arrow17 Comments
  1. Bonnie MEyers
    Jun 27 - 2:09 pm

    Thank you for all of the wonderful info. Have been waiting for 30 somewhat years

  2. Issie
    Jun 27 - 2:34 pm


    I appreciated this article. Since this is something that I have felt may be playing a role in POTS and have been doing research on it myself. I find the symptoms/presentations of POTS and ME/CFS to be so similar – yet different. There must be a connection, as some people have both.

    One thing of note – from what I can gather from my reading, there can also be a mutation in the BHMT pathways of the methylation cycle that can mimic a COMT mutation. Especially an issue with BHMT4, can act the same and cause similar issues with glutamate function. It also can cause too much ammonia and using Yucca can help to neutralize that and helps in keeping the gut flora in balance and in breaking down proteins properly so that ammonia is eliminated. It is also suggested that B12 will help in the proper conversions necessary. This is explained in an article by Dr. Mullan and Yasko, it’s entitled “Gastrointestional Balance and neurotransmitter formation”.

    Interestingly, in regards to myself – it was found that I have a protozoa that is very similar to malaria (FL1953 – Protomyxzoa Rheumatica), and I also had a co-infection that goes along with Lyme disease. Working on breaking down the bio-films that can prevent the immune system from recognizing these organisms and virus, bacteria etc. and eliminating things that could affect their flourishing, along with anti-malarial herbs and low dose antibiotics – has been of great help to me. I think it will be a long slow process – but, I’m considerably better. There is a close connection between the protocol for this and the mutations that I found in my methylation pathways. That connection may also exist in the connections with ME/CFS and POTS. Could it all be the same issues? Why might one persons immune system work properly and they never get sick, even from the same exposures. While another person gets sick and can’t seem to pull themselves out of it. Could these mutations in our genetics be causing these issues? I think time will tell.

    Thanks for this article. It has given me a little more to think about and research.


    • Marco
      Jun 27 - 11:40 pm

      Thanks Issie

      That’s an interesting article.

      Gastro issues (upper and IBS) have been a constant problem for me. A full work up showed ‘idiopathic’ malabsorption (no treatment recommended) and I was on Tagamet and Zantac for years until the upper gastro symptoms just disappeared.

      I was tested for and clear of H-pylori.

      If I could sort my gut issues out I feel there would be major improvements in other areas too. But where to start without positive tests?

      The thing is, prior to ME/CFS I had a pretty cast iron stomach but I still had issues with anxiety etc which suggests a predisposition to develop systemic inflammation.

      Inherited or congenital ‘weaknesses’ plus ‘stressors’ would seem to fit my particular case.

      • Issie
        Jun 30 - 11:53 am

        One of the best things I’ve done for myself is go low-fat vegan. It has helped my digestion, elimination and assimilation so much. I now have moons in my fingernails – showing assimilation of nutrients. Not only has it helped my intestinal issues – it also addresses the immune system. This is one thing that we can do without any type of testing. The hardest part is deciding to do it and then committing to it. Something wonderful that my diet has done is to reverse Chronic Kidney Disease – stage 3 to stage 1. That is unheard of. Most docs will say once your kidneys are damaged there is no redemption. But, my diet has done this.

        Since I have MCAS (mast cell activation syndrome) I also use Allegra and Zantac – but, in much lower amounts than most people with this. One of the best meds I’ve used is GastroCrom. It also helps with the immune system. (I wouldn’t be on it without insurance – it’s unreal expensive.)

        Many of us have found with 23&me testing, genetic mutations that we can work on and maybe prevent future issues with them. It is not a very expensive test. But, will require a whole lot of research on your part to interpret and figure out what to do with the data. This has been very beneficial to me. There is so much to learn about the body and how it works. It’s very intriguing to me and makes me realize how wonderfully made our “Creator” made us. Genetics and those mutations could play a big role in what “illness” we deal with and also in how we eliminate and process supplements, drugs, etc. Having a better picture of our own individual blueprint – can make a big difference in our approach.

        There is a lot we CAN do. We just have to commit to doing them. That’s the hard part. There is no “magic pill”. If we do what we have in our own control and see where that takes us —then maybe doctors can address what is left over. It is very liberating to take over that control – knowing we are doing the best we can for our bodies. I do believe that genetics play a big role with us all. And working with that and the immune system and inflammation may be the best things we could do for ourselves. It has made AMAZING changes for me!


