84 replies to this topic

[dk2011]

It sounds like Myasthenia gravis. Your body started to produce antibodies to acethylcholine receptors (?). Try common treatments for this condition. Maybe immunosuppresants like glucocorticoids? Have you tried this?

 

Well, I do not have most of the symptoms at all of MG.  I do not have facial paralysis, difficult swallowing or chewing, coarse voice, double vision, trouble talking, altered speaking, limited facial expressions, etc.

 

This wouldn't explain how CDP Choline (or possibly Choline Bitartrate) long-term decreased my insane sensitivities. Before that both Ashwagandha (decreased) and Chamomile (increased) them short-term. 

 

I was able to uncover this little nugget:

 

This has been noted in a living system, where aged rats given 100-500mg/kg CDP-Choline daily for 7 months experienced a 6-17% increase in muscarinic acetylcholine receptor concentration (whereas control experienced a decline) although affinity of the receptor was not modified.

 

SOURCE: https://examine.com/...ts/cdp-choline/

 

And I still think I have a type of POTS Syndrome based on my symptoms (even though tests results were inconsistent): 

 

...screened over 150 POTS patient volunteers and healthy controls for three different muscarinic receptor antibodies. These antibodies are known to be associated with dysautonomia, and were found in more than 87% of POTS patients in a smaller preliminary study...

 

SOURCE: http://www.dysautono...page.php?ID=240

[dk2011]

Also...

Muscarinic receptors have a very different mechanism of action. They are part of a large family of G-protein-coupled receptors (GPCRs) which are used as an intracellular secondary messenger system.

 

G proteins work by binding neurotransmitters, hormones, growth factors, cytokine, odorants and photons at the cell surface to the GPCR, and activating that receptor. Everything you see, hear, smell, or taste goes through this signaling process.

 

 

SOURCE:  https://nootropicsexpert.com/sam-e/

[dk2011]

That last post was supposed to be in quotations.  Does anybody think G Proteins could be a missing element here that could help explain things?

[Mind_Paralysis]

Right, I think there might be a connection, but I'm honestly not sure about it... There's a detail you're unaware of though, and that's the fact that there is NEW, growing evidence that the nACH-alpha-7-receptor is a type of G-protein coupled receptor as well - well, sort of... it seems to control activity out of G-protein receptors in a secondary way, it's a bit unclear still how it actually does this... might be a previously unknown method of modulation.

 

Connecting the Dots between G Proteins, G Protein Coupled Receptors and Neuronal Nicotinic Acetylcholine Receptors

https://www.ncbi.nlm...les/PMC4357228/

 

The alpha7 nAChR is considered to be ancestral in many respects as its presence extends to a wide number of invertebrate species. Phylogenetic analysis supports this view as well as the fact that the alpha7 nAChR nicotinic acetylcholine receptor is a pentamer consisting of only one type of subunit, i.e., alpha7, unlike all other nAChRs, which have apparently evolved through gene duplication and selection

 

 

Alpha-7 is, name withstanding, apparently the O-G nicotinic receptor - the things it process are more fundamental and important to base physiology than other receptors. Don't look at it as one of the others... that's not its function.

 

Alpha 7 nicotinic receptor coupling to heterotrimeric G proteins modulates RhoA activation, cytoskeletal motility, and structural growth.

https://www.ncbi.nlm...pubmed/27167578

 

This image depicts the hypothesized interaction of the traditionally ionotropic α7 nicotinic acetylcholine receptor (α7 nAChR) and its ability to interact and signal through both large and small G proteins

 

 

 

Eyes front, man... back to Alpha-7 - it has properties of BOTH nicotinic and muscarinic receptors - pointing towards an exciting key-role in animal existence.

