34 replies to this topic

[StevesPetRat]

DISCLAIMER: What worked for me is quite likely to kill you. Consult your physician before making any potentially lethal changes in your health care routine, like eating a pound of blueberries.

It's been a bit over a month and the results haven't abated (though some of the initial euphoria has worn off), so I'd like to share the most effective stack additions I've found in the past ~18 months of cognitive decline and dreaded "brain fog". You can skip the few narrative paragraphs in the spoiler, if you're in a hurry.

Spoiler

To give you an idea of where I started, at the nadir around February/March (these are presented as objectively as possible not for pity but as points of reference),
1) I could not walk in a straight line
2) Had to make 3 or 4 attempts to pick up any object as it would slip through my fingers
3) My working memory was as close to zero as I can imagine -- had to repeat to myself what I was doing constantly, all the time, or I would lose track almost immediately ("I'm going to the bathroom to brush my teeth, I'm going to the bathroom to brush my teeth...")
4) Focusing on anything more cognitively demanding than a stupid sitcom for 15 minutes would leave me literally feverish
5) Any movement, any sound, even as benign as a bird chirping, would startle me

Improvement was extremely slow, and even slight stress would throw me back a week or two in progress. Which was really inconvenient, as being broke and out of one's mind is sort of a stressful circumstance.

So, many months went by, I finally decided to try eliminating every conceivable food anti-nutrient (histamine, salicylate, oxalate, lectins, phytic acid (though now learning that stuff is probably way healthier than the paleo folks realize), and saponins) through a diet of fresh meat, white rice, boiled lettuce, ghee, and safflower oil. Two months on this diet helped my energy and strength a bit, but did not have much effect on my mental state. I tried aspirin, had no reaction to 1000 mg in a day, so I reintroduced salicylates to the diet, along with whey protein, and eventually fermented goat dairy.

At roughly this point I realized that I had nearly every symptom of anti-cholinergic use, along with a few that weren't on the list but connected anyway. This paper saved my life. It has 3 main points in the full text:
1) Acute stress (or nootropic abuse) leads to an acetylcholine surge (perhaps life flashing before one's eyes?)
2) the cFos gene is activated (in other tissues this is a general response to oxidative stress)
3) cFos in turn triggers long-lasting changes in gene expression: upregulation of AChE, downregulation of ChAT and VAChT

It is unclear how a several-day change in their experimental animals translates to years-long effects in humans -- perhaps our big brains allow us to re-traumatize ourselves better than those sweet, dumb animals. But days or weeks would be consistent with many people's experiences after choline overload.

There are so many posts around here about brain fog after cholinergic abuse, memory problems, etc... Now that I know, I see ACh dysfunction everywhere. Not saying it's THE answer, but ACh deserves more respect than as something you maybe need to supplement a little when you use racetams.

Alright, the stack:
1) 1 pound of wild Boreal blueberries daily (smoothified, usually). This alone made a noticeable improvement in days. Wild blueberries are so dark they're almost black -- I figure they're likely much denser in proanthocyanidins, and they're definitely a bit lower in sugar, than the cultivated kind. Even if they're the same as regular blueberries, that's a bit over 1000 mg of pro- and anthocyanidins daily. US$3.50/day
2) Fisetin, 100 mg x 2 daily. cFos inhibitor. Many health benefits. Found in "high" concentrations in strawberries, but I think all commercial extracts come from wax trees. This was a definite "light switch" type addition. There are plenty of other cFos inhibitors out there. $0.80
3) 20 g sunflower lecithin. Unfortunately high in omega 6. Oh well. Mostly eat bison which is low, as are the oils I use. Planning to reduce and start using αGPC. US$0.50
4) Acetyl-CoA support: 1g L-Carnitine fumarate, 1g ALCAR, 450 mg pantethine (these were not nearly as effective without the other elements in place) $1.20
5) Additional ACh synthesis support: Magnesium Glycinate (600 mg elemental Mg), allithiamine (300 mg) $1.25

So, this stack runs at just over $7 a day. The results have been pretty amazing. 75% cognitive recovery in a week. Whereas I couldn't work at all before, getting a fever from a few minutes of modest intellectual exertion, I can tutor two students online simultaneously in topics I don't really know while reading the wikipedia articles in other browser tabs, for several hours a day. Plus, it's been kinda nice to, I dunno, have a sense of humor again. Anybody who's pumping money into research chems (like yours truly, haha) might be advised to drop $50 to give this a go for a week.

