Excitotoxicity

Hip

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the bigger mystery, why a fucking (excuse me) vaccine would bring this on so much.
Hard to say, occasionally vaccines (of any sort) have been known to trigger ME/CFS in healthy people, especially the hepatitis B vaccine. So there is a mysterious link between vaccines and ME/CFS. Although those who have ME/CFS triggered by coronavirus (long COVID) often improve after the coronavirus vaccine.


If you have anxiety along with your suspected high glutamate, I found N-acetyl glucosamine worked very well to reduce this anxiety, by reducing brain inflammation and glutamate, I suspect. See my thread here:

Completely eliminated my severe anxiety symptoms with three supplements!
 

Boba

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@Hip

Although those who have ME/CFS triggered by coronavirus (long COVID) often improve after the coronavirus vaccine
May I ask if you have data backing this information? I have long Covid with cfs symptoms including PEM (mostly in bed since 2,5 months) and wasn’t really sure if I should get the shot. Could get Moderna in 2 weeks.
 

judyinthesky

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@Boba I have read articles on this and can just say be careful with interpretations of the media. Some improve, most stay the same, but some do also get worse.

@Hip sure, that link is established. It is just such a lottery as to why it happens with some and some not. I found a few people who crashed very hard after the vaccine, but nobody really knows why and recovery for some takes weeks and months. So this begs the question from when one can actually say it's trigger or onset of new symptoms or crash.

Anxiety: very physical way. More depression in crash, but of a wired kind. If that is possible.
 

Hip

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May I ask if you have data backing this information? I have long Covid with cfs symptoms including PEM (mostly in bed since 2,5 months) and wasn’t really sure if I should get the shot. Could get Moderna in 2 weeks.
There have been a lot of anecdotal reports of long COVID patients getting substantially better after the coronavirus vaccine, but no studies as far as I am aware. Other long COVID patients have found the vaccine did nothing much for them, however.

You can Google search for more info.


Bear in mind that long COVID includes not only ME/CFS, but also coronavirus patients with heart and lung damage after COVID, who display ME/CFS-like symptoms.

And long COVID also includes those with an ongoing acute infection which never cleared up (which is different to the ME/CFS post COVID). I have not looked into which of these subtypes has benefitted from the vaccine, but if you find any info on it, I'd be interested.
 

nerd

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The source of the glutamate in ME/CFS may be from brain inflammation, since the activated microglia in neuroinflammation release copious amounts of glutamate.
The other theory with some evidence is that the alpha-ketoglutarate dehydrogenase in the CAC is inhibited, and glutamate dehydrogenase is overstimulated by this blockage.

Please consider that elevated glutamate will always reflect in elevated GABA eventually because glutamate is converted to GABA by glutamate decarboxylase. Only the short-term peaks, which can be triggered by exertion, would cause a dysbalance in the glutamate-GABA system. This is why I consider this a general excitotoxic issue and not a glutamate-specific one. Fortunately, receptors adapt to the amount available agonists. It's only the short-term effects that can be troubling.

One indicator for an oversaturation of the complete system would be high glutamine levels in the blood.
 

Hip

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Please consider that elevated glutamate will always reflect in elevated GABA eventually because glutamate is converted to GABA by glutamate decarboxylase. Only the short-term peaks, which can be triggered by exertion, would cause a dysbalance in the glutamate-GABA system.
Yes, good to bring up this interesting enzyme glutamate decarboxylase (also called glutamic acid decarboxylase), which is involved in the glutamate dynamics of the brain.

This enzyme is not the only process responsible for clearing glutamate, though, because the brain also has glutamate transporters to remove excess glutamate from the extracellular spaces of the brain.

I experimented with taking certain drugs (like ampicillin) to increase the number of glutamate transporters in my brain, and I did notice a calmer, less wired and less anxious mind as a result — see this post for details. A list of glutamate transporter boosters is given here. Riluzole is the drug used clinically to boost glutamate transporters in the disease amyotrophic lateral sclerosis.

Researchers are looking into boosting glutamate transporter expression with drugs in order to help treat neurodegenerative diseases like Parkinson's, Alzheimer's, multiple sclerosis, epilepsy, etc.



But regarding glutamate decarboxylase and glutamate:

A while back I found an interesting paper which mentions the possibility coxsackievirus B4 and other Coxsackie B viruses might induce autoantibodies that disable glutamate decarboxylase (more specifically, the GAD65 form of this enzyme).

This autoimmune attack may arise because of molecular mimicry between the 2C protein of CVB4 and glutamate decarboxylase.

If glutamate decarboxylase were to be disabled by such autoimmune attack, you would expect higher levels of glutamate in the brain, and you might expect some people to feel anxiety, since high glutamate in brain areas like the amygdala have been linked to anxiety in animal studies.



When I first caught the coxsackievirus B4 which later caused my ME/CFS, I soon developed moderate-to-severe generalized anxiety disorder, as well as other mental symptoms, and it was clear that the physical effects of this virus on my brain was responsible.

