Pots & Excitotoxicity

[POTLUCK]

http://bpainfreetherapy.hubpages.com/hub/POTS-and-Excitotoxicity

My computer does not seem to be working well tonight. Anyway, a friend sent me this link they came across. Not sure what to make of it. Thought it was interesting.....

To paste the first few lines....

Excitotoxicity in the pathogenesis of POTS, Fibromyalgia, Chronic Fatigue Syndrome, and other disorders. Excitotoxicity is a cause of nerve damage that occurs when neurons become overly excited, begin to malfunction, and sometimes commit cellular suicide.

[POTLUCK]

I found this article...

http://www.webmd.com/fibromyalgia/news/20050523/cough-drug-may-help-fibromyalgia-pain

Also read it can cause histamine release and I know there are people on this site with mast cell issues etc. who would not want to try this.

[looneymom]

Good articles. The last one really caught my attention because there is only one prescription cough syrup that I can use with my son. If my son has a really bad cough that's croupy, it puts him to sleep. It's not covered by insurance but worth every penny when he's that sick. I know this cough syrup has that ingredient with another combination because I always have to show my drivers license to purchase.

In the first article, I notice a combination of unisome and clonidine. Has anyone tried this combination? If it relieves pain and sleep issues, be sure to post.

[POTLUCK]

I found some more links.

An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.

http://www.ncbi.nlm.nih.gov/pubmed/22401777

They are saying it may have a similar rapid acting action to Ketamine for depression. Ketamine has been quoted to be one of the Top 10 developments in psychiatry for the coming decade by at least one source. ( Ketamine is by the way an old horse tranquilizer with hallucinogenic effects which was abused by some in the past- do not know if it still is. ) I tossed in a link on Ketamine and depression here...

http://www.ncbi.nlm.nih.gov/pubmed/23214398

Dextromethoraphan and Fibromyalgia pain.

http://www.sciencedaily.com/releases/2005/05/050519141247.htm

Dextromethoraphan and Pseudobulbar affect

http://www.sciencedaily.com/releases/2010/04/100413151909.htm

Could not find a lot on Dextromethoraphan and POTS. There is a lot on NMDA/Excitotoxicity.

Found this link from Rama HERE ON DINET while searching, but the post does not go through anymore, maybe Rama still has the article.

http://forums.dinet.org/index.php?/topic/15292-nmda-antagonists-in-cfs-and-fibro/

[issie]

Potluck,

Tramadol has the same properties. Works on serotonin, dopamine and NMDA antagonist - and works on opiate receptors (but is not an opiate) - used off label for those that SSRI's and SNRI's not effective for. I've been questioning the possibility of high glutamate levels vs. Gaba balance for awhile now. There are also some with ME/CFS questioning this balance. There could also be a connection with mutations in COMT and/or BHMT pathways that could play a part in this. If there is a BHMT pathway problem - it is suggested to use methyl B12 and Yucca to help stop build up of ammonia from protein.

Just a side note - if there is a BHMT problem and a mito issue - that could be a big problem because some of the aminos used to help with a mito problem could increase the dysfunction of the BHMT pathways. A problem with this could mimic a problem with COMT.

Interesting articles - thanks for posting.

Issie

[looneymom]

My son has tried Tramadol but it makes his vocal tic worse. It didn't help with his headache either. He has been checked for mito and it was negative. The cough syrup, he's only had to use it when he caught the second round of flu.

Thanks for posting the other articles Potluck. I will check them out.

Issie, Could the mutations be found in genetic testing? What doctor checks for this?

[issie]

The testing that I did was with 23&me. It takes a whole lot of research, testing, reading and learning to figure it all out. Once you get your genetic testing you download your info into Genetic Genie and that sorts out your methylation pathways and that figures out for you if you have any mutations. Then you have to sort out what to do about the mutations. There is a certain order that you address the mutations to get the pathways to working properly. There are a couple of doctors that are working with this "theory" and getting good results. I think this is one thing that is really helping me - in addition to my vegan - low fat diet and the protocol that I'm using for the protozoa and Lyme co-infections that I have.

