that it actually seems to be the preferred option for pharmacological reasons, rather than merely price (if, that is, we get a good price).

 

And Playground, where are you getting the idea that GK-2 is in any way comparable to Memantine? They seem like two completely different drugs. Also, in the study I linked above, GK-2 actually matches NGF in promoting cell survival, while increasing rather than decreasing pain threshold in rodent tests. I don't see why anyone would hesitate to try this stuff, at this point, if they were looking at trying NGF.
 

Edited by Debonaire_Death, 04 October 2015 - 06:23 PM.

[ceridwen]

Group buy ? I'd need to be this forever though

[resveratrol_guy]

I've been drinking 20 mL of liquid ashitaba chalcone daily, since I mentioned starting it above. I feel great, and seem to be quite alert, although it's possible that's just a longterm effect of something I did earlier, such as betaNGF or my continuing juicing diet or whatever. My sense of smell is currently very good. The only obvious effect from the chalcone has been appetite suppression, above and beyond what pterostilbene had afforded me. (I'm still taking pterostilbene.) For once, I have concrete evidence of this: I was crossing the street this afternoon when, suddenly, my shorts dropped to the ground! I guess I had gotten used to them hanging on my hips, and didn't notice the slow downward progression until it hit the critical point. Luckily, no one else was within eyesight. Having fallen below the minimum size of shorts that I can find in my local men's department, I now have no choice but to visit the tailor and spend a lot of money altering my clothes. If I actually wanted to lose weight, that would be fine. But I'm about 69 kg now, and I don't envy losing any more than I already have. As a precaution, I had some granola bars with butter. That ought to put a baseline under it for a while.

 

@ Debonaire_Death: What side effects of NGF? Anything other than pain? And yes, I'm staring at an 850 nm LED array for one minute in each eye, aimed roughly at each lobe of the hippocampus in the hopes that some of that infrared will penetrate that deep, as the vitreous humor doesn't cause nearly as much attenuation as the skull. I'm intersted in reading more about GK-2, but I'm not optimistic that it's easy to create an NGF analog which is actually safer, given NGF's already excellent safety profile. All else being equal, I would feel safer personally with (beta)NGF just because it's such an ancient molecule. But practicality might favor GK-2 if the price is much cheaper.

 

Edited by resveratrol_guy, 05 October 2015 - 05:40 AM.

[dz93]

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.

I should have a quote on a price within the week.

HI dz93,

Looking at the paper you cite, it seems that GK-2 has a weaker effect than Memantine (or a comparable effect to Memantine).
But that's no recommendation. Since Memantine is basically ineffective.

See here (wikipedia)

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA receptors. It was first synthesized by Eli Lilly and Company in 1968. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Mimetix by Abbott in Latin America, as well as in various generic formulations. Memantine has been shown to have a modest effect in moderate-to-severe Alzheimer's disease^[1] and in dementia with Lewy bodies.^[2][3] Despite years of research, there is little evidence of effect on mild Alzheimer's disease.^[4]

Surely, NGF would be better.

Playground.

That study was comparing the effects of GK-2 to Memantine in terms of effectiveness in treating AD. It actually showed GK-2 to be more potent than memantine.

"The effective dose of GK-2 by weight is 20 times lower than that of memantine; the effective dose by amount of matter is 80 times lower.
The results obtained suggest that further development of GK-2 as a neuroprotective medicinal product that could prevent the development of AD is rather promising."

Also, playground mentioned that he prefers NGF due to excellent safety profile, however, even though it seems safe it still has some annoying side effects, which GK-2 has been shown to lack.

It seems like no one cares to even look into GK-2 for some reason. Am I missing something? Is there a reason why GK-2 doesn't pique anyone's interest? I don't see why we would keep focusing on bNGF, especially when it has some annoying side effects, is extremely expensive, and isn't stable for extended periods of time. I'd appreciate it if someone could explain to me why they believe GK-2 isn't something that should be looked into.

[playground]

hi dz93,

 

Maybe you're right, maybe GK-2 has merits and should be considered seriously.

Why not start a thread about it.  I'll join it if you do... and probably others will too.

 

regards

 

Playground.

 

 

[resveratrol_guy]

When I awoke this morning, I noticed that I could sense the position of both of my hands on my chest. (This is a form of proprioception which occurs in normal individuals.) Ever since my stroke, I've had this problem where I wouldn't be able to determine whether or not my hands were touching, or merely close together; this only occurred during twilight consciousness on the edge of sleep, not during the day. I mentioned this a while back on my stem cell thread. At first, this was also occurring in my right foot, along with chronic tingling, but both phenomena disappeared months ago. The hand clasping sensation failure, however, remained. Basically, when lying very still with my hands on my chest, I would be unable to determine the status of anything above the wrists, until I moved my hands, thereby generating enough sensation to confirm their relative positions. This morning, I could feel everything, fingers and all.

