97 replies to this topic

[computeTHIS]

I wanted to start this thread in an attempt to condense an incredible amount of information regarding the supplemented-aided production of neurotrophic factors. Some supplements may have mechanisms that interfere with one another or have little supporting scientific evidence. Often, the lesser known neurotrophic factors aren't addressed in supplement marketing either. Hopefully, this discussion will help identify the "best working" supplements for neurotrophic factors and possibly serve as a guide.

The neurotrophic factors being a family of proteins: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) which promote the survival of existing neurons while stimulating the growth of new neurons.

Neurotrophic factors also refer to the GDNF family of ligands (GFL): glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN), and persephin (PSPN) which pertain to cell survival, neurite outgrowth, cell differentiation and cell migration.

Idebenone
Stimulates NGF, antioxidant properties have been disputed. (http://www.ncbi.nlm..../pubmed/9062669)

Pyrroloquinoline quinone (PQQ)
An antioxidant that also stimulates NGF. Found to be a potent enhancer for the regeneration of peripheral nerves. (http://www.ncbi.nlm....pubmed/15915445)

Selegiline
A metabolite of Selegiline, desmethylselegiline, elevates NGF, BDNF, and GDNF. (http://www.ncbi.nlm....pubmed/11162424)

Rasagiline
Offers neuroprotection via stimulation of PKC phosphorylation; upregulation of PKCepsilon mRNA; induction of Bcl-X(L), Bcl-w, and BDNF mRNAs; and downregulation of PKCgamma, Bad, and Bax mRNAs. (http://www.ncbi.nlm....pubmed/16179541)

Ladostigil (experimental drug)
A reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor. Enhances expression of GDNF and BDNF. (http://en.wikipedia....wiki/Ladostigil)

L-Theanine
Increases BDNF and attenuates cortisol-to-DHEAS, also has low affinity for AMPA, kainate, and NMDA receptors. (http://www.ncbi.nlm....pubmed/21617527)

Lion's Mane Mushroom (Hericium erinaceus)
Stimulates NGF. An isolated biopolymer in Lion's Mane was found to be more effective than NGF or BDNF. (http://www.ncbi.nlm....pubmed/19003308)

Lithium
Elevates BDNF by inhibition of GSK-3, which also increases skeletal muscle growth. (http://www.longecity...__fromsearch__1, and http://www.ncbi.nlm....pubmed/21886605)

Curcumin
Produces neuroprotective effects via activating BDNF/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons. (http://www.ncbi.nlm....pubmed/19879308)

Magnesium-l-threonate
Elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, density of presynaptic puncta, and synaptic plasticity in the prefrontal cortex. (http://www.ncbi.nlm....pubmed/22016520)

Huperzine A
An acetylcholinesterase inhibititor and NMDA receptor antagonist. Increased NGF in rats. (http://en.wikipedia....iki/Huperzine_A, and http://www.ncbi.nlm....pubmed/15916732)

Beta-Alanine
Increases BDNF. (http://www.ergo-log....ineanxiety.html)

[computeTHIS]

I would be interested to know how the 'racetams compare in neurotrophic activity.

[Erstwhile]

Great post!

How about ALCAR? I hear it increases NGF levels, at least in rats.

[gamesguru]

I've tried everything on that list except rasagiline and ladostigil (which appear VERY promising), and none of them struck me as profound, though I still take a few. PQQ does not help my 83 year old grandmother with peripheral neuropathy.

[Ark]

I would add Cannabis to that list.

[Lufega]

I have a few things I can add to this list.

Ghrelin.

Polygonum multiflorum (fo ti ) - also enhances Wnt signaling.

Enhancing Wnt signaling.

Panax ginseng

Milk Thistle

[Lufega]

I've been experimenting with intermittent fasting and I can attest to the effects of ghrelin on memory and cognition. I'm also going to try a round of fo ti and see what effect that has. Milk thistle is good and it seems to protect the brain from amphetamine use but it also raises prolactin which might be a problem for guys.

[computeTHIS]

I would add Cannabis to that list.

Hah!

I laughed, and then I did a Pubmed search...only to find that neurotrophics are typically decreased by Cannabis, lol, rats!

Thanks guys, I'll probably update the list tomorrow.

[Lufega]

I'm going to repost this study here because it shows just how important Wnt signaling is in neurogenesis.

Wnt signalling regulates adult hippocampal neurogenesis.

Lie DC, Colamarino SA, Song HJ, Désiré L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, Gage FH.

Source

Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA. chichung.lie@gsf.de

Abstract

The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population. The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development. We also show that the Wnt/beta-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function.