Of course, this is a work in progress. Future phases (not necessarily in this order):
1) αGPC, Noopept, for cholinergic repair
2) Cerebrolysin, TB4, Dihexa: because if I'm injecting one thing, might as well inject everything. Expected synergy between TB4 and Dihexa via HGF receptor, see 10⁷ x as much BDNF thread
3) NSI 189, not sure if this stuff is pro- or anti-cholinergic though from user experiences. Have only tried a little bit personally.

4) Long term: repair ChAT and VAChT genes. Most promising candidates are through CNTF and NGF, though I'm a bit worried that NGF will backfire in two ways: overexpression may drive the body further into a sympathetic state, and it also blocks CNTF's effects. Any experts in gene expression please weigh in. Also, hell, it looks like some forms of vitamin A might work...

 

But, that said, I think the path ahead is pretty clear for the mental stuff. Will update with whatever additions come next. Now on to fix the physical damage caused by having the cholinergic anti-inflammatory pathway all but shut down for a year. (Any suggestions on spinal arthritis, venous reflux, dry eye, lingering dysautonomia, cellulite despite weighing less than I have in 16 years, maybe kidney damage, etc...? [yeah, sounds vaguely autoimmune, did take a drug with lupus as a side effect before this all started, oops])

 

Feedback, comments, questions welcome. I invite anyone interested to try the stack on their rats, after consulting a health care professional, health care amateur, priest, rabbi, high school Spanish teacher, and John Elway, and report back here.

Edited by StevesPetRat, 23 December 2014 - 02:57 AM.

[oppenheimer82]

how fast did you notice results?

[mindpatch]

Where did you get Boreal blueberries?  A pound a day?  Really?  You piqued my curiosity and I looked around and found some blueberry powder.  I make a lot of smoothies, and a good source of either powder or wild type blueberries would be a good addition. 

[bocor]

Ur regimen sounds awesome there was a while back I ate 1 lb blueberries and felt really good I think I might try it least the blueberries me personally I'm dealing with nerve pain and damage in my low back and neck causing widespread pain so im looking for ways to regenerate nerve tissue unfortunately I live in Pensacola now I used to live in Nashville where there is a trader joes to buy those blueberries for 3 fifty blueberries here are 4 a pound and they are NOT organic either like the boreal man I miss trader joes! I recently did start acetyl l carnitine 3 gr day along with r lipoic acid 300 mg to start I'm really curious about the fiseton though what are ur impressions of it? Thx
I would be willing to bet though that the pound of blueberries per day is the muscle here

[LDK]

dude, you are wayyy focused on the wrong things.

 

read my topic, especially the last post. It may help you recover from an overactive stress response system.

 

Some supplements to consider

 

Melatonin

Rhodiola Rosea

Green tea + L-Dopa

and methylcobalamine (vitamin b-12) very important to buy the sublingual methyl one.

also include sunflower seeds in your daily diet.

Edited by Lambiek de Kanter, 23 December 2014 - 06:33 PM.

[StevesPetRat]

how fast did you notice results?

Blueberries alone started lifting my mood within 3 days. The fisetin gave me a reaction -- sleepiness and a kind of calm happy feeling shortly after the first dose. I found myself singing for no reason and laughing to myself, just like when I was much younger, after about 2 days of use. So if it's going to work for you, I'd expect it to be noticeable within a week. The lecithin may have added a subtle cumulative effect; I used to think I was "choline sensitive" because I would get sad when I ate a lot of choline, but guess what? That was because I was sad and it kinda turned my emotions back on.
 

Where did you get Boreal blueberries?  A pound a day?  Really?  You piqued my curiosity and I looked around and found some blueberry powder.  I make a lot of smoothies, and a good source of either powder or wild type blueberries would be a good addition.

Trader Joe's. Studies suggest that Alaskan bog blueberries are far more antioxidant-rich than southern varieties; I figured that the Boreal blueberries would at least be close cousins (though I'm not a botanist; I've no real clue about that). As I mentioned, they're certainly darker than the usual kind. In case you're wondering, the nutrition content for the entire bag is: 55 g carb, 13 g fiber, 39 g sugar, 26% RDA vit C, pretty negligible other nutrients. I get virtually no other sugar from my diet, so not too worried on that account.
 

