• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 11 votes

Benefits - real or illusory - and side effects to stimulating NGF


  • Please log in to reply
291 replies to this topic
⌛⇒ new years donation: support LE labs

#61 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 19 April 2010 - 03:22 PM

I think the big hang up in supplementing with it is finding a reliable source (isn't this always the case :-P).

Please do post any other sources you dig up...you've found a bunch so far that I missed in my searches. :) At 50¢/g it's going to be pretty expensive to supplement, so it would be nice to have other options, perhaps for bulk.

Have you come across anything in your reading on other forums regarding safety concerns? I know in some instances mushrooms/mycelia can grow with mold on them if not "incubated" in sterile conditions, but I don't know if it applies here. Also be on the lookout for any info about techniques for harvesting mycelium, separating it from growing medium, etc., in case it would still be viable to cultivate this non-professionally.

The other question that arises is dosage. This is going to need some guesswork. Perhaps finding relative concentrations of E&Hs in mycelium and fruit body, and cross-referencing it with any data about relative strengths of NGF induction, will allow us to derive an equivalent dose to the Alzheimer's study. lol. But just finding a recommendation (even based on tolerability/anecdote) would help us define a range, so be on the lookout.

So do you have a good source for Lion's Mane mycelium ?
Perhaps the negative effect was due to the fruit body.

Babcock found this Myco Essentials raw mycellium product, and is looking for more.

Which negative effect are you speaking of? The tiredness that some people reported? To clarify, I should mention that I haven't taken Lion's Mane yet. We're still trying to pin down what the literature says about how active each of these two groups of molecules is, and how best to supplement with each.

Edited by chrono, 19 April 2010 - 03:23 PM.


#62 rwac

  • Member
  • 4,764 posts
  • 60
  • Location:Dimension X

Posted 19 April 2010 - 03:29 PM

Which negative effect are you speaking of? The tiredness that some people reported? To clarify, I should mention that I haven't taken Lion's Mane yet. We're still trying to pin down what the literature says about how active each of these two groups of molecules is, and how best to supplement with each.


I get very slight tiredness or brain fog after taking some fruiting body extract.

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#63 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 19 April 2010 - 04:21 PM

Have you come across anything in your reading on other forums regarding safety concerns? I know in some instances mushrooms/mycelia can grow with mold on them if not "incubated" in sterile conditions, but I don't know if it applies here. Also be on the lookout for any info about techniques for harvesting mycelium, separating it from growing medium, etc., in case it would still be viable to cultivate this non-professionally.


Hmm, I would imagine it's a distinct possibility due to the habitat growing fungus in would lend to itself to growing other fungus :). Personally, I'm not that concerned about mold in general as we take in millions of mold spores anytime we walk outside. Don't get me wrong, I'm not chowing down on the green hamburger buns in the back of the pantry but I imagine it would be pretty hard or costly to isolate your mushroom growing environment from mold. I'll do some research on the myco boards I've bookmarked when I get home today but from the pictures I've seen of people who myco at home, their setup generally consists of a log with holes drilled in it with the spore/sawdust growing medium packed into the holes (generally in what looks to be a damp dark basement). Not exactly a clean room setup lol.

On the subject of growing mycellium I actually have read some articles about growing it. Apparently, what the supplement producers do to harvest the mycellium is grow the lion's mane on plexiglass panes. They "water" the plexiglass with a nutrient formula which encourages the mycellium to grow out across the plexiglass. Then they just scrape the mycellium off the glass and puree it or whatever the magic extraction process is.

⌛⇒ new years donation: support LE labs

#64 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 19 April 2010 - 05:17 PM

Here are the mycelium products I've found so far. In all of these instances, I'm guessing that the weight of the mycelium refers to the mycelium + milled growing medium.

Fungi Perfecti Host Defense Lion's Mane: "activated, freeze-dried, Certified Organic mycelium," in brown rice. Famous mycological company. From what I can tell, all "activated" means that the mycelium isn't the kind of culture they use for storage, and has been growing before it was harvested. 500mg per capsule, 58¢ /g. Suggested dose is 1g/day

Eclectic Institute Mycetobotanicals Lion's Mane Liquid extract. 30mL 25% alcohol/h2o. 1g/mL extract equivalence. Few process details. 41¢ /g. Suggested dose is .5-2g/day.

Myco Essentials Lion's Mane. Raw mycelium in rye grain. Detailed methods. 50¢ /g.

I like the look of the Fungi Perfecti and Myco Essentials products. Both companies provide descriptions of key quality control issues. I don't know if freeze drying is necessary or harmful for erinacines and hericenones, but it might help to preserve any other polysaccharides, fatty acids, etc. Probably a good idea for long-term storage, or in non-cool/dry conditions.

