Post Orgasmic Illness Syndrome (P.O.I.S.)

POIS Cause/Treatment Discussions => Hormonal Causes and Treatments => Topic started by: Quantum on May 11, 2016, 08:20:16 PM

Title: Mast Cell Activation Syndrome
Post by: Quantum on May 11, 2016, 08:20:16 PM
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 (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 (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 (https://poiscenter.com/forums/index.php?topic=3236.msg33461#msg33461)
Title: Re: Mast Cells Activation Syndrome
Post by: b_jim on May 19, 2016, 03:02:58 AM
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 ?
Title: Re: Mast Cells Activation Syndrome
Post by: b_jim on May 19, 2016, 03:06:23 AM
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 ? :)
Title: Re: Mast Cells Activation Syndrome
Post by: Quantum on May 19, 2016, 08:50:10 PM
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 !

Title: Re: Mast Cells Activation Syndrome
Post by: Quantum on May 20, 2016, 07:48:57 AM
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.
Title: Re: Mast Cells Activation Syndrome
Post by: b_jim on May 21, 2016, 02:21:36 PM
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.
 

Title: Re: Mast Cells Activation Syndrome
Post by: VagSmasher on May 21, 2016, 10:39:27 PM
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.
Title: Re: Mast Cells Activation Syndrome
Post by: FloppyBanana on May 22, 2016, 12:37:12 AM
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
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on May 06, 2019, 01:56:24 PM
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.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on May 06, 2019, 03:26:32 PM
Great compilation (navigate via the bar at the top of the webpage):

https://www.mastattack.org/
Title: Re: Mast Cells Activation Syndrome
Post by: b_jim on May 06, 2019, 03:35:36 PM
Brilliant, very nice job.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on May 06, 2019, 05:03:48 PM

POIS is most likely a mast cell activation disorder
It's not for my case, since therapy against MCAS was fruitless.
Title: Re: Mast Cells Activation Syndrome
Post by: demografx on May 06, 2019, 09:59:26 PM
Brilliant, very nice job.
I agree.
Title: Re: Mast Cells Activation Syndrome
Post by: aswinpras06 on May 07, 2019, 12:56:26 AM
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
Title: Re: Mast Cells Activation Syndrome
Post by: aswinpras06 on May 23, 2019, 10:03:46 AM

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
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on May 23, 2019, 01:11:37 PM

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.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on June 29, 2019, 05:20:42 PM
''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? (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)

''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 (https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1504-6)

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 (https://lirias.kuleuven.be/2798215?limo=0)
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on June 29, 2019, 10:03:49 PM
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.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on June 30, 2019, 05:29:36 AM
Here you can find publications from Dr. Theoharides which are free:

https://www.mastcellmaster.com/publications.php
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on June 30, 2019, 10:30:09 AM
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?
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on August 05, 2019, 12:02:18 PM
Mast Cells in Gut and Brain and Their Potential Role as an Emerging Therapeutic Target for Neural Diseases (https://www.frontiersin.org/articles/10.3389/fncel.2019.00345/full)

Describes gut-brain axis dysfunction. Introducing tryptophan producing microbiotica could be a therapeutic tool.
Title: Re: Mast Cells Activation Syndrome
Post by: OpiesDad on August 16, 2019, 07:19:27 PM
Guys this is it.  I would bet $100k bucks my POIS is a MAST cell activation related disorder.  I am booked to see a specialist next week.  As an aside, that linked presentation was brilliant.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on August 16, 2019, 07:32:25 PM
Guys this is it.  I would bet $100k bucks my POIS is a MAST cell activation related disorder.  I am booked to see a specialist next week.  As an aside, that linked presentation was brilliant.
Bet me, I'd use some of that 100k myself.
I bet you 100k it's not MCAS.
Title: Re: Mast Cells Activation Syndrome
Post by: OpiesDad on August 16, 2019, 09:25:50 PM
I'd need to see your proof of funds, and we'd put both in escrow, but yeah I'd bet.  :)
Title: Re: Mast Cells Activation Syndrome
Post by: aswinpras06 on August 17, 2019, 02:51:18 AM
Hi OpiesDad

Even I am 100% sure it is mast cell activation disorder.  Only drawback is it is very complex problem only a few specialists understand and each one of us require individualised treatment.  Current biologic therapies for mast cell are promising and may soon reach mainstream medicine.  Once they are approved we can get rid of this monster.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on August 17, 2019, 03:50:57 AM
I'd need to see your proof of funds, and we'd put both in escrow, but yeah I'd bet.  :)
I don't have that much. Honestly if I had this amount I'd spend it on research for POIS. So if you actually have this amount why not help with research funding?
Title: Re: Mast Cells Activation Syndrome
Post by: OpiesDad on August 18, 2019, 10:39:11 PM
Nas, I promise when we have another research oppty I'm pitching in $$$.  In any event, I am meeting with a well regarded immunologist in LA this week who has background in mast cell conditions.  Let's pray for all of us that he takes an interest in the case and has a novel approach.....
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on August 19, 2019, 08:25:11 AM
Nas, I promise when we have another research oppty I'm pitching in $$$.  In any event, I am meeting with a well regarded immunologist in LA this week who has background in mast cell conditions.  Let's pray for all of us that he takes an interest in the case and has a novel approach.....
An advise from me would be to spend money studying your brain chemistry. Study your brain pathways and neurotransmitters during POIS. That's in my opinion money well spent. You will need to gain access to PT/MRI for that, which will showcase changes in brain chemistry during POIS. It serves the purpose of knowing the mechanism through which POIS causes us the brain symptoms. PT/MRI is expensive so if you have money you'd do us a great service if you undertook one.
Title: Re: Mast Cells Activation Syndrome
Post by: demografx on August 20, 2019, 10:48:04 AM

...when we have another research oppty I'm pitching in $$$. 


Hello OpiesDad,

Wonderful to hear.

T H A N K   Y O U!

Demo
(on behalf of the entire Forum
and for POISers everywhere!)



Title: Re: Mast Cells Activation Syndrome
Post by: aswinpras06 on September 03, 2019, 10:14:57 PM
Hi Nas

You've always said any mast cell medicine never worked for you,  but only Corticosteroids such as dexamethasone. Do you know that 

Corticosteroids such as dexamethasone are effective inhibitors of mast cell activation and a proven treatment for mast cell-associated diseases . In fact, it is recently found that dexamethasone inhibits not only IgE- but also IL-33-mediated mast cell function.

https://www.frontiersin.org/articles/10.3389/fimmu.2018.00868/full
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on September 04, 2019, 06:37:12 AM
Dexamethasone is not really a cure so I stopped taking it. It helps a bit since it has a bit of psychoactive properties but other than that it doesn't stop POIS.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on September 15, 2019, 02:55:57 PM
Interesting video, a short Lecture by Professor Theoharis C Theoharides:
 
https://www.youtube.com/watch?v=HNNPsZlDTEQ

Interview, Episode #58: Mast Cell Master with Dr. T.C. Theoharides, PhD, MD:

https://www.youtube.com/watch?v=6gfTFwJgIVQ
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on October 23, 2019, 10:09:21 AM
Video about 'Brain Allergy':

'Brain Allergy' and ASD - T. Theoharides, MD, PhD (https://www.youtube.com/watch?v=9QbZp3WcC1Q)
Title: Re: Mast Cells Activation Syndrome
Post by: b_jim on October 24, 2019, 02:05:55 PM
In USA, ketamine spray is for sale now for depression. It might be a potential cure for Pois.
We already talk about ketamine effect on tryptophan.

It seems ketamine blocks mast cells inflammatory activity.
If Pois works like mast cells syndrome, I think using the spray could be interesting.
 
Title: Re: Mast Cells Activation Syndrome
Post by: Guts on October 24, 2019, 05:19:46 PM
I tried different NMDA recepter antagonist ( i think it was cant remember if its agonist or not )
Basically all kinds of ketamine analogues, I'm not that impressed, still had massive amounts of brainfog and itching.
It only helped depression, anxiety and neuropathy and probably gut function. It surely got rid of severe nerve pain in the spine

I would defo go for the ketamine nosespray, but i don't think its a cure especially at lower dosages
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on October 24, 2019, 06:23:29 PM
There is communication between the Vagus nerve and intestinal mucosal mast cells. I wonder if there is communication between the same nerve and mucosal mast cells of the genitourinary system.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on November 05, 2019, 12:34:24 PM
I did send the following email to http://brain-gate.org :

Hello,

Would Dr. Theoharides be interested in investigating mast cell involvement in Post Orgasmic Illness Syndrome?
I'm a POIS patient myself and have a suspicion mast cell activation might play a role in this disease.

I'm thinking about setting up a crowdfunding project for this. Patients can be recruited from the poiscenter forum: https://poiscenter.com/forums/index.php

Paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001999/

All Papers:
https://poiscenter.com/forums/index.php?topic=3127.0

Video:
https://www.youtube.com/watch?v=KrgZIkAEGW0

Patients also have all kinds of other sensitivites like food and environmental ones, some of these can actually trigger the same symptoms as POIS. There is also some overlap with autistic like symtpoms, avoiding eye contact etc.

Perhaps Dr. Theoharides could investigate this and report his findings in a paper. Study could be funded by community crowdfunding.

Best Wishes,
Muon

And received an answer from Dr. Theoharides himself:

''This is a very interesting topic.

See my somewhat related publications attached.

Unfortunately, I am presently trying to find funds to continue my mast cell research and cannot divert the focus.

Please keep me posted.

TCT.
''

The full articles he attached to his email:
 
- Genitourinary mast cells and survival (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708553/)
- Intimate Contact Could Be Dangerous for Your Health (https://sci-hub.se/10.1016/j.clinthera.2019.04.010)
- Neuroendocrinology of mast cells: Challenges and controversies (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)
Title: Re: Mast Cells Activation Syndrome
Post by: Hopeoneday on November 05, 2019, 01:50:30 PM
Muon, nice moves.
Title: Re: Mast Cells Activation Syndrome
Post by: demografx on November 05, 2019, 04:40:16 PM
Muon, as you suggested, sent post to NORD researchers.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on November 08, 2019, 06:32:03 PM
Apparently testosterone exerts an inhibitory effect on mast cells, thus TRT could act as a mast cell stabilizer. See table 1 in 'The neuroendocrinology of mast cells' (https://www.dropbox.com/sh/i4ploderhgty86o/AAABk_eHd89Af66YjyGLZa7Ta?dl=0)
Didn't we have a few poisers who were using Progesterone with succes? Take a look at the table again, it's capable of exerting an inhibitory effect on mast cells as well.

Ok now, go to the supplementary data etable1: https://www.smoa.jsexmed.org/article/S2050-1161(18)30019-9/fulltext

Look at the hormone balance. Estradiol is high which is a mast cell stimulant at the same time Testosterone is low which is an inhibitor.

The net effect favors mast cell stimulation according to table 1 and figure 1 in 'The neuroendocrinology of mast cells' (https://www.dropbox.com/sh/i4ploderhgty86o/AAABk_eHd89Af66YjyGLZa7Ta?dl=0).

You might generalize this by every other imbalance in the body like dysbiosis(TLR) and other immune parameters which favors mast cell stimulation. Some people tend to be more sensitive to stimuli than other people. These people have less locks to unlock before getting triggered. Now these imbalances already unlock a few locks, the stronger the imbalance, the more locks will open up thus increasing the tendency for mast cells to react on stimuli and making you more sensitive.

Mast cells support autocrine actions. They can grow receptors on themselves by their own actions. Some imbalance in the body might grow receptors on genitourinary mast cells which let them act on molecules in seminal fluid.

The long lasting POIS reaction (days to weeks) could be explained by the autocrine actions which keeps positive feedback loops or self perpetuating loops intact.

Now to think of it this might explain my short lived dampening of arousal/precum exposure symptoms by strong orgasm before hell breaks loose after ejaculation as time goes by. Each hormone might have a different concentration vs time curves, the inhibitory ones might have the upper hand at the start of orgasm interfering with genitourinary mast cell activation by ejaculation. My POIS is heavier when orgasm is weak. There is a competition going on between orgasm and ejaculation while orgasm itself could be a double edged sword.

It could all lead to the same cell type but there could be hundreds of ways.
Title: Re: Mast Cells Activation Syndrome
Post by: nanna1 on November 09, 2019, 04:13:06 PM
A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.

"The particularity of the case is that the patient had no obvious local or generalized allergic reaction, which can delay and even obscure the diagnosis...
2. Systemic Mastocytosis;... The second differential diagnosis was invalidated, because of the absence of major and/or minor criteria for mastocytosis. There were no obvious rashes or hematological changes in the number or morphology of mast cells."

POST COITAL ALLERGY - A CASE REPORT OF POST ORGASMIC ILLNESS SYNDROME. Med. Surg. J. - Rev. Med. Chir. Soc. Med. Nat., Iaşi - 2019 - vol. 123, no. 2 (https://www.revmedchir.ro/index.php/revmedchir/article/view/1798/1449)

  They looked at the mast cells of this patient under the microscope and found them to be normal in quantity and appearance. The researchers could not observe any signs of mast cell activation.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on November 09, 2019, 04:38:30 PM
A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.
I haven't read anything about the testing of a MCAS model.

