1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
ME/CFS: A disease at war with itself
We can all agree that ME/CFS is a nasty disease, particularly in its severe form, but there are abundant nasty diseases in the world. What is unique and particularly confounding about our disease is that so much controversy surrounds it, and not only surrounds it, but invades it too.
Discuss the article on the Forums.

Relationship between adrenal fatigue and glutamate release / NMDA hyperactivation

Discussion in 'Adrenal Dysfunction' started by hixxy, Feb 7, 2012.

  1. hixxy

    hixxy Woof woof

    Messages:
    724
    Likes:
    107
    Russell Island, Australia
    Hello,

    Just wondering if anyone has found any relationship between adrenal fatigue and glutamate release / NMDA receptor hyperactivation.

    I'm certain there's got to be some sort of link where either one exacerbates the other. I'm just not sure in which direction it flows!

    Maybe it's hypoglycemia from adrenal fatigue? Or something else? Does adrenal fatigue even exist!? So much controversy.

    Thanks,
    Troy Heron
  2. Graeme

    Graeme almost there...

    Messages:
    361
    Likes:
    224
    Montreal
    Hi Troy,

    I'm pretty sure the adrenals play a big part in controlling the excitotoxicity and energy problems associated with NMDA hyperactivity, and it may be possible this works in reverse too. It's my belief the adrenal medulla is more important in this regard, but I base this mostly on observations of my symptoms.

    Recently I used a homeopathic remedy (Adrenal Energy) that seemed to increase adrenal output/functioning for a short while and this improved all symptoms significantly, including excitotoxicity. Unfortunately the effect was transitory and left me feeling even more wiped out when I stopped taking it.

    My cortisol levels have always been in the normal range and I've never experienced any benefit at all from taking hydrocortisone.

    Vasodilation from magnesium, garlic, and even hot baths provoke a worsening of symptoms for me as I can't seem to counter this effect due to, I think, weakened adrenal medullas. Although another possibility could be low ADH (vasopressin).

    I've read the adrenal medulla is made up of nervous-like tissue. Here's a study that seems to indicate there are NMDA receptors on the adrenals, and in particular the medulla -at least that's what I think I read.

    Page 172

    books.google.ca/books?id=l25fw-jhJRIC&pg=PA172&lpg=PA172&dq=nmda+receptors+on+adrenal+medulla&source=bl&ots=TA3NbCxAFx&sig=IVREyBwDMnh6f_F1OCjXoaq896c&hl=en&sa=X&ei=FrAyT9z4FKfk0QHj1oD5Bw&ved=0CEAQ6AEwBA#v=onepage&q=nmda receptors on adrenal medulla&f=false
  3. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    I'm one who is struggling pretty bad with this symptom too. I was doing well and had zero excitotoxicity symptoms when I was doing methylation and had my glutathione up. I was able to go on hour long hikes and they made me feel better, not worse. However, methylation caused me severe cognitive dysfuntion, so while I suffered no physical aspects of the illness anymore, I could not hold conversations with people. My brain speed was ridiculously slow.

    I went off all methylation supps, and it took 9 months or so, but I crashed physically. Then, I went to Las Vegas, and something in the environment did not agree with me. I started having severe tinnitus, and anxiety, basically severe excitotoxicity started. There are only 2 options for why this happend 1)mold, bacterial, or other neurotoxin got into my brain or 2) Heavy metals like aluminum got into my brain. In las vegas there is a TON of airplane trails that are known to release aluminum into the environment.

    This leads me to hypothesize that excitotoxicity is caused by neurotoxins OR heavy metals. We eventually have to get whatever is infecting our brains out of there. I am currently looking for a doctor that can help me figure this out. I am going to do a hair analysis test too.

    Glutathione levels going up helps a ton, however, catch 22 happens because once excitotoxicity gets bad enough the brain will not accept b12, and b12 will only worsen excitotoxicity. I once was able to handle b12, but now it makes my brain hurt.

    To answer your question about adrenals, yes they will help, cortisol is anti inflammatory and counteracts neurotoxins in the brain. I think this is why some of us experience restlessness and an atractiveness to stress, our bodies are craving stress in order to stimulate more cortisol.
    jeffrez likes this.
  4. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    Oh yeah, I am trying gabapentin and so far it seems to do absolutely nothing. I think the only reason I have seen a little bit of difference is because I am taking klonopin 1 time a week and I think it helps a bit. I don't want to do it daily until I have exhausted all other options though.

    I have memantine (namenda) to try as well.
  5. Graeme

    Graeme almost there...