Hmm, I would imagine it's a distinct possibility due to the habitat growing fungus in would lend to itself to growing other fungus :). Personally, I'm not that concerned about mold in general as we take in millions of mold spores anytime we walk outside. Don't get me wrong, I'm not chowing down on the green hamburger buns in the back of the pantry but I imagine it would be pretty hard or costly to isolate your mushroom growing environment from mold.

Exactly. I think the issue is in the incubation period of the mycelium. When you isolate mushroom spores and encourage them to grow into a mycelial network, other spores will be encouraged likewise. So theoretically you could get some spores which aren't harmful when you just get a couple of them in the air, but could be if you eat a zillion of them. I think sterility is only an issue until the mycelium is "established," at which point you take it and dump it out on a log, mix it with rye, etc.

Apparently, what the supplement producers do to harvest the mycellium is grow the lion's mane on plexiglass panes. They "water" the plexiglass with a nutrient formula which encourages the mycellium to grow out across the plexiglass. Then they just scrape the mycellium off the glass and puree it or whatever the magic extraction process is.

Interesting, I haven't heard of this method. I think you can use some kind of liquid culture medium as well. But it seems that neither of the products I've seen so far do this (see above). Maybe this method is used more for scientific purposes, when you don't want a bunch of grains mixed in? Would like to see this article if you can find it, if they mentioned Lion's Mane specifically, it might also mention who uses that technique.

I get very slight tiredness or brain fog after taking some fruiting body extract.

In that case, I would be very interested in your results with mycelium products. I suppose that cytotoxicity might manifest in that way.

Edited by chrono, 19 April 2010 - 05:18 PM.


#65 nito

  • Guest
  • 996 posts
  • 26

Posted 19 April 2010 - 05:19 PM

seems like it's a daily dosage under long term usage which seems costly before you notice the effects of Lion mane. I better start saving lol!

#66 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 19 April 2010 - 05:40 PM

Interesting, I haven't heard of this method. I think you can use some kind of liquid culture medium as well. But it seems that neither of the products I've seen so far do this (see above). Maybe this method is used more for scientific purposes, when you don't want a bunch of grains mixed in? Would like to see this article if you can find it, if they mentioned Lion's Mane specifically, it might also mention who uses that technique.


I'll see if I can find some references when I get home. I think it may have been on one of the Myco boards I was checking out not too sure though. Doing it at home cuz I don't really want to do a lot of searching that could be confused with "shr00m" interest at work. lol

I'm also going to try to research how the actual extraction process works. That'll be fun since I hate chemistry...

⌛⇒ new years donation: support LE labs

#67 tritium

  • Guest
  • 384 posts
  • 68

Posted 19 April 2010 - 07:51 PM

Has anyone seen any studies using pure synthesized NGF such as the one listed below?

http://www.prospecbi...eta_NGF_Human_6

#68 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 19 April 2010 - 08:44 PM

Has anyone seen any studies using pure synthesized NGF such as the one listed below?

http://www.prospecbi...eta_NGF_Human_6

Lots! There are literally tens of thousands of papers on pubmed dealing with NGF. Are you wondering about humans treated directly with supplemental NGF, or something else?

Edited by chrono, 19 April 2010 - 08:57 PM.


#69 tritium

  • Guest
  • 384 posts
  • 68

Posted 19 April 2010 - 08:58 PM

Yes, I was wondering if there was a significant difference with regard to supplementing with synthesized NGF and NGF extracted from Lion's Mane. Also, what kind of dosage have been used in studies with humans and synthesized NGF.

Edit: Nevermind, I found an answer here: http://www.imminst.o...showtopic=29480

Edited by tritium, 19 April 2010 - 09:22 PM.


⌛⇒ new years donation: support LE labs

#70 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 19 April 2010 - 09:46 PM

Yes, I was wondering if there was a significant difference with regard to supplementing with synthesized NGF and NGF extracted from Lion's Mane. Also, what kind of dosage have been used in studies with humans and synthesized NGF.

Edit: Nevermind, I found an answer here: http://www.imminst.o...showtopic=29480

Oh, I assumed you got that source from that thread in the first place. There's some info there, but not enough to answer all your questions that well.

The short answer is that NGF dropped into your eyes might be more reliable (though insanely expensive). But even if this is the case, things like ALCAR and Ashitaba have been shown to increase sensitivity to NGF, so they would probably work even better in conjunction. And even if straight NGF works well, NGF inducers like Lion's Mane may still be able to increase NGF in different areas than NGF reaching the brain through the optic nerve.

Edited by chrono, 20 April 2010 - 01:30 AM.


