The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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NMDA Experts! Your Input Needed!

Discussion in 'General ME/CFS Discussion' started by Prefect, Mar 4, 2017.

  1. Prefect

    Prefect Senior Member

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    Lately I've been obsessed with NMDAr for 2 reasons:

    a. I have many neurological and psychiatric symptoms of CFS/ME which hint at NMDAr activation (or as Hip put it in one of his posts, the mental "Tired by Wired" phenomenon) in his post which discussed NMDAr extensively. For years I thought it was primary fatigue, but I'm beginning to think it's a mental sensory exhaustion in response to a dysfunction in sensory input filtering process. I've also noticed mornings after I dream a lot I have more mental fog/anxiety, indicating REM sleep is somehow involved in NMDAr excitotoxicity.

    b. My 2.5 year old son has begun displaying signs of autism spectrum, which has been viewed as NMDAr hypo-function, as it is also in case of schizophrenia. Lately I've begun wondering if there is a connection between the two conditions.

    I've been reading many posts on this site that discusses NMDAr and getting very confused. My sources of confusion are:

    1. Caffeine is likely an NMDAr agonist? In which case why does coffee improve CFS mental symptoms?

    2. Glutamine. Why does supplementation help some CFS patients if it converts to the neurotransmitter that excites NMDAr? And by the same token, shouldn't it help people with Autism?

    3. Acetyl L Carnitine (ALCAR) has been known to help both CFS and Autistic people. I'm getting the indication it's an NMDAr antagonist, so it makes sense that it would help CFS, but why would it improve Autism?

    4. Some people on this site have come out and said they had CFS because of Anti-NMDAr antibodies. Would they not develop more autistic or schizophrenic symptoms rather than CFS?

    5. Alcohol is an NMDAr antagonist, and should help CFS patients (also because it's a vasodilator). Why is it so detrimental then to most CFS population? (I find helps me though)

    6. Curcumin appears to be an NMDAr agonist, so it should make CFS mental symptoms worse. It seem tumeric has helped many (including Hip), but that may be because curcumin bioavailability from straight tumeric supplements is low.

    7. Ketamine helps many CFS patients. This makes sense, because it is a strong NMDAr antagonist. This one doesn't confuse me.

    I was hoping the NMDAr knowledgeable folx here can weigh in and clear up some of the confusion here?

    I think there is something to NMDAr dysfunction that would help our community immensely if we dug more deeply.

    Thanks!
     
    helen1 and WillowGris like this.
  2. WillowGris

    WillowGris

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    Is there any chance you would be open to a private conversation? I have a personal experience related to what you're saying here that would be better not to share in public yet -- and I have been looking for some similar answers myself! I got very excited when I saw your post and I am hoping that maybe sharing some info might possibly help both of us out.

    If that's okay with you, my email address is willowgris@gmail.com. I was trying to find a private message function in this forum but I'm afraid my brain is not quite keeping up with me :) do feel free to private message me in the forum if you know how to do it, though -- I'll watch this inbox :)

    Hoping there are others who have knowledge about this too who will also post here.

    thank you for starting this conversation!
     
  3. Prefect

    Prefect Senior Member

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    Just sent your inbox in this forum a message. It's easy you just click on my name, go to my profile and it's offered as an option.
     
  4. juniemarie

    juniemarie Senior Member

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    I hope you post more about this subject and especially answers to questions you posted if you find them
     
  5. Prefect

    Prefect Senior Member

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    Yeah, all I'm getting on this post is tumbleweeds, not sure why, because it seems to have been historically a subject of ample interest on this site.
     
  6. Basilico

    Basilico Florida

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    A few things jumped to mind when reading this post that maybe could address some of your questions.

    When consuming whole foods/beverages/herbs, the way the body breaks down and makes use of the components is extremely complex and may be different from person to person (if a person has a methylation or krebs cycle block or some kind of deficit, they may not convert precursors into the expected final product). If someone has low stomach acidity, they may not be absorbing certain nutrients like B12...there are so many things that can stand in the way of a body assimilating every component of what it ingests.

    Additionally, each item may have multiple effects (not only on NMDA receptors) which may explain some of the positive or negative effects.

    For example, coffee is a strong methyl donor. For someone who is an undermethylator, this may be the cause for a temporary feeling of improvement. In that same person, the NMDA action may be inconsequential because perhaps they don't have serious issues with this particular receptor - while many with CFS/ME may have NMDA issues, it's possible this is a minor or nonexistent issue for others. Additionally, caffeine in coffee is a vasoconstrictor, and since many people with CFS/ME have low BP/low blood volume, the constriction or increased BP or pulse might be what is providing temporary improvement.

    Alcohol has a variety of actions as it's metabolized as well - it is a CNS depressant, which for some people may be a good thing for others, a bad thing. Alcohol also binds to GABA receptors and inhibits glutamate, so if you are prone to a lot of glutamate excitotoxicity, this might cause a temporary reduction. I'm not sure why it's vasodilator action would help a group of people who are prone to low BP/volume, but some people feel better with alcohol; perhaps this subgroup has 'thicker' blood or other issues.

    Additionally, I think that it's not just important whether something is an agonist or antagonist; what is really important is how strong the affinity is to bond to a particular receptor. Something with a weak affinity will end up not playing a very important role in activating that particular receptor.

    Also, when you are constantly activating or over-activating receptors, they have a tendency to downregulate. This is how drug tolerance and diabetes develop. When you flood a specific receptor with a constant oversupply of neurotransmitters or hormones, the body reduces the number of receptors, preventing that substance from binding to receptors. It's hard to know how many and what state a person's receptors are in, and this could also account for people reacting differently to NMDA agonists/antagonists.

    And lastly, it could be that some people are consuming a combination of NMDA agonists and antagonists that are effectively canceling each other out. Not sure if it works like that, but I don't see why it couldn't be possible.
     
    Last edited: Mar 14, 2017

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