The researchers could not observe any signs of mast cell activation.
Where did you read that? I can't find it.
Title: Re: Mast Cells Activation Syndrome
Post by: nanna1 on November 10, 2019, 08:13:58 PM
A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.
I haven't read anything about the testing of a MCAS model.

The researchers could not observe any signs of mast cell activation.
Where did you read that? I can't find it.
  To make a long story short, the paper "POST COITAL ALLERGY - a case report of post orgasmic illness syndrome (https://poiscenter.com/forums/index.php?topic=2301.msg31659#msg31659)" looked for signs of anaphylaxis in the POIS patient they studied. They did not find that anaphylaxis was apart of this patient's POIS. With the exception of abdominal pain-nausea, the POIS patient's symptoms (see Section: CASE REPORT) do not match the characteristic features of mast cell activation syndrome (MCAS) and anaphylaxis. Anaphylaxis is the first diagnostic criteria for MCAS given by the American Academy of Allergy Asthma and Immunology.

  I used a standard definition of mast cell activation syndrome (MCAS). There are many non-standard descriptions of MCAS on the internet. But without a clear definition (diagnostic criteria), the concept of MCAS can be stretched to include any disease. The definition of MCAS that I used, comes from the American Academy of Allergy Asthma and Immunology (AAAAI) (https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas). They state the following:
"Section: IDIOPATHIC MAST CELL ACTIVATION SYNDROME
MCAS is a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis - allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing and severe diarrhea....Evaluation for MCAS starts with determining whether the symptoms occur in separate attacks and are typical symptoms of an anaphylactic reaction without a clear cause.
" -American Academy of Allergy Asthma and Immunology: MAST CELL ACTIVATION SYNDROME (MCAS) (https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas)

The AAAAI states that there are three stages to diagnosing MCAS. In summary,
  The POIS patient in this paper (https://poiscenter.com/forums/index.php?topic=2301.msg31659#msg31659) failed the first diagnostic criteria for MCAS (anaphylaxis), which also overlaps with mastocytosis. So under the AAAAI definition of MCAS, the patient would not be diagnosed with MCAS. Below, I have added additional quotes from the paper to make this clearer:

"The particularity of the case is that the patient had no obvious local or generalized allergic reaction, which can delay and even obscure the diagnosis...
Past medical history: no history of allergy...
Family history: one of his children was diagnosed with atopic dermatitis. No family history of allergies or diabetes...
Physical exam: absence of physical signs or symptoms, no local or generalized eruption or swelling, normal blood pressure and pulse...
2. Systemic Mastocytosis;... The second differential diagnosis was invalidated, because of the absence of major and/or minor criteria for mastocytosis. There were no obvious rashes or hematological changes in the number or morphology of mast cells."

POST COITAL ALLERGY - A CASE REPORT OF POST ORGASMIC ILLNESS SYNDROME. Med. Surg. J. - Rev. Med. Chir. Soc. Med. Nat., Iaşi - 2019 - vol. 123, no. 2 (https://www.revmedchir.ro/index.php/revmedchir/article/view/1798/1449)

  Furthermore, it is unclear how an IgE allergen could past from the prostate to the blood stream and diffuse throughout the entire body without causing anaphylaxis-allergy. Mast cell are in every part of the body. The paper also claims that injecting the POIS patient's autologous semen caused different symptoms than the patient's typical POIS symptoms. Is there something about the allergy-hypothesis that I do not understand?
Title: Re: Mast Cells Activation Syndrome
Post by: Quantum on November 23, 2019, 12:25:35 PM
Video about 'Brain Allergy':

'Brain Allergy' and ASD - T. Theoharides, MD, PhD (https://www.youtube.com/watch?v=9QbZp3WcC1Q)


Interesting, lots of info in the video.  He seems to show a preference for luteolin as a good mast cells stabilizer.   It is a great natural mast cells stabilizer, indeed.  It was part of the list I made in 2016:   https://poiscenter.com/forums/index.php?topic=2372.msg19856#msg19856 .  It would be great if this autism research would lead to the availability of luteolin supplements.  For now, I have been using artichoke, rosemary oil, chamomile and the like, as sources of luteolin.  By comparison, it is much easier to have good quercetin or L-theanine supplements.   

The article I give the link to in my above mentioned post is still a very good reference for natural mast cells stabilizers:  https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12138
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on December 17, 2019, 02:29:38 PM
Episode #106: Bartonella and MCAS with Dr. Tania Dempsey, MD (https://www.youtube.com/watch?v=937sZJDNVGw)

She also mentions getting results with carnivore and ketogenic diet.

Key Takeaways:

- What are the vectors for Bartonella transmission?
- What are the hallmark symptoms of Bartonella infection?
- Is Bartonella more common and more devastating than Lyme itself?
- How does Bartonella impact the neurological system and result in symptoms that may appear to be mental and emotional?
- What testing approach has been most helpful for identifying Bartonella?
- What is the role of Bartonella in autoimmunity and in conditions such as PANS, Rheumatoid Arthritis, POTS, dysautonomia, insulin resistance, and Type 1 diabetes?
- What is the connection between Bartonella and MCAS?
- What is MCAS, and how does it impact the body?
- How common is MCAS in the general population and in the chronically ill population?
- What are the best tools to test for the presence of MCAS?
- What is the QEESI, and how do MCAS and MCS overlap?
- What is the role of the vagus nerve in MCAS?
- How does one detoxify the body if toxins themselves lead to mast cell activation?
- Is CIRS a mast cell activation syndrome induced by mold?
- How is MCAS treated? 
- What is the role of genetic and epigenetics in MCAS?
- What is the role of neuroplasticity or limbic system retraining in MCAS?
Title: Re: Mast Cells Activation Syndrome
Post by: romies on December 17, 2019, 04:09:43 PM
Great work guys. I have also been in the camp too that a lot of POIS cases are under the umbrella of MCAS.
Title: Re: Mast Cells Activation Syndrome
Post by: aswinpras06 on December 18, 2019, 12:29:36 AM
Luckily for Animus he doesn't have POIS caused by hot/cold showers, extremes of temperature and other allergies.  Because for all these, surgery will never work.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on December 25, 2019, 11:55:43 AM
Check the tables for an overview:

Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders? (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on January 12, 2020, 08:29:58 PM
Interstitial cystitis/BPS:

Mast cell activation syndrome (https://tau.amegroups.com/article/view/8090/8845)

Her second suggestion applied to other locations within the genitourinary system would be of interest to POIS research, replace the words bladder biopsies and IC/BPS patients by urethra/prostate biopsies and POIS patients:

''If there appears to be no difference between the two groups, next steps should include use of an electron microscopy using time lapse photography on bladder biopsies from IC/BPS patients and controls to see if the mast cells in the biopsies of IC/BPS patients are degranulating at a more frequent rate, or releasing inflammatory mediators without degranulating compared to the control group.''

Rheumatoid Arthritis:

Mast Cells Mediate Rheumatoid Arthritis - Inhibitory Role of IL-37 (http://www.dl.begellhouse.com/journals/2ff21abf44b19838,forthcoming,33176.html)
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on January 13, 2020, 01:24:34 PM
MCAD genetics:

See figure 3 for an overview:
The genetic basis of mast cell activation disease - looking through a glass darkly (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S1040842814001498)

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2567.2012.03627.x)

Familial Occurrence of Systemic Mast Cell Activation Disease (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076241)

MCAS family symptom frequency:

Characterization of Mast Cell Activation Syndrome (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/)

Extensive list in Supplementary Material.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on January 13, 2020, 07:08:46 PM
Table 1: Symptoms and findings in mast cell (MC) activation disease, Potential manifestations of mast cell disease:

Often seen, rarely recognized: mast cell activation disease - a guide to diagnosis and therapeutic options (https://sci-hub.se/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231)

The supplemental data including therapeutic options is not included in the paper itself but can be downloaded for free in docx format:

https://www.tandfonline.com/doi/suppl/10.3109/07853890.2016.1161231?scroll=top
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on January 14, 2020, 09:03:46 AM
Luckily for Animus he doesn't have POIS caused by hot/cold showers, extremes of temperature and other allergies.  Because for all these, surgery will never work.
He actually has allergies. I wonder if the allergies have contributed to the increased responsiveness of his genitourinary mast cells.

Because I have Allergies, and POIS never ever felt like an Allergy to me.
That's because POIS probably isn't an allergic activation of the mast cell.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on January 14, 2020, 11:11:21 AM
A recent POIS paper (2019) tested the MCAS and systemic mastocytosis models for POIS.
I haven't read anything about the testing of a MCAS model.

The researchers could not observe any signs of mast cell activation.
Where did you read that? I can't find it.
  To make a long story short, the paper "POST COITAL ALLERGY - a case report of post orgasmic illness syndrome (https://poiscenter.com/forums/index.php?topic=2301.msg31659#msg31659)" looked for signs of anaphylaxis in the POIS patient they studied. They did not find that anaphylaxis was apart of this patient's POIS. With the exception of abdominal pain-nausea, the POIS patient's symptoms (see Section: CASE REPORT) do not match the characteristic features of mast cell activation syndrome (MCAS) and anaphylaxis. Anaphylaxis is the first diagnostic criteria for MCAS given by the American Academy of Allergy Asthma and Immunology.

  I used a standard definition of mast cell activation syndrome (MCAS). There are many non-standard descriptions of MCAS on the internet. But without a clear definition (diagnostic criteria), the concept of MCAS can be stretched to include any disease. The definition of MCAS that I used, comes from the American Academy of Allergy Asthma and Immunology (AAAAI) (https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas). They state the following:
"Section: IDIOPATHIC MAST CELL ACTIVATION SYNDROME
MCAS is a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis - allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing and severe diarrhea....Evaluation for MCAS starts with determining whether the symptoms occur in separate attacks and are typical symptoms of an anaphylactic reaction without a clear cause.
" -American Academy of Allergy Asthma and Immunology: MAST CELL ACTIVATION SYNDROME (MCAS) (https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas)

The AAAAI states that there are three stages to diagnosing MCAS. In summary,
  • Measure the presence of anaphylaxis (hives, low blood pressure, vomitting, etc... see Section: SYMPTOMS (https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas))
  • Measure mast cell mediators (tryptase, N-methyl-histamine, etc...) during acute phase and baseline (see Section: MEDIATORS)
  • Block mast cell mediators and observe symptom reduction
  The POIS patient in this paper (https://poiscenter.com/forums/index.php?topic=2301.msg31659#msg31659) failed the first diagnostic criteria for MCAS (anaphylaxis), which also overlaps with mastocytosis. So under the AAAAI definition of MCAS, the patient would not be diagnosed with MCAS. Below, I have added additional quotes from the paper to make this clearer:

"The particularity of the case is that the patient had no obvious local or generalized allergic reaction, which can delay and even obscure the diagnosis...
Past medical history: no history of allergy...
Family history: one of his children was diagnosed with atopic dermatitis. No family history of allergies or diabetes...
Physical exam: absence of physical signs or symptoms, no local or generalized eruption or swelling, normal blood pressure and pulse...
2. Systemic Mastocytosis;... The second differential diagnosis was invalidated, because of the absence of major and/or minor criteria for mastocytosis. There were no obvious rashes or hematological changes in the number or morphology of mast cells."

POST COITAL ALLERGY - A CASE REPORT OF POST ORGASMIC ILLNESS SYNDROME. Med. Surg. J. - Rev. Med. Chir. Soc. Med. Nat., Iaşi - 2019 - vol. 123, no. 2 (https://www.revmedchir.ro/index.php/revmedchir/article/view/1798/1449)

  Furthermore, it is unclear how an IgE allergen could past from the prostate to the blood stream and diffuse throughout the entire body without causing anaphylaxis-allergy. Mast cell are in every part of the body. The paper also claims that injecting the POIS patient's autologous semen caused different symptoms than the patient's typical POIS symptoms. Is there something about the allergy-hypothesis that I do not understand?

If you use to first criteria of AAAAI's definition then yes you are right, you can discard MCAS. This is also the only criteria which differs between other MCAS diagnostic algorithms btw.

Mast cells can release selectively. Mast cells being triggered by stress for example would not release tryptase nor histamine but release cytokines only.  Her investigation is not sufficient to exclude mast cell activation. Measuring tryptase alone while there are over 200 mediators, looking for spindle shaped mast cells and proliferation which doesn't play a role in most MCAS cases and saying she tested a model for MCAS is like shooting yourself in the foot. She cleary stated that she investigated Mastocytosis rather than a more generalized form of mast cell disorder like MCAS or hyperresponsive mast cells without degranulation.

''the concept of MCAS can be stretched to include any disease''
The diagnostic criteria of MCAS is more like a placeholder at the moment.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on January 14, 2020, 01:46:58 PM
I agree with many of your points Muon but my experience with MCAS group and talking to many people had sent me to the conclusion that MCAS is strongly identified by anaphylaxis and histamine. Anti-histamines should work even if slightly but in our case it's a not at all situation. If Mast Cells turned out to be truly involved then it would be an oddity within the MCAS spectrum.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on January 14, 2020, 02:14:41 PM
However I do have a mucusal issue with my urethra after orgasm. I tried so many mast cells stabilizers but not even a slight improvement.
Title: Re: Mast Cells Activation Syndrome
Post by: aswinpras06 on January 15, 2020, 06:24:56 AM
An excellent recent article on influence of mast cells in gut and brain on neural diseases.