#71 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 19 April 2010 - 10:37 PM

OK so first off here are some places I found that might not be the "mass produced" Lion's Mane powder that I was fretting over.

http://www.cordyceps...oom_extract.htm

http://www.fungiheal.../buy/lions-mane

http://www.maitake.c...?product_id=37

I have emails out to all of these sellers as well as the sellers Chrono mentioned above asking about their extraction process. I have heard back from the team at the first link (Responded two mins after I sen the email). Their Response follows:

Hello Babcock,

Both alcohol extraction and hot water extraction is used for our Lion's Mane extract. The two are then mixed together. This way, all medicinal compounds get extracted, both water soluble and alcohol soluble compounds. Please read about it here:

http://www.cordyceps...hol_extract.htm

ReEgarding the fruit body vs. the mycelium again, both are used to make the extract.

Sincerely,


Not knowing anything about how chemical extraction works I guess this makes sense. There simpleton breakdown of extract methods here and that link in the quote:

http://www.cordyceps..._difference.htm

Interesting, I haven't heard of this method. I think you can use some kind of liquid culture medium as well. But it seems that neither of the products I've seen so far do this (see above). Maybe this method is used more for scientific purposes, when you don't want a bunch of grains mixed in? Would like to see this article if you can find it, if they mentioned Lion's Mane specifically, it might also mention who uses that technique.


After doing some searching I can't seem to locate anywhere that specifies growing the myceliuim on plexiglass. I read in one of the studies that (http://findarticles....ag=content;col1) they needed to gather Lion's Mane quickly so they just grew the mycelium. Maybe my brain just assumed that's how they did it. Anyway, point is I found a picture of mycelium growing in a petri dish here:

http://www.mycoessen...oto_gallery.htm

Top right hand picture. You can zoom in pretty far (using your browser zoom) to get a better idea.

I've found many sites detailing how to grow mycelium in agar. I'm going to leave out the links as most are related to growing magic shrooms. You can read a;; about them by googling "growing mushroom mycelium agar". It appears the standard agar to use is made out of dry malt extract which I happen to have a lot of since I home brew so I might pick up a Lion's mane innoculant and try it out.

I think that's all for now, hopefully another update when I get some emails in.

#72 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 20 April 2010 - 12:51 AM

Growing these at home sounds like a very fun project, but obtaining an amount of mycelium sufficient for supplementation would require a large operation, I'm guessing. Since it's very pertinent to what we're trying to find out, here's an easy explanation of the extraction process (feel free to ask if anything is still unclear):

Extraction is based entirely on solubility: how easily a molecule dissolves in a liquid solvent. Some molecules dissolve only in water, ethanol, or more esoteric solvents like chloroform. You grind up the mushroom and soak it in your solvent, dissolving some active ingredients. You run it through a filter and discard the insoluble parts. Then you evaporate the solvent to get your extracted powder, or leave it in the solvent for a liquid extract/tincture.

The most common example of this process is brewing coffee. You soak it in hot water to extract the caffeine, and various other molecules which give coffee its flavor, leaving the bulk of the insoluble plant matter in the filter. If you used a different solvent, it would dissolve different components of the plant—for instance, using DCM dissolves caffeine more selectively, leaving you with decaf coffee beans.

The mushroom extractions we're talking about here are exactly this simple. The two important variables are what part of the mushroom is used, and what solvent is used. If you look at the graph in post #47, different solvents (water, ethanol and ethyl acetate (nail polish remover)) had differing ability to increase NGF, because these solvents dissolved the active molecules to varying degrees during extraction.

Any product which extracts from the fruit body will probably contain the cytotoxic hericenones A-B. If you look at the second quote in #55, they had to use chromatography to separate these from the actives C-H. This process allows you to separate ("fractionate") very similar molecules by exploiting minute solubility differences in mixtures of more obscure solvents. It takes a long time, and is difficult to perform on large quantities (and therefore, costs a lot).

I think your concern about the efficacy of extracts is quite founded. We know that ethanol extracts both erinacines and hericenones, but there are many other molecules which give Lion's Mane its medicinal properties, some of which we haven't identified yet. Extractions are never 100% effective, so some important things might be left behind in the filter.

I had skipped over Cordyceps Reishi Extracts because they use the fruit body. Using both alcohol and water is a lot closer to eating the raw material, because you get any actives which might be soluble in just one solvent. However, you also get any undesirables (A-B). But the fact they use fruit bodies and mycellium is impressive.

Fungi Health uses a hot water extract, which is questionably effective at extracting the active ingredients (post #47):

All of our mushroom product lines are USDA Certified Organic and are grown in the United States. The mushrooms are then extracted using a hot water technique, which leaves only the most medicinally beneficial extract.