Ur regimen sounds awesome there was a while back I ate 1 lb blueberries and felt really good I think I might try it least the blueberries me personally I'm dealing with nerve pain and damage in my low back and neck causing widespread pain so im looking for ways to regenerate nerve tissue unfortunately I live in Pensacola now I used to live in Nashville where there is a trader joes to buy those blueberries for 3 fifty blueberries here are 4 a pound and they are NOT organic either like the boreal man I miss trader joes! I recently did start acetyl l carnitine 3 gr day along with r lipoic acid 300 mg to start I'm really curious about the fiseton though what are ur impressions of it? Thx
I would be willing to bet though that the pound of blueberries per day is the muscle here

You may want to look into Lion's Mane, Ashitaba, and ALCAR-arginate for nerve regeneration, maybe the Rx drug nardosine.
Fisetin seems really good for stress resistance. Now that things are humming along a bit better I can go without it for a couple days, but if I'm getting overworked it seems to be helpful keeping things from going off the rails.
I would agree with your assessment. Might've gotten the same results if I just stuck with the blueberries longer on their own, but I'm not the patient type.
 

dude, you are wayyy focused on the wrong things.
 
read my topic, especially the last post. It may help you recover from an overactive stress response system.
 
Some supplements to consider
 
Melatonin
Rhodiola Rosea
Green tea + L-Dopa
and methylcobalamine (vitamin b-12) very important to buy the sublingual methyl one.
also include sunflower seeds in your daily diet.

Dude, I know you're trying to help, but I've got atypical genetics. To quote from the other thread:

I'm homozygous for COMT V158M, COMT H62H, and MAO-A R297R, which means lots of dopamine with impaired neurotransmitter breakdown.

In the brief window where I was prescribed Adderall, every time I even took half a dose I'd be awake for 72 hours straight.
In the past year and a half I've tried everything you suggest except the mucuna pruriens.

• Melatonin makes me depressed if I use it more than once or twice a week (even at a 1 mg dose). A lot of people have this problem; some may not even realize it because they never think to question the health benefits of amazing melatonin
• Rhodiola was nice for two days and then it pooped out, never did anything much again
• I can finally handle a little caffeine again, but for a while even green tea made me extremely agitated and worsened tinnitus
• MethylB12 was helpful to reverse effects of excessive B6 / P5P (along with riboflavin). However, I've taken up to 25 mg (yes, mg) sublingually in a day, which made me feel a little sick, but otherwise have noticed no beneficial effects from it

Still, your advice may help others; I do appreciate your reading / feedback.


So there are a couple things missing from the original post:

• SIRT3 activation upregulates AcetylCoA synthesis. Therefore, NR / NAD are logical (albeit expensive) additions. I still can't get a straight answer on whether or not resveratrol activates or inhibits SIRT3, though.
• It's hard to find any info on CNTF increasing substances. Does anything know about that? It probably merits its own discussion. I may have even started a thread to no avail some months back...
• cFos inhibition may decrease the effects of NGF,1,2,3,4. This could be problematic long-term, though perhaps useful in PTSD treatment. It's probably a good idea to cycle such things, just like almost everything else. 

Edited by StevesPetRat, 24 December 2014 - 01:25 AM.

[tjnqmfnbo]

So what happens when you stop using these supplements? For example fisetin, can it induce long lasting changes?

 

[normalizing]

stevespetrat, where the hell did you find allithiamine? i been searching high and low for it on google with no results. there is plenty of sulbutiamine tho.

[StevesPetRat]

So what happens when you stop using these supplements? For example fisetin, can it induce long lasting changes?

Blueberries promote neurogenesis, so I assume those changes will be relatively long lasting. Fisetin seems still to be necessary to prevent stress/overwork induced brain fog for now.

stevespetrat, where the hell did you find allithiamine? i been searching high and low for it on google with no results. there is plenty of sulbutiamine tho.

Amazon

I've just found that black rice is high in anthocyanins, so I may add that to my "stack" and cut out half the blueberries. Thinking about doing some dramatic self-experimentation with diets ranging from 80/10/10 to 5/15/80 in the new year; seems like black rice would make an excellent carb source.

Edited by StevesPetRat, 27 December 2014 - 05:22 PM.