        • Marco
          Jul 01 - 3:34 am

          ‘Self-help’ approaches are the only things that have had any benefits for me Issie, often discovered by chance.

          Realistically speaking also, even if the science identified the core problem tomorrow there would be a long lead time even for drug repurposing and new drug development could be 15 years away – assuming the money and will was there.

          Many of us don’t have much of a life to look forward to 15 years from now.

          What the emerging science can do though is give us pointers to better target our own efforts.

          In the context of the proposed glutamate/GABA imbalance I really should try to reduce my meat intake – it wouldn’t be hard as my wife is vegetarian. I’m just such a committed carnivore and I do feel that I need the protein.

          It might be worth a try though – just to see if my digestion improves.At the moment lunch (usually light) if immediately followed by bloating and a major slump in energy such that I usually need an hour or two sleep afterwards.

          • Issie
            Jul 01 - 12:15 pm

            Give it a try and just see if it makes a difference. You have to make up your mind to commit. That’s the hard part and then once your committed, doing it is the easy part. It was an absolute necessity for me and I’m so glad that I embraced it. Keep us posted.


  3. Gijs
    Jun 28 - 5:10 am

    I think it is time that every study reports the status of noradrenaline levels, cortisol, Glutahione, NK cel function, TNFa and HRV in there CVS population. These findings are consistent.

    • Marco
      Jun 28 - 5:35 am

      I’m inclined to agree Gijs.

      There do appear to a limited number of consistent number of objective abnormalities including certain pro-inflammatory cytokines, reduced NK function and ANS dysfunction that should point to the underlying pathology even if we can’t nail it down causally to a certain pathogen, gut issues or whatever. I’d also like to see neurotransmitters such as glutamate and GABA measured but blood measures don’t necessarily equate to what’s happening in the brain and levels may vary by brain area.

      But we do know many of the detrimental effects of high TNF-a. If so can it be treated (Fluge and Mella are currently trying Etanercept) and what effect would this have on the symptom burden – even without knowing exactly why they are raised.

      I think the problem is that these findings are far from specific to ME/CFS. That’s a problem if you’re looking for a biomarker and want to demonstrate that you can distinguish X condition from Y. It’s not a problem however if you accept that the same pathological process may be common to many neurological conditions, merely manifesting in different symptom patterns.

      • Issie
        Jun 30 - 12:02 pm

        It would be nice to be able to measure all these things – with science. But, with some things science isn’t there yet. We need to go with what our “gut” is telling us and work on what IS within our control. Things that we — with good sense — CAN do, this minute. For us, with scientific minds and wanting concrete proof of something, that may be hard. We want the science behind it. But, until that is available – maybe just addressing what we suspect – may make a huge difference in our “quality of life”. Hey, we’re all looking for that “purple Band-Aid”. It may be up to us to find it.


    • Cort Johnson
      Jun 28 - 3:59 pm

      I’m trying to think of something I would add……

  4. Marilee Mouser
    Jun 29 - 8:34 pm

    A citation page would be nice; there’s something I’d like to show my doctor and now I have to google it and hope I find it!!!!

  5. Doug
    Jul 06 - 6:10 pm

    Fantastic articles!
    I never post anything, but these were the most excitement in reading I have ever had in the ME world!
    I thought I maybe could add a litlle.

    Since I have a son with spastic diplegia (cerebral palsy) and relatives with Aspberger’s autism, ADHD etc, after reading the articles I did a little research and found the below quotes…

    “In spastic diplegia (cerebral palsy) in humans, GABA absorption becomes impaired by nerves damaged from the condition’s upper motor neuron lesion, which leads to hypertonia of the muscles signaled by those nerves that can no longer absorb GABA.”

    and from Pub Med:
    “The current understanding of contributors to the risk for cerebral palsy is still incomplete. Multiple causes may interact by way of excitotoxic, oxidative, or other converging pathophysiologic pathways.”

    So here’s my thought:
    I wonder now if cerebral palsy should now be added to the conditions to look for on the family tree of medical concerns, as another possible indicator of a familial pattern of GABA / Glutamate dysregulation.

    This would address a medical issue (cerebral palsy) that I have never seen included in any lists of a family of conditions (with ME) also having no known etiology.

    • Marco
      Jul 07 - 1:12 am

      Thanks a lot Doug.

      That’s really interesting. It sounds as if the hypertonia in cerebral palsy has similarities to stiff person syndrome.