On the other hand, I'm very intrigued by the Maitake product. They mention that they fractionate the extract, and they've standardized the amount of hericenones. Along with the outrageous price, this suggests to me that they might have taken the time to separate out the cytotoxic hericenones. I sent them an e-mail earlier today asking about this specifically. I still think the mycellium is superior because the erinacines are stronger NGF inducers, but taking both groups of molecules might be advantageous if they work in slightly different ways.

Maybe the cytotoxicity issue is less dire than I'm making it out to be. It obviously isn't killing anyone, but it just seems like an undesirable element when you're taking something for its effect on your long-term cellular well-being.

Thanks for your initiative babcock, be sure to let us know what you hear from those other companies!

Edited by chrono, 20 April 2010 - 01:23 AM.


#73 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 20 April 2010 - 02:03 AM

Growing these at home sounds like a very fun project, but obtaining an amount of mycelium sufficient for supplementation would require a large operation, I'm guessing. Since it's very pertinent to what we're trying to find out, here's an easy explanation of the extraction process (feel free to ask if anything is still unclear):

Extraction is based entirely on solubility: how easily a molecule dissolves in a liquid solvent. Some molecules dissolve only in water, ethanol, or more esoteric solvents like chloroform. You grind up the mushroom and soak it in your solvent, dissolving some active ingredients. You run it through a filter and discard the insoluble parts. Then you evaporate the solvent to get your extracted powder, or leave it in the solvent for a liquid extract/tincture.

The most common example of this process is brewing coffee. You soak it in hot water to extract the caffeine, and various other molecules which give coffee its flavor, leaving the bulk of the insoluble plant matter in the filter. If you used a different solvent, it would dissolve different components of the plant—for instance, using DCM dissolves caffeine more selectively, leaving you with decaf coffee beans.

The mushroom extractions we're talking about here are exactly this simple. The two important variables are what part of the mushroom is used, and what solvent is used. If you look at the graph in post #47, different solvents (water, ethanol and ethyl acetate (nail polish remover)) had differing ability to increase NGF, because these solvents dissolved the active molecules to varying degrees during extraction.

Any product which extracts from the fruit body will probably contain the cytotoxic hericenones A-B. If you look at the second quote in #55, they had to use chromatography to separate these from the actives C-H. This process allows you to separate ("fractionate") very similar molecules by exploiting minute solubility differences in mixtures of more obscure solvents. It takes a long time, and is difficult to perform on large quantities (and therefore, costs a lot).

I think your concern about the efficacy of extracts is quite founded. We know that ethanol extracts both erinacines and hericenones, but there are many other molecules which give Lion's Mane its medicinal properties, some of which we haven't identified yet. Extractions are never 100% effective, so some important things might be left behind in the filter.


Thanks a lot for the info Chrono you really cleared things up. I guess I understood why it needed to be done I was just hoping to come across the details of the process (i.e. extraction times, alcohol concentrations etc.)

Anyway, here's what Fungi Health emailed me back tonight, somewhat excited about this if we can determine NGF benefits can be derived from the hot water extract as prices through these guys gets us down to $.07/g:

Hello!
Or Lions Mane mushroom extract is 100% mushroom fruitbody and mycelium, no fillers, it is extracted using a hot water process, so there are no alcohol or other solvents used.
Hope that’s helpful


BTW I found the Maitake product for 20 bucks cheaper at an online supplement dealer but 60 bucks is still god awful expensive. I'm interested to hear back from them. The question I asked was if they extracted any erinacines in their process since it sounds to be the most intensive. They extract hericenones but the product is marketed for the other stuff. I'm curious as to whether or not the amy-whatever might actually be erinacines that they've proprietarily named.

Ohh also free sample of the Amyloban stuff through this link (supposedly):

http://www.nutrition...ort_Sample.html

#74 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 20 April 2010 - 04:08 PM

Just came across an anecdotal comment on a youtube video about collecting Lion's Mane. Someone posted that Lion's Mane activates your bodies NK (natural killer) cells and raises T cell count which could be a good thing when fighting viral infection but could also be a bad thing if you are exposed to streptococcus bacteria. Streptococcus I guess proliferates by piggybacking with NK activation. No references given so this is anecdotal at best but I'm just trying to document any negatives when I find them.

#75 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 20 April 2010 - 05:16 PM

This is the only data I've found to suggest that a water extract is beneficial: Patent Application US20040175396: "Remedies." (I've also attached the original document as a PDF) Patent language is some of the most miserable writing known to man, but the extraction process is detailed at paragraph [21], and the experiment in [56].

In short, it shows that a hot water extract from the mycellium, fruit body, or perhaps both was astonishingly effective at increasing NGF in mouse some body cells. But the veracity is highly suspect, I think.

I made a few graphs to illustrate the difference they showed between water and alcohol extracts. The Y-axis indicates the % increase (or decrease) of NGF (with control group being 100%). The x-axis is the % of the cell culture (by weight) comprised by the extract+solvent. The first shows a zoom in of the alcoholic extracts, and the second includes water extracts.