 

I don't know when this started, exactly, as it's something that I've grown so used to that I haven't made much effort to monitor it. I just woke up and noticed it. It's been at least days, and possibly a month, since this occurred previously, whereas it used to be a routine occurrence. I should have kept a journal, but I suppose I never expected it to go away.

 

[playground]

Ever since my stroke, I've had this problem where I wouldn't be able to determine whether or not my hands were touching, or merely close together; this only occurred during twilight consciousness on the edge of sleep, not during the day.

 

Hi RG,

 

This is normal.  I think you're finding deficits in yourself where there are none.

 

It's typical and to be expected that, if you keep your hands (or feet) still for long enough

they become "invisible" in a sensory sense.  You lose any perception of where they are

and the only way to make them visible again is to move them. (That's completely normal)

 

This sensory invisibility is used in meditation as a 'cue' to your level of bodily relaxation. 

Typically it's done with the hands and fingers.

Monitoring hands and fingers provides a clue as to meditation depth.

 

If when meditating, you lose all sense of your arms and legs, so that you feel as though

you've melted into the chair / mat / bed  underneath you... that's a very good sign.

(Although, in practice, that's the point at which i tend to fall asleep. :-| )
 

regards

 

PG

[resveratrol_guy]

 

Ever since my stroke, I've had this problem where I wouldn't be able to determine whether or not my hands were touching, or merely close together; this only occurred during twilight consciousness on the edge of sleep, not during the day.

 

Hi RG,

 

This is normal.  I think you're finding deficits in yourself where there are none.

 

It's typical and to be expected that, if you keep your hands (or feet) still for long enough

they become "invisible" in a sensory sense.  You lose any perception of where they are

and the only way to make them visible again is to move them. (That's completely normal)

 

This sensory invisibility is used in meditation as a 'cue' to your level of bodily relaxation. 

Typically it's done with the hands and fingers.

Monitoring hands and fingers provides a clue as to meditation depth.

 

If when meditating, you lose all sense of your arms and legs, so that you feel as though

you've melted into the chair / mat / bed  underneath you... that's a very good sign.

(Although, in practice, that's the point at which i tend to fall asleep. :-| )
 

regards

 

PG

 

 

Really? Well, maybe you're right, but I never had this problem before my stroke. Maybe it's a sign that I had become better at sitting still after the stroke, but recently got worse. I'll have to see if the disappearing sensation recurs.

 

Meanwhile, I just made #1 on Pinball Recall twice in a row (by playing only twice), after not having played for over a month, and not having made a top 5 score since March, when I hit my plateau after something like 100 trials. On other games, my scores seem typical of prior performance. This YouTube video shows the game play, if anyone has any idea what its neurological significance may be.

 

Edited by resveratrol_guy, 07 October 2015 - 04:04 AM.

[resveratrol_guy]

I need to set the record straight on xanthohumol (from beer hops) vs. xanthoangelol (from ashitaba), as I believe I've been misinformed by faulty sources. I stumbled upon some chemical structure data, and they are distinct compounds. Furthermore, xanthohumol has several different forms.

 

Having said that, they are structurally similar, with a chalcone backbone being common between them, as is the case for all chalconoids. So when discussing "ashitaba chalones", for example, people are incorrectly referring to the chalconoids in ashitaba. (To make things really complicated, Wiki says that "chalcones" (plural) is equivalent to "chalconoids"; I'll try to use the latter term exclusively.)

 

On further research, although the link between NGF upregulation and xanthohumol appears to have been studied in some detail, I can't find any study that says the same of xanthoangelol. As shown in the US patent which I presented previously, however, there was a rat study (see sections [0075] and [0083]-[0087]) directly linking ashitaba root consumption to the upregulation of NGF in peripheral tissues (the brain not having been studied, unfortunately). (They did not test stems, where most of the yellow chalconoid sap resides, based on a survey of photos on the Web.)

 

In the first ashitaba study described in the patent, NGF in the "gastrocneminal" (gastrocnemius?) muscle increased about 16%; the author cites 0.75 g/kg/d of the root powder as the "effective dose", which I assume means the dose used to obtain the 16%.

 

In the second, streptozotocin was injected in order to cause diabetes mellitus. It's not clear whether this was type 1 or 2. But in any event, predictably, it resulted in peripheral neuropathy. Ischiadic nerve dissection revealed 840 pg/g concentration of NGF in the controls (no induced diabetes) vs. 497 in the untreated diabetic group. In the diabetic group given root powder (presumably at the "effective dose" of 1.6 g/kg/d, in this case), the NGF concentration rose to 628 -- an increase of 26%.