Major depression, emotional, and chronic stress lead to the activation and alteration in limbic regulation of the hypothalamic–pituitary–adrenal (HPA) axis, whose altered regulation is usually associated with centralized pain syndromes (Menke, 2019). Under normal conditions, an acute stress induces the hypothalamus to release the corticotrophin-releasing factor (CRF) that induces the anterior pituitary gland to release adrenocorticotropic hormone (ACTH), which causes the adrenal cortex to release glucocorticoids that play metabolic roles (Herman et al., 2003). A negative feedback loop turn off the HPA axis activation (Kageyama and Suda, 2009). Subjects with pain syndromes present altered signaling from HPA axis but also mood disorders, including depression and anxiety (Bao and Swaab, 2019). The crucial link connecting these disorders is the inflammation mediated and modulated by cells, whose leaders are the mast cells (MCs).


It also explains nicely why mast cell stabilizers don't work for many because still more research is needed in effective mast cell stabilizers.

https://www.frontiersin.org/articles/10.3389/fncel.2019.00345/full
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on January 17, 2020, 10:19:46 AM
IBS:

Mast Cells in Irritable Bowel Syndrome: A Systematic Review. (https://www.jgld.ro/jgld/index.php/jgld/article/view/229/166)

Symptoms of mast cell activation syndrome in functional gastrointestinal disorders (https://sci-hub.se/10.1080/00365521.2019.1686059)

The Emerging Role of Mast Cells in Irritable Bowel Syndrome (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009183/)

Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta‐analysis (https://onlinelibrary.wiley.com/doi/full/10.1111/nmo.13718)

Colitis:

Increased Mast Cell Counts and Degranulation in Microscopic Colitis (https://new.hindawi.com/journals/grp/2020/9089027/)

Chronic spontaneous urticaria:

Evidence for bradykinin release in chronic spontaneous urticaria (https://onlinelibrary.wiley.com/doi/abs/10.1111/cea.13558)

Innate and adaptive Immunity

''however, as shown in Fig. 1, there is evidence that, depending on the circumstances, mast cells can either enhance innate responses that help to clear bacterial infections or exacerbate pathology associated with infections.''

See Figure 1:
Mast cells in allergy and infection: Versatile effector and regulatory cells in innate and adaptive immunity (https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201040559)

See Table 2, Salient features of mast cells and traditional phagocytes:
Mast Cells in Infection and Immunity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC175499/pdf/653501.pdf)

See Figure 1 for mast cell receptors which are involved in pathogen recognition:
The Role of Mast Cells in the Defence against Pathogens (https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002619)

POTS

Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome (https://n.neurology.org/content/84/14_Supplement/P1.277)

Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders (https://www.ahajournals.org/doi/full/10.1161/01.HYP.0000158259.68614.40)

Restless Legs Syndrome

Restless legs syndrome is associated with mast cell activation syndrome (https://jcsm.aasm.org/doi/abs/10.5664/jcsm.8216)

I wonder how long it will take before we'll see a paper like: Symptoms of mast cell activation syndrome in Post Orgasmic Illness Syndrome or The Emerging Role of Mast Cells in Post Orgasmic Illness Syndrome.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on February 12, 2020, 09:06:37 AM
''that POIS is caused by Type‐1 and Type‐IV allergy to the males' own semen, as soon it is triggered by ejaculation.'' Ref (https://www.jsm.jsexmed.org/article/S1743-6095(15)33455-X/fulltext)

Mast cells are part of the innate and adaptive immune system. They can behave both as a type 1 and type IV hypersensitivity. Doesn't the above conclusion insinuates two type of cells are involved, mast cells and T-cells? I think the mast celll is the culprit here behaving as it is a type I and type IV allergy but not antibody mediated. There is something going on with the mast cell itself. They can also undergo phenotypic changes by the way.

If there is something wrong with mast cell behaviour other true parallel allergies perhaps might change the phenotype of mast cells.  IgE can activate mast cells in MCAD without the need for allergen-IgE binding, coupling to high affinity IgE receptors is sufficient, same for IgG receptors.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on February 12, 2020, 09:57:13 AM
So Muon what would you say the cause for mast cell activity in the CNS? Ejaculation or orgasm?
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on February 12, 2020, 11:00:26 AM
So Muon what would you say the cause for mast cell activity in the CNS? Ejaculation or orgasm?
In my mind...mutations in genes of epigenetic regulators could be the cause. POIS symptoms could be ignited by any potential change in the body induced by sexual activity that is able to interact with mast cells. Mast cells are close to nerves and can tap into the CNS. God knows what it's doing from there on. The symptoms may not even come from the mast cells itself directly but from other cells by CNS signaling. These are my two cents, ask someone else and you will get a different answer. If gene mutations are involved people can be sorted into groups of mutations and those groups might respond to the same 'treatment'.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on February 12, 2020, 11:13:52 AM
In my mind...mutations in genes of epigenetic regulators could be the cause. POIS symptoms could be ignited by any potential change in the body induced by sexual activity that is able to interact with mast cells. Mast cells are close to nerves and can tap into the CNS. God knows what it's doing from there on. The symptoms may not even come from the mast cells itself directly but from other cells by CNS signaling. These are my two cents, ask someone else and you will get a different answer. If gene mutations are involved people can be sorted into groups of mutations and those groups might respond to the same 'treatment'.
Genetic POIS sounds very reasonable given how rare POIS is. But the question that is left to be answered is, what is the bases for your POIS theory? The thing or things that convinced you the most that the culprit is Mast Cells? Since we don't know what cause the symptoms Orgasm or Ejaculation, what drove you into this conclusion as opposed to any other theory?
Title: Re: Mast Cells Activation Syndrome
Post by: drop247 on February 12, 2020, 11:43:53 AM
It seems like every treatment that works for POIS also works for Mast Cell disease. Anti-histamines, NSAIDs, Quercetin, etc. How Niacin works towards mast cell induced POIS I'm not sure. Though I imagine the flushing might be emptying the cells acutely to leave them unable to react to orgasm.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on February 12, 2020, 11:55:57 AM
Most people seem to base their theory off of their own symptomatology, myself included. That's logical but they tend to go in-depth with it. You should not zoom in with this phenomena but observe it as broad as possible as in involving other cases and entire histories of patients.  I'm not concluding anything yet (although this is at the top of my list), that's why the words 'in my mind' come in as in thinking in that direction. You are saying orgasm or ejaculation but that was not what I was saying, I was generalizing even more, it can be either one of them or both plus more.

Environmental factors, diet (and I suspect age) seem to affect some poisers which could be related to epigenetic mechanisms. My family got overlap in symptomatology, other cases where family members not having POIS but some minor 'seemingly' unrelated symptoms hidden from the untrained eye. The rarity. Other triggers present causing strange symptoms in people. The sheer amount of symptoms people can have and diversity. They complement eachother basically in symptomatology when comparing it to all potential MCAD symptoms. They also don't have solely POIS and if they got other conditions it often seems mast cell associated conditions. Also the point what drop247 said about treatment, that's what I meant with complementing (as in adding) eachother.

Again in your question you say the 'thing' that convince you the most. It's not the thing but it's a collection of 'things' that comes forth from looking at it at an extreme wide angle in combination with up to date knowledge of mast cell diseases. But I'm not trying to convince people I'm just throwing my thoughts on the forum, actually I don't really care if people agree with this. It's like a tic of mine dumping info on this forum all the time, not sure why I'm still doing it though.
Title: Re: Mast Cells Activation Syndrome
Post by: Muon on February 12, 2020, 12:12:33 PM
It seems like every treatment that works for POIS also works for Mast Cell disease. Anti-histamines, NSAIDs, Quercetin, etc. How Niacin works towards mast cell induced POIS I'm not sure. Though I imagine the flushing might be emptying the cells acutely to leave them unable to react to orgasm.

Flushing from Niacin is actually PGD2 release from mast cells so you might have a point there (it was long thought to be related to histamine release but it's not, it's a PGD2/serotonin related mechanism). Niacin also did something to the synthesis of certain prostaglandins I believe.

This is also why spontaneous flushing is a big red flag for suspicion of MCAD, because of PGD2 release.
Title: Re: Mast Cells Activation Syndrome
Post by: drop247 on February 12, 2020, 12:45:30 PM
Your contributions are valued Muon. I think I have other triggers for POIS symptoms as well. High histamine foods may be a trigger for me. Stress is for sure.

I just found that Taurine is a mast cell stabilizer too. B_Jim's treatment. Anything that increases GABA in fact is good for mast cells which could explain why I find some relief from anything GABAergic.
Title: Re: Mast Cells Activation Syndrome
Post by: Hopeoneday on February 12, 2020, 02:27:34 PM
We discussed a lot of mcas on the medicall test results page, then one member went to a lot of mcas specialists but couldn't get a diagnosis for mcas, but was later diagnosed with lyme disies.
https://poiscenter.com/forums/index.php?topic=2695.225
I am of the opinion that damaged intestines and digestion, with certain toxins and then with certain chronic infections, affect our immunity and the CNS.
DAO is the major histamine processor
https://mthfrsupport.com.au/2016/09/hnmt-cofactors-and-inhibitors/,
and after him comes HNMT.
Histamine in the brain HNMT:
https://selfdecode.com/blog/article/brain-histamine-hnmt-13

And to think that bad guts, toxins and pathogens (which can cause a cytokine storm), all of these together interfere with our immune system and have a POIS cascade.
Because some of us are known to have POIS triggers beyond ejaculation, and the worst is with.
Title: Re: Mast Cells Activation Syndrome
Post by: Hopeoneday on February 12, 2020, 02:42:31 PM
This is wery intresting that cromolyne sodium we sugested to test cured pois in this man.
https://poiscenter.com/forums/index.php?topic=3216.0;topicseen


Title: Re: Mast Cells Activation Syndrome
Post by: Muon on February 12, 2020, 07:44:57 PM
I feel better after midnight (just like my brother). Take a look at this again, see figure 1, melatonin:

(https://onlinelibrary.wiley.com/cms/asset/9f55dc75-f396-4772-a300-fdb7db5adbd9/exd13288-fig-0001-m.png)

Neuroendocrinology of mast cells: Challenges and controversies (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)

Now compare to the circadian rhythm:

(https://www.howsleepworks.com/images/melatonin.jpg)

I bet the same concept could be applied to hormone change after/during orgasm, arousal etc.
Title: Re: Mast Cells Activation Syndrome
Post by: Nas on February 12, 2020, 09:00:07 PM
Most people seem to base their theory off of their own symptomatology, myself included. That's logical but they tend to go in-depth with it. You should not zoom in with this phenomena but observe it as broad as possible as in involving other cases and entire histories of patients......     
........my thoughts on the forum, actually I don't really care if people agree with this. It's like a tic of mine dumping info on this forum all the time, not sure why I'm still doing it though.

Ever since I was on this forum you struck me with your scientific accuracy and broad analysis, I was actually never expecting you to endorse any theory seeing how you take things broadly and at the same time precisely.
This is why I kind of trust your judgement. Seeing you convinced by a certain theory is no small thing.
I also saw connections with Mast Cells, but I didn't realize how much of a spectrum it is. I just thought it was purely a case of chugging anti-histamines and feeling better.
Also seeing itsmee's post about Cromolyn Sodium I'm kind of convinced to try it too. We'll see what it does.
Title: Re: Mast Cells Activation Syndrome
Post by: drop247 on February 13, 2020, 07:55:11 AM
I feel much better in the evening too. Interesting that Quantum and Romies take 5-HTP in their prepack treatment which the body can convert into melatonin.
Title: Re: Mast Cell Activation Syndrome
Post by: Spartak on February 13, 2020, 08:24:03 AM
This is wery intresting that cromolyne sodium we sugested to test cured pois in this man.
https://poiscenter.com/forums/index.php?topic=3216.0;topicseen
Do you have any info could it be find somewhere in our region?
I googled but no success.


Out of mast cell stabilizers Quercetin with bromelain did nothing to my POIS , side effect was that outside of POIS it cuased me dull headache, brain fog paired with apathetic anxiety and discomfort around people.

If 5htp is included, I don?t think I have problem with Serotonin, so  outside of POIS it did not do much,  just makes me a bit hyped and excited and a bit obsessed about what others think of me and so.. but speaking of POIS just side effects .. makes me very sleepy during POIS , I can literally oversleep POIS without being able to wake up in the morning, and just cause that after typical 2 days of POIS I feel sleepy and anxious and uninterested to do anything for few more days.
Title: Re: Mast Cell Activation Syndrome
Post by: Investigator on February 13, 2020, 09:21:12 AM
Very interesting, I also feel better in the evenings during POIS attacks. I've always observed the seasonality (spring is worst, summer and winter are best), but never thought about the day cycle.
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on February 13, 2020, 01:01:17 PM
This is wery intresting that cromolyne sodium we sugested to test cured pois in this
Do you have any info could it be find somewhere in our region?
I googled but no success.
Unfortunately no, I couldn't find information anywhere if I could get cromolyne, even I didn't find anywhere to have a nasal spray.
In our area I tried to go to specialists, from neurologists, allergists ... they all sent me to a psychiatrist when I started listing the symptoms of MCAS. :)

Ivestigator, i think this wary from person to person, same like symtpmes in us.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 14, 2020, 07:42:38 AM
I have chronic stress but my testosterone is high/normal. I think it's more likely stress is causing mast cell degranulation. It's a known trigger for that. I used to self medicate with cannabis but can't anymore due to work. I just started Ashwaganda daily to see if it helps.