[dk2011]

Stinkorninjor, you are 1,000x’s smarter than me and this is helping so much. Can we create a hypothesis for the following somehow based on PubMed and science:

1) There is some way that whichever receptors herbal medicines (and some meds) act upon were 100x's hyper-responsive when I was a teenager.
2) How Ashwagandha would decrease it for 24-hours
3) How Chamomile would increase it for 24-hours
4) How either Choline Bitartrate or CDP Choline permanently made the sensitivities decrease

For instance, if my Vagus Nerve was partially blocked or something... The reason Ashwagandha and Chamomile were temporary is because they only agonized or antagonized those receptors temporarily. Now, Choline being intricately involved in the parasympathetic nervous system and the vagus nerve obviously caused some permanent shift. I keep being unsure which version of Choline it was but now I’m leaning towards Choline Bitartrate being the culprit. It’s extremely difficult to describe feelings inside our body but there is some set of receptors that needs to be stimulated (agonized) and I don’t know what would do it.

Your thoughts Stinkoninjor? And everyone else?

[jack black]

Hopefully, someone smarter than myself will reply.

 

my wish came through.

IMHO, there is no smarter person on this forum than Stinkorninjor and he is always ready to help.
 

[dk2011]

 

my wish came through.

IMHO, there is no smarter person on this forum than Stinkorninjor and he is always ready to help.
 

 

Agreed.

 

I think something about this is "right track" although I don't think it's as simple as starving myself of acetylcholine.  Seems like a balance/counterbalance involving Vagus Nerve and choline bitartrate or something.

 

[dk2011]

Apparently, I'm not the only one!!!!!

 

 

sensitivity to meds/supplements

Started by mealz13, Jul 21 2012 11:19 AM

http://www.longecity...edssupplements/

 

"Hello everyone, I decided I need a second opinion on my extreme sensitivity to all meds & supplements. Basically, microdoses of anything will have a profound effect on me, positive and negative, and I'll literally feel the effects overnight. For example, I took a very small dose of zoloft and had immediate anxiety relief the next day. I've taken 4 grams of inositol and felt like I was stoned. I took 3 tablets of chlorella and got crazy energy and agitation the next day. One day I had a small iced tea and was up the entire night. And the list goes on.
Basically, what I want to know is if there is any illness that could cause extreme sensitivity, and if I'm a placebo driven maniac. My doctors assure me there are people who are extremely sensitve and that it's not all in my head, but I'm not so sure. I've also seen this can be caused by a "leaky gut". Any insight would be appreciated, thanks."

Edited by dk2011, 24 December 2017 - 09:37 PM.

[dk2011]

Can anyone let me know if this article may hold the key for whatever CDP Choline or Choline Bitartrate did to me?
http://phoenixrising...ohnson-aug-2005

[dk2011]

It may seem difficult to explain but:

When I was a teenager and was 100x’s sensitive to herbs and meds, countless experts told me that I should get psychological therapy such as for stress and that other than that there was nothing I could do. THEY WERE 100% WRONG! I found out after over 10 years that it can be controlled/modified on my own. I was already in “direction the body would not normally go” from the beginning and it was stuck like that until I discovered how to modulate it myself. If I hadn’t taken anything, I would still be 100x’s sensitive to meds to this day. But I’m not.

I spent 5 years after I discovered Ashwagandha & Chamomile having complete 100% control because Ashwagandha would decrease my sensitivity and Chamomile would increase them (for the 24 hours it was in my system).

By using more and more Choline supplements gradually, my body went from 100, 80, 50, 20, 0, -20, -50, -80, -100. It wasn’t an On/Off switch. There was a gradual shift. If I can give analogy, most people have an automatic thermostat for this, but mine is manual. I managed to discover the “down button” (CDP Choline) and I was free to lower the thermostat, however I can’t find the up button, so for now all I can do it press the down button so to speak, until I discover the other “button.”

I can promise with 100% certainty there is a reverse feedback mechanism in the body for this, because otherwise my body wouldn’t have spent an entire decade being abnormally sensitive, nor would the shift have been so gradual.

Being that I’m so convinced that CDP Choline was a permanent and gradual “down button” on the thermostat so to speak, where would I find help with locating the “up button?” Is this something you can help with? There are 1,000’s of studies on CDP Choline, Chamomile, and Ashwagandha that would help give clues as to why the affected me the way that they did. I desperately need help, and my determination is an effort to get my life back. My symptoms are so bad that I have no life until this issue is resolved.

Thanks for your responses.

