42 replies to this topic

[Rational Madman]

As for ashwagandha and lion's mane: supplement companies can't really make many more claims than they already are. Cerebral Health got a warning from the FDA recently for mentioning that Galantamine is approved to treat alzheimer's, which it is. They had to remove all mentions of the disease from their website. And drug companies aren't that anxious to spend money on trials, when the medicine is a mix of molecules from a plant. While they could patent certain molecules, or maybe an extraction process, the fact remains that there will always be a generic alternative on the market which will be considerably cheaper. This makes it highly problematic that they will recoup the excessive cost of clinical trials.

dfowler, be careful of choline overload if you're doing this. You'd be increasing acetylcholine from all three directions: ALCAR's increase of choline acetyltransferase (makes ACh), increased choline precursors through CDP/GPC, and inhibition of acetylcholine esterase (breaks down ACh). Watch for headaches and neck/shoulder tension, I'd be very surprised if it didn't happen at these dosages. Alzheimer's studies combining these methods are correcting for a pretty severe dysfunction of the ACh system.

I tend to agree that depending on vague countermeasures to known carcinogens seems like an astonishing risk, especially at very high dosages over time. If you're not going the nicotinic route, dropping the Alpha GPC might be a good idea to ease up on the choline system.

Perhaps, but I still think that supplement prices are still largely a function of their proven efficacy and potential. If you have some full texts, though, I'd be interested in examining the studies more closely.

Edited by Rol82, 04 May 2010 - 10:25 PM.

[bacopa]

As for ashwagandha and lion's mane: supplement companies can't really make many more claims than they already are. Cerebral Health got a warning from the FDA recently for mentioning that Galantamine is approved to treat alzheimer's, which it is. They had to remove all mentions of the disease from their website. And drug companies aren't that anxious to spend money on trials, when the medicine is a mix of molecules from a plant. While they could patent certain molecules, or maybe an extraction process, the fact remains that there will always be a generic alternative on the market which will be considerably cheaper. This makes it highly problematic that they will recoup the excessive cost of clinical trials.

dfowler, be careful of choline overload if you're doing this. You'd be increasing acetylcholine from all three directions: ALCAR's increase of choline acetyltransferase (makes ACh), increased choline precursors through CDP/GPC, and inhibition of acetylcholine esterase (breaks down ACh). Watch for headaches and neck/shoulder tension, I'd be very surprised if it didn't happen at these dosages. Alzheimer's studies combining these methods are correcting for a pretty severe dysfunction of the ACh system.

I tend to agree that depending on vague countermeasures to known carcinogens seems like an astonishing risk, especially at very high dosages over time. If you're not going the nicotinic route, dropping the Alpha GPC might be a good idea to ease up on the choline system.

Perhaps, but I still think that supplement prices are still largely a function of their proven efficacy and potential. If you have some full texts, though, I'd be interested in examining the studies more closely.

what do you mean about "full texts?" I'm assuming you're including abstracts to which the study on NRT was a full text, at least I thought. I'm deeply considering Galantamine, but will go cautiously if not use at any way, NRT as soon as I can resist this terrible addiction.

[chrono]

what do you mean about "full texts?" I'm assuming you're including abstracts to which the study on NRT was a full text, at least I thought. I'm deeply considering Galantamine, but will go cautiously if not use at any way, NRT as soon as I can resist this terrible addiction.

I think this was referring to the question about the efficacy of Lion's Mane and ashwagandha.

Perhaps, but I still think that supplement prices are still largely a function of their proven efficacy and potential. If you have some full texts, though, I'd be interested in examining the studies more closely.

Undeniably. The greater the demand, the greater the price. And demand is largely driven by perceived value. But on the other side of that see-saw is the fact that these are traditional medicines, with many suppliers even though demand is relatively small. And the demand/perceived value/efficacy continuum is greatly influenced by the market factors I mentioned before. Who will pay for advertising so people hear about it, and overcome the public's general against "herbal remedies"? And even for people like us who can do their own research, who will shell out huge gobs of money for those large clinical trials we all love? These elements which create demand are only realistic if you have a patent which chokes the supply. But even considering these factors, an adequate dose of a quality Lion's Mane product would cost about $1-2 per day, so it's a bit of a luxury atm.

Like I said, the evidence for Lion's Mane is more indicative than comprehensive. Awesome in vitro tests, with some animal studies and a few small dementia trials—with no downsides apparent at any point—make what I would consider a "good bet." And lots of general evidence on the effectiveness of NGF for neuroprotection/generation, of course. Some free full papers are mentioned in the "benefits real or illusory to increasing NGF" thread. Should have a few more good ones later this week.