They do NOT degranulate by stress, they are getting activated by other means. In fact degranulation is rare compared to selective release ('activation'), which is more common behaviour. My skin on my forearms can slightly burn by acute stress, I bet this is mast cell activation (POIS can do the same).

Healthcare is completely stuck at the degranulation picture regarding mast cell activation diseases. It's possible people with chronic stress might have mast cells with a higher density of CRH receptors. Certain pathways are getting activated.

In MCAS certain pathways are getting activated unlike mastocytosis which is degranulation.

Two examples of papers that are mentioning stress and mast cells:

Critical role of mast cells in inflammatory diseases and the effect of acute stress (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0165572803004636)

Neuroendocrinology of mast cells: Challenges and controversies (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)

Also chronic stress might increase receptor densities of mast cells( these can be autocrine effects, meaning they can release mediators which act back on there own cell and alter receptor expression).

Example:

CRH (not from mast cells)---> increased Neurotensin receptor expression on mast cells

A little bit of neurotensin release in general can have a bigger impact on mast cells than usual. This will activate NT receptors.

Neurotensin can lead to ---> increase of CRH receptors

You will end up with an increase of CRH receptors. Making you more susceptible to stress. Mast cells themselves can even release CRH and can be used for the same sequence all the way at the top of the given example.

Mast cells can also release Substance P which can act back on the same mast cell and leading to an increase in CRH receptors on that same cell. Making you again more susceptible to stress. If there is some primary mast cell activation disorder then mast cells might release stuff like SP spontanously.

From my own experience I can fall into spirals of symptoms and I bet some similar mechanisms as described above are at play.

Source: Scroll all the way down to Table 8, autocrine effects and receptor expression:

Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders? (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)

Some Poisers here that had chronic stress prior to their POIS might have altered their mast cells in some ways making them act different than usual leading to POIS. That is why I was asking people if they had stress prior to their POIS and/or if they were more susceptible to stress during POIS.

Me and bluesbrother might share the same trigger. I got elevated IL-8, he got TNF-alpha elevated. If you go to table 4 of the last paper mentioned then IL-33 might be a shared immune trigger. People with elevated IL-33 which activate mast cells can respond well to certain steroids (via STAT5).

I'm not sure whether people get a grasp of what I am saying here.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on February 14, 2020, 08:55:58 AM
If POIS truly turns out to be a mast cells disease I believe this forum can add great amount of knowledge to the Mast Cells phenomena.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 14, 2020, 09:00:04 AM
If POIS truly turns out to be a mast cells disease I believe this forum can add great amount of knowledge to the Mast Cells phenomena.

A mast cell disease and/or it could be possible there is a chronic trigger present that keeps activating the mast cell in a normal way (so not a primary MCAD) but chronic and persistent that it will alter itself in the long run and ending up acting differently, creating disease that way.

Maybe there could be something wrong with mast cells that they keep changing their phenotype. Symptoms would come and go. Developing symptoms out of the blue and disappearing spontaneously after another change in phenotype.
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on February 14, 2020, 09:48:27 AM
My mistake, I thought degranulation and activation were the same thing.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 14, 2020, 10:09:42 AM
My mistake, I thought degranulation and activation were the same thing.

Most people on this forum tend to think that way, that a mast cell trigger always leads to degranulation when it's being triggered. Degranulation is basically what happens in Allergic activation and mastocytosis, it's exploding handgrenade behaviour.

There are papers that go deep into all those release mechanisms. It's important people are aware of different release mechanisms.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 14, 2020, 02:58:50 PM
Leptin is a stored mast cell mediator.

''Leptin acts on receptors in the lateral hypothalamus to inhibit hunger and the medial hypothalamus to stimulate satiety.''

https://en.wikipedia.org/wiki/Leptin#Hypothalamus

Poisers can complain about loss of appetite and/or early satiety after sexual related activity. IronFeather complains about this and got fever as well, the hypothalamus regulates body temperature. Are mast cells firing within the hypothalamus in these poisers?

Leptin itself can stimulate mast cells, see pic: https://poiscenter.com/forums/index.php?topic=2301.msg33094#msg33094

So could it create a positive feedback loop where it shifts equilibrium in body temperature? IronFeather gets fever for weeks on end, is this Perpetual motion of mast cells? https://en.wikipedia.org/wiki/Perpetual_motion

The POIS reaction itself in general could be perpetual motion of mast cells by autocrine effects (https://en.wikipedia.org/wiki/Autocrine_signaling).

I do remember I wrote something on this forum about leptin and testosterone, can't remember what it was about.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 14, 2020, 04:04:58 PM
My mistake, I thought degranulation and activation were the same thing.
You are not entirely wrong about stress causing degranulation though. See table 3 (https://sci-hub.se/https://www.tandfonline.com/doi/abs/10.1080/1744666X.2019.1596800). But this is physical stress applied to the cell itself.
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on February 15, 2020, 03:34:54 AM
I did posted this link before , but here again:
https://en.wikipedia.org/wiki/Mast_cell_activation_syndrome#Treatment

Common symptoms include:[4][8]

   
1.        Dermatological
        flushing
        hives
        easy bruising
        either a reddish or a pale complexion
        itchiness
        burning feeling
        dermatographism
2.    Cardiovascular
        lightheadedness, dizziness, presyncope, syncope, arrhythmia, tachycardia
3.    Gastrointestinal
        diarrhea and/or constipation, cramping, intestinal discomfort
        nausea, vomiting
        swallowing difficulty, throat tightness
4.    Genitourinary
        interstitial cystitis; burning in the bladder and urinary tract
5.    Psychiatric & Neurological
        brain fog, short term memory dysfunction, difficulty with recalling words
        headaches, migraines
        co-morbid psychiatric and behavioral symptoms as a result of mast cell mediators being released in the brain (i.e.: anxiety, depression, mood swings, etc.)
5.   Respiratory
        congestion, coughing, wheezing
        Nonallergic rhinitis with eosinophilia syndrome (NARES) [9]
        Obstructive Sleep Apnea
6.   Vision/Eyes
        ocular discomfort, conjunctivitis
        redness
7.    Constitutional
        general fatigue and malaise
        food, drug, and chemical allergies or intolerances (especially fragrances)
        Cold and Heat Intolerance
7.    Musculoskeletal
        osteoporosis and osteopenia are possible symptoms of mast cell activation disorders

I fit in 1. all (except flushing, hives easy ,bruising), 2.(all except syncope) 3.(all except vomiting), 4.(all except interstitial cystitis wich is unkown) 5.  all( except eosinophilia syndrome-unknown) 6. all (except unknown food and durg alergies)
7.unknown

This all fit in pois complete.

I like to call my pois reaction anaphylaxis wich meaning:
Anaphylaxis If too many mediators are spilt into a patient's system, they may also experience anaphylaxis, which primarily includes: difficulty breathing, itchy hives, flushing or pale skin, feeling of warmth, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.

So diagnosis are wery dificult beacause of non specific symptomes and diagnostic cryteria :
MCAS is often difficult to identify due to the heterogeneity of symptoms and the "lack of flagrant acute presentation."[8] The condition can also be difficult to diagnose, especially since many of the numerous symptoms are non-specific in nature. Mast cell activation was assigned an ICD 10 code (D89.40, along with subtype codes D89.41-43 and D89.49) in October 2016.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 15, 2020, 08:51:36 AM
Yes, POIS is probably a symptom of a variant of MCAD (Mast Cell Activation Disease) and in our case HOD defined by genetic mutations. Your mother probably got MCAS as well and I bet we both share a genetic mutation. POIS is in my opinion not a new disease entity. It's a set of MCAD symptoms triggered by any changes sexual activity makes inside the body that potentially activates mast cells improperly is in my mind POIS. Could be hormone changes, urethral mast cell sperm contact etc.

You will see people including researchers still going in depth with symptoms, the answer is right in front of them. The symptoms individually are massive distractions. Good luck talking to a doctor about this. There are many things I can try but they will need a prescription and thus the help of doctors but they won't even listen. I have made an appointment in april with a former colleague of Waldinger and that's basically a last ditch-effort to make someone understand the disease, if that is not working I will call it a day.

It's probably trial and error in finding mast cell stabilizers at this point, at least for our cases. I don't see much point discussing it any further though.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 15, 2020, 12:12:10 PM
Yes, POIS is probably a symptom of a variant of MCAD (Mast Cell Activation Disease) and in our case HOD defined by genetic mutations. Your mother probably got MCAS as well and I bet we both share a genetic mutation. POIS is in my opinion not a new disease entity. It's a set of MCAD symptoms triggered by any changes sexual activity makes inside the body that potentially activates mast cells improperly is in my mind POIS. Could be hormone changes, urethral mast cell sperm contact etc.

You will see people including researchers still going in depth with symptoms, the answer is right in front of them. The symptoms individually are massive distractions. Good luck talking to a doctor about this. There are many things I can try but they will need a prescription and thus the help of doctors but they won't even listen. I have made an appointment in april with a former colleague of Waldinger and that's basically a last ditch-effort to make someone understand the disease, if that is not working I will call it a day.

It's probably trial and error in finding mast cell stabilizers at this point, at least for our cases. I don't see much point discussing it any further though.

Which mast cell stabilizer would you consider to be most likely to work in counteracting POIS?

I have a fairly sympathetic doctor who may be willing to write a prescription for me after talking through all the issues, but I want to be able to point her in the right direction.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 15, 2020, 12:46:50 PM
Which mast cell stabilizer would you consider to be most likely to work in counteracting POIS?

I have a fairly sympathetic doctor who may be willing to write a prescription for me after talking through all the issues, but I want to be able to point her in the right direction.

There isn't any that is more likely to work than others yet, it varies from person to person. One stabilzer that blocks the entire mast cell is methoxy-luteolin but that one is being poorly absorbed by the body.

These patients are getting through an entire scheme of options by trial and error until you hit the right one. Some meds need to be taken weeks to months before you start seeing any effect. And sometimes multiple ones have a minor effect and a stack is being created.

Here is an example of that which you could show to your doctor, click on download: https://www.tandfonline.com/doi/suppl/10.3109/07853890.2016.1161231?scroll=top

Quantum posted another one here that goes more into flavonoids:
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12138

The more important papers about MCAS itself are on page 4 of this thread. Some papers in literature give similar therapeutical option schemes/algorithms. Also other triggers need to be avoided or minimized.

If I had to make a top 3 of papers in descending order that I would recommend to a doctor then it would be like this:

1) Often seen, rarely recognized: mast cell activation disease - a guide to diagnosis and therapeutic options (https://sci-hub.se/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231)

2) Characterization of Mast Cell Activation Syndrome (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/)

3) Recent advances in our understanding of mast cell activation - or should it be mast cell mediator disorders? (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)

The first paper also proposes the following diagnostic criteria, table 2:

1) Major criteria 1 + Major critera 2

Or 2) Major criteria 2 + at least one minor criterion
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 15, 2020, 05:18:41 PM
Thank you, there are a number of interesting candidates for a mast cell stabilizer in your links.

Quote
One stabilzer that blocks the entire mast cell is methoxy-luteolin but that one is being poorly absorbed by the body.

Which pharmaceutical company manufactures methoxy-luteolin? Or is it available in supplement form?

I need to be able to give my doctor an option that is somewhat easy to obtain.

Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 15, 2020, 05:52:11 PM
Which pharmaceutical company manufactures methoxy-luteolin? Or is it available in supplement form?
I need to be able to give my doctor an option that is somewhat easy to obtain.

I think methoxy-luteolin is not available yet, it is used in research. I don't want to promote products here but there is a company that makes flavonoid based supplements with high purity. Easy to obtain but expensive though: https://algonot.com/neuroprotek/

Your doctor should be able to obtain most of the meds listed in the word file.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 15, 2020, 06:08:13 PM
hurray, I couldn’t find it

Regards!
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 15, 2020, 06:12:14 PM
Which pharmaceutical company manufactures methoxy-luteolin? Or is it available in supplement form?
I need to be able to give my doctor an option that is somewhat easy to obtain.

I think methoxy-luteolin is not available yet, it is used in research. I don't want to promote products here but there is a company that makes flavonoid based supplements with high purity. Easy to obtain but expensive though: https://algonot.com/neuroprotek/

Your doctor should be able to obtain most of the meds listed in the word file.

That supplement looks like a good possibility. Have you tried any mast cell stabilizers yourself? If so, how effective were they?

Perhaps mast cell stabilizers could end up helping us to overcome our POIS symptoms!
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 15, 2020, 06:23:58 PM
hurray, I couldn’t find it

Regards!