And a few friends who caught the same Coxsackie virus from me also developed pretty severe anxiety. One person for example was hit with anxiety so bad that she locked herself in her apartment for 6 months, and never saw a single person, except for her daughter, because of the intensity of anxiety.

Because of my experience with CVB4 triggering major anxiety in several people, I became interested in speculative theories of why this virus might trigger anxiety.

I think virally-triggered microglial activation and the glutamate it releases could be part of the picture. And possibly a virally-triggered autoimmune attack on glutamate decarboxylase might also play a role.



If coxsackievirus B can trigger autoantibodies which disable glutamate decarboxylase, then this could help explain the "wired" symptoms of ME/CFS, the anxiety disorder which is sometimes present in ME/CFS, and the central sensitization (CS) symptoms found in ME/CFS (like amplification of pain by central nervous system), since CS is linked to glutamate.

There are quite a few diseases which have glutamate decarboxylase autoantibodies, including type 1 diabetes (which is linked to coxsackievirus B4).
 
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If you are OK one day, and wake up worse the next, possibly the food you ate the evening before might have an effect, if the food promotes gut inflammation
I recently ate some delicious Thai food- take out....and got a couple of things which likely had sugar in the sauce..

WOW did I blow up with inflammatory symptoms from that it seemed.
 
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@judyinthesky
It seems to me as Xanax helps me, that there is something like this going on.
I'm not sure what you mean by " ..... something like this going on ....", so not sure how applicable my answer will be, but the bottom line is that if you've been taking Xanax for a while, you may be dealing with tolerance withdrawal. This happens when your brain gets used to the current dose and no longer reacts to it, requiring a higher dose to create the same effect.


This is a deadly spiral.

Xanax, and all other benzos, will almost immediately start down-regulating your GABA receptors, since they all provide the effects of GABA exogenously, which tells your system that it can start shutting down its own endogenous production, since it appears that it's no longer needed. This is what causes tolerance withdrawal to a large extent.
Are there any other potential treatments apart from opiates and Xanax/benzos?
We're all different, so what worked for someone else might or might not work for you.


Another poster (forgive me Other Poster, too tired to go back and find your name in order to give you proper credit .... EDIT: My moderate OCD forced me to do it, the poster's name is @Krokus ) mentioned magnesium, which is an NMDA antagonist, and blocks the binding of glutamate to the NMDA receptor. NMDA stands for N-methyl-D-aspartate, which is an amino acid derivative that's very similar to glutamate, and just as deadly when out of balance.

Both zinc and magnesium are potent antagonists of the NMDA receptor complex, but taking a lot of zinc is a very bad idea. Taking a lot of magnesium, however, isn't, since it's used in hundreds and hundreds of enzyme and other conversions in your body, and most people are deficient in it to one degree or another.

I had very good luck with magnesium glycinate, which, being bound to a large molecule (glycine), doesnt cause the bowel effect that other forms do, and believe me, I tried almost all of them. I found that large doses did nothing, and the recommended 'normal' doses of magnesium did a little less than nothing.

It wasnt until I started taking 50 mgs of mag glycinate at very tight intervals of 30 - 60 minutes, adding about 250 to 500 mgs of Vit C every 2nd or 3rd dose, along with .25 mgs of melatonin, that I started to get some calming effect. This isnt a quick fix. It took about 3 to 4 weeks before I was sure it was actually reducing the panic/anxiety episodes, and after that the benefits just kept increasing. It was a total miracle.

Also, would antidepressants help that in any way?
No, altho doctors will prescribe them on the theory that if they just throw enough stuff at the wall, something's bound to stick.


And anti-d's can also potentially create a whole new set of problems for you to deal with, and in all likelihood will make you even more miserable than you are now. I'd avoid them, but that's just me. You need to do what you need to do.
 
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Do you have source for this GABA excitation? I always thought GABA was an excitatory inhibitor ...
No. GABA is the neurotransmitter connected with calm and balance, It's the polar opposite of excitatory.

Glutamate is the excitatory neurotrans, and if the balance between GABA and glutamate gets out of whack, it's a really devastating Toad's Wild Ride.
 
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Try magnesium and taurine.
Taurine was little to no help for me, but we're all different .......
Glutamate also inhibits Melatonin production so you may benefit from this one.
I threw that into the mix, too, and I believe it was helpful ....
L-Theanine is an NMDA-specific coactivator, which would be counterproductive in the presence of glutamate-mediated excitotoxicity (10.1021 / acschemneuro.7b00036).
Totally !!!! Any form of theanine was a disaster for me, increasing suicidal ideation and deepening the depression and anxiety til I wanted to just peel my skin off. It was horrible. But we all react differently, so ....
 

Boba

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There have been a lot of anecdotal reports of long COVID patients getting substantially better after the coronavirus vaccine, but no studies as far as I am aware. Other long COVID patients have found the vaccine did nothing much for them, however.

