Potential linking FM, mast cells, sleep deprivation, food intolerance, exercise intolerance and ME?

Issie

Well-Known Member
I did not read all of this but with the sleep depreviation issue, could be a MAJOR factor...I don't deal with ME but other stuff and since using the HGH homeopahtic gel now 2 yrs soon I sleep 8-10 hrs of good restorative REM healing sleep nightly....I've posted about this and if only a member or more would get on the HGH and see if they do improve.....if only, but no one does.
I did do this back in my earlier days. We used a homeopathic one, as my insurance wouldn't approve injections. And the risk is high for diabetes with HGH. even homeopathic formulations warn if there is insulin resistance or having high blood sugar, you have to keep a watch on it, even with its dilutions. Back then, I did feel it helped some, but evidently not enough for me to stick with it.

Glad it works for you. It was found back then I needed HGH. Not sure where my levels are now. Thanks for reminder about it.
 

jaminhealth

Well-Known Member
The product I use is rather new on the market, and about 20 yrs ago an integrative MD wanted to give me "injections" and I did NOT want to go there....not only the cost but just didn't feel good about the heavy duty injections;....this HGH homeopathic gel, rubbed into my skin, is pretty new and my daughter is using it 2.5 yrs and me 2 yrs soon....

As we age, everyone's HGH levels drop.
 

Perfson

New Member
I read all your posts, but didnt study this stuff completely, basically i barely know anything about byochemistry, but i may ask you some questions. If you think that i misunderstood your information, tell me.
1. As we know from this article, some patients had dorsal root ganglion inflammation. I want to know your thoughts if it's possible that they also had "glutamate excitotoxicity", but maybe not because of excessive amount of glutamate, but because their nerves were very sensitive to glutamate, due to inflammation?
2. And do you think it's possible that ME/CFS/Fibro is simply autoimmune reaction to something like GAD? But i also heard stories that people cured CFS-like illness after treating ear infection, and probably because immune system calmed down after that.
3. Also this one poor study shows that GABA supplementation + l-arginine can help GABA cross BBB. Any thoughs on it? This might be interesting, but l-arginin increases nitric oxide levels, and some people think that NO might play huge role in ME/CFS, as i understand, because of oxidative stress. Yet as i undersand, NO can help things like GABA cross BBB?
 

dejurgen

Well-Known Member
I've posted about this and if only a member or more would get on the HGH and see if they do improve.....if only, but no one does.

I can see your dissapointment here. I didn't tried it yet as I have a cabinet full of products (next to plenty other health changes) to test. With a slow rate of testing roughly one change a month to see a clear deviation from baseline, it takes some time...

That, going with lowest cost options first and availability in Europe make testing it being at the end of the queue for me. But I can see it has some potential... Thanks for sharing and maybe one day I get to that point in the queue. Or better, my health could be good enough to need no more changes before reaching that point. One can always dream big :).
 

jaminhealth

Well-Known Member
I'm not disappointed, maybe that you people are not benefitting with the HGH homeopathic for your health issues.
 

dejurgen

Well-Known Member
1. As we know from this article, some patients had dorsal root ganglion inflammation. I want to know your thoughts if it's possible that they also had "glutamate excitotoxicity", but maybe not because of excessive amount of glutamate, but because their nerves were very sensitive to glutamate, due to inflammation?

Hi Perfson,

This question comes timely as I just wrote something about the "spinal cord escalator" idea in https://www.healthrising.org/blog/2021/02/05/attention-deficit-fibromyalgia-rheumatoid-arthritis/ and a while ago in https://www.healthrising.org/blog/2020/12/11/nucynta-opioid-small-fiber-neuropathy-fibromyalgia/.

I am sure no expert on the dorsal root ganglion, but I do tend to believe that more easily excitable / inflammable spinal cord neurons might make it easier for getting trapped in an ME/FM/... like vicious circle. In this idea, it would be but one of many components making a person more vulnerable to get trapped in ME/FM/... when being hit by things like infection, long term overexertion... where less vulnerable people may escape getting trapped in these diseasses.

Neuron signal transmission is not only dependent on extracellular glutamate content. It is also dependent on the amount of receptors, calcium (channel) signalling and plenty of other intermediate steps. Anything affecting that can tip the scale or balance. That IMO includes excessive ROS as discussed in the second link. Excessive ROS sure can be produced by inflammation.

So: yes, inflammation might IMO sway that balance too. Actualy, both excessive glutamate, excessive ROS and inflammation IMO will often go hand in hand near neurons.
 

dejurgen

Well-Known Member
2. And do you think it's possible that ME/CFS/Fibro is simply autoimmune reaction to something like GAD? But i also heard stories that people cured CFS-like illness after treating ear infection, and probably because immune system calmed down after that.

*Simply* a(n autoimmune) reaction to something like GAD, as in this is the case with all ME/CFS/FM patients? No. I highly doubt that.