(The alcoholic->DMSO extract was 10x more concentrated than the water, which I corrected for here. Also corrected for the fact that DMSO weighs 1.1x as much as water. This correction didn't alter the NGF %, only moved the line for water over to the left.)

At first glance, these look like amazing results. But there are several critical factors to consider here:
  • The cells used were mouse fibrolast cells—body tissue. The study showing no NGF expression (post #47) with h2o extracts used human 1321N1 glial cells, which "release neurotrophic factors that maintain neurons functionally." Behavior in body tissue does not necessarily correspond to behavior in brain cells.
  • Patent language tries to include as many options as possible, so as not to exclude any commercial application. In this case, they mentioned that fruit bodies or mycellium could be used, but did not say which was employed in this experiment.
  • The water extract was inserted into the cell culture still in water, while the alcoholic extracts were evaporated and re-dissolved in DMSO before insertion. The control group had no solvent added. This means the cell cultures had some differences in growing conditions which were not accounted for.
  • I corrected for the fact that the water experiments were 9x heavier than an alcoholic extract containing the same amount of material. However, it is unclear why they chose to do this in the first place. Growing cells in 10x the volume of a different solvent raises questions about comparability.
  • They admit that all other studies/patents previously used ethanol, and that these water results were "surprising." Yet they made no effort to explain their findings.
  • Several alcoholic extracts showed a decreased expression of NGF compared to control at certain concentrations. This contrasts with the human 1321N1 tests, which showed increasing effectiveness at increasing concentrations. No explanation was attempted.
  • It should always be remembered that patents are not peer-reviewed to determine if experiments were done correctly, and that the authors are always interested in "selling" their argument for commercial benefit. Even so, this patent wasn't granted.
Taken together, I find these results highly dubious. I think all that can be concluded is that water extracts something from some part of Lion's Mane, which increases NGF in body tissues. This is probably more useful for wound healing than cognitive enhancement, but could still translate to some effect in the brain. I'm hoping one of the Kawagishi papers will make a mention regarding solvent preference.

Attached Files


Edited by chrono, 20 April 2010 - 07:23 PM.

  • like x 1

#76 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 20 April 2010 - 05:58 PM

Just came across an anecdotal comment on a youtube video about collecting Lion's Mane. Someone posted that Lion's Mane activates your bodies NK (natural killer) cells and raises T cell count which could be a good thing when fighting viral infection but could also be a bad thing if you are exposed to streptococcus bacteria. Streptococcus I guess proliferates by piggybacking with NK activation. No references given so this is anecdotal at best but I'm just trying to document any negatives when I find them.

Collecting mushrooms in the wild always sounded kind of scary to me, but Lion's Mane is distinctive enough that it would probably be hard to eat a poisonous one by mistake.


This might be the paper regarding NK cells (full text available):

Soluble components of Hericium erinaceum induce NK cell activation via production of interleukin-12 in mice splenocytes.

AIM: To investigate the immunoregulatory functions of water extracts of Hericium erinaceum (WEHE) focusing on natural killer (NK) cell-based anticancer activities. METHODS: Mouse splenocytes or purely isolated NK cells were stimulated with 1-100 mg/L WEHE for 24 h followed by co-culture with (51)Cr-labeled Yac-1 cells for 4 h, then NK cell-derived cytolytic activity was measured using a radio-release assay. Neutralizing antibodies against mouse interleukin-12 (IL-12) were added into the WEHE-stimulated splenocytes, thereafter, cytotoxicity was measured to examine the involvement of IL-12. RT-PCR and ELISA analyses were performed to confirm the induction of transcription and the translation of IL-12 and interferon-gamma (IFN-gamma) in the WEHE-treated splenocytes. RESULTS: WEHE enhanced the cytolytic activity of total splenocytes towards Yac-1 cells in a dose-dependent manner. However, this activation was not observed when the NK cells isolated from the splenocytes were treated with WEHE. Furthermore, the treatment with antibodies against IL-12 abolished the effect of WEHE on splenocyte-derived cytolytic activity. RT-PCR and ELISA analyses showed the induction of IL-12 and IFN-gamma in the WEHE-treated splenocytes. CONCLUSION: WEHE indirectly activates the cytolytic ability of NK cells via the induction of IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular components.

NK cells fight tumors and viruses. But they also appear to magnify the effects of Streptococcus (15776374) and E. coli (12219013) infections, at least if you're a mouse. I wonder what the consensus on this board is about increasing NK?

Nothing on T-cells yet, though there are several papers concerning general immunomodulation.

Edited by chrono, 03 August 2010 - 03:27 PM.


