Mast Cell Activation Syndrome

[Quantum]

Hi,

I have found this video most interesting.  It is rather long, and this brilliant lady speaks quite fast and in medical terms, but I suggest you can watch it a small section a day, and pause on the graphics to read the info at your pace:

https://vimeo.com/143033968


This gives a clear picture that the immune system is very, very complicated and implies a lot of pathways and substances, and that, for example, simply blocking one branch, like histamine, may help, but usually is far from complete relief, considering all the other branches that can also be activated by the same initial trigger.

This is not about POIS, obviously, but I still believe that, like Dr Waldinger says, a hypersensitivity reaction is involved in POIS, and this is what this video is about.


For a list of natural mast cell stabilizers, see my post at https://poiscenter.com/forums/index.php?topic=2372.msg19856#msg19856

For information about Mast Cell Activation Disease, see https://poiscenter.com/forums/index.php?topic=3236.msg33461#msg33461

[b_jim]

Thanks for the vid.
At 21" minute, she shows a mast cell communication schéma. Can you give the different meditors involved ? (Hitamines and .... ? )

If there is mast cell activation without histamines as dr W said, it necesserly involve these other mediator, isn't it ?

[b_jim]

Other vid from the same author :
https://www.youtube.com/watch?v=ktFdr-9rpIM

Her web site: http://www.drannemaitland.net/index.html
Should we contact her ?

[Quantum]

Thanks for the vid.
At 21" minute, she shows a mast cell communication schéma. Can you give the different meditors involved ? (Hitamines and .... ? )

If there is mast cell activation without histamines as dr W said, it necesserly involve these other mediator, isn't it ?

Hi b-jim,

thanks for your comments.

At 21 mins and around, many pro-inflammatory substances, that can be release by mast cells depending of the circumstances, are listed.  Histamine, of course, but also many cytokines and pro-inflammatory mediators, like TNF-alpha, Interleukin-1 ( IL-1), Interleukin-6 ( IL-6), Leukotriene C4 ( LTC4), Granulocyte-macrophage colony-stimulating factor (GM-CSF), CXCL8 ( = IL-8), substance P.  She explains that, depending on what is activating the mast cells and triggers the degranulation, the substances that are released will vary.

In the image at 21 mins, the substances that are shown to act directly on nerve endings are substance P, TNF-alpha, NGF ( Nerve growth factor), Histamine, and tryptase.


Did you noticed the chart at 9:58, showing the possible symptoms of Masts Cells Activation Disorder ?  It sure look a lot like a list of POIS symptoms !

[Quantum]

Thanks for the vid.
At 21" minute, she shows a mast cell communication schéma. Can you give the different meditors involved ? (Hitamines and .... ? )

If there is mast cell activation without histamines as dr W said, it necesserly involve these other mediator, isn't it ?

I forgot to add that I also think that more than histamine is responsible for the cascade of metabolic events producing the many clusters of symptoms that manifest in POIS.  Even if histamine is present and some symptoms can be associated with it, I think that the complexity of the immune system suppose that many other pro-inflammatory mediators are released in addition to histamine.   

So stabilizing the mast cells and prevent them to release pro-inflammatory mediators seems to be a better strategy than just blocking histamine. 

The use of quercetin in then very interesting in POIS, from my point of view, because it acts direclty on the mast cells, stabilizing them and preventing them to release cytokines and other immune messengers, so not only histamine, but the whole arsenal they hold in their granules.  By preventing degranulation ( the process by which they release their immune messengers in our tissues), quercetin or other mast cells stabilizers temper the cytokine storm that is usually seen in a hypersensitivity reaction.  Studies have proven this effect of quercetin ( for example, see http://www.ncbi.nlm.nih.gov/pubmed/22470478 and http://www.ncbi.nlm.nih.gov/pubmed/27187333 )  My personal experience with quercetin is in agreement with this, I get relief from using it, and it is one of the most important "member" of my pre-E pack of supplements.

Chrysin is another bio-flavonoid, which, like quercetin, have mast cells stabilizing properties ( see http://www.ncbi.nlm.nih.gov/pubmed/21515303 ).  I lately found about this one, so I have bought bee propolis, which contains chrysin.  I am at the beginning of my experiment with it, but so far, I tolesrate well bee propolis ( no side effect), and I feel more energized when taking it.  I am slow in my introduction of a new products, because I had bad surprise in the past, so I did not take it yet in the context of a POIS acute phase. 