But do people with (different sorts of) GAD problems are more prone to ME/FM/...? I sure think so. But I believe that plenty of other vulnerabilities can result in ME/FM/... too. Actually, I believe plenty and plenty of people with ME/FM/... have multiple (?often many?) (epi)genetic challenges rather then a single one. The more epigenetic challenges, the higher to get stuck with ME/FM/... after a strong event like a bad infection I'd say.
 

dejurgen

Well-Known Member
3. Also this one poor study shows that GABA supplementation + l-arginine can help GABA cross BBB. Any thoughs on it? This might be interesting, but l-arginin increases nitric oxide levels, and some people think that NO might play huge role in ME/CFS, as i understand, because of oxidative stress. Yet as i undersand, NO can help things like GABA cross BBB?

From the abstract (can't easily access the full paper) of the paper: "Dose-dependent increase in nitric oxide production was observed 10 min after i.p injections of L-Arg (400, 800, 1000, and 2000 mg/kg b. wt.) "

I know rats have a different metabolism then people. But just let me calculate the lowest dose, 400 mg/kg b. wt. to the dose for a 70 kg human: 28 grams of pure L-Arg *injected* as a single dose into the veins. So 100% uptake and all in a matter of seconds. That's insane!!! The bigger dose, 140 grams (recalculated to human weight) of pure L-Arg *injected* as a single dose into the veins? I can only wonder that any of the rats survived. That must be sturdy creatures!

Blood volume of a healthy human adult IMO is about 5% of body weight, or 3.5 liter or 3.5 kg in this case. Administring 2000 mg/kg b. wt. would creat a sudden jump of near non to 4% of blood weight being pure L-arg! even at the lowest dose it would be 0.8%! That's beyond insane.

That would crowbar the urea cycle (key in removing ammonia waste from protein use), blood vessel dillation (might sound good to some, but again crowbaring it in one extreme), crowbar the iNOS part of the immune system and creates massive nitrosative stress and crowbar much of all amino acid metabolism in a single go. I wonder what valid conclusions can be drawn from such studies? I don't know how much different this would be from studying the effect of humans drinking 10 liter of water a day in order to fight constipation. It sure would do something, but valid conclusions???

BTW: from the abstract I did not find what such absurd overload with L-arg does to glutamate levels. If both glutamate and GABA levels in the brain would rise equally much, you likely would be quite a bit worse off. The balance between both is key here.

That said, I am not keen to "just" mess with key parts of the urea cycle unless knowing very well what one does and why it is appropriate for ones particular case. The urea cycle is just to important. Mess it up and you can easily disrupt ammonia and glutamate balance. Both affect NMDA excitability. Other nasty side effects of disrupting the urea cycle could happen too.
 

Issie

Well-Known Member
"2. And do you think it's possible that ME/CFS/Fibro is simply autoimmune reaction to something like GAD? But i also heard stories that people cured CFS-like illness after treating ear infection, and probably because immune system calmed down after that."

I had my GAD antibodies checked. (I was okay.) It is part of a good workup for POTS that is done. Some people are found with issues here. But not all POTS people have this autoimmune response with it. But as Dejurgen mentioned, it does appear that some of us do have issues with balance of glutamate. It is an excitatory thing and can trigger sympathetic nervous system response, along with other not so good or desired things. Sort of a hyper feel. (But, to note **** HyperPOTS people seem to have way too much norepinephrine when we stand. And that too gives that feeling of being hyped. And also increases heart rate and contributes to the "tachycardia " part of this syndrome.)

But we do need glutamate. It helps with our brain function and other things necessary for our bodies to function. The key is balance or homeostasis. Some have too much and the balance between glutamate and GABA is thrown off. But GABA is an inhibitory response and too much of it could make one more tired.

Having had ME and a whole lot of other things connected to it, that seem to go hand in hand......its hard for me to even imagine someone would have true ME/CFS and be cured by curing an ear ache. There is fatigue and then there is FATIGUE along with it soooooooo much more than just being tired. ME/CFS is wayyyyyyy more than "just" tiredness.
 

Perfson

New Member
Thank you very much for answers.
I was trying many things to cure my ME (or at least make it easier), and nothing helped short term. I want to share my little success with you, i was moderate and became mild after 6 months. Maybe because i almost instantly learned about Pacing. About drugs - i tried all vitamins and stuff, 1 by 1 testing, nothing helped (didn't try high dose b1 tho, only mid dose), but i was also taking naltrexone. I think it could have helped with brain fog only, but it can be coinsidence. My illness onset was very graduate and improvement as well. Though, i think the most helpful thing for me was Abilify, that i started trying 3 weeks ago. I think i improvent significantly just in 3 weeks. But not all symptoms improved, only how easy to reach PEM and my overall energy capacity. That's probably most important. My sleep, shortness of breath, chest pain, heart palpitations didn't improve at all, but i recently found that im also having acid reflux, and it few weeks ago it became worse, so who knows what symptoms are coming from this.
Why do you think abilify help people with ME/CFS? How is it related to your theory?
I heard it helps to balance out dopamine, but why is that even important in ME/CFS? Because i expected it to improve my sleep more, but it probably improved PEM only.
 

dejurgen

Well-Known Member
I want to share my little success with you, i was moderate and became mild after 6 months. Maybe because i almost instantly learned about Pacing.