#77 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 20 April 2010 - 05:59 PM

Nice work chrono. I'm going to see if I can find any points of contact in the Kawagishi experiments to see if I can get the low-down on their extraction process. Extraction is mentioned in the papers but I'm pretty sure it refers to extracting the NGF out of the mice brains as opposed to extracting the H&E's.

⌛⇒ new years donation: support LE labs

#78 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 20 April 2010 - 06:16 PM

Nice work chrono. I'm going to see if I can find any points of contact in the Kawagishi experiments to see if I can get the low-down on their extraction process. Extraction is mentioned in the papers but I'm pretty sure it refers to extracting the NGF out of the mice brains as opposed to extracting the H&E's.

No, definitely not mouse brains. Take a look at the second quote in post #55, it's from a Kawagishi paper (first link in this thread). I omitted most of the process from my quote, but both H&E used an ethanol extract. Several of their key papers are in US chemical journals, and will almost certainly give more details about how they isolated these molecules than one focusing on dementia. I don't know if their in vitro studies used administration of mouse-derived NGF as a basis for comparison, but I've yet to see a mention of it.

Several of the relevant papers are easily available in US journals, and are going to have some conclusive information about these molecules. I just haven't been able to get to the library yet this week (I'm just getting over the flu). Possibly tonight, or tomorrow. I've been thinking of trying to contact one of these Japanese scientists as well, but I figured they would be much more likely to respond if it's apparent I looked through their readily available publications and was familiar with their work.

Edited by chrono, 20 April 2010 - 06:21 PM.


#79 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 20 April 2010 - 06:20 PM

Good call. Came across this:

http://www.faqs.org/...app/20090274720

Patent application for the process of extracting fat soluble fraction of the fruit body. Produced by Hirokazu Kawagishi.

#80 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 20 April 2010 - 06:58 PM

I just read through the patent pdf you posted chrono. Correct me if I'm wrong but is it odd that when they demonstrate example 2 just about all of the mushroom extracts presented there give similar NGF results to the water extract of Lion's Mane? I do find it odd that the water extract gives such a large performance over any of the alcohol based extracts since I seem to recall from reading the Kawagishi experiments that the extracts were made using several alcohol or ethanol based extractions.

#81 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 20 April 2010 - 07:21 PM

http://www.faqs.org/...app/20090274720

Patent application for the process of extracting fat soluble fraction of the fruit body. Produced by Hirokazu Kawagishi.

Nice, those guys really know how to write a patent.

This one doesn't deal explicitly with erinacine or hericenone. They use an interesting ethanol -> water extraction method (see below) to derive a certain portion which is useful in protecting against the neurotoxicity of amyloid beta-peptide (thought to be one of the neurochemical causes of alzheimer's). This fraction also increases NGF significantly in mice, and improved performance in spatial recognition and memory.

What I found important here was that this fraction from the fruit body, which is neuroprotective and increases NGF, is extracted with ethanol and (because of the extraction algorithm) is definitely insoluble in water. This doesn't rule out that water will extract some things which increase NGF, but demonstrates that it definitely doesn't extract some of the things which do. I'm guessing this is the hericenones at work. It also raises the possibility that the other components of Lion's Mane might protect against the cytotoxicity of hericenone A-B, but I'm sure it depends on the mechanism.

(For extraction, they first use 95% alcohol (everclear) on the fruit bodies. They evaporate this, then soak the powdered extract in water. This causes things which aren't soluble in water to float to the top. They skim this off the top and dry it. The only company which might do something like this is Maitake, especially since their product is called "Amyloban")

I've attached the original patent, as the text versions make the tables unreadable.


I just read through the patent pdf you posted chrono. Correct me if I'm wrong but is it odd that when they demonstrate example 2 just about all of the mushroom extracts presented there give similar NGF results to the water extract of Lion's Mane? I do find it odd that the water extract gives such a large performance over any of the alcohol based extracts since I seem to recall from reading the Kawagishi experiments that the extracts were made using several alcohol or ethanol based extractions.

God, that patent gets worse and worse. I almost wish I'd ignored it. But yes, you're quite correct, almost all of those mushrooms show NGF increases which are many times more potent than that alcoholic extract of Lion's Mane. I hadn't even read that experiment, because at the end of Example 1 they conclude that "only the extract of Hericium erinaceum has a potent enhancing activity for NGF production."

I don't know anything about those other mushrooms, but I find it pretty dubious that they're all roughly equipotent with Lion's Mane, or that the simplest extraction possible is 10x more effective than the standard. I hesitate to dismiss any data, but I'm inclined to think that this is horribly skewed at the very least.

Attached Files


Edited by chrono, 20 April 2010 - 07:30 PM.