Ashgawandha is something I didn't look at until very recently. There are a half-dozen recent abstracts concerning the ability of the withanolide molecules to promote neurite outgrowth, and specifically to reconstruct damaged dendrites and axons. Not sure yet, but it sounds like a direct action of these molecules, rather than induction of endogenous growth factors. And the necessary concentrations are incredibly low, such that achieving by oral supplementation should be quite easy. Haven't had time to look into in vivo efficacy at all, yet, but it sounds like a promising MOA to add to a neuroprotection regime.

Taking a much-needed day off from research to watch some cartoons today. I should have a lot more texts after visiting the library later this week; I'll be sure to send them along if there's anything worth considering.

Edited by chrono, 04 May 2010 - 11:18 PM.

[bacopa]

what is your theorized dosing on lions mane, and Ashgawandha if you've arrived at that point yet?

[chrono]

what is your theorized dosing on lions mane, and Ashgawandha if you've arrived at that point yet?

It looks like the dosage range for Lion's Mane is pretty wide. One study on the elderly with varying dementias found improvement after 6 months of 5g /day, and one on mild cognitive impairment used 4x250mg /day. Depending on the product, I would personally use somewhere between 1.5-2g /day for general neurotrophic purposes at our age.

The therapeutic use of NGF is still in its infancy, and there is not much information about its effect on the young/healthy (i.e. non-demented). I'm toying with the idea of using NGF inducers on some kind of cycle, in case this increased growth factor expression is something the brain might regulate for over longer periods. But that's just an idea at this point.

As for ashwagandha, I haven't even begun to look at the wider research yet. Been too focused on NGF this month. But the necessary amounts in the in vitro tests were so small (1 microM?) that I would imagine any reasonable dose based on other criteria would also yield this benefit.

When I find more specific into about these factors, I'll definitely bring it to your attention.

[bacopa]

In case you haven't realized, I suffer from schizoaffective disorder, which I wanted to keep secret into Rol82 opened up. With my condition there is at least an 80% correlation with cognitive impairment ranging through a full spectrum to, in extreme cases sufferers becoming borderline "retarded", and I mean that in a clinical sounding way, not in an abusive/mean spirited way, to much milder cases mild cognitive impairment.

In my case I have an extremely good prognosis as was told from a top doctor in schizophrenia as related to cognitive dysfunction. My progress has been increasingly progressively forward, in terms of overall cognition, since my second acute onset of psychosis which initially rendered me almost illiterate! I couldn't comprehend simple magazine articles in mags like people magazine, and now I'm reading the pathologies of aging. Talk about an aggressively progressive upward learning curve.

In short schizophrenia's impair 80% of subjects cognitioin, and in my case my decline was so acute, during the second onset of psychosis, that I lost seemingly all my mental abilities in a matter of days. I thought at the time that some advanced brain erasing weapon was destroying my brain, and although illogical to the most unscientific of minds, my delusions, which go hand in hand with this diagnosis, made it harder for me to discern illusion from reality, plus the obvious point that I never had experienced anything quite like this.

So in a matter of a week I went from an IQ of upper 120's to god knows how low. I lost short, working, long term memory functions, as well as processing, problem solving and other abstract thinking skills. I went through a prolonged period of being convinced I had early onset Alzheimer's, once I reasoned my way out of the deluded thinking mind set I was in.

Over just a few years I aggressively got back much of my intellect, but still pale in comparison to where I used to be. The prodrome, (before first psychotic onset) period in schizoid disorders includes massive pruning of synapses, neuronal shrinkage including loss of gray matter in early onset subjects of up to 25%; in very extreme cases, and enlarged brain ventricle sizes. I had an MRI and my brain appeared from mere observation from a reputable neurologist, to be within the normal range. Ventrical enlargement is often the norm, and mine, so far, has not increased in size; obviously a great thing! But schizophrenia can degenerate over long periods of time, and has been thought to be either neurodegenerative, neurodevelopmental, and the latest thinking is it's a hybrid of the too. They used to call it dementia praecox, or "early dementia" as was coined by one of the fathers of psychiatry Emil Kraephlin.

Now they see this as wrong as neuroleptics/anti-psychotics have saved so many people from this degree of decline.