      Cerebral palsy didn’t turn up in my initial list of related conditions as there doesn’t seem to be any research indicating a sensory gating deficit which was the issue that suggested that ME/CFS may share a pathology with other neuroinflammatory conditions.

      But a quick googling around suggests that those with cerebral palsy may also have sensory processing issues as well as motor problems. Have you by any chance recognised these sorts of issues with your son?

      Re familial predisposition, the problem with family studies is that they look for increased incidence of one condition be it ME/CFS; fibro or whatever whereas I would suggest that they really need to look for increased incidence of a wide range of disorders that may be underpinned by the same neuroinflammatory pathology.

      The same pathophysiology may show up in a family as a variety of seemingly separate and apparently unrelated conditions and conventional ‘diagnosis based’ surveys wouldn’t pick this up.

      • Doug
        Jul 07 - 9:55 pm

        Hi Marco,

        I should point out by way of a starting point, that the vast majority of cases of cerebral palsy have no know cause, no lesions, nothing remarkable (as of the last researching of this done by me years ago). I’m not a good researcher, and I don’t have the free access to follow up on this on scholastic databases as I would like.

        I do know that my son had an operation called a “selective dorsal rhizotomy” operation (neuro-surgery on the sensory nerves of the dorsal root ganglia of the lower end of the spinal column).

        This surgery was done, as it was explained to me 20 years ago, to address an over amplification by the brain of what were “normal sensory inputs” from an extremity of such as: proprioception (ability to sense the position and location and orientation and movement of the body and its parts), pain, temperature, or pressure etc.

        Said another way, in C. P., the brain’s interpretation of certain normal sensory inputs (as seen when the surgeon’s milli amp signal is applied to the patient’s sensory nerves inter-operatively on the exposed spinal column during the surgery) elicit a motor response back to the legs that is many times what was “normal” (hence resulting in the “spasticity” that was immediately seen in those dysfunctional brain responses during the surgery).

        In electrical systems we would call this an “excessive gain” in the circuit.

        In a brain however, it seems we can’t get away from the aspect of “the perception” by the brain of the signals being provided to it…
        … and this perception could very well have something to do with the a hyper-arousal state of the brain’s interpretive circuits.

        It would be more than interesting to see family medical histories of CP patients regarding the:
        1. occurrence of the medical conditions that also currently have no know etiologgy (e.g. MS autoimmune, autism ADHD etc. that you so well list)
        2. occurrence of aberrant genetic SNPs regarding the methylation cycle etc

        … to get a reasonable and scientific explanation of cerebral palsy, other than the “hypoxia” theory.

        The hypoxia theory let’s remember, has had it’s application in the MECFS world as well (see Dr, Bell’s book “Cellular Hypoxia” 2007 – a book I would love to edit if it were to be released again…

  6. Marco
    Jul 08 - 6:29 am

    Hi again Doug

    I must say that even with the little I read the hypoxia explanation did seem a little ‘pat’.

    The dorsal root ganglia do seem to keep cropping up in ME/CFS.

    Interesting that you talk about excessive gain. My earlier articles on sensory gating suggested that the problem may be one of a reduced signal to noise ratio and that the constant bombardment of sensory input could contribute to a self perpetuating neuroinflammatory cycle. But excessive gain, as you know, also has a tendency to result in feedback loops especially if, in the brain, clearance of glutamate or inhibition by GABA is impaired which would normally attenuate these signals.

    Hypoxia, Ischemia and energy starvation (see Cort’s recent blog : all appear to result in the same neurotoxic state, as does thiamine deficiency (see Cort’s other recent blog : which interferes with astrocytic transporters that usually clear extracellular glutamate.

    Thiamine supplementation and N-acetycysteine (NAC) may help prevent Wernicke’s encephalopathy in alcoholics :

    Interestingly NAC is one substance I keep coming across (just taken some actually to help deal with heat intolerance) and has been proposed as potentially helpful (presumably within a window of opportunity) in cerebral palsy :

    So many overlaps in ‘medically unexplained’ conditions.

  7. OM
    Sep 07 - 1:20 pm

    LDN seems to help with “auto-immune” conditions and works very well for some people with ME/CFS it is inexpensive and worth a try at least. Not compatible with opiate drugs for pain but otherwise very few side effects once the body gets used to it. Best to start low and go slow. Works for me!

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