[Lufega]

Retinoic acid. I assume other neutrophins wouldn't work if vit.a is insufficient.

[MrHappy]

I think you may have missed the uridine+dha+epa+choline+b vitamins+e thread, too

[JChief]

^^ this

[JChief]

PQQ does not help my 83 year old grandmother with peripheral neuropathy.

Darn! Seems the rat study only applies to rats. What dose was she taking if you would please?

[JChief]

I have a few things I can add to this list.

Ghrelin.

Polygonum multiflorum (fo ti ) - also enhances Wnt signaling.

Enhancing Wnt signaling.

Panax ginseng

Milk Thistle

Speaking of Milk Thistle.. most of us familiar with it think of the beneficial effects for the liver but I also just read that it may help curb lung cancer too!

Just realize that it won't go very public. Big Pharma won't be feeding the media any press releases on the Colorado milk thistle for lung cancer study because milk thistle can't be patented. It's surprising that it was published at all.

But if you're up to coping with biochemical technical nomenclature, here's her journal report:
http://onlinelibrary.wiley.com/doi/...

Other sources of information:
http://www.coloradocancerblogs.org/...

http://altmedicine.about.com/cs/her...

http://timesofindia.indiatimes.com/...

http://www.mayoclinic.com/health/si...

http://www.liversupport.com/milkthi...

http://en.wikipedia.org/wiki/Silibinin

Edited by JChief, 30 November 2011 - 02:21 PM.

[nito]

Exercise? As it "supplements" your quality of life.

[matter_of_time]

I would add Cannabis to that list.

lol, i have never seen a very clever pothead

[hippocampus]

THC (and other cannabionids) have different effects, depending on age. it makes adolescents stupid but it may help those with alzheimers (at least according to rat studies).

about milk thistle: http://www.longecity...lymarin-thread/ (bad "side" effects: may decrease libido, increases prolactin, it's estrogenic)

Edited by hippocampus, 30 November 2011 - 11:53 PM.

[Ark]

Sigh... Don't believe everything you hear from a friend of a friend of a friend who know's the MAN.
Instead try to open your mind and do your own research.

J Psychopharmacol. 2003 Dec;17(4):439-45.
Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naive schizophrenic patients.

Jockers-Scherübl MC, Matthies U, Danker-Hopfe H, Lang UE, Mahlberg R, Hellweg R.

Source

Department of Psychiatry and Psychotherapy, Charite-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. maria.jockers@medizin.fu-berlin.de

Abstract

Long-term cannabis abuse may increase the risk of schizophrenia. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein that is implicated in development, protection and regeneration of NFG-sensitive neurones. We tested the hypothesis that damage to neuronal cells in schizophrenia is precipitated by the consumption of cannabis and other neurotoxic substances, resulting in raised NGF serum concentrations and a younger age for disease onset. The NGF serum levels of 109 consecutive drug-naive schizophrenic patients were measured and compared with those of healthy controls. The results were correlated with the long-term intake of cannabis and other illegal drugs. Mean (+/- SD) NGF serum levels of 61 control persons (33.1 +/- 31.0 pg/ml) and 76 schizophrenics who did not consume illegal drugs (26.3 +/- 19.5 pg/ml) did not differ significantly. Schizophrenic patients with regular cannabis intake (> 0.5 g on average per day for at least 2 years) had significantly raised NGF serum levels of 412.9 +/- 288.4 pg/ml (n = 21) compared to controls and schizophrenic patients not consuming cannabis (p < 0.001). In schizophrenic patients who abused not only cannabis, but also additional substances, NGF concentrations were as high as 2336.2 +/- 1711.4 pg/ml (n = 12). On average, heavy cannabis consumers suffered their first episode of schizophrenia 3.5 years (n = 21) earlier than schizophrenic patients who abstained from cannabis. These results indicate that cannabis is a possible risk factor for the development of schizophrenia. This might be reflected in the raised NGF-serum concentrations when both schizophrenia and long-term cannabis abuse prevail.

http://www.ncbi.nlm....pubmed/14870957


I have some more studies on my laptop at work, will try to post them soon.

[gamesguru]

Cannabis is very difficult to understand, but the fact that some eminent scientists (Sagan, Feynman, Mullis, Weil, Gould, Freud, & Leary)claim to gain insight from cannabis use shows us that something is up, and that it's not all harmful. matter_of_time's suggestion that all cannabis users are mere dunces is downright laughable, and an ignorant insult to many responsible people. I won't name names, but there are a surprising amount of successful stoners in the higher echelons of intellectuals.

