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Could the Brain’s Mast Cells Be Causing Chronic Fatigue Syndrome (ME/CFS)?

“We propose that stimulation of hypothalamic mast cells by environmental neuroimmune pathogenic and stress triggers activates microglia leading to focal inflammation in the brain and disturbed homeostasis.” Theoharides et. al., 2018

Dr. Theoharis Theoharides is an MD and PhD who has published almost 400 papers. A pioneer in the field of mast cell research, Theoharides runs the mastcellmaster.com website and has produced a line of dietary supplements to tamp down mast cell activity. Just a couple of days ago he led an NIH sponsored workshop “Mast Cell Triggers and Mediators Beyond Allergy and Tryptase”.

Recently he took up the subject of chronic fatigue syndrome (ME/CFS), energy metabolism and mast cell activation in a paper “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis?

First Theoharides examines the idea that problems with energy metabolism are causing ME/CFS. He agrees that the energy problems ME/CFS patients experience are due to problems with energy depletion, stating that, “Much evidence suggests that the pathophysiology of ME/CFS is highly associated with alterations in normal energy metabolic processes and abnormalities in cellular bioenergetics”, but then spoils it a bit by suggesting that deconditioning could be the cause.

Similarly, in his section on metabolic syndrome and ME/CFS, Theoharides proposes that problems with blood pressure regulation and insulin resistance, “most probably reflect the lack of physical activity and prolonged lack of muscle use in ME/CFS patients”.

low energy production ME/CFS

Theoharides agrees the energy production problems in ME/CFS are real and posits a new cause for them.

But then Theoharides agrees that a hypometabolic state which reduces energy production (ATP) is probably present.  He also agrees that the typical ME/CFS phenotype, i.e. the way the disease presents itself clinically, largely matches that found in people with mitochondrial diseases. He notes that muscle biopsies do show signs of mitochondrial problems.

On the other hand, people with ME/CFS don’t have the mitochondrial DNA mutations, enzyme issues or drops in ATP production typically found in those diseases.

He suggests that free radicals produced by pro-inflammatory cytokines could be whacking the mitochondria in ME/CFS so hard so as to blunt their ATP production, but then notes that no consistent evidence of cytokine upregulation, has been found.

After basically concluding that energy production is a problem in ME/CFS but that none of the usual suspects are the likely answer, and citing the fact that physical, mental and/or emotional stress tends to do people with ME/CFS in, Theoharides, like the Cortene group, turned to the HPA axis.

Many ME/CFS studies, after all, have found problems in the HPA axis – one of the two stress response systems in our bodies – and the axis does affect metabolism. Could it be ground zero for ME/CFS?

Mast Cell Activation

Theoharides thinks so. He proposes that mast cell activation, smack dab in the heart of the HPA axis – the hypothalamus – is occurring in ME/CFS.

If mast cells are involved in ME/CFS it wouldn’t be that much of a surprise.  They are, after all, extraordinarily versatile immune cells which have the capability to produce the extraordinary number of symptoms found in ME/CFS.  Containing hundreds of immune mediators, they can respond to a wide range of stimuli – from pathogens (including mold) to hormones to toxins to immune and neuronal factors.

Best known as mediators of allergic reactions, they’re also “sensors of environmental and psychological stress.” These “sensors” can secrete localized “danger signals” which stimulate the microglia in small pockets of the body/brain.  Theoharides proposes that a mast-cell induced inflammation in the hypothalamus could be causing chronic fatigue syndrome (ME/CFS).

The Mast Cell / Hypothalamus Inflammation Connection

Several studies suggest that inflammation is present in the brains of people with ME/CFS and/or fibromyalgia and Theoharides thinks he knows how this occurs.

It turns out that most of the brain’s histamine is located in the hypothalamus. Plus mast cells are also found in the pituitary gland (as well as the thyroid, the thalamus and the pineal gland).

Theoharides’ mast cell ME/CFS hypothesis begins with a hormone – corticotropin releasing hormone (CRH) – which is released by the hypothalamus during stress and which has been implicated in a series of neuroinflammatory disorders.

hypothalamus chronic fatigue syndrome

Theoharides believes that mast cell activation in the hypothalamus – a key hormone regulator with connections to the limbic system- could play a key role in ME.CFS.

Theoharides believes CRH stimulates the mast cells in the hypothalamus (and elsewhere) to produce something called vascular endothelial growth factor (VEGF), which then increases the permeability of the blood-brain barrier (BBB). That leaky BBB then allows more immune cell (e.g. mast cell) and perhaps pathogen infiltration into the brain and bingo, you have inflammation.

Once in the hypothalamus those activated mast cells produce more CRH, further tweaking the hypothalamus and producing compounds such as histamine, tryptase and mtDNA which send the microglia into a frenzy, causing them to release inflammatory cytokines/chemokines (IL-1B, IL-6, CCL2) that further disrupt hypothalamic functioning.