    Messages:
    361
    Likes:
    224
    Montreal
    PokerPlayer,

    I too believe ET is often caused by the immune response to neurotoxins. I think the adrenals help control this reaction, limiting oxidative stress and NMDA receptor hyperactivity.
  6. ramakentesh

    ramakentesh Senior Member

    Messages:
    525
    Likes:
    81
    vasodilation worsens your symptoms because you have impaired vascular control, possibly one of many forms of endothelial disfunction present in POTS/NMH. I dont see how you can jump to the conclusion that it is caused by a speculative diagnosis like adrenal fatigue.

    Rather than looking down the adrenal fatigue road id be looking at the work of Julian Stewart on the abnormal circulatory and reflex controls found in POTS/CFS.
  7. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    The most frustrating thing is that I was doing pretty bad 2 years ago when I first had my big crash, but I did an hour of meditation a day for 2 months straight and took zinc every night and physically recovered A LOT. Then I found methylation supplements and physically did great.

    But now, I cannot even meditate at all without getting worsened excitotoxicity. I also can't take zinc without get severe excitotoxicity. The zinc thing really makes me think about metals and/or toxins in the brain, because I now know that metals attract toxins.

    So how do we get out of this? How do we figure out which exactly toxins are in our brain? We need a skilled practicioner to figure this out. I am looking all over seattle right now and am going to travel to a few doctors starting with jeff harris http://www.jeffharrisnd.com/, then maybe buscher http://www.drbuscher.com/, and then maybe a klinghardt doctor http://www.klinghardtacademy.com/Protocols/Klinghardt-Neurotoxin-Elimination-Protocol.html .
  8. Graeme

    Graeme almost there...

    Messages:
    361
    Likes:
    224
    Montreal

    And not just any old adrenal fatigue, but that of the medulla. Yeah I guess this could be considered speculative. However, I should have elaborated on what I meant by "worsening symptoms". I'm at the point in my illness where I sensitize to anything ingested, injected, insufflated, or absorbed after more than a day of exposure. From what I've read this is not a good sign. Recently I've noticed sensitization takes place with single exposures for a day or two following adrenal stressors. Vasodilation is one way this has happened, inadequate sleep proceeded by overdoing it is another. Caffeine, and homeopathics directed at the adrenals are others still.

    Here's another clue. When this problem first began it was in response to medicinal agents; I could not benefit from the intended effects of a drug or herb for more than a day or so due to my system's intolerance. Interestingly, I found I could override this by taking methylphenidate, which of course works on catecholamines. So apparently increased catecholamines staves off the sensitization I'm prone to. Now since I know sensitization occurs following vasodilation and other adrenal stressors, isn't it reasonable to suspect it's the loss of the adrenal buffer that's lead to my problems with adrenergic tone and not POTS/NMH? Well, that, and the fact that Drs. Hyde and Schondorf agree it's not POTS/NMH based on the results of my tilt table test.
  9. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    Yeah methylphenidate stimulates adrenalin, which can help the immune system. When I was living in a moldy basement in college when these symptoms first arose I felt terribly depressed, low energy, couldn't concentrate, etc. I found that by playing online poker I felt better. I would get huge adrenaline rushes all the time, and if I played long enough I would be running on adrenaline. Definitely stimulation helps battle infections and such. Problem is that the infection will eventually win out as the body cannot constantly stimulate itself over years.

    Also, I have thought for a while that a lot of anxiety disorders are just the body responding to some sort of infection by stimulating itself.
  10. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    By the way, I find that klonopin is the only thing doing anything for me and my nmda overstimulation symptoms. Its also helping with depression a lot too. I only take it once a week so far but I notice the effect for about 4 days, and it makes sense because the half life o the drug is like 40 hours. Still, klonopin is ok but finidng something else would be better.
  11. troydheron

    troydheron Guest

    Messages:
    1
    Likes:
    0
    Banora Point, NSW
    What dosage do you take of Klonopin? Have you found the dose to creep up over time (tolerace)? I've been curious about gabapentin / pregabalin... Anyone tried these?
  12. August59

    August59 Daughters High School Graduation

    Messages:
    1,480
    Likes:
    405
    Upstate SC, USA
    I have used memantine before, at a low does (5mg / day) as more of a preserve the brain type thing. I never had any adverse effects from it and as well never noticed any major advantages either. My understanding is that is good for keeping the channels (probably wrong word) in the NMDA receptors cleaned out might be the way to put it. I know we all try a lof things to try to feel better, but I feel like we may leave some crud a lingering around and I hoped the it helped in that sense.