I've seen studies which indicate that THC and related cannabinoids are neurogenic and neuroprotective, but I've also seen studies which indicate that these cannabinoids actually decrease neurotrophic factors.
This might suggest that nerve formation and nerve connection growth are distinct, or equivalently that, while young nerves may be killed by excessive stimulation, excessive stimulation usually always strengthens and increases connections between robust, adult nerves (through axons or dendrites). It is also known that learning is a great factor in determining the proportion of newly born nerves which survive, mature, and integrate; neurogenesis has a higher rate of success in those who do many mental puzzles daily.

We might, on this basis, imagine that THC enhances one or more memory faculties by its dopaminergic, stimulative effect upon the forebrain, and decreases some activity in the hippocampus&prefrontal cortex by its anti-cholinergic, depressive effect upon the forebrain (+other regions with many CB1 receptors/regions controlled by regions with many CB1 receptors), and that this makes possible for insightful wonder as well as for some undesirable, deleterious effects upon short-term memory.

In any case, whatever the truth is about cannabinoid pharmacology, I haven't found that cannabis is profoundly beneficial to the intellectual or the layman; though it may have some useful effects, most people use it primarily for the euphoria it produces after releasing dopamine into their nucleus accumbens.

Huperzine is another interesting, and perhaps promising, one; so is theanine. But no one has talked about them yet. It seems cannabis is hot and has hijacked the topic.

[computeTHIS]

In any case, whatever the truth is about cannabinoid pharmacology, I haven't found that cannabis is profoundly beneficial to the intellectual or the layman; though it may have some useful effects, most people use it primarily for the euphoria it produces after releasing dopamine into their nucleus accumbens.

Euphoria is nearly the only thing I felt from DLPA, and it certainly wasn't a very productive experience. I think the effect is potentially more beneficial for things like depression, anhedonia, and stress-control. It's unfortunate that legislation prevents Cannabis from being a cheaper alternative. I think there needs to be a shift from anti-Cannabis to healthy-use advocacy. I've seen people walking down the sidewalks of streets and universities with it (in broad daylight, no less) with no fear of repercussion. It makes a joke of current drug legislation.

Huperzine is another interesting, and perhaps promising, one; so is theanine. But no one has talked about them yet. It seems cannabis is hot and has hijacked the topic.

Speaking of Huperzine, I've taken it often enough that the choline-rebound effects finally stopped occurring after it leaves my system. I still have skepticism of long-term use of Ach inhibitors. As for L-Theanine, it's become something I take every night before bed now. It helps me fall asleep, awake refreshed, and may counteract the effects of caffeine before bedtime. Way better than Melatonin, in my opinion.

Edit: Is there some reason I can no longer edit/update my original post? If a moderator could help me out I would greatly appreciate it.

Edited by computeTHIS, 01 December 2011 - 06:58 AM.

[JChief]

about milk thistle: http://www.longecity...lymarin-thread/ (bad "side" effects: may decrease libido, increases prolactin, it's estrogenic)

I read the thread and I see nothing that tells me it decreases libido, estrogenic or otherwise? What did I miss? Someone made a comment about it in passing with nothing to back it up. I take tongkat ali which is great for libido/testosterone anyhow. Not worried at all.

[hippocampus]

it's listed under side effects on other sites (not scientific articles) and I can tell you it does for me try it, maybe it won't decrease libido for you.

[bacopa]

guys I'm trying to find the right combo to keep my brain alive from the multiple insults see the thread about my problems here, http://www.longecity...161#entry485161

today I just found out that I ground away approx 1.2 mg of mercury per tooth out of 8 amalgams, the 4 on the bottom are thick and with a large area...I'm a huge believer in mercury toxicicty from amalgam poisoning, and I always read people who grind their teeth, are in the highest risk category.

Anyway, regardless, I have limited energy, and capacity to simply think, as my brain has taken lots of abuse, so I'm not going to hijack the thread, and I will try to activley contribute.

Lions Mane, high DHA, uridine, and choline, (cdp not a big fan in my situation due to low mood/lethargy etc.) seems to jumpstart my ability to think, even out of semi delirious states, or even amnesic.

So I'm a good case study for someone who NEEDS to have NGF, and neruogenesis, assuming this is the same thing. (I used to know this stuff) But anyway, the OP posted some great ones, and I would recommend the DHA, uridine, CDP choline and lions mane as it seems to have a mood uplift which was also detailed in Mr. Happy's thread.