While the pro-inflammatory cytokines are busy doing that, Theoharides also believes they’re likely whacking the mitochondria in the brain and body, causing centrally (brain induced) as well as peripherally produced (body induced) fatigue, sleep problems, etc.

The main problem, though, is a not an overt threat but hyper-sensitized microglial cells pouring out inflammatory factors in response to the slightest stressors.

(Meanwhile, mast cell activation in the pineal, pituitary and thyroid glands may also be disturbing sleep and producing more fatigue.)

And there you have it. Mast cells – which just happen to be concentrated in several of the brain areas implicated in ME/CFS – have gone off the rails. They’re causing microglial cells to produce pro-inflammatory factors which are producing inflammation in key parts of the brain that are involved in the stress response, fatigue, sleep, etc.

The Hypothalamus – A Central Player

A couple of years ago, though, Dr. Bateman of the Bateman-Horne Center came to a similar conclusion: she believes that inflammation in the lower part of the brain containing the thalamus, hypothalamus and pituitary plays a key role in ME/CFS.  The hypothalamus, which sits just above the brain stem, regulates blood pressure, temperature, and hormone and water content.

Dr. Bateman noted that these organs control the hormones (the hypothalamus is the hormonal control center of the brain) and much of the autonomic nervous system, and then pointed out a long list of hormonal problems (corticotrophin releasing hormone (CRH), growth hormone, thyroid, LH/FSH, vasopressin, oxytocin) that have been uncovered in ME/CFS and fibromyalgia.

She believes that a “limbic encephalitis” is causing a cascade of problems going both ways; up into the cortex and down into the thalamus, pituitary and the autonomic nervous system.

A Mystery No Longer? The Big Picture Emerging In Chronic Fatigue Syndrome? Dr. Bateman Talks

Treatment

Theoharides blasted through several possible mitochondrial enhancing treatments (bezafibrate, angiotensin II inhibitors, CoQ10, Losartan) which he didn’t find all that much promise in, before focusing on magnesium, which he noted plays a “critical role in energy metabolism and in maintaining normal muscle function(ing)”.

Theoharides cited studies indicating that magnesium supplements are able to significantly increase muscle strength and endurance and did so, interestingly enough, by enhancing glucose availability in the brain (possibly low in ME/CFS) and muscles, and by delaying and/or reducing lactate accumulations (possibly high in some people with ME/CFS/FM).

Then it was on to flavonoids, which Theoharides reported have anti-inflammatory, anti-oxidant and neuroprotective effects. Genistein can reduce muscle fatigue while epigallocatechin, naringin and curcumin have been shown to ameliorate ME/CFS symptoms in experimental models.   Astragalus flavonoids, olive extract, and quercetin may have similar effects.

Luteolin was the highlight of the bunch.  With its mast cell inhibiting, anti-oxidant, anti-inflammatory, microglia inhibitory and neuroprotective properties, luteolin is very high on Theoharides’ list, and in 2015 he produced a paper extolling its benefits.  (One study found that tetramethoxyluteolin or methlut appears to be the most effective mast cell inhibiting form of luteolin and is more effective than cromolyn.) Theoharides cited studies that luteolin improved symptoms in autism spectrum disorder (ASD), post-Lyme Syndrome and brain fog in (the not particularly rigorous) open-label trials.

Theoharides has hailed fatigue and mast cell inhibiting properties of flavonoids before and has even produced his own line of supplements, but his statement that, “novel treatment approaches are required to address the central pathogenic processes” in these diseases indicates that, in their current form, these flavonoids are not the answer.

One of the problems has been that it’s hard to get these substances into the brain.  At the end of the paper, though, Theoharides proposes a different way of supplement administration that may be more effective.

Intranasal Administration

“Intranasal administration of select flavonoids may reduce inflammation in the hypothalamus and correct the central pathogenesis of ME/CFS.”

Intranasal administration – basically a shot of volatilized factors into the nose and hopefully eventually into the hypothalamus- is getting more and more attention. Theoharides even suggested if it worked it could even correct the problem.

intranasal spray chronic fatigue syndrome

Theoharides proposes that intranasal sprays may be able to get at the inflammation in the brain

No studies have been done, but since the hypothalamus sits behind the amygdala, which is right behind the nose, it’s possible intranasal supplementation could help dampen down inflammation there.

Flavonoids are just the beginning of the intranasal administration story, though. Over the last couple of years more and more people with ME/CFS/FM have been experimenting with intranasal administration of insulin and glutathione.

Plus, Theoharides mentioned another intranasal option -microvesicle trapped curcumin – that is emerging. Curcumin is perhaps the most scintillating of all the natural anti-inflammatories, but bioavailability has been a challenge.