[normalizing]

thats some expensive questionable quality stuff. i checked amazon many times over for allithiamine, this is the first time i see an actual page of contents with it having overpriced supplement on the front. i know allithiamine is created in japan and it has patent, i dont trust those 3rd party based overpriced turds.

[StevesPetRat]

thats some expensive questionable quality stuff. i checked amazon many times over for allithiamine, this is the first time i see an actual page of contents with it having overpriced supplement on the front. i know allithiamine is created in japan and it has patent, i dont trust those 3rd party based overpriced turds.

Well, TTFD is patented, anyway. This stuff smells and tastes garlicky and foul. I didn't mention this but it virtually eliminated my POTS in two days. I had no expectation that it would have any such effect. Been trying to do something about that for a year now... pretty sure it's the real deal, though you can buy a small bottle for $14 if you wanna trial it.

[normalizing]

what POTS stand for....

[mind_offset]

Identification of the 100 richest dietary sources of polyphenols :

 

http://www.nature.co...n2010221t1.html

 

 

It looks like cloves are ranking #1

 

Interestingly, clove extract supplements are branded for high ORAC antioxidant value.

 

[ceridwen]

Hydergine is good

[StevesPetRat]

what POTS stand for....

Postural Orthostatic Tachycardia Syndrome. It's a type of autonomic nervous system dysfunction. My heart rate goes from 55-60 lying down to 95-100 standing up. Well, now it's usually more like 75-80, which is pretty much normal. Have a bunch of other dysautonomic symptoms, but that one is the easiest to quantify and monitor. Didn't get that much of a result from benfo or straight up thiamine (though I never took more than 300 mg benfo a day, I did try up to 1g thiamine).

Edit: Found another allithiamine (TTFD) source

Edited by StevesPetRat, 30 December 2014 - 02:35 AM.

[ceridwen]

I think I probably have POTS too that is if my heart measurement ape are to be believed
Sorry I meant aps

[StevesPetRat]

I think I probably have POTS too that is if my heart measurement ape are to be believed
Sorry I meant aps

You also have Alzheimer's-like cognitive problems, too, if I recall, correct? This stack, particularly the (alli)thiamine, might do you some good. Be careful, there is a "paradoxical" reaction some people get when correcting a thiamine deficiency. It is supposed to go away with time, but it is more severe the longer / worse the deficiency is.

[strider]

what brand/where do you source the Fisetin from? / where do you source all your supplement from?

[StevesPetRat]

what brand/where do you source the Fisetin from? / where do you source all your supplement from?

I started with Doctor's Best brand on Amazon; it's fairly cheap. Then I bought a big bag from some guy on ebay: drarthurwells@hotmail.com ... seems legit, but I have a higher risk tolerance than most.

I get most of the rest of my supplements from PureBulk, random Amazon vendors, and noots from Peak Nootropics, Liftmode, and Powder City (only folks who seem to have UMP bulk powder).

None of these should necessarily be construed as endorsements.

Edit: Also wanted to add a warning -- seems like high dose B1 really increases my need for magnesium.

Edited by StevesPetRat, 03 January 2015 - 09:17 AM.

[Plasticperson]

Shilajit, especially in high doses of .5-1 gram, is amazing for pots and ebv related symptoms

[StevesPetRat]

Shilajit, especially in high doses of .5-1 gram, is amazing for pots and ebv related symptoms

Interesting, though at that dose it could get pricey... would you take a look at this product and let me know what you think? Seems like it should be the same.

[Plasticperson]

That would work perfectly however if you ever want to try legitimate shilajit, lotus blooming is the best around.

[strider]

im going to try some parts of your regimen. theres a trader joes near me so stocked up on some of those wild blueberries. $3.50 for a pound seems like a bargain and your right prolly does more for you then some supplement. probably try out some Fisetin later and see how that goes.

 

also regarding shilajit, how does lotus blooming compare to purblack? http://www.amazon.co...ywords=Shilajit

 

30g instead of 10g and seems very high quality if not higher?(higher percentage of 5*'s)

[Plasticperson]

just wanted to comment on the negative effects from racetams.. racetams are shown to up regulate NMDA receptors by 20 percent, drugs like dxm, pcp and ketamine trigger this same phenomenon. Bacopa is know to down regulate NMDA receptors and block the up regulation of NMDA receptors when co-administered with pcp.