    For what purpose were you going to use memantine? I have that about going back on another 1 month cycle
  13. hixxy

    hixxy Woof woof

    Messages:
    724
    Likes:
    107
    Russell Island, Australia
    I found memantine useless. My understanding is that if you don't have any symptom improvement, then it's probably not helping? Being symptomatic probably indicates that the NMDA receptors are still being activated, calcium channels opened and damage being done....

    I found memantine gave me lots of side effects at any dose.
  14. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    I would use memantine to stop excitotoxicity symptoms. By that I mean severe tinnitus, overactive brain etc. A real biggie is even meditation is too hard on my brain, it causes severe anxiety and depression 8 hours or so later like clockwork. It was not like this at all when this illness first started 2 years ago.

    My worst symptom is really an overactive brain sort of depression.
  15. PokerPlayer

    PokerPlayer Guest

    Messages:
    125
    Likes:
    5
    Seattle, Washington
    I just use .25mg klonopin every once in a while, there are a few threads on it if you use the search function. Klonopin may develop tolerance in some, but other stay at the same dose. I am observant of that so I do not want to rely on klonopin until I exhaust other options.

    Gabapentin could be tried. It is a harmless drug for most people and may provide benefit so there is nothing to lose.
  16. Graeme

    Graeme almost there...

    Messages:
    361
    Likes:
    224
    Montreal
    Troy and PokerPlayer,

    Have you two tried many different forms of magnesium? I've always found the non-oral deliveries far more effective. Also lithium orotate might be worth investigating if you haven't already. Guaifenesin as well, which can of course be picked up at the local drug store.
  17. adreno

    adreno 3% neanderthal

    Messages:
    2,332
    Likes:
    1,480
    Tundras of Europa
    Compounds that protect against exitotoxicity:

    Memantine
    NAC
    Taurine
    Curcumin
    Methylcobalamin
    Lithium
    GABA
    Magnesium
    P5P

    And forget about "adrenal fatigue". It doesn't exist. It's very possible (and normal) to have mild hypocortisolism in CFS, but it's caused by a dysregulated (hypoactive) HPA axis, not organ fatigue. In short, it's a signaling problem, not a structural problem.

    Besides, cortisol is neurotoxic at high doses. On the other hand, too low cortisol will lead to increased inflammation in the brain, which is also neurotoxic.

    It's possible that exitotoxicity can lead to CFS (and hypocortisolism) through kindling; at least there are theories about that. Whether blocking exitotoxicity will actually bring the cortisol back up is questionable, though. But it might come up slowly over time, if chronic stressors can be avoided.
  18. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,245
    Likes:
    4,568
    australia (brisbane)
    It might be easier for people to understand if u said adrenal fatigue does exist but really the adrenals arent fatgiued but the signalling from the hypothalimus has gone whacky, the other side of the coin with 'adrenal fatigue' is low dhea which seems to happen before cortisol drops to a low level. Im starting to find that before you can try and increase cortisol by what ever means eg hydrocort or pregnenolone etc that u first need to bring dhea levels up to normal before pushing cortisol levels up. Im now finding very small doses of pregnenolone help with inflammation within my joints, less cracking and creeking going on, not sure about inflammation in the brain but pregnenolone does seem to help cognitively.

    Interesting subject,

    cheers!!!
  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,245
    Likes:
    4,568
    australia (brisbane)
  20. adreno

    adreno 3% neanderthal

    Messages:
    2,332
    Likes:
    1,480
    Tundras of Europa
    Yes, this is a somewhat accurate description of what is going on. There are some more factors, that I didn't see mentioned.

    It's possible to have adequate amounts of CRH or ACTH, but still produce too little cortisol. This can happen if those messengers are high for long periods, which then causes the receptors on the pituitary or adrenal gland to become desensitized.

    It's also possible to produce high levels of cortisol for long periods of time, after which the adrenal glands sends a feedback signal to the hypothalamus to slow down production. An enhanced feedback loop is often seen in CFS.

    The problem with calling it adrenal fatigue is that this implies that the glands are worn out, or tired. This is not the case. Also, adrenal fatigue is not described anywhere in the medical literature for this reason.

    So it's simply a question of the HPA axis becoming downregulated, or hypoactive. This can happen after long periods of intense stress, to protect the body from the catabolic effects of high cortisol. It might also happen because of chronic inflammation or infections.

    As far as I remember, CRH, ACTH and cortisol are all low in CFS, whereas in PTSD, CRH and ACTH are high, while cortisol is low.

    A good way to test the adrenal glands is with the ACTH stim test. If the glands respond by producing adequate amounts of cortisol, they are all right, but simple not receiving the ACTH they need. The glands will atrophy (shrink) when not stimulated, and thus be able to produce less cortisol. But they will grow back if adequately stimulated.

See more popular forum discussions.

Share This Page