In 2015 Theoharides proposed that intranasal administration of tetramethoxyluteolin might be useful as well.

A blog on intranasal administration is coming up.

Conclusion

Dr. Theoharides agrees that problems with energy metabolism are likely present in ME/CFS but proposes that their genesis probably lies in mast cell activation in the hypothalamus and other brain organs. Theorharides suggests that corticotropin releasing hormone produced by the hypothalamus activates masts cells to produce substances that activate the microglia, causing the production of pro-inflammatory substances which produce centrally or brain induced fatigue and autonomic nervous system issues. Mast cell activation in the pituitary and thyroid produces further problems with sleep, fatigue and cognition.

Theorharides also proposes that intranasal application of anti-inflammatory substances such as cucurmin and luteolin may be able to access the hypothalamus thus tamping down the neuroinflammation he believes may be at the heart of ME/CFS.

 

 

 

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47 Comments

  • Chris

    September 28, 2018 at 11:16 pm - Reply

    Which might explain why HRT for my dying thyroid might look good in blood tests but doesn’t do much for restoring my energy and stamina. As usual, every possible answer throws up two more questions.

    I am liking this Health rising series a lot, Cort. The finer points fly over my head about 20 feet up but I get the gist. Thankyou.

  • Issie

    September 28, 2018 at 11:58 pm - Reply

    As I’ve mentioned before – I didn’t really start getting better until I addressed MCAS (mast cell actovation syndrome). Treating that was a turning point for me with POTS and how I felt. The good thing is one can experiment with over the counter antihistamines to see if they make a difference. (I use Allegra and 1/2 Zantac at bed time. I also use a mast cell stabilizer that has made a huge difference but is very expensive and an RX. The one I use is GastroCrom.) Hoping this will make a difference for others too. One new thing I’m trying is Histamine Block by Seeking Health. It is an enzyme that helps prevent such a strong surge of histamine response. I’m now not needing to use the antihistamines as much. Finding it to be a big help.

    Issie

    • Cort Johnson

      September 29, 2018 at 12:49 am - Reply

      Thanks again for relaying your experience. How did you discover mast cells? How did you get onto that?

      • Issie

        September 29, 2018 at 1:26 am - Reply

        I was on a forum for POTS and one of my associates mentioned it to me. I had a hospitalization of what seemed like a heart attack. But there was no heart damage. It happened after I had chewed a pack and a half of gum with aspartame. I was also writing a very long, detailed article and doing a lot of research about POTS and it was going to be controversial and go against the thinking of how to treat POTS as it was known at that time. So I was under stress and knew I would get push back. Yet, felt it important enough to say it. Come to find out – aspartame ups glutamate and can trigger a mast cell response and activates a sympathetic response in the body. Stress can also do this. There is an illness called Kounis Syndrome where mast cells attack the heart. It looks like a heart attack. The treatment is massive antihistamines and nitroglycerin. I took antihistamines before I went to the hospital because I had heard about mast cell problems and had started researching it. Then, when the hospital gave me nitroglycerin and it made huge improvements – it looked like a heart attack. My blood pressure was up and my heart rate was crazy high. We already knew I had Hyper POTS with higher blood pressure and also knew that traditional medicines for POTS made me worse. But here was another puzzle piece – instead of vasoconstrictng I needed vasodilation to get my blood pressure down and to ease the tachycardia. Along with massive antihistamines. Took me on another journey of questioning the way POTS was treated. At least for me and how my body was presenting. Come to learn, antihistamines and nitro are the treatments ysed for Kounis Syndrome.

        I was a patient at Mayo AZ and was going through evaluation and diagnosis process. I started research on this little known about issue, at that time, from a POTS associate suggesting I look at Kounis Syndrome as to what happened with my heart. I presented my research to a neurologist and an immunologist at Mayo. They neither one knew much about it. I kept insisting there was a connection and to please look into it. I didn’t test positive for mastocytosis. So they just sort of wanted to excuse my ideas and not pursue it. But, thankfully, the immunologist read my book of research and felt I was onto something that needed pursuing. They called in another doc from another Mayo to help look into it further. Now, nearly every POTS diagnosed person, who goes to Mayo is evaluated for Mast Cell Actiavation Syndrome. I also pushed for evaluation of myself for Ehlers Danlos. Which was also DX by a rheumatologist based on physical symptoms and maifestations. Now that too is considered and is the 3rd part of a trilogy with my subset type of POTS.

        That’s how I came to know about MCAS and how we got to where we are today. I was the first pattention to push my docs here to research it. (I was told later by my neurologist that I had given the immunologist such a time that he was insisted he had to have help to look into it. I’m so glad they did.