 

It's interesting that both the dose and the NGF increase in the second case are roughly double that in the first case, so we have a crude idea of the dose-response curve.

 

This strikes me as consistent in magnitude with the up-to-31% intracerebral increase in NGF found with xanthohumol (see [0079]). The upshot of this similar effect and similar chemical structure is the hypothesis that it is in fact the xanthoangelol in ashitaba which is responsible for the above effects.

 

For the record, here is a toxicological assessment of ashitaba chalconoid liquid.

 

It's also noteworthy that an artificial chalconoid has high binding affinity for beta amyloid; perhaps there's a plaque disaggregation story to all this as well, although I have no evidence of that presently. Granted, there are other components in ashitaba, such as 4-hyroxyderricin, which have neurological effects as well, which do not involve NGF.

 

Finally, note that beer hops contain 8-prenylnaringenin, a potent phytoestrogen, whereas ashitaba does not, as far as I can see in a Web search. As a result, beer hop and even xanthohumol supplements can contain this substance. All else being equal, I wouldn't want to mess with this stuff while trying to increase NGF, hence my personal preference for ashitaba and its extracts. Maybe I'm overreacting, but I thought I should point this out.

 

Edited by resveratrol_guy, 08 October 2015 - 07:45 PM.

[resveratrol_guy]

I just watched the John McMichael video again, and I realized the obvious: NGF does cross the BBB in humans! (This would be consistent with the radiotagged NGF rabbit study discussed previously, which was compelling but never proven to apply to humans.) How else could his team have obtained antidepressant-like effects following sublingual administration, especially in animals who are immune to placebo? BTW he says NGF weighs 30+ KDa, so that's bigger than the betaNGF I took. He also notes that some of his human subjects have taken it for as long as 5 years, apparently without adverse effects. He frequently speaks of "drops per day", which clearly isn't referring to intramuscular or subcutaneous administration; it must be sublingual.

 

Is the BBB any stronger behind the eyes, than it is in the tongue? I don't see any reason why that should be the case. The only advantage to sublingual as opposed to transocular would be the ability to hold the entire drop in one's mouth for long enough to absorb most of the NGF, whereas with eye drops, most of it drips out. Neverheless, some fraction of eye drops remain in the eyes for minutes if not hours. Otherwise eye lubricant products would not work.

 

For these reasons, I'm strongly compelled to believe that Rita's prodigious intellect in old age was owed in part to NGF.

 

Which begs the question... is nasal insufflation comparatively inferior, because most of the NGF gets blown out, or drawn into the stomach acid and presumably destroyed, within minutes?

 

I think McMichael is chasing ants with the antidepressant effects; the elephant in the room is longterm cognitive performance. But I couldn't find any papers on this.

 

On the plus side, I think we can now quantitatively compare various methods of increasing NGF, directly or indirectly, via the use of various substances and routes of administration. Check this out! It shouldn't be too hard to replicate with the right ELISA equipment...

 

Edited by resveratrol_guy, 10 October 2015 - 03:17 AM.

[resveratrol_guy]

I have noticed a few things that should probably be reported.

On the minus side, I would say that I feel dumber now, particularly in the last few days, than the last time I took NGF. I'm not sure why this is the case. My sleep quality has been poor, but then, it was probably just as bad when I had the brain chatter, which has now subsided. I wonder whether this has anything to do with my recent cessation of both oxaloacetate and PQQ. I'm still doing LLLT, and had a session yesterday.

On the plus side, the connection between olfactory sensation and memory seems to be functioning very well indeed. I seem to be able to identify smells almost immediately, whereas I recall many instances in the last couple years when I knew that I should be able to identify a certain smell (for example, baking bread), but was not able to, sometimes for up to minute. It was sort of like seeing a photo of a famous actor, and knowing that you know his name, without being able to recall it. Empirically, it seems to me that my maximum performance occurs within an hour or so of drinking juice containing kale; this is just a repeated observation, for which I can offer no explanation. A couple examples: (1) I walked into a model unit in an apartment complex where I had never been before. Instantly, upon my host opening the door, a distinct mold smell hit me, which I recalled to be the smell of a hotel room I stayed in as a child, in 1981. This has never occurred since, so far as I recall; it's an unusual mold odor, quite unlike the musty smell which one usually encounters in this part of the country. (2) I was in the juice aisle of the grocery store, when I suddenly caught wind of a smell which reminded me of a metal tin I had in around 1983. The tin contained fragments of burned popcorn. I found this quite unnerving, because clearly this was not an appropriate odor to detect in the juice aisle. But when I turned around, I noticed that the door to the deli kitchen had swung open, and behind it was a popcorn machine, turned on with a few remants still hanging around at the bottom.