[Mind_Paralysis]

You may already have the answer. Chamomille is a nAch-Alpha-7-antagonist - and as you recall, that receptor is fairly important for immune-system regulation, from previous threads.

 

Why not just get back on chamomille, but this time... you're going to increase the dosage - A LOT. (and use a highly purified extract - you need a lot of Bisabolol)

 

That, or try out the choline-elimination diet, which have helped multiple other people whom developed cholinergic sensitivity (from gross overdose admittedly) - there's a chance it could help.

 

 

Bisabolol - active constituent in Chamomile

https://en.wikipedia.../wiki/Bisabolol

 

Inhibitory actions of bisabolol on α7-nicotinic acetylcholine receptors

http://www.sciencedi...306452215007435

[dk2011]

Thanks for your reply Stinkorningor. On multiple times, I have tried enormous doses of Chamomile for extended periods of time and if simply no longer works post-Choline. I also have been reducing Choline intake from foods.  But....  I made an interesting discovery last night and perhaps you can help me with this!

 

 

 

CDP Choline allegedly "enhances the expression of the EAAT2 glutamate transporter, leading to increased glutamate uptake."  Is this theory plausible in that perhaps EAAT2 got up-regualted or something and never got down-regulated, and perhaps back when Ashwagandha/Chamomile were working they were affecting this system?  If this is plausible for what happened to me, how would I decrease expression of EAAT2?  And do you think this theory makes sense?

[dk2011]

Glutamate transport is the only mechanism for maintaining extracellular glutamate concentrations below excitotoxic levels. Among glutamate transporters, EAAT2 is responsible for up to 90% of all glutamate transport and has been reported to be associated to lipid rafts. In this context, we have recently shown that CDP-choline induces EAAT2 translocation to the membrane.

 

...In summary, we have demonstrated that CDP-choline redistributes EAAT2 to lipid raft microdomains and improves glutamate uptake.

[dk2011]

Stinkorninjor & everyone,

 

I recently had a medical test confirm that POTS Syndrome is what I have suffering from all along.

 

I'm sorry the conversation got off track.

 

But this still leaves the underlying issue:  Somehow taking Choline supplements made me less & less sensitive to meds until I was left having horrible reactions to everything and left feeling extremely bad 24 hours a day 365.  Please help.  Any additional ideas are appreciated.  What could Choline (Choline Bitartrate or CDP Choline) have do to me that was so bad and how can I reverse it?  How do I reverse what Choline did to me?

[Mind_Paralysis]

Stinkorninjor & everyone,

 

I recently had a medical test confirm that POTS Syndrome is what I have suffering from all along.

 

I'm sorry the conversation got off track.

 

But this still leaves the underlying issue:  Somehow taking Choline supplements made me less & less sensitive to meds until I was left having horrible reactions to everything and left feeling extremely bad 24 hours a day 365.  Please help.  Any additional ideas are appreciated.  What could Choline (Choline Bitartrate or CDP Choline) have do to me that was so bad and how can I reverse it?  How do I reverse what Choline did to me?

 

The underlying issues could be your DYSAUTONOMIA (and whatever causes that) - your reaction to choline supplements is but a symptom of that - you describe dysautonomic symptoms from a early age.

However, let's not get too hung up on that part, we may return to it later - at the moment, let's instead have a look at what causes POTS, and see what we can find.

 

You've mentioned Mast-Cell Disease, and that seems to be a theme among several of the diseases associated with dysautonomia and POTS - what kind of tests and treatments is there to find there?

 

You can apparently get POTS from viral infections as well - as I understand it, if you can figure out what type of infection you had, you can then improve symptoms by defeating the viral infection.

What kind of viruses can cause POTS?

Have you been tested for viral infections?

 

This neat article on POTS actually mentions something interesting...

 

 

Postural Tachycardia Syndrome

http://circ.ahajourn...ent/117/21/2814
 

 

"A promising new therapy is pyridostigmine (Mestinon), an *acetylcholine*sterase inhibitor that is thought to facilitate ganglionic neural transmission in both the sympathetic and parasympathetic nerves.¹⁴ The drug appears most effective in patients with postviral POTS, as well as in those with POTS secondary to an autoimmune disorder (such as lupus or Sjögren syndrome)."