        It wasn’t until later that the mast cell stablizers were given. Initially we treated ourselves with H1 (Allegra) and H2 (Zantac) blockers. We knew it made a difference. Some used H3 blockers (Singular)

        • Karen

          September 29, 2018 at 11:40 pm - Reply

          Hi Issie, most of that went over my head, but I get the idea and you certainly know your stuff. I am new to all this and too ill to look at all the detail. Could you recommend what to try first please? I’m in the UK so brand names might be different but I’ll try anything! Thanks.

          • Issie

            September 30, 2018 at 6:45 am -

            I really can’t recommend anything. Only talk about what I did that worked for me. I don’t know your history and I’m not a doctor. But what some of us did was try an H1 and an H2 blocker. (Histamine blockers.) I was told to never just take an H2 without an H1 as the histamine 2 would turn into a histamine 1 and allergies would be even worse. I found I could only use a half of an H2 or it hurt my stomach. The ones I use are Allegra and Zantac. I use GastroCrom as my mast cell stablizer. Right now, the new enzyme I’m using is by Seeking Health and called Histamine Block. My taking one in am and one at bed is allowing me to mostly be off the other things. I have changed my diet drastically though. I know if I were still eating things I was before – I’d still need the mast cell medicines. I have to be on a low amylose diet with CIRS and also going low lectin has been very beneficial. You have to be aware of triggers and try to avoid them. There are some on this site that I know their names and some of their history who used to be on Mast Cell Forums. I didn’t do too much on those. I don’t know if those forums are still around. But getting on a forum with like people would be beneficial as they can give more varied ideas as to what works for them. There was one in Canada that we had some in depth discussion.

            There is a site that once was called Histamine Chef. I know she changed the name and I haven’t talked to her in awhile. She was able to get off all her medicines and does it with a few supplements and foods. She feels meditation and yoga have been a huge help to her. (She was once a CNN reporter. Very knowledgeable gal and very helpful.) I mention this, because she has some cookbooks out that some have found helpful. She helps you incorporate certain things in your menu that helps with histamine response.

            Dr. Afrin has written a book on Mast Cell that has been helpful. He is one of the doctors that helped us older ones sort through a lot of this before it was as well known as it is today. There is also a doc in the UK that I can’t come up with her name that is also an expert on this. Brain fog moment…..starts with a J.

            Do a Google search. There is a lot of info out there.

            Issie

          • titch

            October 3, 2018 at 1:02 am -

            For the UK, the most available H1 blockers are standard antihistamines, such as cetirizine and loratidine. The most available H2 blocker is probably ranitidine, which can be bought over the counter. Personally, I found little difference when taking the ranitidine. However, I’m more impaired now, so have been thinking about trying it again.

            I’m not a doctor though, so can’t recommend for or against trying them, can only give you the names as a starting point 🙂

    • Kim

      September 29, 2018 at 10:04 pm - Reply

      Yep, i’ve lived with allergies for over 30 years, diagnosed awhile ago with mc/cfs which then they said was because of under ctive immune system, didnt make sense to me under the circumstances when i saw neurologist was already taking prednisone for yet another severe reaction , now all these years later they finally catching up to me, i also have been using antihitamine, and antiinflammatories and with bad bad relapses where i become severe, we found prednisone i the got to small 20mg dose tappering off over 9 months, its actually alot lower than for my severe allergic reactions but works, my gp thought I had PMR not fibro because of the problems with eye pain. Now we know what works we dont muck around.

  • Issie

    September 29, 2018 at 1:34 am - Reply

    I wasn’t finished and hit send.

    When GastroCrom got added into the mix that’s when big differences happened. Now I’ve recently started this new enzyme product. I’m actually being able to almost be off my antihistamines and mast cell stablizer. Not completely – but almost.

    I’m also doing a new treatment for MARCONS and really think it is making huge differences. I’m almost off my medicines that I used for POTS now too. I can’t really talk about this new treatment yet. I’m the guinea pig and we will see if it works. I failed 2 other treatments for it. This one I’m encouraged by. And, I can make it myself.

    Issie

    • Issie

      September 29, 2018 at 1:57 am - Reply

      Want to give a thanks to Julie G who helped me learn about Mast Cell issues and what likely happened with my heart. She figured out her own mast cell issues and has helped many of us find a path of answers.

      Issie

    • Cort Johnson

      September 29, 2018 at 7:49 pm - Reply

      So interesting and validates Goodman case report that POTS can be caused by mast cell activation. Also a demonstration that it’s good to keep on trying different things. Sometimes one thing will work while other closely related treatments do not.

      https://www.healthrising.org/blog/2018/09/19/winning-the-lottery-novel-treatments-return-severely-ill-pots-patient-to-near-health/

      • Issie

        September 29, 2018 at 9:50 pm - Reply

        Dr. Goodman knows me well. LOL! Poor man, I wouldn’t let up. But we all have learned. I’m sure he got tired of patients coming in there saying — “Issie said”. It has been long years of trial and error. But I’m finally in a much better place, and we all have more pieces of our puzzles. It’s been kinda cool being one of the earlier patients and seeing how much science and our knowledge has progressed.