Thanks Demo :)

I too was struggling to find it, apart from a possibility from an expensive company selling research chemicals. I'm interested in finding some options that are either supplements or generally available medicines, Muon has already given one good example.

https://poiscenter.com/forums/index.php?topic=3216.msg33034#msg33034 (https://poiscenter.com/forums/index.php?topic=3216.msg33034#msg33034)

itsmel's successful reports of using Cromolyn Sodium sound like one promising possibility.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 15, 2020, 06:51:32 PM
I'm wanting to try cromolyn for the last 5 years but I need a prescription. Anti-histamines have a minor effect on my POIS symptoms. Also they have used I believe it was a steroid injection in my leg in the past with good results but short lived. I'm unable to retrieve what they have used. The neuroprotek has to be built up towards 3 times a day 2 capsules I believe, have to look it up I'm not sure, but that's pretty expensive. You will have to pump your system full of it, keeping the concentration constant for the entire day, and observe what it does in the long run. It's not a matter of taking a capsule prior to your O. No I haven't tried any flavonoids. Oh and I have tried montelukast but that did nothing.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 15, 2020, 07:05:11 PM
hurray, I couldn’t find it

Regards!

Thanks Demo :)


Many thanks, hurray, for your many contributions here over the years!
Title: Re: Mast Cell Activation Syndrome
Post by: Quantum on February 15, 2020, 09:08:29 PM
Which pharmaceutical company manufactures methoxy-luteolin? Or is it available in supplement form?
I need to be able to give my doctor an option that is somewhat easy to obtain.

I think methoxy-luteolin is not available yet, it is used in research. I don't want to promote products here but there is a company that makes flavonoid based supplements with high purity. Easy to obtain but expensive though: https://algonot.com/neuroprotek/

Your doctor should be able to obtain most of the meds listed in the word file.

That supplement looks like a good possibility. Have you tried any mast cell stabilizers yourself? If so, how effective were they?

Perhaps mast cell stabilizers could end up helping us to overcome our POIS symptoms!


Hi Hurray,

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

At least 4 of them are part of the pre-pack that controls my POIS symptoms   (quercetin, green tea, curcumin, milk thistle, and L-theanine)

Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 16, 2020, 12:49:56 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 16, 2020, 05:26:11 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?
I have no idea.

Well well well what do we have here, it seems mast cells express cannabinoid receptors:

Medical Cannabis & Mast Cell Activation Syndrome (https://ibcnj.com/medical-cannabis-mast-cell-activation-syndrome/)

Cannabinomimetic Control of Mast Cell Mediator Release: New Perspective in Chronic Inflammation (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01674.x)

Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1138953/)

Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. (https://www.pnas.org/content/92/8/3376)

Differential Roles of CB1 and CB2 Cannabinoid Receptors in Mast Cells (https://www.jimmunol.org/content/170/10/4953.short)

Cannabinoid receptor 1 controls human mucosal-type mast cell degranulation and maturation in situ (https://www.sciencedirect.com/science/article/abs/pii/S0091674913000572)

I have tried a commercial CBD oil in 2019 for a short period of time but developed mucosal reactions in my throat from it and stopped for that reason while I felt a bit better systemically. This probably has to do with different types of mast cells and their ratio of CB1/CB2 receptor triggering or with the purity of content.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 16, 2020, 05:29:17 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?
I have no idea.
Anyone else? Thoughts?
Title: Re: Mast Cell Activation Syndrome
Post by: Quantum on February 16, 2020, 07:09:14 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?
I have no idea.
Anyone else? Thoughts?

Obviously, for me, the next step in POIS research as a whole will depend on what is found by the upcoming NORD POIS study  :)
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 16, 2020, 07:19:21 PM
I'm wanting to try cromolyn for the last 5 years but I need a prescription. Anti-histamines have a minor effect on my POIS symptoms. Also they have used I believe it was a steroid injection in my leg in the past with good results but short lived. I'm unable to retrieve what they have used. The neuroprotek has to be built up towards 3 times a day 2 capsules I believe, have to look it up I'm not sure, but that's pretty expensive. You will have to pump your system full of it, keeping the concentration constant for the entire day, and observe what it does in the long run. It's not a matter of taking a capsule prior to your O. No I haven't tried any flavonoids. Oh and I have tried montelukast but that did nothing.

Good information, thanks. Have you tried Cromolyn nasal spray? It's available over the counter, although it may not be as effective as the oral version.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 16, 2020, 07:51:16 PM

Hi Hurray,

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

At least 4 of them are part of the pre-pack that controls my POIS symptoms   (quercetin, green tea, curcumin, milk thistle, and L-theanine)

That's an excellent summary, thank you.

Fenugreek has been the main thing that has given me relief from POIS for several years now. I just did a little research, and I was surprised to find out that fenugreek seeds contain luteolin, quercetin and apigenin (3 of the stabilizers that you mention in your list):

Quote
Five flavonoid compounds were isolated from fenugreek seeds and identified as vitexin, tricin, naringenin, quercetin and tricin-7-O-beta-D-glucopyranoside.
https://www.ncbi.nlm.nih.gov/pubmed/11599360

Quote
A systematic study of the obtained MS spectra and the observed fragmentation showed that most of the identified compounds were acylated and non-acylated flavonoids with apigenin, luteolin and kaempferol as aglycons.
https://www.ncbi.nlm.nih.gov/pubmed/25393509

An interesting coincidence, or perhaps something else?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 16, 2020, 07:57:00 PM
No I didn't know the nasal spray was over the counter stuff.

My elevated CXCL8 (IL-8) could be a mast cell mediator. This paper also proposes a diagnostic algorithm for mast cell mediator disease. The principle is that you measure mast cell mediator profiles, could be unique from person to person:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/figure/F1/

The shift in Th1/Th2 in my case could be caused by MC mediators interacting with Th cells.

The abnormalities of immunoglobulins seen in poisers could be caused by MC mediators affecting B-cells driving Igs up or down.

There is a high density of mast cells within the interface of the body and environment. This is also the first line of defense against infection. Mediators might alter local immune homeostasis in mucosal layers making you susceptible to local infection by opportunistic pathogens. You won't see systemic infections in poisers.

They could spill mediators in endocrine organs leading to abnormal hormone levels. Or the other way around an abnormal hormone balance leading to a lower threshold trigger level of mast cells. I'm curious whether mast cell stabilizers could bring hormone levels back to normal.

They might interact with oral taste receptors leading to a 'metallic' like taste.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 16, 2020, 08:03:38 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?

That's a very good question, Demo. I'd be interested to know how many members of this forum have had positive outcomes as a result of using mast cell stabilizers or similar.

What evidence do we have?  :)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 16, 2020, 08:28:07 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?

That's a very good question, Demo. I'd be interested to know how many members of this forum have had positive outcomes as a result of using mast cell stabilizers or similar.

What evidence do we have?  :)

1) You can measure MC mediators (there are more than 200) in poisers and compare it to healthy controls.

2) Get a group of poisers to go through a list of potential stabilizers one by one and draw concusions from that.

3) One paper mentioned that electron microscopy can be used to monitor mast cell activity in biopsies.

If you look at the entire forum closely you will start to see MCAD all over the place, at least, that's my experience. The different cases are probably due to different mediator profiles and location of activity.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 16, 2020, 08:42:52 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?
I have no idea.
Anyone else? Thoughts?

Obviously, for me, the next step in POIS research as a whole will depend on what is found by the upcoming NORD POIS study  :)
Perfect answer, Quantum!

Not “The cart before the horse”

I also brought it up as a hypothetical to see what people’s thinking is re the perceived solidity of “MCAS vs POIS”. Not suggesting this as the next study. You taught me the proper sequence :)
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 16, 2020, 09:10:06 PM

1) You can measure MC mediators (there are more than 200) in poisers and compare it to healthy controls.

2) Get a group of poisers to go through a list of potential stabilizers one by one and draw concusions from that.

3) One paper mentioned that electron microscopy can be used to monitor mast cell activity in biopsies.

If you look at the entire forum closely you will start to see MCAD all over the place, at least, that's my experience. The different cases are probably due to different mediator profiles and location of activity.

Those would all be interesting ways to gather new evidence. However, I was thinking more in terms of evidence that we currently have.

There is a treasure trove of information on this forum and the NSF forum. If we had some case studies of people who had been successfully helped by mast cell stabilizers, those case studies would strongly support the MCAS/POIS hypothesis, particularly in the eyes of medical professionals.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 16, 2020, 09:17:16 PM
I was thinking more in terms of [“the treasure trove of”] evidence that we currently have.
Same here.
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on February 16, 2020, 09:59:43 PM
What is the next step? Validate/invalidate the MCAS/POIS hypothesis via scientific testing? Do we have enough evidence to submit this for serious research?
I have no idea.

Well well well what do we have here, it seems mast cells express cannabinoid receptors:

Medical Cannabis & Mast Cell Activation Syndrome (https://ibcnj.com/medical-cannabis-mast-cell-activation-syndrome/)

Cannabinomimetic Control of Mast Cell Mediator Release: New Perspective in Chronic Inflammation (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01674.x)

Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1138953/)

Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. (https://www.pnas.org/content/92/8/3376)

Differential Roles of CB1 and CB2 Cannabinoid Receptors in Mast Cells (https://www.jimmunol.org/content/170/10/4953.short)

Cannabinoid receptor 1 controls human mucosal-type mast cell degranulation and maturation in situ (https://www.sciencedirect.com/science/article/abs/pii/S0091674913000572)

I have tried a commercial CBD oil in 2019 for a short period of time but developed mucosal reactions in my throat from it and stopped for that reason while I felt a bit better systemically. This probably has to do with different types of mast cells and their ratio of CB1/CB2 receptor triggering or with the purity of content.
CBD oil from a pharmacy worked for me. I got it from my POIS doctor. A small bottle was 300 dollars. But I got it for free. It worked untill I took too much of it. Maybe also because at that time I took Amitryptiline for my prostate infections. I got sick and did not know what it was. When I look back I think cbd+ssri caused me anxiety.
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on February 16, 2020, 10:09:12 PM
Good information, thanks. Have you tried Cromolyn nasal spray? It's available over the counter, although it may not be as effective as the oral version.
In The Netherlands you need a prescription for Cromolyn. Nalcrom is the oral version for food allergies. And Lomudal for inhalation or spray. Nalcrom was one the medicines I had on a list to suggest to my POIS doctor. Back then I got another medicine to try but that did not work. There is also a POIS paper of a researcher who used it with succes at a POIS patient.
Title: Re: Mast Cell Activation Syndrome
Post by: Mushnikk on February 17, 2020, 02:11:57 AM

1) You can measure MC mediators (there are more than 200) in poisers and compare it to healthy controls.

2) Get a group of poisers to go through a list of potential stabilizers one by one and draw concusions from that.

3) One paper mentioned that electron microscopy can be used to monitor mast cell activity in biopsies.

If you look at the entire forum closely you will start to see MCAD all over the place, at least, that's my experience. The different cases are probably due to different mediator profiles and location of activity.

Those would all be interesting ways to gather new evidence. However, I was thinking more in terms of evidence that we currently have.

There is a treasure trove of information on this forum and the NSF forum. If we had some case studies of people who had been successfully helped by mast cell stabilizers, those case studies would strongly support the MCAS/POIS hypothesis, particularly in the eyes of medical professionals.

I also benefit from mast cell stabilizer (CBD oil, curcumin), I will cromolyn and quercetin soon.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 17, 2020, 09:11:11 AM
Another research option:

"Single cell laser microcapture and qRT-PCR should be used to identify mast cell phenotype variability and mediator synthesis/release in situ." Ref (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on February 17, 2020, 11:03:50 AM
In The Netherlands you need a prescription for Cromolyn. Nalcrom is the oral version for food allergies. And Lomudal for inhalation or spray. Nalcrom was one the medicines I had on a list to suggest to my POIS doctor. Back then I got another medicine to try but that did not work. There is also a POIS paper of a researcher who used it with succes at a POIS patient.

Can you please link the paper? If I show my doctor I think I can get a prescription.
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on February 17, 2020, 07:11:39 PM
I am sorry Drop. It is not a paper, but a topic from a member who has got results. I was confused by another paper, I think about TRT.

https://poiscenter.com/forums/index.php?board=7.0
Title: Re: Mast Cell Activation Syndrome
Post by: Quantum on February 17, 2020, 08:21:59 PM

Hi Hurray,

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

At least 4 of them are part of the pre-pack that controls my POIS symptoms   (quercetin, green tea, curcumin, milk thistle, and L-theanine)

That's an excellent summary, thank you.

Fenugreek has been the main thing that has given me relief from POIS for several years now. I just did a little research, and I was surprised to find out that fenugreek seeds contain luteolin, quercetin and apigenin (3 of the stabilizers that you mention in your list):

Quote
Five flavonoid compounds were isolated from fenugreek seeds and identified as vitexin, tricin, naringenin, quercetin and tricin-7-O-beta-D-glucopyranoside.
https://www.ncbi.nlm.nih.gov/pubmed/11599360

Quote
A systematic study of the obtained MS spectra and the observed fragmentation showed that most of the identified compounds were acylated and non-acylated flavonoids with apigenin, luteolin and kaempferol as aglycons.
https://www.ncbi.nlm.nih.gov/pubmed/25393509

An interesting coincidence, or perhaps something else?

Yes, very interesting.   If we had the quantity of these flavonoids per gram of fenugreek, we could see if we get a significant amount from from a normal dose of fenugreek.