There is a prescription mast-cell stabilizer  ( montelukast, brand name Singulair), but like I have already mentioned, I have chosen not to use prescription drugs, as long as I can get relief with a stack of natural products.  Keep in mind that drugs are classified "prescription only" because they have at least one potential serious side effect, so yes, they are powerful, but it is always a give and take.  Sometime, this severe side effect is rare and occur in only a small fraction of users, but I do take a very safe approach.... I had enough problems just with POIS itself, so I prefer quercetin, omega-3, flaxseed oil, and the other supplements that are part of the pack I take before E.

[b_jim]

Did you noticed the chart at 9:58, showing the possible symptoms of Masts Cells Activation Disorder ?  It sure look a lot like a list of POIS symptoms !

Yes, absolutely.

Omega 3 never helped me but taurine does.... and I would like to know why .

If you have improvments it's a good thing.
 

[VSmasher]

Thanks for the vid.
At 21" minute, she shows a mast cell communication schéma. Can you give the different meditors involved ? (Hitamines and .... ? )

If there is mast cell activation without histamines as dr W said, it necesserly involve these other mediator, isn't it ?

I forgot to add that I also think that more than histamine is responsible for the cascade of metabolic events producing the many clusters of symptoms that manifest in POIS.  Even if histamine is present and some symptoms can be associated with it, I think that the complexity of the immune system suppose that many other pro-inflammatory mediators are released in addition to histamine.   

So stabilizing the mast cells and prevent them to release pro-inflammatory mediators seems to be a better strategy than just blocking histamine. 

The use of quercetin in then very interesting in POIS, from my point of view, because it acts direclty on the mast cells, stabilizing them and preventing them to release cytokines and other immune messengers, so not only histamine, but the whole arsenal they hold in their granules.  By preventing degranulation ( the process by which they release their immune messengers in our tissues), quercetin or other mast cells stabilizers temper the cytokine storm that is usually seen in a hypersensitivity reaction.  Studies have proven this effect of quercetin ( for example, see http://www.ncbi.nlm.nih.gov/pubmed/22470478 and http://www.ncbi.nlm.nih.gov/pubmed/27187333 )  My personal experience with quercetin is in agreement with this, I get relief from using it, and it is one of the most important "member" of my pre-E pack of supplements.

Chrysin is another bio-flavonoid, which, like quercetin, have mast cells stabilizing properties ( see http://www.ncbi.nlm.nih.gov/pubmed/21515303 ).  I lately found about this one, so I have bought bee propolis, which contains chrysin.  I am at the beginning of my experiment with it, but so far, I tolesrate well bee propolis ( no side effect), and I feel more energized when taking it.  I am slow in my introduction of a new products, because I had bad surprise in the past, so I did not take it yet in the context of a POIS acute phase. 

There is a prescription mast-cell stabilizer  ( montelukast, brand name Singulair), but like I have already mentioned, I have chosen not to use prescription drugs, as long as I can get relief with a stack of natural products.  Keep in mind that drugs are classified "prescription only" because they have at least one potential serious side effect, so yes, they are powerful, but it is always a give and take.  Sometime, this severe side effect is rare and occur in only a small fraction of users, but I do take a very safe approach.... I had enough problems just with POIS itself, so I prefer quercetin, omega-3, flaxseed oil, and the other supplements that are part of the pack I take before E.

Did you know your brain can release Histamine in neurotransmitter form without mast cells? I take all the herbal mast cell stabilizers before O and I still get symptoms. I think it's our brain release of Histamine that causes POIS and not the mast cell release of histamine.

[FloppyBanana]

VagS,

histamine n-methyltransferase breaks down histamine in the brain. See link its damn expensive to buy though. I don't think this type of product is available for personal use.

https://www.rndsystems.com/search?common_name=Histamine%20N-Methyltransferase/HNMT

Please note I have no financial interest in the above site.

Patrick

[Muon]

POIS is most likely a mast cell activation disorder. 

Mast cells are primitive cells of the immune system which act as “sentinels,” present in all tissues but standing guard most prominently at the body's environmental interfaces, e.g. the skin, the gastrointestinal tract, the respiratory tract and the genitourinary tract. Unlike lymphocytes, which have great specificity, mast cells use non-specific chemical mediators as their dominant mechanism of attack against foreign invaders (e.g. parasites). More than 200 different mast cell mediators have been identified, including histamine, tryptase, heparin, prostaglandins and leukotrienes.