        Issie

  • Issie

    September 29, 2018 at 2:53 am - Reply

    One thing about MCAS – it’s not a true allergy. You may have negative allergy test. But react one day and be fine the next to something. It’s an over response of histamine by mast cells. As mast cells degranulate they dump all sorts of things into your system and you not only have allergy type symptoms with possible anaphylaxis but it also dumps other things to cause inflammation and pain. (I’ll just keep it simple instead of going into the technical/science.) Also exercise can cause a mast cell degranulation. As can strong emotion, being tired, getting too hot. I found with myself that a lot of times my hot flashes are mast cell related. Also, mast cells tend to degranulate at night when we are trying to sleep and then we can’t sleep. (Therefore mast cell medicine before bed.) It has really been a huge help addressing this for me.

    Issie

    • Cort Johnson

      September 29, 2018 at 7:45 pm - Reply

      A new way to get better sleep – take a mast cell blocker before bed 🙂

      • Issie

        September 29, 2018 at 9:53 pm - Reply

        Hope it’s helped you! Been talking to you about 3 years now about how much it’s helped me. Not all antihistamines affect each person the same. May need to try different ones to find best fit for you.

        Issie

    • dejurgen

      September 30, 2018 at 10:26 pm - Reply

      Hi Issie,

      First: thanks for all your pioneering work for our community!

      Second: “It’s an over response of histamine by mast cells.”

      Could this relate to my idea of poor blood flow equals to more receptors per cell to a wide variety of chemicals? I’ve written about it elsewhere, but let me repeat as it’s easier than looking up where I posted it.

      We ME/?FM?/?POTS? patients have often low blood volume and low blood flow especially through the smaller capillaries. If amounts of signal molecules per milliliter of blood were the same as in healthy people, the (very) low flow of blood through the capillaries would mean that very few amounts of signal molecules (compared to numbers in healthy people) pass through these capillaries per second. That would mean that all functions depending on signal molecules transported by the bloodstream would fall flat to a very low rate of activity. Think about vasodilation but also things as immune or mast cell activation.

      One possible reaction of the body could be to increase those molecules in the body a *lot*, like seems to be true with adrenaline in ME patients. But in the big arteries, where the blood flow is far less effected then in the capillaries, that would lead to a strong surge and over activity. More likely is a more moderate increase in blood based signal molecules, combined with a strong increase in receptors in the capillaries (in order to fetch more molecules out of the blood stream leading to greater activation) and less receptors in the main arteries (to account for the increased amount of signal molecules combined with only moderate blood flow reduction in these vessels).

      That would work somewhat under conditions of low blood volume and low blood flow, but it still would be a makeshift solution. Every little shift in blood flow by activating a certain area, be it muscle, brain, nerves, organs… would cause a very strong difference in local blood flow. That would very strongly amplify the reaction/activation of these chemicals. That can be receptors to adrenaline, receptors to immune modulators or other blood chemical modulated reactions.

      Would that make sense in the context of mast cell activation syndrome too? If so I would imagine that pacing and not quickly shifting from one activity to another dampens mast cell activation. Would that match with your experience?

      Also, such mechanism would be pretty unstable when blood flow is at worse. Let’s say at night and some hours after exertion/exhaustion. That should probably cause very strong peaks of unrest and a decent amount of fluctuation in ones emotional state (as long as the adrenals are not exhausted). Does that align with your experience too?

      • Issie

        October 1, 2018 at 12:16 am - Reply

        @dejurgen, I’m sort of following you……we know that the body can uptake different things differently and in different organs based on the physiological state of the body. There may be variance according to function or dysfunction — heat, moods, hormones, nutrition status etc. We do “tweak” various receptors and neurotransmitters for desired levels with many things we do (antidepressants, hormones, herbs, amino acids, beta blockers, calcium channel blockers……you get the point). We are trying to bring the body back to a state of homeostatis – with whatever we do. With mast cell activation syndrome there is a “dumping” of what’s in a mast cell that is created with a degranulation due to stressors, allergies and pathogens. With this syndrome we get an over histamine response to what should just be processed and eliminated. That mast cell degranulation release sends out an attack to a perceived issue. Therefore, maybe it’s not a true allergy – just an over response to what is perceived as one. Therefore releasing histamine and other things to “attack” what is perceived as something that shouldn’t be there. It is a part of the immune system and a very important part of it. We need it. It can assist in removal of pathogens. But with some, this over response happens and can lead to anaphylaxis.