The longitudinal studies of schizophrenics with a poorer outcome, show some regressing dramatically often to a demented state in ages past 65, in more acute cases, and usually correlates with many hospitalizations and basically follows a poor prognosis outcome. The majority of sufferers, though, actually stabilize and stay at a consistent cognitive state at least until old age, and a smaller subset, and hopefully as is the case with me, make amazing recoveries and improve in overall cognition throughout their lives.

As I mentioned already, I went to a world renowned doctor, Dr. Goff, who specializes in cognitive dysfunction in the schizoid disorders, and is perhaps the most well esteemed in the country for his specialty, and based on what I told him, and from communicating with me, he told me I had an immensely favorable prognosis and that if I continue to exercise, adhere to a good diet, exercise my mind, (and my personal belief of taking nootropic supplements), that I should stabilize if not continue to progress in intellect even throughout my life into older ages, taking into account the normal cognitive loss in the geriatric population, even in healthy people.

I'm telling you my history to explain my extreme interest in cognitive enhancing supplements/drugs, and because Rol82 mentioned it already. Roll82 has been trying to give me the best advice possible for my diagnosis, and I totally appreciate that!

So I'm hoping to continue my upward progress, and your input on dosage for such supplements as Lions Mane helps greatly. My interest in Lithium obviously correlates with the many studies showing extreme gray matter increases in bipolar subjects; often on higher doses, and with increases up to 15%, as well as it's alleged neuroprotective properties.

But wanting to avoid any potential toxicity, I want to take the lowest dose, and best possible form of Lithium to help with brain function while not damaging my overall health.

Edited by dfowler, 05 May 2010 - 01:40 AM.

[chrono]

Well, I'm certainly glad I could help in some small way. Sorry we ended up talking about something you preferred be kept private, but I hope you can find some support here. I imagine the cognitive difficulty must be very frustrating, to put it mildly. But it really sounds like you have the right attitude to make that prognosis a reality; for this, my sincerest admiration.

I've come across several abstracts suggesting that continued learning and environmental novelty are helpful, or perhaps even necessary, for certain kinds of neurogenesis to take place. I too consider constantly challenging myself to be a key component of my long-term neural health.

Concerning your original question, the carbonate is probably fine. I suspect that the liver problems you mention would occur using any lithium salt at sufficient dose. Carbonate is a pretty innocuous counterion. It might be what I would go with, if I could get it non-prescription. Is the 300/56mg pill in a form that you could easily break up (into 1/5 for a 10mg dose, for instance)? Orotate would probably be more convenient for controlling smaller dosages. I'd stay away from the aspartate; there was a paper posted here showing it to be neurotoxic and memory-impairing.

I'm hoping to start low-dose lithium this month as well, and even though I'll probably go with 5mg, I'm going to try to find some kind of correlation in the literature between dosage, serum levels, and possibility of toxicity. I'll also be on the lookout for any correlation between dosage and amount of neurogenesis.

[bacopa]

the carbonate is in ecapsulated powder form, and I wouldn't be sure how best to estimate that 1/5, but I suppose I could simply open the capsule and divide accordingly, although maybe getting on the 150 dose of carbonate, or it may be best to just switch to oratate.

I mean it's a pain to break open a capsule and estimate a dose, unless you know of a better way?

[chrono]

Unless you have a gemological milligram scale, the easiest way is to dissolve it in water. 100mL of water will dissolve 1300mg lithium carbonate at room temp (20ºc). So a 300mg pill would need 24mL of water to dissolve—let's say 30mL to make it round.

Get a nice oral syringe at the pharmacy and fill up a shot glass (or anything) with 30mL water, and dissolve your powder (stirring will help). Each mL of this solution will have 10mg Lithium carbonate, 1.9mg of which is elemental lithium. So a 5mg dose would require 2.6mL solution, 10mg in 5.2mL, etc.

You could dissolve it in 60mL h2o if you can't find a small syringe, for 5mg=5.2mL, 10mg=10.4mL, etc.

Then you can squirt it into a glass of water, or some kind of flavored beverage; no idea how this stuff tastes I recall seeing a mention that obtaining lithium in drinking water increases the bioavailability to some extent, so bear this in mind if you're taking more than a "supplemental" dose.

[bacopa]

thanks I'll probably do that! Seems easy enough...I just want to reap the benefits of the gray matter increases as seen in those bi-polar patients, in the studies. But I"m going back and forth in my thinking of how much elemental Lithium is too much.