 

I did a 2-3 week cycle with bacopa and i still feel the positive effects 2 weeks after cessation. I believe that my thought process is a lot more like pre racetam usage which always left me feeling weird and dull. I'm starting to discover that not all receptors down/up regulate after stimulus changes receptor density. SSRI's are a good example of drugs that may cause permanent changes in receptor density.. perhaps the NMDA receptors don't return to a homeostasis either?

 

Just food for thought,

Cheers

[normalizing]

^ you mean just the basic piracetam causes this or all of them?

[Plasticperson]

^ you mean just the basic piracetam causes this or all of them?

 

Just the piracetam afaik

[EFTANG]

im going to try some parts of your regimen. theres a trader joes near me so stocked up on some of those wild blueberries. $3.50 for a pound seems like a bargain and your right prolly does more for you then some supplement. probably try out some Fisetin later and see how that goes.

 

also regarding shilajit, how does lotus blooming compare to purblack? http://www.amazon.co...ywords=Shilajit

 

30g instead of 10g and seems very high quality if not higher?(higher percentage of 5*'s)

 

Have you noticed Pur black on Amazon has -with a few exceptions- only 'bought' reviews ? All 5 and 4 star reviews are written in xchange for a free product, as can be read in the reviews themselves. Red flag !

 

Lotus Herbs is doing the same though, but with them even the 'bought' reviews are quite often unfavorable. I would not trust any of them, and ignore the slick marketing. That being said, resin is the way to go, though, NOT powder or pills. The stuff you see on eBay from Uzbekistan, Ukraine and such countries, packed usually in blisters is loaded with gums (and who knows what else) to keep it manageable.

 

If you are considering a brand, ask for a COA that shows not only the level of heavy metals but also the active ingredients. In particular fulvic acid; should be between 7 and 17%, according to Russian research.

 

Less means it's comparable to e.g. powdered peat (not much to expect from that) and more means it has been spiked or processed to death. In that case the synergy between the different elements will be gone and you are left with isolated fulvic acid, which is in the core just fertilizer and as such available from every store selling gardening supplies for very little. Shilajit in its optimal form can achieve excellent results though, in particualr in combination with other herbs (like Rhodiola rosea).

[tolerant]

StevesPetRat, 

 

Do you have access to the full text of that study? This study comes to a completely opposite conclusion...

 

I did a little more research into this, and in the book "Cholinergic Mechanisms" it says: "Following stress, the rapid up-regulation of AchE-R may therefore serve to dampen cholinergic neurotransmission... However, this very same feature may cause hypersensitivity in cholinergic synapses post-stress." This text is freely available on books.google.com

 

I guess it's figuring out by experimenting which side you're on: whether you need your cholinergic neurotransmission increased or decreased.

Edited by tolerant, 19 May 2016 - 09:47 AM.

[gamesguru]

Sci hub should give anyone access

http://www.longecity...research-papers

[tolerant]

I should have taken StevesPetRat's disclaimer more seriously. 

 

As a background, I suffer from generalised anxiety with some depression. Yesterday, I tried a modified version of his stack using what I had at hand. Within about an 8-hour period I ate 0.5 kg of blueberries, took 1 g of ALCAR, 500 mg of GPC choline, and a handful of walnuts (also AchE inhibitors). It was after the walnuts that I began to feel nausea. Now I never feel nausea, so it could not have been a coincidence. Today, I woke up with feelings of increased and different kind of anxiety and just feeling worse overall. Since then I read the paper that StevesPetRat refers to in his original post. Crucially, it says that the c-Fos activation is triggered by stress and administration of AchE inhibitors. Now, eating 0.5 kg of blueberries in one day may well constitute administration of AchE inhibitors referred to in the paper and give the person additional symptoms, just as I had earlier proposed here. So I have fallen victim to my own stupidity and impatience, and now I sit and wait to see whether I develop delayed-onset anticholinergic symptoms, none of which I really had to begin with.

 

People, please be careful, read StevesPetRat's disclaimer and story carefully and don't start by eating 0.5 kg of blueberries a day. 

 

EDIT: I just thought that a quicker way to find out if my c-Fos has been messed with is to take Fisetin. If I find it helpful, the the answer is probably "yes", although it won't of course mean that it was messed with by the 0.5 kg of blueberries and other cholinergics I took yesterday.

Edited by tolerant, 20 May 2016 - 09:07 AM.