        As I mentioned being over tired, over heated, strong emotion, reaction to food or chemicals – all can cause this degranulation. That may be a normal response to those things – just in this syndrome it’s over expressed. We also tend to not have high tryptase levels unless we have a mast cell degranulation. Then it has to be caught within a few hours or that higher level won’t be caught. Many times doctors are looking for mastocytosis that has higher tryptase levels and when they don’t find that – they miss this syndrome.
        Issie

  • Tee

    September 29, 2018 at 1:54 pm - Reply

    I’ve been in a state of inflammation for so long that I am almost at the point of not being able to comprehend, or remember most of what I read or am told. I believe the chronic inflammation has affected my brain, most definitely. It’s a constant challenge and frustration that I cannot put into words. I’ve been tested for foods and my IgE is high on everything except for cod and salmon. I’ve been skin tested for chemicals and came back high to the most common products used on the market. Basically everything I come in contact with, makes me feel sick, inflamed, nauseated, and saying I am chronically fatigued, is an understatement. I can no longer function in the world, nor work and my financial situation is a huge stressor I live with daily as I am barely able to afford food. I live in a vicious cycle of trying to find the right doctor/help who understand, and those WHO do and are familiar with Mast Cell disease, do not take my insurance or any insurance at all. Thus I am left to suffer. The doctors I’ve seen scratch their heads and grasp at straws as to what to do with me. The last doctor I saw said that it’s not a matter of “if,” it’s a matter of “when”- I will get cancer, if I do not get my inflammation markers down. (not a very professional thing to tell a patient IMO). He then went on to tell me that I need to take Cellcept which is a strong drug w many side effects and can damage the liver. I did not walk out of his office, I ran. I am not sure what category I fall into as to whether or not I am a “minority” in this disease, or not, but so far doctors are perplexed leaving me to feel completely at a loss. I do not trust their judgement or recommendations. And when I take any supplements, medications, etc…I usually always get sick, break out in hives, etc…and further impede my already weak immune system. I am looking for answers, help or perhaps a doctor that could work with me on a very small pay scale? I am at my wits end, but my inability of letting go and my strong will, will not let me. In closing I also cannot tolerate any antihistamines, I’ve been on them for soo long, my body just doesn’t want ANYTHING synthetic or manmade. Does anyone know if the BBB can be so damaged to the point that anything will pass through? I am sorry if I am not even making sense, as I mentioned earlier, I am shot. 🙂

    • Issie

      September 29, 2018 at 2:25 pm - Reply

      @Tee, Sorry to hear how bad it has gotten for you. I found with myself that I also have LYME and CIRS and another fungal/mold that is in my blood and organs. Using antifungal and enzymes have helped tremedously. Lumberkinanase has actually gotten these molds out of people’s blood and biofilms have gone down. (There is scientific proof of it.) I too am one with high inflammation and a faulty immune system. I think the dysfunction of the immune system comes first and that sets us up for inflammation. I found treatment for MCAS to be only one piece of my puzzle. Treating Lyme and CIRS has taken me to a whole other level.

      Issie

    • Rebecah

      October 2, 2018 at 3:28 am - Reply

      Have you looked into any and all potentially available sources of assistance; EBT, disability, housing, etc? A doctor needs to certify that you can not work. If you are in the US there may well be programs out there for you. Not easy to get assistance, but it’s possible. I’m just about at the same stage you are, but fortunately I received SSDI. I am so sorry for your suffering. Good, healthful food as pure as possible is essential for healing inflammation. If you are anywhere near a Mayo facility you may try to see if you can go there, and also look into qualifying for state insurance.

  • Issie

    September 30, 2018 at 7:01 am - Reply

    Here’s a good article from the doc in the UK I was thinking of.

    https://www.histamine-sensitivity.com/histamine_joneja.html

    Issie

  • Guido den Broeder

    September 30, 2018 at 11:53 am - Reply

    Intranasal sprays could be helpful to combat the chronic rhinovirus co-infection that many ME patients develop. It’s not likely to treat ME itself. The model presented here doesn’t fit the data.

    • Issie

      September 30, 2018 at 3:07 pm - Reply

      With me, as I’ve said before – MCAS is only one piece of my puzzle. It is not the whole picture. But it can make someone very miserable.

      Issie

    • Rebecah

      October 1, 2018 at 12:32 am - Reply

      Something that can deliver needed products more closely to the hyopthalamus could indeed help M.E. patients, I really believe that.