Unlike allergies, which involve specific IgE-mediated activation of mast cells, mast cells in MCAS are activated inappropriately by specific and non-specific triggers, such as positive or negative emotional or physical stress, extremes of temperature or temperature or barometric pressure change, environmental chemicals, alcohol, high histamine foods, odors, physical stimuli (e.g. pressure from a tourniquet), drugs, and the non-drug ingredients (excipients) in medication products. Since mast cells are present in all organs, and since their chemical mediators enter the bloodstream, inappropriate mast cell activation can produce a large number of signs and symptoms that may vary and occur in a fluctuating pattern, often creating a complex clinical picture. Like most diseases, MCAS exists on a spectrum, ranging from very mild to extremely severe, and it has been estimated to affect up to 17% of the population.

Symptoms of MCAS may be acute and/or chronic. Skin flushing, itching, fleeting rashes and hives are very common, but not all patients have grossly obvious cutaneous manifestations. Other common symptoms include bone, muscle, joint and/or neuropathic pain; paresthesias; gastroesophageal reflux; abdominal pain; nausea/vomiting; bowel motility issues (gastroparesis and/or diarrhea alternating with constipation), presyncope/syncope, heart rate and/or blood pressure lability, chest pain, dyspnea (often subtle, typically described as an occasional brief inability to take a deep breath), unexplained weight loss or gain (which may be significant), anxiety, depression, mood lability, cognitive dysfunction, sleep disturbance, lethargy, fatigue, malaise, fevers, night sweats, headache and vertigo. Many patients experience mast cell “flares” or “spells,” but more severely affected patients also have chronic symptoms due to constitutive mediator release aside from mediator release related to aberrant reactivity. Prior to adulthood, patients with MCAS often initially enjoy symptom-free intervals interspersed amongst symptomatic periods. Over time, symptom-free intervals shorten, and finally symptoms become chronic with an intensity which fluctuates, but with an overall trend toward steadily increasing severity. An increase in disease severity often follows major stress. Mast cells are also intimately involved in growth regulation.

Patients with MCAS have often experienced a lifetime of multi-system unwellness with broad themes of inflammation, allergy, and disordered growth. For most MCAS patients, signs of the disease first emerge in childhood (median age at symptom onset is 9 years), but there is an average delay in diagnosis of MCAS of 30 years In one evolving model, MCAS increasingly is being suspected to arise proximately from mutations in one or more mast cell regulatory genes, and these mutations – usually somatic, heterozygous, and multiple – themselves likely emerge due to complex interactions among other mutations which are germline (i.e., inborn) and both genetic and epigenetic6, 7. Stressor-induced cytokine storms, too, may significantly impact these interactions and the development of the consequent somatic mutations (that is, mutations which are acquired, not inborn, but often beginning relatively early in life). MCAS may also occur secondary to an underlying allergic, infectious, immunodeficiency or an autoimmune disorder.

Most of the pois treatment prepacks work  largely by blocking the mast cell activaton or histamine release.

Niacin
http://getwellstaywellathome.com/blog/2015/06/seasonal-allergies-and-the-niacin-flush/

Taurine
https://www.ncbi.nlm.nih.gov/pubmed/28694089

TRT
https://journals.aace.com/doi/pdf/10.4158/EP161530.CR

Relief with Antihistamines, flavanoids in fenugreek&garlic, oral corticosteroids ,methylation support,pre-pack with  IDO/TDO/NMDAr blockers+ anti-oxidants and gluten free diet etc  all point to mast cell activation disorder.

Most of our members get relief with one of the above mentioned ways which also fits with MCAD where everyone has individual triggers and get relief with personalised treatment.

So POIS  is most likely to be MCAD triggered by mast cells present in the urinary tract and causing systemic inflammation which many a time crosses blood brain barrier and results in neural inflammation.

[Muon]

Great compilation (navigate via the bar at the top of the webpage):

https://www.mastattack.org/

[b_jim]

Brilliant, very nice job.

[Nas]

POIS is most likely a mast cell activation disorder. 

It's not for my case, since therapy against MCAS was fruitless.

[demografx]

Brilliant, very nice job.

I agree.

[aswinpras06]

Brilliant, very nice job.

I agree.