You can Google search for more info.


Bear in mind that long COVID includes not only ME/CFS, but also coronavirus patients with heart and lung damage after COVID, who display ME/CFS-like symptoms.

And long COVID also includes those with an ongoing acute infection which never cleared up (which is different to the ME/CFS post COVID). I have not looked into which of these subtypes has benefitted from the vaccine, but if you find any info on it, I'd be interested.
@Hip
Thanks for your reply. I was asking because I hoped that you knew sth I wasn’t aware of. As you mentioned long covid is more than cfs, including all sorts of organic damage, viral persistence etc. I‘m a little desperate for a quick fix and was curious about the vaccine maybe helping with my symptoms. It’s just a big mess what Covid did to me. Sorry if my question sounded rude.

@judyinthesky thanks for your reply!
 

nerd

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A while back I found an interesting paper which mentions the possibility coxsackievirus B4 and other Coxsackie B viruses might induce autoantibodies that disable glutamate decarboxylase (more specifically, the GAD65 form of this enzyme).
Thanks for pointing this out. I wasn't aware of this possibility.

So there are viruses that can affect whether CFS/ME manifests as general excitotoxicity or as a glutamate-specific one, which probably is much more expressed because there wouldn't only be an oversupply of glutamate, but also the lack of GABAergic counterbalance.

Can anxiety be a specific indicator for glutamatergic excitotoxicity? Is there any other explanation for anxiety?
 

judyinthesky

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@nerd I think it depends on whether we even think of it as toxic. But lack a better word now.
To me what I have is like anxiety, but isn't like when I am anxious. Yet I exhibit many features then: sweaty hands/state, hot head.
Not sure. I know that classic CFS isn't like that unless very severe
 

Hip

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As you mentioned long covid is more than cfs, including all sorts of organic damage, viral persistence etc.
As I understand it, long COVID is thought may consist of 4 different illnesses, one of which is an ME/CFS-like condition. See this article. So it would be good to figure out what type of long COVID you have. There may also be some overlap between these 4 illnesses: for example, you may have ME/CFS-type long COVID, but also have some of the lung damage-type long COVID (which might go away if the lungs heal).
 
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@judyinthesky
the bigger mystery, why a fucking (excuse me) vaccine would bring this on so much.
Vaccines contain a wide variety of excipients, including notably:

  • Gelatin, which is composed of free-form amino acids (including excitatory ones like aspartate and glutamic acid which converts to either GABA or glutamate) and which once unlinked from their companions can cause all kinds of difficulties, particularly if you're susceptible ....
  • "....various amino acids..." (glutamate is derived from an amino acid)
  • Poly-Y-Glutamic acid
  • Poly-Gamma-Glutamic Acid
  • Vaccine stabilizers utilizing L-glutamic acid
  • Y-d-glutamic acids
  • Glycine (also potentially excitatory when unbound)
  • Monosodium salts of glutamic acid (commonly known as MSG, a MAJOR excitatory)
  • MSG (as a stabilizer)
  • There's more, but I'm too tired to look them up.
MSG, or monosodium glutamate, a hotly contested (mostly by drug companies and producers of fast foods, convenience foods, diet foods, reduced sodium foods, and pretty much any packaged or canned or frozen food you can find, who all make a nifty living off of MSG, which is a cheap and reliable flavor enhancer, or umami mimic, and therefore don't want to see it go way, and produce reams of purported disclaimers about MSG's toxicity) excitatory predator, is commonly used in just about ALL vaccines as, among other things, a stabilizer.

I've often wondered if the higher-than-average incidences of glutamate sensitivity, anxiety, depression and panic attacks in the ME community isn't connected to this, since from birth, we're all assaultd with armies of vaccinations and booster shots.

I know that this post is going to draw fire, so I'll state right now that the facts speak for themselves, which is fortunate, since I dont intend to ....

EDIT .... for crappy grammar ...
 
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Boba

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I‘m pretty sure I have the me/cfs type. I had mild covid for 5 days and 10 days later the fatigue (molasses fatigue) hit me. Since then I crashed several times not knowing what was going on with me. My organs were checked, all tests came back fine. :(
 
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Please consider that elevated glutamate will always reflect in elevated GABA eventually because glutamate is converted to GABA by glutamate decarboxylase.
Only over a painfully extended period of time, and in the absence of other sensitizers, like anti-d's and anti-anxiety drugs, among others.


Chronic, sometimes genetic, glutamate dysregulation will not self-correct, unlike normal transitory glutamate dominance ....
Only the short-term peaks, which can be triggered by exertion, would cause a dysbalance in the glutamate-GABA system.
This is apparently only true in a narrow, limited population. The serious GABA/glutamate imbalance that I fought through for nearly 3 years would beg to disagree, as would the numerous posters in these thread enduring the more commonly imposed variety, precipitated by a broad range of prescription medications, not limited to benzos.
 
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