    • Issie

      October 1, 2018 at 4:02 pm - Reply

      I decided to add this comment here. Since I’m treating MARCONS with this latest concoction we formulated……I’m being able to stay off almost all my mast cell and POTS medicines. Makes me wonder if my mast cell responses were in connection with this and an attempt to correct this infection. This is me thinking out loud. But, what if……… We have somewhat corrected my CIRS and Lyme is at bay now too. Possible these 3 things was contributing to my mast cell issues and POTS. I still have both….but it’s good to not be so bad with either of them. Let’s home this new spray gets rid of the staph (MARCONS) and I continue to get better. My diet change has definitely helped and my pain from FMS and EDS is better too.
      Issie

      • Issie

        October 9, 2018 at 2:09 pm - Reply

        Well, with all the rain we have been having – FMS in a flare and along with it MCAS. So back on Allegra and occasional GastroCrom. Also had to add back 1/4 pill of my best medicine I use for my POTS. Feeling more functional and slept last night. At least I know what works for me. Even though it doesn’t “fix” the core issue – at least it’s a nice “bandaid”.
        Issie

  • TK

    September 30, 2018 at 5:48 pm - Reply

    Funny, I always described CFS as an allergy to exertion. Stress tends to increase my tolerance though. Whatever wakes my brain up — Sudafed, traveling, new hobby, emergency in the family — tends to help as long as I carefully watch my pace.

    I’m not sure how this theory of mast cell causing microglia to produce inflammation reconciles with Younger’s theory that microglia’s CCL2 recruiting monocytes through BBB to trigger inflammation. There seems to be some parallel, but then they could be competing theories.. I wish they would establish the brain inflammation as an indisputable fact first before going down too far with the theories. Once that happens, the first order of business will be then to rename CFS as ME, period.

    • Rebecah

      October 1, 2018 at 12:31 am - Reply

      True CFS *IS* M.E. I strongly believe that. New parents, shift workers, etc can be ‘chronically fatigued’. Laura Hillenbrand, author of ‘Seabiscuit’ and ‘Unbroken’, who has M.E. says, ‘This illness is to fatigue what a nuclear bomb is to a match. It’s an absurd mischaracterization”. Her illness is why it took ten years to complete a book!

      I’m curious about what you mean by ‘wakes up’ your brain. Most of the time in M.E., extra stimuli and excitement tends to shut people down.

      • TK

        October 1, 2018 at 2:56 am - Reply

        Probably not until they can establish that there is indeed brain inflammation. Seems like evidences are piling up though, so maybe they will when independent groups replicate the Watanabe team’s result, a fascinating study that mapped the symptoms to inflamed regions.

        Too much stimuli/stress could shut you down, I suppose, especially for the severely ill. But they seems to have positive effect for some people within reason. Things like caffeine does bring a partial relief for me especially combined with slow walk, as long as I watch my pace carefully. (Walking to a café half a mile away used to be my favorite exercise, though now I graduated to biking). So does Sudafed, stress of trying to meet previously planned engagement, traveling to a new place, etc. https://www.healthrising.org/blog/2018/06/02/tks-big-adventure-an-me-cfs-cross-country-trip/

        • Issie

          October 1, 2018 at 4:35 am - Reply

          Sudafed is used by some POTS people who need to constrict the blood vessels. It can hike blood pressure and for some helps with blood flow if veins are lax or too dilated. It is a mild stimulant too. Several POTS people, I know, use it a few days and cycle it. Also when needing more alertness. I can take it (with a cold) as long as I make sure my blood is thin enough. I tend to not do well with vasoconstrictors. There is a fine line for me as to what to use and when.
          Issie

        • Cort Johnson

          October 1, 2018 at 4:20 pm - Reply

          Caffeine does that for me too. It used to give me jitters and abdominal pain but those have faded. Nice to get a boost!

      • Cort Johnson

        October 1, 2018 at 4:23 pm - Reply

        Yes it does….It seems like it gets overloaded. Stimulants, interestingly, can temporarily help – perhaps because they help the brain deal with stimulation but so can anti-anxiety drugs and anti-convulsants like Klonopn which calm down the brain.

  • Rebecah

    October 1, 2018 at 12:26 am - Reply

    As someone with M.E. I’m glad to see this site. Having a background in medical terminology is helping me understand. Has Dr T. developed any products to directly potentially help M.E.? I take mag malate and curcumin, Lion’s Mane, and so many other supps. I get the best I can afford from reputable sellers. Would be intersted in a product that combines beneficial things. Would be the first in line to try intranasallly delivered products!

  • Smythe

    October 1, 2018 at 12:35 am - Reply

    I’ve been diagnosed with ME/CFS and am going to Mayo MN immunologist in November for my low immune response. Any ideas for how to best approach this?

  • Marina

    October 1, 2018 at 6:23 pm - Reply

    Regarding Issie’s post:

    Check out this OTC mast cell stabilizer that is a sinus spray:

    https://www.amazon.com/NasalCrom-Nasal-Allergy-Symptom-Controller/dp/B001F1DV1I/ref=sr_1_fkmr0_1_a_it?ie=UTF8&qid=1538417960&sr=8-1-fkmr0&keywords=mast-cell%2Bstabilizer%2Bcromolyn%2Bsodium&th=1

    Also, I am exploring more regular use of H2 tablets. Hydorgen gas easily passes through the BBB, and removes lactate from the body. You can front load before exertion, or use after. Interestingly, the hydrogen gas is created from magnesium!