Title: Re: Mast Cell Activation Syndrome
Post by: Nas on February 18, 2020, 02:52:35 PM
Only eye drops are available in Turkey unfortunately, I wonder is the eye drop solution able to circulate in the blood? or does it only affect the eye? 
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on February 18, 2020, 03:00:36 PM
Also another question is: If mast cell activation does not include degranulation then how do mast cell stabilizers help?
Title: Re: Mast Cell Activation Syndrome
Post by: Mushnikk on February 18, 2020, 03:01:38 PM
Only eye drops are available in Turkey unfortunately, I wonder is the eye drop solution able to circulate in the blood? or does it only affect the eye?

This apparently varies widely by country. Here in Germany I can get cromolyn in oral form over the counter without an prescription. Perhaps you have a relative or friend who travels that get buy for you at some point?

Edit: oral form
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on February 18, 2020, 03:06:12 PM
Only eye drops are available in Turkey unfortunately, I wonder is the eye drop solution able to circulate in the blood? or does it only affect the eye?

This apparently varies widely by country. Here in Germany I can get cromolyn over the counter without an prescription. Perhaps you have a relative or friend who travels that get buy for you at some point?
You can get it in what form? is the oral form also over the counter?
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 18, 2020, 03:14:15 PM

Yes, very interesting.   If we had the quantity of these flavonoids per gram of fenugreek, we could see if we get a significant amount from from a normal dose of fenugreek.

I could only find a percentage figure for quercetin:

Quote
Dried fenugreek seed samples were found to contain diosgenin in the range of 0.113–0.135% (w/w) and quercetin in the range of 0.009–0.012% (w/w).
https://www.hindawi.com/journals/isrn/2014/583047/

If my calculations are correct,  0.001% of 1 gram is 0.0001 grams, or 0.1mg. Not a lot!

It just goes to show, it's very easy to draw conclusions based on incomplete evidence. Over the years, I have come up with various "scientific" explanations as to why fenugreek works for me. And I am no nearer to understanding why 10 years later! I'm just glad that it does.


Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on February 18, 2020, 03:23:26 PM
Fenugreek is a 5-alpha reductase inhibitor. It could be doing something to your hormones that benefits you. Personally I'm afraid of it due to a bad experience with finasteride.
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on February 18, 2020, 03:27:13 PM
I am sorry Drop. It is not a paper, but a topic from a member who has got results. I was confused by another paper, I think about TRT.

https://poiscenter.com/forums/index.php?board=7.0

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 18, 2020, 03:33:41 PM
Fenugreek is a 5-alpha reductase inhibitor. It could be doing something to your hormones that benefits you. Personally I'm afraid of it due to a bad experience with finasteride.

Excellent information, thank you drop247  :)

Coincidentally, I took finasteride for a few months (not for POIS). Unfortunately, it had no effect on my POIS symptoms  :( I did feel run down for months even after stopping, and I wouldn't recommend that anybody tries finasteride.

I've taken fenugreek for more than 10 years, and fortunately I still have a full head of hair and an active sex drive  ;D
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 18, 2020, 03:41:37 PM
I am sorry Drop. It is not a paper, but a topic from a member who has got results. I was confused by another paper, I think about TRT.

https://poiscenter.com/forums/index.php?board=7.0

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.

Good news drop247, a lot of us have struggled to find a doctor who even believes that POIS is a real thing! I wish I was joking.

I will be interested to hear your reports  :)
Title: Re: Mast Cell Activation Syndrome
Post by: Mushnikk on February 18, 2020, 04:04:29 PM
Only eye drops are available in Turkey unfortunately, I wonder is the eye drop solution able to circulate in the blood? or does it only affect the eye?

This apparently varies widely by country. Here in Germany I can get cromolyn over the counter without an prescription. Perhaps you have a relative or friend who travels that get buy for you at some point?
You can get it in what form? is the oral form also over the counter?

I meant the oral form. Allergoval is the brand name. And quite inexpensive, too. 50 capsules (100mg per capsule) are about 25 euros.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 18, 2020, 04:07:47 PM
...I still have a full head of hair and an active sex drive  ;D
I’m jealous! Not about the sex drive but the full head of hair! ;D
Title: Re: Mast Cell Activation Syndrome
Post by: Mushnikk on February 18, 2020, 04:10:28 PM
I am sorry Drop. It is not a paper, but a topic from a member who has got results. I was confused by another paper, I think about TRT.

https://poiscenter.com/forums/index.php?board=7.0

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.

Which study are we talking about?
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on February 18, 2020, 04:55:05 PM

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.
Ok great. I read that it could take up to 3 weeks before it works. I hope it will help you.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 18, 2020, 05:29:10 PM

I meant the oral form. Allergoval is the brand name. And quite inexpensive, too. 50 capsules (100mg per capsule) are about 25 euros.

Very useful information Mushnikk. It seems to be far cheaper in Germany than in the US. A quick Google for "Allergoval" showed several cheap suppliers.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on February 18, 2020, 05:30:38 PM
...I still have a full head of hair and an active sex drive  ;D
I’m jealous! Not about the sex drive but the full head of hair! ;D

It's a lot whiter than it used to be  ;D
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on February 18, 2020, 05:47:48 PM
;D
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on February 18, 2020, 06:16:24 PM
I meant the oral form. Allergoval is the brand name. And quite inexpensive, too. 50 capsules (100mg per capsule) are about 25 euros.
dude, that is way cheaper than in some countries.
25 euros is very reasonable for 50 capsules.
Title: Re: Mast Cell Activation Syndrome
Post by: Mushnikk on February 19, 2020, 01:41:31 AM

I meant the oral form. Allergoval is the brand name. And quite inexpensive, too. 50 capsules (100mg per capsule) are about 25 euros.

Very useful information Mushnikk. It seems to be far cheaper in Germany than in the US. A quick Google for "Allergoval" showed several cheap suppliers.

But so is about every drug when compared to the US, because of their deregulated market. ;D
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on February 21, 2020, 10:53:04 AM
I've started taking the sodium cromolyn. I was surprised to find the effect feels somewhat similar to niacin. I have a warm sunburnt feeling on my upper back which I assume is a flush. It's not as intense as Niacin though. From my reading nobody really knows why it works as a mast cell stabilizer. I have used high doses of niacin in the past to cause a large flush before an O which I assume works because the mast cells are pre-activated and drained. I'm wondering if taking sodium cromolyn daily does the same thing and just keeps the mast cells empty? Any thoughts? I'm unable to take the full dosage since it makes me feel a bit woozy but I will try to work up to full daily dosage.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on February 21, 2020, 03:12:12 PM
I've started taking the sodium cromolyn. I was surprised to find the effect feels somewhat similar to niacin. I have a warm sunburnt feeling on my upper back which I assume is a flush. It's not as intense as Niacin though. From my reading nobody really knows why it works as a mast cell stabilizer. I have used high doses of niacin in the past to cause a large flush before an O which I assume works because the mast cells are pre-activated and drained. I'm wondering if taking sodium cromolyn daily does the same thing and just keeps the mast cells empty? Any thoughts? I'm unable to take the full dosage since it makes me feel a bit woozy but I will try to work up to full daily dosage.
I'm so happy that it works for you!!!
Are you taking the oral form of the inhaler form?
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on February 21, 2020, 04:11:33 PM
It's the 100mg capsules. I was prescribed 2x100mg capsules 4 times a day. I can't say it works for me yet. I haven't even tried having an O. And frankly if these side effects persist I won't be able to continue taking this drug.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 25, 2020, 12:47:53 PM
Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis (https://www.mdpi.com/2073-4409/8/2/135/htm)
Title: Re: Mast Cell Activation Syndrome
Post by: Mushnikk on February 25, 2020, 01:52:04 PM
Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis (https://www.mdpi.com/2073-4409/8/2/135/htm)

I've always thought that my preexsting gut problems are the cause of my lately developed POIS symptoms. It's also listed to as the most common comorbidity in poll on the forum according to which 2/3 have irritable bowl syndrom.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 26, 2020, 07:54:47 PM
"SIBO with hydrogen and methane plateau patterns are common in MCAS subjects. MCAS could cause SIBO due to alterations of the GI immune system or altered motility by local release of MC mediators. Antibiotic therapy appears to improve GI symptoms in MCAS patients."

Small Intestinal Bacterial Overgrowth Is Common in Mast Cell Activation Syndrome (https://journals.lww.com/ajg/Fulltext/2019/10001/Small_Intestinal_Bacterial_Overgrowth_Is_Common_in.1194.aspx)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 27, 2020, 12:30:19 PM
Pharmacological treatment options for mast cell activation disease (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/)
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on February 27, 2020, 04:55:08 PM
Intresting article for non clonal mcas
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545645/

You can see how diagnosis is hard... bone marow biopsy... if...

Under treatmant , tabele one.

You can se that treatmant should be from 6-7 angles.
From histamine 1-2 blockers to mcas stabilizers, antileukotrines....
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 27, 2020, 05:12:04 PM
HOD check table 13 from the paper I posted prior to your post. They are targeting all sorts of receptors there or giving potential options for meds that bind to mediators.

Anyway, I have posted this before but here it is again, it stretches the criteria somewhat:

This paper proposes the following diagnostic criteria for MCAS, table 2:

Often seen, rarely recognized: mast cell activation disease - a guide to diagnosis and therapeutic options (https://sci-hub.se/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231)

1) Major criteria 1 + Major critera 2

Or 2) Major criteria 2 + at least one minor criterion
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on February 28, 2020, 10:32:11 AM
Yes Muon.
Did you noticed connections with POTS and MCAS in studies we mentioned lately,
it says -POTS linked to vasoactive amines linked to histamine.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 28, 2020, 11:11:35 AM
Yes Muon.
Did you noticed connections with POTS and MCAS in studies we mentioned lately,
it says -POTS linked to vasoactive amines linked to histamine.
I did notice it in 2015. I have put many mast cell associated conditions into this poll:
https://poiscenter.com/forums/index.php?topic=3188.0
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on February 28, 2020, 11:19:24 AM
Didnt notice this, this is briliant poll.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on February 29, 2020, 04:09:25 PM
See table 3. This will give you an insight of potential complexities encountered when investigating selective release.

"Mast cells commonly respond to non-allergic triggers leading to mediators may also be released selectively without degranulation making it difficult to identify these mast cells with routine histology"

Differential release of mast cell mediators and the pathogenesis of inflammation (https://sci-hub.se/10.1111/j.1600-065X.2007.00519.x)

Mast cells and mast cell mediators as targets of dietary supplements (https://sci-hub.se/10.1016/s1081-1206(10)61484-6)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 02, 2020, 10:23:12 AM
We had a discussion years back about taking epinephrine for POIS. Take a look at this:

"Epinephrine can inhibit TNF release from MC.137 Beta‐receptor agonists were shown to be better inhibitors of PGD2 release than cromolyn.138 Such beta‐agonists also inhibited IgE‐induced histamine release from human gastric MC.139 However, such drugs do not appear to inhibit chronic inflammation in asthma.140" Ref (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)

Norepi seems to have an inhibitory effect on mast cells as well. There was a doctor with POIS who went into anaphylactic shock during desenz treatment. After applying an epipen during the shock he completely recovered from POIS. The epi shots might have done something to his mast cells. Epinephrine shots as treatment for POIS or MCAS?

There was also a guy who was shocked for a moment when his horse ran wild while riding that horse. He temporarily inhibited his POIS symptoms.
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on March 04, 2020, 10:25:01 AM
Sodium Cromolyn seems effective in me when already in a POIS state. I take just a single 100mg capsule and it noticeable reduces symptoms for at least a few hours. I'm still experimenting. I have a long stretch of days off coming up which I will test only Sodium Cromolyn before an O to see if it's effective in preventing POIS from developing if taken ahead of time. Ideally I should be taking it everyday but there are a few side effects I've noticed such as a weird disassociated feeling and some fatigue. I'm told you need time to adjust to the medication and to up the dosage very slowly. I just haven't had a good stretch of days off where I can introduce the drug and not worry about the side effects messing me up for work.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 07, 2020, 07:56:25 AM
Mediator(s): Phospholipases (including PLA2) ---> Major pathophysiologic effects: Arachidonic acid generation, inflammation

Table 1:

Differential release of mast cell mediators and the pathogenesis of inflammation (https://sci-hub.se/10.1111/j.1600-065X.2007.00519.x)

"Eicosanoids (prostaglandins, leukotrienes, and thromboxanes) are produced by catalytic conversion of arachidonic acid by the action of phospholipase A2 on membrane phospholipids. Mast cells express COX1 and COX2, which converts arachidonic acid into prostaglandins and thromboxanes with the action of specific isomerases (38). Prostaglandins increase vascular permeability and attract neutrophils. Leukotrienes are involved with smooth muscle contraction, airway constriction, and mucous secretion (39). Eicosanoids act at the local area of mast cell degranulation. "

Mast Cell: A Multi-Functional Master Cell (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701915/)

Also MCs can release mediators which upregulate COX enzymes.

This is why NSAIDs are being used in MCAD patients. A subset of POIS patients may experience release of phospholipids from MCs or mediator release which upregulates COX. These people might benefit from NSAIDs.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 08, 2020, 07:08:55 PM
Ideally I should be taking it everyday but there are a few side effects I've noticed such as a weird disassociated feeling and some fatigue.