Like so many I will say: wish I had learned this as quickly as you. I'm very happy you did. It is IMO vital to have any decent change to get better quick enough.

Why do you think abilify help people with ME/CFS? How is it related to your theory?

From the Wikpedia page of Ablify (under its chemical name) https://en.wikipedia.org/wiki/Aripiprazole

Ablify changes dopamine and seratonin behavior, and also a bit histamine behavior in our body. All three strongly are involved in digestion.

"Dopamine is found in blood plasma at levels comparable to those of epinephrine, but in humans, over 95% of the dopamine in the plasma is in the form of dopamine sulfate... ...The bulk of this dopamine sulfate is produced in the mesentery that surrounds parts of the digestive system."

Also, from https://en.wikipedia.org/wiki/Dopamine
"acts as a vasodilator (at normal concentrations)" (dopamine, that is)

"
Serotonin regulates gastrointestinal function. The gut is surrounded by enterochromaffin cells, which release serotonin in response to food in the lumen. This makes the gut contract around the food. Platelets in the veins draining the gut collect excess serotonin. There are often serotonin abnormalities in gastrointestinal disorders such as constipation and irritable bowel syndrome.[27]

If irritants are present in the food, the enterochromaffin cells release more serotonin to make the gut move faster, i.e., to cause diarrhea, so the gut is emptied of the noxious substance."

=>Outside the brain, dopamine and seratonin play a dominant role in the gut and digestion.

So if you had at worst by chance clear gut problems, a drug that *somehow* provided more optimal levels of dopamine and seratonin and more optimal triggering of dopamine and seratonin receptors, your digestive tract could operate significantly better. The combo digestive issues and immune activation against food in the gut can play a big to very big role in ME/FM/... as I experienced myself. If the gut operates better, less (excessive) immune activation in the gut *might* follow. That in turn might help recovery.

From https://en.wikipedia.org/wiki/Dopamine
"it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes. "

=> This hides the following: just increasing dopamine levels blindly is no solution: too much decreased gastrointestal motility will become a side effect, just as well as too strongly reduced lymphocyte activity. Balance is key.

From https://en.wikipedia.org/wiki/Dopamine#Cellular_effects
"For receptors located on neurons in the nervous system, the ultimate effect of D1-like activation (D1 and D5) can be excitation (via opening of sodium channels) or inhibition (via opening of potassium channels); the ultimate effect of D2-like activation (D2, D3, and D4) is usually inhibition of the target neuron.[29] Consequently, it is incorrect to describe dopamine itself as either excitatory or inhibitory "

=> Again, a good balance is needed rather then just upping or decreasing it. OR, triggering the right receptors (STILL at the right doses).

From https://en.wikipedia.org/wiki/Aripiprazole

"It shows differential engagement at the dopamine receptor (D2[46]). It appears to show predominantly antagonist activity on postsynaptic D2 receptors and partial agonist activity on presynaptic D2 receptors,[54] D3,[46][55][56] and partially D4[46][51])"

=> It *seems* that that when combining the above, Ablify has mainly properties of binding to receptors inhibiting target neurons, aka calming them or reducing their firing rate. That in turn *could* allow the neurons to better rest and recover.

The cases https://en.wikipedia.org/wiki/Aripiprazole is used for
"Aripiprazole, sold under the brand name Abilify among others, is an atypical antipsychotic.[5] It is primarily used in the treatment of schizophrenia and bipolar disorder.[5] Other uses include as an add-on treatment in major depressive disorder, tic disorders and irritability associated with autism. "
*seem* IMO to point to reducing "stray processes" and "errant activation" of brain neurons a bit too.

The info from https://en.wikipedia.org/wiki/Aripiprazole#Overdose
"Overdose
Children or adults who ingested acute overdoses have usually manifested central nervous system depression ranging from mild sedation to coma"
Also seems to indicate that Ablify can calm (/ dangerously overcalm in case of overdosis) neurons.

As often researchers say that ME/... brains seem to "light up all over the place" when putting patients under the scanner and asking them to do any activity, it might help them focus and hence become better and more efficient at what they do, wasting less energy again leading to more rest of exhausted neurons.

Note: modifying dopamine / seratonin (/ (nor-)adrenaline / ...) levels by medications is a tricky process that can IMO yield wildly varying results ranging from good to disaster depending on the exact patient and doses taken. For that reason, I try and stay away from such broad acting drugs so long there isn't any more clinical research on what it can do for us. The reason for that is simple: as long as I can have a slow but steady improvement by other (less tricky) things I try and do, I do not wish to risk the chance for a bad backfiring putting me back in ME hell. Even more then improving, I DON'T want to go back to the utter hell of severe ME!!!
 
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Perfson

New Member
I was thinking if lorazepam work well for glutamate/gaba balance? Which seems to make your nervous system to feel better temporarily. It's the drug Whitney Dafoe was using, and it helped him to feel better (with nervous system), but you can get addicted to it quite easy.

Any new thoughts/findings on drugs that can help with excitotoxicity?
My biggest problem atm is my nervous system, always active, im always restless. My guess that restlessness is a symptom of excitotoxicity.
Some people suggest NAC for that, maybe you know why it may help people.
 

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