#82 tritium

  • Guest
  • 384 posts
  • 68

Posted 20 April 2010 - 08:18 PM

I wonder what Rita Levi-Montalcini, the person who discovered NGF, is using in her NGF eyedrops and what her source is. I bet it must be something custom synthesized. I would be interested in trying this if I can find a good source.

⌛⇒ new years donation: support LE labs

#83 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 20 April 2010 - 08:53 PM

I wonder what Rita Levi-Montalcini, the person who discovered NGF, is using in her NGF eyedrops and what her source is. I bet it must be something custom synthesized. I would be interested in trying this if I can find a good source.


Wouldn't we all... :|w Probably terribly expensive and she only has access to it because she was the one who did the lab work to isolate it in the first place. She probably made 1000 gallons of the stuff and hoarded it all for herself so she could be immortal! J/k, but I'm sure she must have access to it via the lab or where ever she did he work.
  • like x 1

#84 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 20 April 2010 - 09:07 PM

I wonder what Rita Levi-Montalcini, the person who discovered NGF, is using in her NGF eyedrops and what her source is. I bet it must be something custom synthesized. I would be interested in trying this if I can find a good source.

Intracerebroventricular NGF administration is much more effective :-D I imagine Rita is taking regular NGF, it's used in experimental ocular treatments too. And she runs a research institute, she can order lyophilized NGF from any supplier on the planet. I'm sure the price drops significantly when you order more than 5mcg at once.

Anyway, intranasal administration might be more effective than conjunctive:

Delivery of NGF to the brain: intranasal versus ocular administration in anti-NGF transgenic mice.

Nerve growth factor (NGF) has a great potential for the treatment of Alzheimer's disease. However, the therapeutic administration of NGF represents a significant challenge, due to the difficulty to deliver relevant doses to the brain, in a safe and non-invasive way. We previously demonstrated the efficacy of a non-invasive delivery of NGF to the brain in animal models, by an intranasal route. Recently, topical eye application of NGF was proposed, as an option for the delivery of NGF to the brain. Here, we compare the efficacy of the two delivery routes of hNGF-61, a recombinant traceable form of human NGF, in the mouse neurodegeneration model AD11. The intranasal administration appeared to be significantly more effective than the ocular one, in rescuing the neurodegenerative phenotypic hallmarks in AD11 mice. The ocular administration of hNGF-61 showed a more limited efficacy, even at higher doses. Thus, NGF nasal drops represent a viable and effective option to successfully deliver therapeutic NGF to the brain in a non-invasive manner.

PMID: 19221427 [PubMed - indexed for MEDLINE]


Edited by chrono, 03 August 2010 - 03:29 PM.


#85 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 21 April 2010 - 12:25 AM

Myco Essentials Lion's Mane. Raw mycelium in rye grain. Detailed methods. 50¢ /g.[/indent]

I heard back from Myco Essentials today. They were very helpful and knowledgeable, and sent me a ton of references with their answers. I was very impressed.

Concerning dosage, they recommend 1600mg daily. As for tolerability, the person answering my e-mail said they've taken 3.2-4g daily without any adverse effect.

I sent another e-mail asking about how the mycelium is harvested, and what they could tell me about the composition with regard to grain content. Here is their incredibly helpful response:

The weight indicated does refer to the myceliated rye grain. We allow the mycelium to fully colonize the substrate, a process which usually spans three to four months. Our Hericium strain has been selected because it thoroughly colonizes and also produces miniature Hericium fruit bodies in the sterile jar environment. At the end of the process the bulk of the material is mycelium! The appearance of the collected material is shown on our web site[here?]. Our procedures utilize a mild stream of warm air to dry the recovered mycelial product, ~50oC which is lower than that used by the Mori et al., (2008) group. We strive to maintain consistent colonization from lot to lot but currently do not standardize against an external standard.

The study she mentions is the one we discussed up around post #43, about NGF increase in human 1321N1 cells. These people know their stuff.

Concerning the tiny fruit bodies, this is merely a consequence of letting the mycelium colonize fully—some of the early-colonized portion takes off (it's called "pinning," I believe). Even if these do contain small amounts of hericenone A-B at this stage, they're such a small amount of the total mycelium/grain mass that it's of negligible concern compared to eating the entire mushroom.

Like I said, I'm very impressed. This is almost certainly the one I'll go with, when it becomes economically feasible. :|w

Edited by chrono, 03 August 2010 - 03:31 PM.


#86 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 21 April 2010 - 01:28 AM

Like I said, I'm very impressed. This is almost certainly the one I'll go with, when it becomes economically feasible. :|w


Good stuff, sounds better than the responses I've gotten. Still haven't received anymore than the ones I got yesterday.

Chrono, do you think the body is capable of extracting the Erinciones from the "raw" mycelium? I also wonder if they might be interested in giving bulk discounts since buying 50g over and over would get pretty costly.