"A possible treatment option with cromoglicic acid was avoided due to intolerance to salicylates.

Salicylate intolerance refers to an altered metabolism of arachidonic acid and eicosanoids leading to a predominance of leukotrienes over prostaglandins.
"

Idiopathic Mast Cell Activation Syndrome With Associated Salicylate Intolerance (https://www.frontiersin.org/articles/10.3389/fped.2018.00073/full)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 09, 2020, 07:01:11 AM
The same receptors in figure 1 are expressed on mast cells. The molecules in the purple boxes, except for OPG, are mast cell mediators as well:

The Anti-Inflammatory Effects of Testosterone (https://academic.oup.com/jes/article/3/1/91/5137187)

Men with low T on this forum could take a look at the cytokines from the above paper. Check out the tables.

"MC Number, Maturation, and Degranulation in the Uterus are Under the Control of Female Sex Hormones"

Role of female sex hormones, estradiol and progesterone, in mast cell behavior (https://www.frontiersin.org/articles/10.3389/fimmu.2012.00169/full)

Bladder mast cell expression of high affinity oestrogen receptors in patients with interstitial cystitis (https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1464-410X.1995.tb07303.x)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 11, 2020, 08:39:09 AM
Food for thought:

"Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses." Ref (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230976/)

Chronic environmental stimuli could have changed the phenotype of MCs in specific tissue and in a reversible way. The phenotype could be unique to POIS. Could a unique MC phenotype define a disease state? Here is an example of a new and unique MC phenotype (Tryptase and CPA3 high, Chymase low) found in Th2-high Asthma patients: Accumulation of intraepithelial mast cells with a unique protease phenotype in TH2-high asthma (https://www.sciencedirect.com/science/article/abs/pii/S0091674910004240)

Figure 1, mast cell characteristics in tissue: Is it time for a new classification of mast cells? What do we know about mast cell heterogeneity? (https://sci-hub.se/10.1111/imr.12636)

Also could changes in your environment (Diet, temperature, pollution) reverse the MC phenotype that induced POIS? Just a free flow of thought here.

Even age seems to be a factor in phenotype switching (=mast cells switching characteristics like mediator content):
Age-dependent phenotypic switching of mast cells in NGF-transgenic mice. (https://europepmc.org/article/med/7669982)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 12, 2020, 08:41:40 AM
Dumping a link here in case people want to investigate mast cell activation through testing:

MCAD Diagnostic Testing & Mediators  (https://poiscenter.com/forums/index.php?topic=3236.0)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 23, 2020, 07:02:48 PM
I highly recommend this video to any doctor. A great presentation about MCAD by Dr. Lawrence B. Afrin. Some pieces may fall into place:

Mast Cell Activation Disease: Current Concepts ("MCAS 101") (https://www.youtube.com/watch?v=lrKqlv6VK_w)
Title: Re: Mast Cell Activation Syndrome
Post by: Iwillbeatthis on March 24, 2020, 09:45:08 AM
Thanks I enjoyed the video Muon, have you tested for any MCAD mediators yourself?
Title: Re: Mast Cell Activation Syndrome
Post by: Iwillbeatthis on March 26, 2020, 10:41:49 PM
Dr Tania Dempsey the mast cell specialist in the video Muon posted said her most effective treatment for her patients was the Dynamic Neural Retraining System DNRS

I was put on this programme by my Functional Medicine doctor, I've only completed day 1 but I can already see this will greatly benefit and maybe could potentially cure POIS and other issues like MCAS, Chronic fatigue, POTS, Chemical senstiivity.

Over firing of protective mechanisms in the limbic system can cause all types of problems such as: release of stress hormones, autonomic dysfunction, inflammation, hypersensitivity, fatigue. The programme rewires the limbic system so it doesn't detect a threat after orgasm and creates new neural pathways in the brain.

They have a very high percentage of patients making a full 100% recovery from these conditions, and a lot of patients feel 80% relieved only after the 3rd day of training.

Obviously I don't think any POIS patients have tried it yet apart from me but it specifically is a cure for Chronic fatigue, Chemical sensitivty, Fibromyalgia, Chronic Lyme Disease, Food Sensitivities, Anxiety, Chronic Pain, Postural Orthostatic Tachycardia Syndrome

Please do not mistake this as a thing similar to therapy, I have tried CBT, and other therapies which haven't helped my POIS and other problems at all, I have also tried mediation a lot and yoga with not much help.

I know it sounds a bit gimmicky and strange but it really does work for a lot of people.

The Dynamic Neural Retraining System™ is a natural, drug- free, neuroplasticity-based program that can assist in relieving symptoms associated with Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Chronic Lyme Disease, Food Sensitivities, Anxiety, Chronic Pain, Postural Orthostatic Tachycardia Syndrome and many other conditions. Many of these conditions are related to a chronic stress response and limbic system impairment.

What is different about our approach?
We directly target brain function and a maladapted stress response that is at the root of suffering for so many. We do not chase your symptoms – we teach you how to change the function and structure of your brain. When you rewire the limbic system, you move your body from a state of survival to a state of growth and repair – where true healing can take place.
Title: Re: Mast Cell Activation Syndrome
Post by: millstone on March 29, 2020, 08:28:30 PM
Dr Tania Dempsey the mast cell specialist in the video Muon posted said her most effective treatment for her patients was the Dynamic Neural Retraining System DNRS

I was put on this programme by my Functional Medicine doctor, I've only completed day 1 but I can already see this will greatly benefit and maybe could potentially cure POIS and other issues like MCAS, Chronic fatigue, POTS, Chemical senstiivity.

My functional doc also recommended this program. I've been thinking about purchasing it for two weeks now.

Your post inspired me to purchase the online course today. I am starting it tonight.

Please keep us posted on how it works for you and I will do the same!
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on March 30, 2020, 03:43:05 PM
Thanks I enjoyed the video Muon, have you tested for any MCAD mediators yourself?
N-methylhistamine, PGD2, tetranor-PGDM, 11-beta-PGF2-alpha. All 24h urine. The only one that is slightly elevated is 11-beta-PGF2-alpha.

Also my elevated IL-8 (CXCL8) could come from MCs but there is no way of knowing.
IL-8 and IgG4 are both elevated. My brother IL-8 and IgE elevated. I know of these pathways:

IL-33 ---> MC activation ---> IL-8 selectively
IL-33 ---> MC activation ---> IL-13 ---> B cells ---> IgE
IL-33 ---> MC activation ---> IL-13 ---> B cells ---> IgG4

Diagnostic parameters which haven't been tested yet are Heparin, Chromogranin A and Leukotrienes. There are some other ones that are interesting but fall outside of diagnostic criteria though.

Also there are pictures of redness at the surface close to my stomach. I wonder what happens when you apply MC-specific staining on that tissue (CD117) since there are reactions to food happening especially when food enters the stomach.

If the alarmin IL-33 plays a role in MC activation then I should respond to Dexamethasone:

Dexamethasone rapidly suppresses IL‐33‐stimulated mast cell function by blocking transcription factor activity (https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.3A0316-125R)
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on April 18, 2020, 08:20:45 AM
Hi guys, for thouse who are intrested, diagnosing of MCAS is simple :) ,
zilions posible a root couses :) , MC hawe over 200 hundreds mediators...


https://hoffmancentre.com/mast-cell-activation-syndrome-histamine-immune-system-runs-rampant/

If you’re interested in getting lab work done to check for MCAS, I recommend the tests listed below. The top five, in bold, are the most important and necessary to establish a diagnosis:

  1.  Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  2.  N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  .  Prostaglandin D2 – plasma – must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  4.  Prostaglandin D2 (PGD2) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  5.  Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.
   6. Prostaglandin 11-beta F2 Alpha (PGF2alpha) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
   7. Serum Tryptase – Quest 34484. Rarely elevated in MCAS. NR less than 11.5 ng/ml. Positive if increase over baseline of 20% or baseline greater than 15.
   8. Leukotriene E4 – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
   9. Plasma heparin Anti-XA (must be off heparin products) – chilled. Degrades quickly.
  10.  Blood clotting profile – Thrombin/PT/PTT/INR.
   11. Anti-IgE Receptor antibody.
    12.Neuron Specific Enolase – Quest 34476.
    13.Plasma pheochromocytoma workup.
    14.Porphyria workup.
    15.Factor VIII deficiency.
    16.Plasma free norepinephrine – Quest 37562.
    17.Urinary metanephrines – can b done in normal Calgary labs.
    18.Immunoglobulins – IgG, IgM, IgE, IgA
    19.Bone marrow biopsy looking for the following markers: CD117/CD25; CD117/CD2.
    20.Gastrin
    21.Ferritin
    22.CBC – eosinophils, basophils.
    23.Antiphospholipid antibodies.
    24.Genetic testing looking for Phase 1 and Phase II liver detox and methylation defects.
    25.Dunwoody Labs – test zonulin, histamine, DAO enzyme deficiency.


Patients who come into my office with MCAS usually have multisystem, multisymptom inflammatory responses. These symptoms have often caused them to trudge from doctor to doctor, undergoing rounds of testing, causing them to feel extraordinarily confused as to what’s happening to their body. Because the symptoms of MCAS have so broad a reach and differ so considerably from person to person I’d like to break them down by nonspecific, general clues, and organ system signs.



Most Common General Symptoms:

    “I’ve been sick for as long as I can remember”
    “I overreact to bee stings, mosquito bites, penicillin and most medications”
    “I can’t take a full breath”
    “Whenever I stand up I get lightheaded”
    Insomnia/sleep disorders starting early in life
    Tinnitus/ringing in the ears from a young age
    Vomiting as an infant
    Abdominal pain as an infant
    Facial and chest flushing ( a red flush when embarrassed or stressed)
    Dermatographism—a red line appearing on the skin when scratched with a blunt object
    Frequent infections, cold, viruses, gut viruses as an infant, adolescent or adult
    Fatigue and malaise
    Frequent fevers
    Edema—“water” accumulation in different parts of body
    Waxing and waning of symptoms
    Food, drug, and chemical intolerances (especially fragrances). This is a very common symptom which may be exacerbated by phase 1 and phase II liver detoxification problems as identified by gene testing
    Sense of being cold all the time
    Decreased wound healing
    Hypersensitivity to much in environment, including medications
    Weight gain or loss
    Heat intolerance
    Frequent family history of cancer, especially intestinal or bone marrow (hematologic)
    Generally feeling inflamed
    Generalized lymphadenopathy (enlarged lymph nodes)

MCAS Symptoms by Organ System

Eyes – Red eyes, irritated eyes, dry eyes, burning eyes, difficulty focusing vision, and conjunctivitis (pink eye).

Nose – Nasal stuffiness, sinusitis, postnasal drip, hoarseness, laryngitis, nose bleeds (epistaxis), and intranasal sores.

Ears – Ringing in ears (tinnitus) and Eustachian tube dysfunction (blocked, popping ears).

Throat – Vocal cord dysfunction, throat swelling, sores on tongue/mouth, itchy throat, burning mouth, and difficulty swallowing

Skin – Hives, angioedema (swelling of the skin), skin flushing, itching, skin rashes, dermatographism (when scratched skin causes a red welt), chronic itching, urticarial pigmentosa (legion/hive-like spots on the skin), flushing, bruising easily, reddish or pale complexion, cherry angiomata (skin growths), patchy red rashes, red face in the morning, cuts that won’t heal, fungal skin infections, and lichen planus.

Cardiovascular – Fainting, fainting upon standing, increased pulse rate (tachycardia), palpitations, spikes and drops in blood pressure, high pulse or temperature, high triglycerides, lightheadedness, dizzy, hot flashes, and postural orthostatic hypotension syndrome (POTS).

Respiratory – Wheezing, asthma, shortness of breath, difficulty breathing deep, air hunger, dry cough, chronic obstructive pulmonary disease (COPD), and chronic interstitial fibrosis.

GI Tract – Left upper abdominal pain, splenomegaly (enlarged spleen) epigastric tenderness, nausea, vomiting, diarrhea and/or constipation, abdominal cramping, bloating, non-cardiac chest pain, malabsorption, GERD/acid reflux, cyclic vomiting syndrome, colonic polyps, and gastric polyps.

Liver – High bilirubin, elevated liver enzymes, and high cholesterol.

Neurological – Numbness and tingling (especially in the hands and feet), headaches, migraines tics, tremors, pseudo-seizures, true seizures, waxing and waning brain fog, memory loss, poor concentration, difficulty finding words, and spells of cataplexy (suddenly becoming disconnected from and unresponsive or unreactive to the world around).

Musculoskeletal – Muscle pain, fibromyalgia, increased osteopenia, osteoporosis, weakness, and migratory arthritis (joint pain).

Coagulation – History of clots, deep vein thrombosis, increased bruising, heavy menstrual bleeding, bleeding nose, and cuts that won’t stop bleeding.

Blood disorders – Anemia, increased white blood cell count, platelets, decreased white blood cell counts, decreased neutrophils, decreased lymphocytes, decreased platelets, reductions in CD4 helper lymphocytes, reductions in CD8 positive suppressor lymphocytes, reductions or excesses of IgA, IgG, IgM, IgE, a known condition called MGUS, myelodysplastic syndrome (reduced red cells, white cells, platelets), and increased MCV (mean corpuscular volume).