Issie

[Guest Alex]

Here is the abstract of the article Rama posted a while back (or so I think) for some reason the original link is not working anymore

NMDA Antagonists, CFS/ME and Fibromyalgia

NMDA receptor overactivity may be an important part of the pathology of CFS/ME and fibromyalgia. Several studies have found NMDA antagonists an effective treatment, supporting this theory. There are many NMDA antagonists with different properties, so if one drug does not feel right, another one could be tried.
NMDA receptor antagonists are usually well-tolerated. Side effects vary depending on the drug, but tiredness, dizziness, headaches and problems concentrating tend to be the most common ones. Memantine and dextromethorphan also have several possible drug interactions.
The Medications
The cough suppressant dextromethorphan has shown efficacy in fibromyalgia treatment. Many studies have found intravenous ketamine, another NMDA antagonist, highly effective, but as this is an expensive therapy and ketamine is also a drug of abuse, it has mostly been used for research purposes.
Amantadine is a drug used to treat influenza and Parkinson's disease. It is also a common choice to combat fatigue caused by neurological illnesses like CFS/ME and multiple sclerosis. It increases the brain levels of dopamine and blocks the NMDA receptor. Unfortunately many people who are sensitive to medications tolerate amantadine poorly.
Other choices are riluzole (Rilutek), used for ALS, and memantine (Namenda), used for Alzheimer's disease. Riluzole, however, is highly expensive and memantine is also somewhat costly. Amantadine and dextromethorphan are very inexpensive, but may not be as well tolerated.
Several other drugs also block the NMDA receptor. They include muscle relaxants dantrolene and orphenadrine, opiates methadone and (dextro)propoxyphene, many anticonvulsants and progesterone. Guaifenesin, a mucolytic drug used experimentally as a fibromyalgia therapy, may be an NMDA antagonist.
Calcium channel blockers, a class of heart medications used in the treatment of CFS/ME, also have NMDA antagonistic activity. So does magnesium, which has been used to treat CFS/ME and fibromyalgia as a supplement and as intramuscular injections.
Medications that increase the neurotransmitter GABA decrease NMDA activity. This includes many anticonvulsants and most tranquilizers, including the benzodiazepines, the "Z drugs" (zolpidem, zopiclone/eszopiclone and zaleplone), L-theanine and valerian root. It may explain why small doses of benzodiazepines offer major relief for some people with CFS/ME/FM.

References
Sarchielli P, Di Filippo M, Nardi K, et al. Sensitization, glutamate, and the link between migraine and fibromyalgia. Curr Pain Headache Rep. 2007 Oct;11(5):343-51.
Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology. 1997;35(1):16-23.
Cohen SP, Verdolin MH, Chang AS, et al. The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients. J Pain. 2006 Jun;7(6):391-8.

[Freaked]

Interesting article, but I don't necessarily buy the diet thing. It doesn't really explain why pots etc comes on people after flus or other physical ordeals, and I for one rarely went near sugary drinks or anything artificial, for all the good it did me. Hated them as a kid.

I do know that the last time I accidentally ate msg (in fried rice) I had a terrifying episode where my heart beat so hard I was scared it might 'tear'. Didn't even think that was possible until now :-/ Could have been a coincidence, and I never had msg intolerance before my pots symps, but terrified of it now.

[issie]

The "diet" addresses your immune system. I personally think - it's THE most important thing anyone can do. If we address what we can and change those things that may be causing problems ---then what's left over ---maybe doctors will be able to help us with. But, addressing the immune system ---may be the key to better quality of life. I think inflammation runs a close second.