 

 

It's apparently used to treat Myastenia Gravis, which someone mentioned earlier... However, it's a bit worrysome though, since this drug causes the body to build up more Acetylcholine, it's basically an MAOI, but it only affects Acetylcholine breakdown, slowing it down.

 

I do wonder... what would happen if you took this drug? Another cholinergic compound put you into a rather troublesome state, would this one bring you out of it, or would it smash you into smithereens?

 

 

Well, find out if you have Lupus, Sjögren Syndrome or a viral infection first, then we can worry about trying it out - but it *IS* interesting, is it not?

[Krocius]

Have you rule out chronic fatigue syndrome/myalgic encephalomyelitis already? Maybe acetylcholine made your prone to infection and you developed CFS. Do you have post-exertional malaise? It’s really a very little chance that you have unknown disorder. POTS is characteristic symptom of CFS actually as well as fibromyalgia

Edited by Krocius, 16 January 2018 - 07:35 PM.

[Mind_Paralysis]

Have you rule out chronic fatigue syndrome/myalgic encephalomyelitis already? Maybe acetylcholine made your prone to infection and you developed CFS. Do you have post-exertional malaise? It’s really a very little chance that you have unknown disorder. POTS is characteristic symptom of CFS actually as well as fibromyalgia

 

I've told him this in the past about some of this - he kind of had a grasp of it prior as well. To my knowledge... he has not yet ruled out CFS or Fibromyalgia in particular, at all.

 

 

He's also shown symptoms of dysautonomia, and symptoms similar to what he has now, except transitory (i.e, he kept jo-joing in-between super-sensitive to almost anything stimulating, to completely insensitive to anything stmulating) in the past, as far back as a young child, so, potentially, the underlying factor is either hereditary/genetic, or the event that caused the process to begin, started a very long time ago.

 

With that said, your post made me think of something... could he have a combination of some kind of auto-immune disorder, and then he contracted a virus during adulthood which made it all worse?

 

Tricky this... we need some testing here! Viral testing should be priority #1 - that the easiest - antibodies, or other traces of viral infection, to rule out some of those things.

Edited by Stinkorninjor, 16 January 2018 - 08:39 PM.

[jack black]

It may seem difficult to explain but:

When I was a teenager and was 100x’s sensitive to herbs and meds,

 

i saw it posted somewhere else on this forum and I thought about you. could be a long shot:

 

 

I am also able to respond to microdoses of psychotropics.

2.5mg of celexa causes a very euphoric feeling for me, and causes sexual side effects at this small dose! As does lexapro.

I can respond well to about 2mg of dexedrine.

Propranolol works for me at a 5mg dosage.

Taking 150mg of buproprian is enough to make me feel like I'm gonna have a seizure, I probably need something like 50mg.

0.125 mg of Xanax is quite strong for me... though strangely I need 1mg of clonazepam to reach similar effectiveness as 0.125mg of Xanax... plus Xanax lasts approximately 8 hours for me compared to about 5 hours for the clonazepam. Weird.


My sensitivity to psychotropic medications is a huge cost saver for me and allows me to safely take some of these substances on a regular basis when needed.

I think it might be something to do with my lyme disease or bartonella.... I read that people with bartonella have strange reactions like these to very small dosages of psychotropic medications.... or some people need humongously huge doses to even get the mildest reaction.


I don't get it...

 

Edited by jack black, 16 January 2018 - 11:09 PM.

[dk2011]

Thanks for the responses everyone.

 

I've been tested by a Rheumatologist for Lupus & Sjogren's.  Ruled out completely.  I don't have those.  By the way, the vast majority of people with CFS (Chronic Fatigue Syndrome) who have a Tilt Table Test (a test for POTS) comes back positive, indicating that they are really the same condition and just synonyms for each other.  ME (Myalgic Encephalomyelitis) also is a synonym for these conditions.

 

Also, a key clue might be that tiny amount of Huperzine A (an acetylcholinesterase inhibitor just like Mestinon) gave me severe acetylcholine poisoning symptoms, mainly severe vomiting from small amounts.  It landed me in the Emergency Room, so I cannot try an acetylcholinesterase inhibitor again.  And acetylcholine inhibitors like Benadryl (Diphenhydramine) make me feel horribly sick and did not resolve the issue for some reason.