I am a poor interpretor of studies, but what holds the most promise that is commercially available in the U.S. today, and my goal is to protect my brain, as I felt like I almos had a stroke this summer, after traumatic incident, and I well may have even though MRI came out normal...either or, I want to protect my brain from further insults, whilst taking agents that show the most promise in neurgeneisis.

So If I feel stronger tomorrow I will try to post studies, I did on Lions mane and it can be found on that thread.

[bacopa]

interesting on Beta Alanine link. Since I lack the abilty to disect these things well enough, I encourage others who have some biochem knowledge to participate in this thread, to dispute any studies that maybe red flags, although perhaps impossible to tell unless you did the study yourself, as studies can be spun in so many directions, or misread, etc.

But perhaps figuring out a theoretical cocktail that might in theory, help with NGF, and growth of new grey matter, dendrites, white matter and so on.

For my purposes I was reading how Progesterone helped literally reverse what would have been severe brain damage in fresh TBI patients, but it saved at least one guy and brought him back 90 percent plus. Here's great new info from LEF on Progesterone's promise as a neuroprotecting agent as well, as how it stops TBI http://www.lef.org/m...sterone and men

Then there is BCAA's which helped with neurogenesis, can't find that link right now. Sorry if this isn't exactly what this thread is about, but it's all in the same "bettering the brain," category.

[JChief]

guys I'm trying to find the right combo to keep my brain alive from the multiple insults see the thread about my problems here, http://www.longecity...161#entry485161

today I just found out that I ground away approx 1.2 mg of mercury per tooth out of 8 amalgams, the 4 on the bottom are thick and with a large area...I'm a huge believer in mercury toxicicty from amalgam poisoning, and I always read people who grind their teeth, are in the highest risk category.

Anyway, regardless, I have limited energy, and capacity to simply think, as my brain has taken lots of abuse, so I'm not going to hijack the thread, and I will try to activley contribute.

Lions Mane, high DHA, uridine, and choline, (cdp not a big fan in my situation due to low mood/lethargy etc.) seems to jumpstart my ability to think, even out of semi delirious states, or even amnesic.

So I'm a good case study for someone who NEEDS to have NGF, and neruogenesis, assuming this is the same thing. (I used to know this stuff) But anyway, the OP posted some great ones, and I would recommend the DHA, uridine, CDP choline and lions mane as it seems to have a mood uplift which was also detailed in Mr. Happy's thread.

I am a poor interpretor of studies, but what holds the most promise that is commercially available in the U.S. today, and my goal is to protect my brain, as I felt like I almos had a stroke this summer, after traumatic incident, and I well may have even though MRI came out normal...either or, I want to protect my brain from further insults, whilst taking agents that show the most promise in neurgeneisis.

So If I feel stronger tomorrow I will try to post studies, I did on Lions mane and it can be found on that thread.

I think your combo of mushrooms, DHA, uridine, and perhaps given your lethargy you may benefit from ALCAR as opposed to CDP or GPC. See chronos post . Also due to mercury and other toxins which may be ailing you may I recommend liquid zeolite? I mentioned this in the BPA thread but I would recommend taking a look at the following:

http://www.liquidzeo...l-cousens2.html

Full study paper

It's safe and appears especially powerful when combined with a green juice fast for a week or so if you want to go all out. Detoxifying should be a priority.

[bacopa]

thanks I am planning to buy a form of zeolite and that write up looks promising. Also ingesting clay, forget the kind but I already ordered it from Mountainroseherbs and in small amounts that could really help, both compounds with detox of heavy metals.

I am well aware of the protocal, get the amalgams out, and chelate with ALA and DMSA which is Andy Cutler's belief is the best two chelating agents and should be taken orally, on a disciplned program, after removal of fillings. Also high dose vitamin C, maybe Pectol C, too tired to look it up, it's cheap enough, and supposedly very absorbable, I'll post the link tomorrow for anyone interested.

In my condition it helps to have people remind me what I forgot. So yes Alcar could be a could choline source that wouldn't burden an already burdened body and brain.

thanks so much, this is what imminst should be about helping people as well as learning

[computeTHIS]

Getting a bit more back on topic, it would appear that anything stimulating GDNF is a pretty rare bird.

[spider]

It's for a rare bee!

[nito]

Which method would stimulate NGF the fastest? Exercise, lions mane, ppq, or idebebone? Any takers?

[Ark]

Δ9-THC increased BDNF levels; this was driven by
the control group. Thus, at +145 min, i.e., at the end of the
20-min intravenous infusion of Δ9-THC, there were group
differences in serum BDNF levels (F1,95=4.83, p=0.03)

http://www.springerl...r2/fulltext.pdf