Issie

[POTLUCK]

Issie- I read somewhere that the 23 & me thing is $100. That seems cheap. Is that the total cost for all the necessary tests. Does it cover those 2 genes involved with the Methylfolate pathways that I have read about a lot of people having defects in. ( This is becoming bigger in the mainstream literature as a cause for several illnesses. Something to do with the ability of the body to convert folate to Methylfolate, and if you have the homozygous mutation they recommend high dose Methylfolate. ) What are BHMT pathways?

Alex74Alex- This is A LOT of information to digest. I will have to look into it more. Thank you!

Freaked- I developed DM at the same time as my POTs so suspect a relation in my case. MSG definitely makes me worse and I try to avoid it, but I never had a problem with it before my POTS. These things are hard to figure out, even with a medical background in my case.

Issie- re: diet-Freaked, I believe is referring to the "diet thing" meaning whether the refined sugars and insulin are causing the excitotoxicity. I do not know if this is the case. It is the theory of the author. I suspect sugars and insulin have something to do with this in my case, because the effect of the running and eating carbs before I run may be lowering insulin resistance. ( But it may be resetting receptors to Epi, NE or something else-who knows-just seems to relate. )

Thank you for all the feedback everyone!

[issie]

Potluck,

Yes, it covers that and other things. Then you have to figure out what to do in regards to it.

If I mis-understood the reference on the "diet" ---sorry, about that. As I do feel it is probably one of the most important things we can do for ourselves.

Issie

[kitt]

Potluck,

Yes, it covers that and other things. Then you have to figure out what to do in regards to it.

If I mis-understood the reference on the "diet thing" ---sorry, about that. As I do feel it is probably one of the most important things we can do for ourselves.

Issie

Issie, I agree.

'The diet thing' is one of the most powerful things any of us can do for ourselves. Much of illness is outside our control, but diet is something that we can control.

It takes determination, dedication, and education, but it's worth it.

Diet, meditation, and moving your body as much as you can goes a long way in helping dysautonomia and most illnesses.

Best,

K

[Dizzysillyak]

Dextromethorphan has been shown to block the action of chemicals that relay pain to the spinal cord. It works by blocking a receptor known as N-methyl-D-aspartate or NMDA, which responds to these pain-transmitting chemicals. For this reason, Staud and colleagues evaluated the drug for pain control in fibromyalgia.

Thanks for the info. I'm going to try dextromethorphan even tho I'm no longer experiencing Fibro pain since I avoid the foods that cause it for me. FWIW tho, taking mast cell meds appear to allow me to eat tomatoes without experiencing fibro pain. I'd have to come off the meds and eat tomatoes to know for sure and I'm not going to do that because they're helping my allergies so much.

I can relate to the excitotoxicity theory and am curious as to how it may relate to my POTS. Gluten and stimulants (coffee and chocolate) are two of my known excitotoxins. I overproduce gluten antibodies (dx via stool test) tho so this keeps my immune system in high gear. I don't feel wound up if I avoid gluten and other stimulants like caffeine.

I'm looking for a way to stop my body's reaction (adrenaline rush ?) to hypoglycemia too tho. I've tried the dietary route and found success in relieving many of my "CFS" symptoms, like ataxia, brain zaps, brain fog, etc but not hypoglycemia from hyperinsulinemia. I over produce insulin so my problem may be purely physical.

The Atkins or Ketogenic diet didn't work for me because I have petite mal seizures and need sugar to stop these. I don't appear to have the chemicals (glycogen ?) necessary to keep my glucose levels up when active and have to rest and eat something sweet every 20 minutes. Resting is just as important as eating something because I need to replenish my blood glucose and can't if I'm constantly using it.