    And am going to look into compounded intranasal magnesium, luteolin, and curcumin.

    Such a great series and amazing job you do, Cort!

    • Cort Johnson

      October 3, 2018 at 3:08 am - Reply

      🙂 Thanks!

    • Issie

      October 3, 2018 at 4:40 am - Reply

      NasalCrom is same medicine as GastroCrom. 2 vials of GastroCrom is 10 ml 8 vials is equal to 100mg. Or 12.5 mg per vial. Each spray of Nasal Crom is 5.2 mg. There are 200 sprays per bottle. The recommended RX of GastroCrom is 2 vials 4 times a day. (But I only use 2 to 4 vials a day – if I need them.) They do recommend going slow as there can be a little intestinal issues for some. Some have had increased dizziness. But, with time – many have adjusted. One of my friends,one vial was too much for her and she felt effects too strongly. She uses Ketotofin – but that one wasn’t good for me. Each of us are different. GastroCrom seems to have an accumulative affect.

      Hope this helps.

      Issie

    • Karin

      October 4, 2018 at 1:21 pm - Reply

      Thanks Marina, I’ve just ordered ‘NasalCrom’, has to be worth a try with over 800 5 star reviews from sufferers. I’ve also just ordered Intranasal Glutathione Spray. If you find ‘intranasal magnesium, luteolin or curcumin’ please report back here and let us know !
      I’d also like to know more on your findings with “Hydorgen gas easily passes through the BBB, and removes lactate from the body.”

    • Issie

      October 4, 2018 at 2:06 pm - Reply

      Are you drinking Hydrogen water? What source/type are you using?

      • Marina

        October 4, 2018 at 2:39 pm - Reply

        Hi Issie and All, I am using HRW hydrogen tablets, and starting my 3 x a day dosing TODAY. I will let this thread know if I have results. I did a lot of research on hydrogen tablets, and this brand seems to kick off the most hydrogen, or at least they claim to on youtube. But, there are other H2 tablets out there, and Prohealth offers one. I am a 30+ year ME-CFS patient. My best intervention so far has been LDN 4.5mg on a morning empty stomach, but I try a lot of different things, and take a lot of supplements….

  • Sean O'Donnell

    October 2, 2018 at 10:31 pm - Reply

    If you have pathogens…no amount of luteolin is going to do much in the long run. Chris Kresser and Alisson Vickery have good insights on this. https://chriskresser.com/could-your-histamine-intolerance-really-be-mast-cell-activation-disorder/

    http://alisonvickery.com.au/natural-antihistamine/

    • Issie

      October 3, 2018 at 4:50 am - Reply

      Loved this article. I’ve found with treating Lyme and CIRS my MCAS is better. I appreciate that this was addressed in this article. I haven’t found lutolin to be of help for me. I have found the DAO enzyme to be helpful. I’m still needing GastroCrom, but mostly off my H1 and H2. Unless I get into something or eat wrong or get under stress…..then I take liquid to get the antihistamines in my system faster. I do carry an epipen.
      Nice article.
      Issie

  • Dave

    October 7, 2018 at 11:53 pm - Reply

    Maybe use the nasal stray to spritz anti-viral medicine to the brain-base.

  • Marina

    October 8, 2018 at 3:08 pm - Reply

    Dave, that would be incredible! But I wonder about the long term effects of using Flonase or Rhinocort….does anyone know? I have been using them daily for 10+ years in order to control allergic response…have heard that the steroids have a short half life, but the thought of bathing my brain in steroids is not comforting….I also use an antibiotic ointment Bactroban, inside the nose daily as am prone to chronic staph sinus infections, which also produce biofilm. Yucky I know…but the ointment keeps it in check (as my immune system does not).

    As for H2 gas passing through the BBB, there is a ton of info on this online. Simply google. There are also a lot of pubmed studies on H2 gas as well.

    • Issie

      October 8, 2018 at 3:58 pm - Reply

      @Marina, the staph in the nose could be MARCONS. It goes along with CIRS. It could be antibiotic resistant and the antibiotic you are using daily has just made it worse. The test for that is $85. I’m on my 3rd different type treatment for that. Hope the new thing is working. That alone can cause all sorts of issues.
      Issie

  • Marina

    October 8, 2018 at 8:39 pm - Reply

    Issie, you are a wealth of information! FYI, I use this: SinuPulse Elite Advanced Nasal Sinus Irrigation System, which is supposed to clear the sinuses of biofilm. But shall look into MARCONS. Thank you!

    • Issie

      October 9, 2018 at 2:13 pm - Reply

      Welcome. Hard to get rid of if uou have it. Even though they test the sinus – it can be systemic. And it does cause biofilms.
      Issie

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