So what? This is anecdotal. All it means, in my view, is that if you have problems with your sense of smell, then the intranasal betaNGF strategy is probably worth investigating. Just don't forget that fixing your sense of smell could make you pass the olfactory test for early Alzheimer's even though the rest of your brain might not benefit from the therapy, thereby masking the problem.

Anyway, I do think that my observations make sense in light of the brain autopsies discussed above, wherein axons were observed to have sprouted at the site of NGF injection. The least remarkable explanation in this case would be exactly that: the sprouting of axons extending into the olfactory nerve and olfactory bulb, ultimately connecting the sense of smell to memories in the hippocampus.

I wonder how I might better target the hippocampus itself.
 

[dz93]

Price quote for GK-2.

"Currently looking at $400/100mg at 98% purity, with necessity for 25+ people type amount.
6 week lead from point of a go."

Its expensive and alternate synthesis routes are currently being explored. I believe an average HED dose for injection is about ~2mg-6mg.

If you're interested in a group buy, let me know.

[playground]

Hello Denizens of the NGF thread,

 

I received a supply of beta-NGF recently.

I spent two days thinking through the details of reconstitution & administration.

 

I started out by dry-running Resveratrol-Guy's excellent technique of reconstituting

NGF using saline from a nasal dropper bottle.

 

In summary, Resveratrol-Guy's system is as follows:

=> 1, buy a small, 10ml, (nasal/ocular dropper) bottle of saline.

=> 2. use a (diabetic) syringe to transfer a few milliliters of saline from

     the dropper bottle into the vial containing 100ug of beta-NGF

     (this will reconstitute the beta-NGF)

=> 3. use the syringe to transfer the reconstituted beta-NGF liquid in the

     vial back into the dropper bottle.

=> 4. administer the beta-NGF by dripping X number of drips into

     your nasal passages.

 

Resveratrol-Guy's system is excellent in terms of it's emphasis on sterility.

However i modified it slightly because i felt i would never have sufficient control

over dosaging. 

 

You would always need to know how many drops from

the dropper equal 1ml.  When you try to measure this by counting drops

you realise (i realised) that ... any one drop from a saline dropper was

unique, it seemed to me virtually impossible to arrive at a 'standard drop'

whilst the dropper was up your nose.

 

With practice, you might be able to train your eye and hand to produce

a regular drop....only if you could *see* the dropper bottle.

But you could never do this with the dropper up your nose.  In this case

the size of a drop of saline is determined by exactly how much pressure

you apply to the dropper bottle between thumb and forefinger.

 

I have modified Resveratrol-Guy's system as follows.

 

As soon as the beta-NGF is reconstituted it begins to break down.

So i ordered 100ug in 5 X 20ug vials.  This is more expensive than

ordering a single 100ug vial.  However, i want to start with small dosages

and I also want to avoid unnecessary beta-NGF decomposition.

 

 

=> 1, buy a small, 10ml, (nasal/ocular dropper) bottle of saline.

=> 2. use a (diabetic) syringe to transfer a few milliliters of saline from

     the dropper bottle into the vial containing the beta-NGF

     (this will reconstitute the beta-NGF)

=> 3. buy an empty, dark brown, glass dropper bottle, with glass dropper.

     (sterilise it by sitting it in freshly boiled salt water for 5 minutes)

=> 4.  begin a process of filling the brown glass dropper bottle in the following way:

     4a.  use the syringe to add 2.5ml of saline into the vial containing the beta-NGF

     4b.  use the syringe to remove 2ml of saline from the vial, empty this into the brown dropper bottle.

     4c.  use the syringe to add 2ml of saline into the vial

     4d.  use the syringe to remove 2ml of saline from the vial, empty this into the brown dropper bottle.

     4e.  repeat 4c and 4d until brown dropper bottle is nearly full.

     4f.   empty the final 0.5ml saline from the vial and add to the brown dropper bottle.

=> 5.  store brown dropper bottle in the fridge (temp 0-8 degrees)

 

The maths here is easy.

Let's imagine you reconstituted 20ug of beta-NGF into a total volume of 10ml saline.

That's 2ug beta-NGF per ml.

 

A standard glass 10ml dropper bottle has a dropper which will hold 1ml when completely full.

(i spent an hour playing around with the dropper bottle to determine that this is true)

In the case of 20ug per vial, that's 2ug per full dropper. 