It will be interesting to see if dextromethorphan will stop this reaction. I have the feeling that my OI is from physical problems (LBBB, lung scarring, brain damage, etc ) and not excitotoxins since I've eliminated all the ones within my control. Still I want to see if it helps my reaction to hypoglycemia. TX ... D

[issie]

http://snpedia.com/index.php/Yasko_Methylation

This is a list of the different things used in Methylation pathways and what each thing could potentially cause if there is a mutation or dysfunction in this pathway. This doctor is doing most of the work in regards to this. She and another doctor are trying to help people figure out and learn what to do if there are mutations found in this pathway. (There is a lot of controversy about this. Some don't believe it and others swear by it.) 23&me does not test all these genes - but, it test enough that you can figure out where your issues are and then with a lot of study figure out how to address this. There is a certain order that you address it in and there is a diet change and supplements are added to get these pathways to flowing properly. Lots of info on the net about this.

If you click on the links under each snp you will see what it means and what to do if you have mutations with each of these things. Most of the sites that you'd want to visit and read are listed in this article.

I noticed the gene that is complete opposite to COMT is VDR - from looking at this. I need to do some more searching myself. I'm still trying to learn all this and it is very deep and can be confusing. (VDR has to do with metabolizing Vit D and blood sugar regulation.)

Issie

[issie]

http://www.dramyyasko.com/resources/autism-pathways-to-recovery/chapter-6/

This one will be a bit overwhelming. But, once you have your mutations, you can start to figure out what to do about them. This is some of the info you can use to determine what is what and what it all means and how it presents.

She started out working with autistic children and now lots of other people are on-board with this and finding that it is helping things like ME/CFS and some with POTS are finding good results with it. I have been slowly addressing my mutations and for what I've done so-far, I think it is making a difference for me. There are others that are also doing this - here on the forum. Maybe, they will chime in with their experience with what they've discovered so far.

Hope this info will help.

Issie

[looneymom]

Issie

Is there another charge to go online and view your test results or is this all included with the price of the test? I'm also wondering how much this test is accepted by medical doctors. Did you find a doctor that accepted this test and is working with you or have you had to go at it alone. I am really thinking about ordering this test for my son if nothing shows up on the Autoimmune Dysautonomia Evaluation test. This really seems like a valid test. Just trying to do some research. Do you know if its approved by the FDA? Sorry I'm asking so many questions. I did go to the main website and looked around. Do you get a copy of the lab results? I am glad that all information is confidential. Just trying to figure out what to do next.

[issie]

They will store your results for a year or more depending on what you choose when you do your testing. It is confidential, unless you choose to allow someone else to have access to your info. They will also keep your DNA and test it when new things become available.

I have one doctor that is sort of familiar with this. But, mostly it's us trying to sort it out on our own. But, the doctor that I referenced above and several other doctors whom you can find access to on the net are trying to explain this and help others to sort it out. I think this is something that is not mainstream and pretty new. That's why it is controversial. As for genetic testing - this lab is pretty well known and is referred to a good bit when you read anything related to genetics. You find much more out then just the methylation snps. You may find out things that could be upsetting to you to know that genetically you are pre-disposed to certain other illnesses. But, just because you have the genes for this - doesn't mean that you will actually "get or have" the problem. It's all whether or not something triggers it to "turn on" and then there is the problem. Some things you may be a carrier for and can pass this gene along - but you yourself won't get it. It is very complex and deep. It takes an awful lot of research, digging, reading to understand it all. And even more to try to figure out how to apply it. There are some people that you can hire to help you sort out the information.

There is no charge for accessing your info on-line. It is a lot of information that you can download into your computer. But, there is a lot of raw data that will not make sense to you - but, will to someone who understands it. Some of it is broken out and that you will understand. Certain things that are looked for specifically and you will know where you fall as your odds of having that problem. There are two sites that most of us have downloaded our raw data into ---one is Genetic Genie to get our methylation mutations the other is Promethease. That has given me lots of information about myself. There are markers that can indicate if a person has EDS. There are some that "might" indicate issues with MCAS. Markers that can tell about diabetes, heart disease, some other rare diseases, even possible neurological illnesses.

I try to warn that it is hard to understand and very complex. But, for me it was one of the most insightful tests I've done.

Issie

[looneymom]

Thanks Issie for the information. This was very helpful. I think this is probably the next step for my son.