 

I don't think we are going to find the root cause of POTS on this forum, however I do believe there is a biological explanation for how Choline (Choline Bitartrate and CDP Choline) could have affected me this way.  I feel so frustrated it's like banging my head against the wall that I can't seem to find an explanation based on the actions of Choline Bitartrate and CDP Choline in the body to explain exactly what MOA (Method of Action) was used to reduce my sensitivities and how I can increase them again.

Edited by dk2011, 16 January 2018 - 10:50 PM.

[dk2011]

Jackpot possibly?!?!

 

Opposing relationship between Ethanolamine vs. Choline

 

 

QUOTE:  As a polar head group, phosphatidylethanolamine creates a more viscous lipid membrane compared to phosphatidylcholine. For example, the melting temperature of di-oleoyl-phosphatidylethanolamine is -16 °C while the melting temperature of di-oleoyl-phosphatidylcholine is -20 °C. If the lipids had two palmitoyl chains, phosphatidylethanolamine would melt at 63°C while phosphatidylcholine would melt already at 41 °C.  Lower melting temperatures correspond, in a simplistic view, to more fluid membranes.

 

More vicious nerve membranes = more sensitive to meds?

Less vicious nerve membranes = less sensitive to meds?

 

@Stinkorninjor and others, what are your thoughts on this hypothesis?

 

Am I crazy or could this have solved it?  And where would I get an CDP-Ethanolamine supplement or Ethanolamine supplement if you think it's worth a shot?

 

Even if this isn't it, my main goal is to increase my sensitivities again and won't be in this much 24/7 pain and fatigue.  Choline caused this... I need to reverse, but how?

Edited by dk2011, 17 January 2018 - 07:43 AM.

[Caravaggio]

Did you look up late-onset Congenital Myasthenic Syndrome (CMS)?

 

There are currently 28 different types:

 

http://www.uniprot.o...ital&sort=score

 

Here is a very good presentation about all the different types:

 

https://www.slidesha...henic-syndromes

[Mind_Paralysis]

Thanks for the responses everyone.

 

I've been tested by a Rheumatologist for Lupus & Sjogren's.  Ruled out completely.  I don't have those.  By the way, the vast majority of people with CFS (Chronic Fatigue Syndrome) who have a Tilt Table Test (a test for POTS) comes back positive, indicating that they are really the same condition and just synonyms for each other.  ME (Myalgic Encephalomyelitis) also is a synonym for these conditions.

 

Also, a key clue might be that tiny amount of Huperzine A (an acetylcholinesterase inhibitor just like Mestinon) gave me severe acetylcholine poisoning symptoms, mainly severe vomiting from small amounts.  It landed me in the Emergency Room, so I cannot try an acetylcholinesterase inhibitor again.  And acetylcholine inhibitors like Benadryl (Diphenhydramine) make me feel horribly sick and did not resolve the issue for some reason.

 

I don't think we are going to find the root cause of POTS on this forum, however I do believe there is a biological explanation for how Choline (Choline Bitartrate and CDP Choline) could have affected me this way.  I feel so frustrated it's like banging my head against the wall that I can't seem to find an explanation based on the actions of Choline Bitartrate and CDP Choline in the body to explain exactly what MOA (Method of Action) was used to reduce my sensitivities and how I can increase them again.

 

Right, so you've been tested for Lupus and Sjogren's.

 

Have you tested yourself for various viral agents though? Or bacterial diseases like Bartonella? There's several people on these forums whom believed themselves to have unexplainable unknown diseases, which in the end turned out to be merely unusual reactions to various infectious diseases. It's worth having a look at some of the diseases claimed to be causative of CFS for instance, over at the Phoenix Rising Forums.

 

A classic is Lyme disease and various Herpes viruses.