Thanks a lot Muon, B_Jim, Demografx and especially Quantum.

Quantum's compilation of Pois types is of great help to everyone suffering from POIS.

Before joining here I knew nothing about medical causes for Pois.  Now I believe I have gained some medical knowledge by reading the posts on this wonderful forum.

Thanks Demo and other administrators  for running such a great forum.

Some members have only neural symptoms.  I have found some links on mast cell and neural inflammation&diseases

https://www.frontiersin.org/articles/10.3389/fncel.2019.00054/full
https://jhu.pure.elsevier.com/en/publications/a-mast-cell-specific-receptor-mediates-neurogenic-inflammation-an
https://www.omicsonline.org/open-access/the-role-of-mast-cells-and-neuroglia-in-neuroinfectious-diseases-2314-7326-1000190.php?aid=66265
https://www.hindawi.com/journals/mi/2016/1924603/
https://link.springer.com/chapter/10.1007%2F978-3-0348-8131-9_7

[aswinpras06]

POIS is most likely a mast cell activation disorder. 

It's not for my case, since therapy against MCAS was fruitless.

Hi Nas

As per  a recent article from American Academy of Allergy, Asthma & Immunology.  mast cell diseases can only be partially  treated with current medications.
Hence your failure with therapy for MCAS may not rule out whether you have the disease or not unless you meet a immunologist for confirmation.
 
https://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/mast-cells

[Nas]

Hi Nas

As per  a recent article from American Academy of Allergy, Asthma & Immunology.  mast cell diseases can only be partially  treated with current medications.
Hence your failure with therapy for MCAS may not rule out whether you have the disease or not unless you meet a immunologist for confirmation.
 
https://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/mast-cells

Yes well I wasn't even partially treated; I wasn't treated at all. I think my research on MCAS and the methodology I used all conform that MCAS is not involved in my case.

[Muon]

''These unique tissue immune cells are critical for allergic reactions triggered by immunoglobulin E (IgE), but are also stimulated (not activated) by immune, drug, environmental, food, infectious, and stress triggers, leading to secretion of multiple mediators often without histamine and tryptase.''

Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders?

''MC-hippocampal neuron interaction affects neuronal [Ca2+]i and exocytosis signaling through a NMDAR-dependent mechanism.''

Proteoglycans involved in bidirectional communication between mast cells and hippocampal neurons

Don't know where to place this but I found this one interesting as well:
''Importantly, this is the first evidence that the CAIP has a role in modulating type 2 mediated immune disorders, as it was previously only investigated in disorders characterized by innate an Th1/Th17 immune responses, therefore expanding the applicability of VNS as a therapeutic tool to an even wider range of immune disorders.''

The cholinergic tone as a modulator of Food Allergy

[Nas]

I personally lean towards the hypothesis that the flu like/allergy symptoms of POIS are not based on semen auto-immunity, rather on a dysfunction in the limbic system causing a plethora of physical manifestations.
The vagus nerve is incredibly close to the limbic system.

[Muon]

Here you can find publications from Dr. Theoharides which are free:

https://www.mastcellmaster.com/publications.php

[Muon]

I wondered whether we could overcome the problem of bioavailability by vaporising some of the substances. Camomile, fennel and other natural herbs could be consumed this way. For example does this post (https://medium.com/cbd-origin/what-is-cbd-bioavailability-and-why-does-it-matter-69d9a2e37e6c) compare the bioavailability of CBD through digestion (4-20%), sublingual (12-35%) and vaporising (34-46%). Camomile and fennel teas already have a significant influence on my symptoms, even when taken a post medication.

I might do a trail just by inhaling both.

Does anyone have experience with vaporising substances?

https://en.wikipedia.org/wiki/Chamomile#Research

Go to the research section of that page. I'm not surprised, the main compounds are natural mast cell stabilizers.

Apigenin is a mast cell stabilizer, crosses the BBB and is abudant in Chamomile flowers:
https://en.wikipedia.org/wiki/Apigenin#Sources_in_nature

I wonder if these flowers can be vaporized and inhaled without serious side effects.
''Apigenin readily crosses the blood-brain barrier and has not demonstrated toxicity at high doses.[17] It could thus prevent amyloid beta deposition and tau phosphorylation due to neuroinflammation, which are associated with Alzheimer's disease.[17]

Are you thinking about vaporizing these flowers Jacob?