[davecom]

I think the diet side of her theory makes a ton of sense. We already know that untreated diabetes is a precursor for nerve damage leading to small fiber neuropathy...

[Suthrngal]

When my POTS symptoms started (6.5 years ago) I suddenly developed a severe mSG allergy. My neurotransmitter tests show very high glutamate and nutraeval shows high glutamic acid levels. Is there a POtS med that helps with this gabba/glutamate balance? (Exotoxicity). In laymans terms.

[Suthrngal]

Izzie, I was unable to find MCAD markers snps on 23and me. Can you please let me know the snp?

I remember reading on a mthfr site that some were trying DOAsin for MCAD but didn know the snp to search. I haven't heard if it has been helping those with MCAD.

[issie]

I was accepted into 23&me to be studied, with others, because of having MCAS. There are other forums that are talking about the different snps you can look for. There is a group on http://uk.groups.yahoo.com/group/theelephantproject/ that would be able to answer more questions for you on this. I sort of dropped research on this, at least for now.

As for POTS meds that help with Glutamate/GABA balance - there are things that help with this - but not everyone who has tried those things have the same response. One thing that works on NMDA receptors is Tramadol. But, there are some that this hasn't worked well for. I've wondered if people would show up with high levels of dopamine and also high levels of glutamate. It would make sense that this would be the case. I just heard of one person who did find that to be the case, on another forum.

Some are using methyldopa which will help to lower dopamine and that in turn should lower glutamate. Dopamine is a precursor to glutamate. http://forums.dinet.org/index.php?/topic/15376-methydopa-prescribed-today-any-info-on-vandy-trial/page-2 Here is a post talking about how methyldopa works. Note - that it would lower your blood pressure. It would not work on glutamate directly but indirectly by lowering dopamine. It should calm the sympathetic nervous system and would also lower NE. This is used mainly for those that are HyperPOTS with high NE levels. With recent research however, I feel that high NE levels may be compensatory and the bodies way of trying to correct an imbalance and trying to get blood to the heart and brain. It is trying to increase blood flow by increasing the heart rate in trying to get the blood to circulate and pump blood to where it's desperately needed ---the heart and brain. So, even though this is a horrible feeling and scary - it may be how the body is trying to correct a dysfunction.

There are so many theories out there right now and lots of possible answers that are floating around. I'm not sure that we have the complete answer - but, we have small pieces of the puzzle. We need to determine why the blood is having a hard time circulating and getting to where it needs to go and why does it pool in the lower extremities. Is it catecholamine imbalance or is that compensatory? Is it imbalances in neurotransmitters? Is there something wrong with the veins themselves - something causing problems with constriction (plaque, protozoa)? Faulty valves, or too sludgey blood? There's still so many unanswered questions.

Issie

[issie]

There is a lot of talk going on another forum about possible B1 deficiencies. I posted a thread awhile back on this as it seems to fit our symptoms. Some are titrating this up to see if it will make a difference. It would also moderate the balance between glutamate and GABA.

http://forums.dinet.org/index.php?/topic/22120-b-1-dysautonomia-autism-mito-miagraines-issues-with-wheatmilksugar-problems-with-glutamates-heavy-metals-epigenetics/?hl=thiamine#entry205796

Issie

[Suthrngal]

Thanks issie. I feel zingy currently. i streat clear of even natural forms of glutamate. and even still, Glutamate and glycine were high on neurotransmitter test and seretonin and epinepherine were low. Dopamine was fine. Thoughts on this. I find it interesting I never had an allergy and then a severe MSG allergy coincided with POTS symptoms. Right now I am only fighting muscles seizing up in neck and back (6 years) and a vibrating current that I can only imagine is an adrenaline issue. Although I feel this sitting worse than standing. So b1? I saw a post on a b1/b12 cream. Thoughts on that?

Issue, your meds that you discussed help which POTS symptoms?

My heart rate, dizziness etc is helps to a degree from sodium pills and fluids.