It follows that 1/2 of a dropper will hold a dose of 1ug of beta-NGF.

 

In my experiments i found that 0.5 ml of saline can be comfortably absorbed nasally with minimal

or nil loses down the back of the throat (and swallowed).

And... i resolved to start my experiments by taking 1ug per day in 0.5 ml saline.

(i may alter this in the future, subject to experience, but for now, it's 1ug in 0.5 saline applied nasally)

 

I took my first dose tonight.

I haven't noticed any particular effects... but then 1ug per day is a deliberately small dose.

Resveratrol-Guy's experiences show that beta-NGF *can* have psycho-active effects.

If i notice any interesting effects, i will report it to these to this thread.

I've also taken the preparatory step of recording my last 60 days worth of Sudoku results

on an electronic (hand-held) Sudoku game.  It's my standard cognitive task.

I'm not expecting any significant reductions in my Sudoku times.... but... there again,

at higher dosages, perhaps reductions will be observed... We'll have to wait and see.

 

My gratitude goes to Resveratrol-Guy for sharing his thoughts, methods and experiences.

 

regs

 

playground.

 

Edited by playground, 25 December 2015 - 05:47 AM.

[resveratrol_guy]

I think playground's method of transferring to a dropper bottle is a good idea. I probably didn't explain it in the video, but with the saline bottle, I was dripping into my nose from a few millimeters away, so I never did have it in contact with my nostril. But droppers are still more accurate, so I agree with that modification. Again, sterilization is paramount.

 

I also agree that 1 ug intranasal won't do anything. However, it might do something if delivered sublingually, where absorption efficiency would be much higher after a few minutes. I haven't tried anything sublingual yet, but it's on my list.

 

As I mentioned in my thread, I've stopped all NGF activators for several weeks now, in order to avoid neuroregeneration in my mouth and nose, where I least want it while healing from jaw surgery. I plan to resume in January.

 

As to Sudoku, 60 days of history is probably a good plateau. It's an excellent test because it provides not only a measurement of memory and executive function, but actively stimulates new neurons to integrate themselves into useful networks. We need to remember, in all this, that new neurons don't translate to better memory or intelligence unless they're forced to work for a living.

 

One update... it only recently occurred to me that since my experiments in this thread, I have never again experienced parosmia, hyposmia, or anosmia. (Parosmia is the scariest of these. Imagine squirting out some liquid lemon soap that you've used for years, but smelling burning rubber instead. It's a jolting wakeup call that you have a serious neurological problem. I've been there.) At some point, perhaps documented in the foregoing pages, I experienced my last episode, and that was it. This, despite having periodic attacks on and off since being infected by nasal bacteria in 10/2013. The episodes continued long after the infection was cured. I don't think it's a huge stretch to imagine that betaNGF and/or precursors like lion's mane or ashitaba chalcone regrew my olfactory network. After such a long time without a lasting cure, bouncing back and forth between high and low function, the timing is rather coincidental.

 

Finally, readers here will no doubt want to have a look at the breakthrough research brought to us by mag1 regarding copper-2 exposure and AD risk. Bottom line: it's time to find a copper-free vitamin pill (e.g. LEF 2-per-day or others) and filter your way out of risks associated with copper plumbing. The discussion starts here on 12/12/2015.

 

[stefan_001]

There has been some research with the eye drops. They seem safe and interesting results:

 

Safety and Pharmacokinetics of Escalating Doses of Human Recombinant Nerve Growth Factor Eye Drops in a Double-Masked, Randomized Clinical Trial

http://link.springer...0259-013-0079-5

 

We describe the effects of nerve growth factor eye drop treatment in a 94 years old female with ARMD, whose visual acuity was progressively worsening in spite of previous surgical and medical treatments. NGF eye drops improved visual acuity and electrofunctional parameters as early as 3 months after initiation of treatment. These results are in line with previous reports on a neuroprotective effect of NGF on retinal cells and on NGF eye drops bioavailability in the retina and optic nerve. No side effects were observed after five years of follow-up, suggesting that topical NGF treatment may be a safe and effective therapy for ARMD.

http://www.scielosp....ipt=sci_arttext

 

Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma

http://www.pnas.org/...6/32/13469.full

 

 

DHEA an alternative?

http://www.hindawi.c...ps/2013/506191/

The results showed that NGF and BDNF are overproduced after DHEA treatment but there is not any overexpression for NT-3 and NT-4. Also DHEA increased neurite extension and neural cell proliferation significantly. Overall, DHEA might induce NGF and BDNF neurotrophins overproduction in cortical neurons which promotes neural cell protection, survival, and proliferation.