#87 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 21 April 2010 - 01:55 AM

Chrono, do you think the body is capable of extracting the Erinciones from the "raw" mycelium?

Almost certainly! The grain/mycellium/etc will be broken down in the stomach. Probably even more easily than the fibrous material of dried mushrooms. I don't know specifically how these molecules get absorbed and metabolized—but the studies demonstrating increase in NGF in rat brains (like the patent you posted earlier), and the more indirect human cognition studies, show that neuroprotective/NGF-inducing molecules are able to make it into the mammalian brain.

Of course, the process of absorption and metabolism means that a certain amount of actives will be lost. In the absence of adverse effects, it's probably a good idea to err on the side of a larger dose. If the compounds of interest are fat-soluble, as your patent suggested, it might be beneficial to take with a small amount of fat/oil, but not with a large meal which might hinder digestion. Same idea as with fish oil...someone here recommended taking it with a few grams of olive oil away from meals (I need to research this idea more for better options). This might be the perfect time to take Lion's Mane, as well.

I just sent another e-mail asking about bulk discount, but I'd be surprised if they could do that for something with such a long growing cycle.

#88 chrono

  • Guest, Moderator
  • 2,444 posts
  • 799
  • Location:New England

Posted 21 April 2010 - 03:43 PM

This is an abstract mentatpsi posted a while back, which I just realized has some great implications for our supplement hunt:

Effect of an exo-polysaccharide from the culture broth of Hericium erinaceus on enhancement of growth and differentiation of rat adrenal nerve cells

It was found that an exo-biopolymer (M.W. 1,000,000, molar ratio of 1.5:1.7:1.2:0.6:0.9, glucose:galactose:xylose:mannose:fructose, purity 99%) purified from the liquid culture broth of Hericium erinaceus mycelium enhanced the growth of rat adrenal nerve cells. The polymer also improved the extension of the neurites of PC12 cell. Its efficacy was found to be higher than those from known nerve growth factors such as Nerve Growth Factor (NGF) and Brain-Derived Nerve Factor (BDNF). The effect of two standards has not been observed above 0.1 (mg l−1) of supplementation; however, the polymer did show the effect of cell growth and neurite extension at up to 1.0 (mg l−1) of addition. While the polymer improved both cell growth and neurite extension, NGF and BDNF did only outgrowth of the neurites. Maximum cell density and length of the neurites were observed as 1.5×105 (viable cells ml−1) and 230 μm, respectively in adding 0.8 (mg l−1) of the biopolymer for 8 days cultivation. The control growth was observed only as 1.2×105 (viable cell ml−1) of maximum cell density and 140 μm of maximum length, respectively. It was also confirmed that the polymer reacted with the nerve cells within 30 min after adding the sample, compared to 80 min in adding two other growth factors. Number of neurite-bearing cells remained relatively steady in adding the polymer even when the cell growth started to be decreased. It was interesting that the polymer effectively delayed apoptosis of PC12 cells by dramatically reducing the ratio of apoptotic cells to 20% from 50% of the control.

Exo-bipolymer is something which mycelium produces outside of itself (in the agar or rye grain). So far from being "dead weight" in the supplement, the growing medium actually contains a substance which is incredibly efficacious for inducing nerve growth.

While ericanine and hericenone induce cells to produce more natural NGF, this molecule causes neurite growth directly upon target cells. It does so more effectively than NGF or BDNF, with a higher ceiling of effective concentration (i.e. more is allowed to act upon the cell) and neurite outgrowth length. And it causes these changes faster than BDNF or NGF can. And it can cause the cell itself to grow (expressed as cell density?), which the endogenous growth factors can't.

I wonder how readily polysaccharides cross the BBB? This is a pretty huge molecule.

Edited by chrono, 21 April 2010 - 03:45 PM.


⌛⇒ new years donation: support LE labs

#89 babcock

  • Guest
  • 299 posts
  • 73
  • Location:USA

Posted 21 April 2010 - 03:48 PM

Just received this response about the extraction process from Eclectic Institute about their Lion's Mane Liquid Extract:

The Lion's Mane mycelia is grown on a base of organic brown rice. It is covered with the menstruum a combination of alcohol and water then macerated for at least 2 weeks. Product is pressed, filtered then bottled.



sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#90 NDM

  • Guest
  • 343 posts
  • 7
  • Location:North America

Posted 21 April 2010 - 05:05 PM

Re: adverse effects

I take 1.2 g/day in 4 doses and I suspect that it acts as a blood thinner (though the reason I got some mild nose bleeding is that this is one among many blood thinners I happen to take).




2 user(s) are reading this topic

0 members, 2 guests, 0 anonymous users