 

BTW - when did you try the Huperzine A? It sounds like it was PRIOR to your current, unaffectable state, wherein no drug affects you - if so, it's quite possible that Pyridostigmine will affect you completely differently this time around. Also, don't forget that direct agonists and reuptake-inhibitors can have wastly different effects - as well as different effects from different reuptake inhibitors or MAOI's. Although it's likely that the effects of Pyridostigmine would be similar, it's not a given, as odd as that may seem - that just seems to be the par for the course when it comes to the complexities of the body.

[dk2011]

Right, so you've been tested for Lupus and Sjogren's.

 

Have you tested yourself for various viral agents though? Or bacterial diseases like Bartonella? There's several people on these forums whom believed themselves to have unexplainable unknown diseases, which in the end turned out to be merely unusual reactions to various infectious diseases. It's worth having a look at some of the diseases claimed to be causative of CFS for instance, over at the Phoenix Rising Forums.

 

A classic is Lyme disease and various Herpes viruses.

 

BTW - when did you try the Huperzine A? It sounds like it was PRIOR to your current, unaffectable state, wherein no drug affects you - if so, it's quite possible that Pyridostigmine will affect you completely differently this time around. Also, don't forget that direct agonists and reuptake-inhibitors can have wastly different effects - as well as different effects from different reuptake inhibitors or MAOI's. Although it's likely that the effects of Pyridostigmine would be similar, it's not a given, as odd as that may seem - that just seems to be the par for the course when it comes to the complexities of the body.

 

 

I've had all the bloodwork run that a person possibly could.  I assure you the root cause is autonomic system dysfunction, aka POTS/CFS.

 

Huperzine A was only used to attempt to REVERSE the choline problem, and it failed after I tried multiple times after Choline caused such an imbalance.

Edited by dk2011, 18 January 2018 - 11:41 PM.

[dk2011]

Enhancement by cytidine of membrane phospholipid synthesis.

G-Coviella IL1, Wurtman RJ.

 

Abstract

Cytidine, as cytidine 5'-diphosphate choline, is a major precursor in the synthesis of phosphatidylcholine in cell membranes. In the present study, we examined the relationships between extracellular levels of cytidine, the conversion of [14C]choline to [14C]phosphatidylcholine, and the net syntheses of phosphatidylcholine and phosphatidylethanolamine by PC12 cells. The rate at which cytidine (as [3H]cytidine) was incorporated into the PC12 cells followed normal Michaelis-Menten kinetics (Km = 5 microM; Vmax = 12 x 10(-3) mmol/mg of protein/min) when the cytidine concentrations in the medium were below 50 microM; at higher concentrations, intracellular [3H]cytidine nucleotide levels increased linearly. Once inside the cell, cytidine was converted mainly into cytidine triphosphate. In pulse-chase experiments, addition of cytidine to the medium caused a time- and dose-dependent increase (by up to 30%) in the incorporation of [14C]choline into membrane [14C]-phosphatidylcholine. When the PC12 cells were supplemented with both cytidine and choline for 14 h, small but significant elevations (p less than 0.05) were observed in their absolute contents of membrane phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, all increasing by 10-15% relative to their levels in cells incubated with choline alone. Exogenous cytidine, acting via cytidine triphosphate, can thus affect the synthesis and levels of cell membrane phospholipids.

 

I really do wonder if Cytidine was the culprit via up-regulation of phospholipid synthesis.

Remember that CDP Choline is one of the types of Choline I was taking that did this to me.  It seems that it stimulates the increased production of all the phospholipids such as PhosphatidylCholine, PhosphatidylSerine, PhosphatidylEthanolamine, etc.

How would I reverse this?  How would I decrease the production of phospholipids?  Assuming that Cytidine is the culprit.

[Krocius]

I don't understand how Postural Orthostatic Tachycardia syndrome and Chronic Fatigue Syndrome can be synonyms? There are related conditions but not synonyms POTs may be developed without CFS actually. I think you are on a wrong way before thinking that you have an unknown disorder you should try common treatments for known disorders like CFS. Check Phoenixrising website for further information about this. Nobody knows what happened in your body after CDP-choline use but judging by your symptoms you have something like CFS. Match your symptoms with common disorders firstly. Obssesive reading studies about receptors and neurochemicals should be your last option.

Edited by Krocius, 19 January 2018 - 08:18 PM.