Is 50 mg too much? Or would it be better, as you said, to stick with a 10 mg solution. I'm racking my brain over this, and is 300 mg tabs of Lithium that unsafe? I've heard of problems in the 1800 mg range or so.

I could always opt for the 150 mg tabs thus getting, according to your calculations 25 mg estimate of elemental Lithium. That would seem not so unreasonable. I wish there were more studies, longitudinal for Lithium Carbonate, as obviously I'm not paying out of pocket, by much, to get this prescription.

If you find any studies saying that doses of 150 to 300 of carbonate over long periods of time are a safety hazard, for whatever reason, be sure to tell me!

Edited by dfowler, 05 May 2010 - 10:43 AM.

[chrono]

Well, from my first few passes at pubmed, my impression is that safety concerns are immediate for very high dosages, or more long-term (like liver issues) for medium dosages. My suggestion that 300/50mg is high is based only on anecdotal research, at this point. The majority of people here seem to use 5-10mg for mild anxiety reduction and supplementation, so 50mg probably falls in the very high end of supplemental doses, but the low end of therapeutic/psychiatric doses. Will be working to quantify this distinction a little better in coming weeks, as it pertains to my intended usage as well.

25mg sounds like a pretty reasonable compromise, pending further research. However, some people have reported pronounced effect on mood even at 5-10mg. Are you already using the 300mg dose, or were you waiting for some answers first? If not, I might suggest starting at 5mg and titrating upward, to give yourself time to adjust and gauge its psychological effects.

If you've already started, I'm curious what you've noticed in terms of subjective effect on mood, headspace, energy, etc. at this 50mg dose?

PS I got the elemental lithium dosage figures from an abstract, and double-checked them using the molecular weights of the compounds. The elemental amount of lithium is 19% of the total Lithium Carbonate dosage, for your reference.

Edited by chrono, 05 May 2010 - 12:36 PM.

[NDM]

Chrono, what's your recommendation, if any yet, for best company for Lion's Mane? I got mine from Mushroom science which I guess uses the fruit.

I tried ordering from Myco Essenials but haven't received it yet.

Sorry to hear that, I hope they come through. They have one of the most promising products at the best price. Others I would recommend at this point are Fungi Perfecti (whole mycelium, on iHerb) and Cordyceps Reishi Extracts's product, which is a combination of alcohol + water extracts of both the mycelium and fruit body (different NGF molecules). I would steer clear of Mushroom Science, as water extraction is at least partially ineffective at extracting the target molecules in question. Am waiting to hear back from several others.

It's true that the efficacy of lion's mane hasn't been clinically demonstrated yet. But as the molecules have been shown to be probably the most potent inducers of NGF in human cell tests, and have shown promise in some dementia trials (suggesting in vivo effectiveness), I'd say it's a pretty good bet.

Same for ashwaganhda, it has some potential for neurite outgrowth and cognitive enhancement. I'd keep it if you can afford it. ALCAR also has potential to increase NGF output and receptor sensitivity independent of its mitochondrial support. Since this can be had for like 5c/g, and can have a subjective benefit in cognition and alertness, I don't see why you wouldn't keep it.

I would go for Hup A over galantamine, for its more effective AChE inhibition, better side effect profile, and other neurogenic/protective effects. Hup A has some effect on nicotinic receptors, but I'm not sure how it compares to galantamine right now. Also not sure what you're going for with that, as this seems to be a continuation of another conversation I haven't read.

Rol82, there was some discussion about cancer in the Nicotine and Vasoconstriction thread, with another paper demonstrating the putative mechanism. While this isn't conclusive, it's well worth considering when constantly megadosing nicotine. A few questions about your other recommendations:

• Do you have any support for pramiracetam being "probably dangerous" outside of TBI? I've read at least one paper suggesting high safety, and haven't heard of this danger anywhere else.
• Can you elaborate on which elements are potentially dangerous/counterproductive in combination with deprenyl? Discussion of that is usually vague here outside the SSRI issue.
• If you've recommended a very large dose of an AChEI, and cautioned against an ineffective ACh precursor like DMAE, why have you recommended titration of Alpha GPC or CDP-Choline up to some nebulous "optimal dose?" This seems potentially problematic.

Chrono, when you click on cordycepsreishi BUY you are actually being offered the Fungi Perfecti product!?!

[chrono]

Chrono, when you click on cordycepsreishi BUY you are actually being offered the Fungi Perfecti product!?!

Thanks for the heads up, it does look like the two companies are connected in some way. I've sent an e-mail asking for clarification.