Psychiatry – Anxiety, panic, depression, obsessive compulsive disorder (OCD), decreased attention span, attention deficit/hyperactivity disorder (ADHD), forgetfulness, and insomnia.

Genitourinary – Interstitial cystitis, recurrent bladder infections, sterile bladder infections, and frequent urination.

Hormones – Decreased libido, painful periods, heavy periods, infertility, and decreased sperm counts.

Dental – Deteriorating teeth.

Anaphylaxis – Difficulty breathing, itchy hives, flushing or pale skin, feeling warm after exposure, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.

Figure 1. Some Potential Mast Cell Triggers2-5

    Heat, cold or sudden temperature changes
    Stress: emotional, physical, including pain, or environmental (i.e., weather changes, pollution, pollen, pet dander, etc.)
    Exercise
    Fatigue
    Food or beverages, including alcohol
    Drugs (opioids, NSAIDs, antibiotics and some local anesthetics) and contrast dyes
    Natural odors, chemical odors, perfumes and scents
    Venoms (bee, wasp, mixed vespids, spiders, fire ants, jelly fish, snakes, biting insects, such as flies, mosquitos and fleas, etc.)
    Infections (viral, bacterial or fungal)
    Mechanical irritation, friction, vibration
    Sun/sunlight

Conditions Associated with Mast Cell Activation Syndrome

Because MCAS is a chronic, multisystem, multisymptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:

    Chronic inflammatory response syndrome
    Irritable bowel syndrome
    Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
    Obesity
    Diabetes
    Asthma and allergies
    Autism
    Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
    Candida overgrowth
    Celiac disease
    Parasite infections
    Skin conditions such as eczema and psoriasis
    Food intolerances and allergies
    Gastroesophageal reflux (GERD)
    Infertility and endometriosis
    Chemical and medication sensitivities
    Postural orthostatic hypotension (POTS)
    CIRS – exposure to mold mycotoxins is a potent stimulator of mast cell activation
    Migraines
    Depression
    Fibromyalgia
    Fungal infections
    Tinnitus
    Multiple Sclerosis
    Cancer



MEDIATOR    POSSIBLE EFFECTS

Histamine    Flushing, itching, diarrhea, hypotension
Leukotrienes    Shortness of breath
Prostaglandins    Flushing, bone pain, brain fog, cramping
Tryptase    Osteoporosis, skin lesions
Interleukins    Fatigue, weight loss, enlarged lymph nodes
Heparin    Osteoporosis, problems with clotting/bleeding
Tumor Necrosis Factor-?    Fatigue, headaches, body aches


MAST CELL MEDIATOR SYMPTOMS
Anaphylaxis
Flushing of the face, neck, and chest
Itching, +/- rash
Hives, skin rashes
Angioedema (swelling)
Nasal itching and congestion
Wheezing and shortness of breath
Throat itching and swelling
Headache and/or brain fog, cognitive dysfunction, anxiety, depression
Diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD)
Bone/muscle pain, osteosclerosis, osteopenia, osteoporosis
Light-headedness, syncope/fainting
Rapid heart rate, chest pain
Low blood pressure, high blood pressure at the start of a reaction, blood pressure instability
Uterine cramps or bleeding


Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on April 18, 2020, 08:21:57 AM
https://www.youtube.com/watch?v=82dmZhCBuBo

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

https://ehlers-danlos.com/2014-annual-conference-files/Anne%20Maitland.pdf

https://tmsforacure.org/symptoms/symptoms-and-triggers-of-mast-cell-activation/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231949/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343118/

https://www.ncbi.nlm.nih.gov/pubmed/16931289

https://www.ncbi.nlm.nih.gov/pubmed/17587883

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/

https://www.ncbi.nlm.nih.gov/pubmed/22957768

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545645/

https://academic.oup.com/humupd/article/14/5/485/812106/Effects-of-histamine-and-diamine-oxidase

https://www.ncbi.nlm.nih.gov/pubmed/24098785

http://ajcn.nutrition.org/content/85/5/1185.long

https://link.springer.com/article/10.1007/BF01997363

https://www.ncbi.nlm.nih.gov/pubmed/25773459

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507480/

https://www.ncbi.nlm.nih.gov/pubmed/15462834

https://www.ncbi.nlm.nih.gov/pubmed/22562473

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374363/

https://www.ncbi.nlm.nih.gov/pubmed/21244748

https://www.ncbi.nlm.nih.gov/pubmed/23784732

https://www.ncbi.nlm.nih.gov/pubmed/18394691

https://www.ncbi.nlm.nih.gov/pubmed/24060274

https://www.ncbi.nlm.nih.gov/pubmed/10415589
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 19, 2020, 03:22:57 PM
You have posted some interesting stuff HOD.

Increased IL-8 as a result of C. Albicans Infection (I had both), β-hexosaminidase piques my interest:

"We found that human mast cells have a versatile and timed response upon fungal encounter. Mast cells first degranulated β-hexosaminidase and were able to transiently reduce 30% of C. albicans viability up to 3 h post infection. In intermediate responses mast cells released pro-inflammatory cytokines, such as interleukin-8 (IL-8) and supernatants of C. albicans-infected mast cells were chemoattractive to neutrophils. In late responses mast cells secreted IL-16 and anti-inflammatory IL-1ra and released mast cell extracellular traps (MCETs) that ensnared, but probably did not kill C. albicans."

Opportunistic pathogen Candida albicans elicits a temporal response in primary human mast cells (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507480/)

Role and Relevance of Mast Cells in Fungal Infections (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374363/)

I made a comment somewhere that perhaps mast cells could take up vitamin D since low levels are seen in MCAS and POIS patients. I was scrolling through the vitamin paper you have posted and stumbled upon this:

"It has been shown that mast cell granules contain vitaminD, which is not synthesized inside the granules. As mast cells may appear within the epidermis or in close proximity to it, it is reported that they do take-up vitamin D contained inside the epidermis' intercellular compartment. Therefore, vitamin D synthesized by the keratinocytes enter the intercellular compartment, where its synthesis is accomplished, and migrates towards the basement membrane. At the basal epidermis layer, or after passing through the basement membrane, vitamin D is taken up by mast cells, where it is stored inside its granules."

I also found this comment interesting, that CRH (stress hormone) could affect vitamin D receptors:
"CRH may influence mast cell activation, direct modulation of immune cells, angiogenesis and induction of some receptors including receptors for steroids, retinoids and vitamin D."

Vitamins and mast cells (https://journals.sagepub.com/doi/pdf/10.1177/039463201002300403)

A histochemical investigation on the percutaneous absorption of vitamin D synthesized into the mammal epidermis (https://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S0065128185800064)

"There is a need for provider education and awareness of this disease that could affect up to 17% of the population (!!!) on a spectrum from very mild to debilitating symptoms. MCAS is often either misdiagnosed or the diagnosis is greatly delayed due to a lack of provider awareness. "

https://europepmc.org/article/med/32282570
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 21, 2020, 09:55:49 AM
Interesting cortisol discussions. I just recently completed CT scans of my adrenal glands, found benign nodules/tumors which might explain my resistance to blood pressure control meds. Under supervision of a nephrologist. I also have high creatinine count. Kidney problems have been a mystery to me.
I have massive reoccurring nasal polyps. After I get them removed my smell came back. Currently my polyps are giant and I can?t get surgery and I can?t smell or taste anything and they are too big to operate on
liver tests: a little fat and a small polyp
I am slightly anemic;)
I tore my knee ACL which is party healed unfortunately there is a cyst on the damaged tissue of my ACL
Also discovered there is a small cyst on my pituitary gland, which produces hCG mentioned in the paper.
-Pyro
i had a cyst removed from the top of my glans many years ago and it didn't cicatrize properly.
In my test results, I posted the doctors notes from my MRI angiogram (MRA). The doctor found what he believed to be a small bulge (aneurysm) in a blood vessel in my brain on the left side
I had a benign astrocytoma (brain tumor) removed when I was 5 years old.

Timestamp: 1:44:30
https://youtu.be/82dmZhCBuBo?t=6270
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on April 22, 2020, 07:00:58 AM
I also noticed this. Nodules/tumors on glands, is this comon in poisers?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 23, 2020, 10:28:47 AM
If POIS is mast cell mediated or a manifestation of MCAS you would expect to see these patients show up at doctors treating mast cell diseases as well. So I have sent Dr. Theoharides an email and asked him if he encounters MCAS patients who are responding to sexual triggers (orgasm, arousal etc). He confirmed this with a 'Yes'.

Are there any poisers living in or close to New York (USA)? Leading expert in mast cell activation syndrome Dr. Afrin treats MCAS patients in New York at Armonk Integrative Medicine. http://www.armonkmed.com/about/dr-afrin/

Perhaps a bunch of POIS patients could try to visit him. Anyone?
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on April 23, 2020, 10:39:07 AM
If POIS is mast cell mediated or a manifestation of MCAS you would expect to see these patients show up at doctors treating mast cell diseases as well. So I have sent Dr. Theoharides an email and asked him if he encounters MCAS patients who are responding to sexual triggers (orgasm, arousal etc). He confirmed this with a 'Yes'.

Are there any poisers living in or close to New York (USA)? Leading expert in mast cell activation syndrome Dr. Afrin treats MCAS patients in New York at Armonk Integrative Medicine. http://www.armonkmed.com/about/dr-afrin/

Perhaps a bunch of POIS patients could try to visit him. Anyone?
I also have talked with MCAS patients who react with sexual triggers. But the symptoms are generally typical MCAS, which usually involves anaphylaxis. What we need is MCAS sufferers who have similar symptoms to us. Also the usual treatment of anti-histamines seems to work for these people while it wouldn't for us.
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on April 23, 2020, 11:24:40 AM
I can see a big pecentage of poisers who helped by antihistamines. This ilnes is multy systemic,
and need multysaystemic aproach, like MC patients the same,
I hawe 90% symptomes of anaphylaxsis.

Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 23, 2020, 06:52:33 PM
In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation?...
  There are two reason given in the POIS literature for a difference between POIS from sex versus masturbation. The first reason comes from the paper:
  Progesterone deficiency, "Benign coital headache relieved by partner's pregnancies with implications for future treatment (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028282/)" (Selwyn Dexter, 2009)
  In this paper, they conclude that the male POIS patient benefited from his wife's progesterone (exchange of sexual bodily fluids). They tested this by giving the man a progesterone mimicking drug which relieved his POIS 95 percent.
  The second reason is given by the paper:
Mu-opioid receptor dysfunction, "Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE‐Mediated Allergy to Semen (https://www.ncbi.nlm.nih.gov/pubmed/25630453)" (Jia Yin, et al, 2015)
  In this paper, they suggest that low beta-endorphin stimulation is the reason that POIS occurs. Beta-endorphin blocks some of the negative (immune suppressing) properties of norepinephrine, epinephrine and prostaglandin PGE2 (see post (https://poiscenter.com/forums/index.php?topic=3151.msg31892#msg31892)). Social interaction (especially with the opposite sex) can increase endorphin release. Laughter (comedy) is also a major endorphin releaser!

...And why do i have to sleep within 20min or so after sex to avoid POIS?...
  The short answer may be that sleep boost your immune system. The sleep response is the immune system telling your body that it is not strong enough to handle POIS. The first thing that happens during sleep is that epinephrine and norepinephrine levels drop, and melatonin levels increase:

Check this out. If you combine above theory with mast cell activation theory, all three parameters point in the same direction, coincidence?:

Melatonin: Inhibits mast cells (Increased melatonin = improved POIS symptoms)
Progesteron: Inhibits mast cells (Increased progesteron = improved POIS symptoms)
β‐Endorphin: Stimulates mast cells (Increased β‐Endorphin = worsening of POIS symptoms)

Table 1:
Neuroendocrinology of mast cells: Challenges and controversies (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)

NSAIDs cause POIS symptoms for me, notably headaches and brain fog. To each there own.

This could be an indication that the ratio of Leukotriene/prostaglandin production might be skewed towards leukotriene production. A urine test for LTE4 can provide some insight. Some MCAS patients feel better while others feel worse on NSAIDs.
https://youtu.be/82dmZhCBuBo?t=6330
Title: Re: Mast Cell Activation Syndrome
Post by: Limejuice on April 23, 2020, 08:04:52 PM
Interesting...
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 24, 2020, 07:43:34 AM
Demografx uses benadryl which is an anti-histamine used in mast cell disorders.
Forced sleep improves his POIS symptoms. This can be explained by a raise in melatonin which inhibits mast cells.
Testosterone can induce inhibitory effects on mast cells as well (especially skin MCs), hence the improvement of symptoms by dermal TRT.

He got multisystem symptoms, which are mysterious and non-specific. Mast cells could be responsible for his benign nodules, MCs guide tissue growth.

He also got other triggers like hot showers. Just do an analysis of every symptom from person to person on this board, list those and you will see a lot of similarities with MCAS.

Same thing with IronFeather. She sensitized to some standard changes of parameters in the body as a result of sexual activity. It gets worse over time. Same thing with her soy sensitivity. She was in a sensitization process up to the point of colitis (which is another condition that could be related to mast cell activation disease).

Maybe you're right. I don't know what to think anymore. I'd never heard about mast cell activation disease, but I've looked up some information recently and it seems a bit exaggerated to me, isn't it an illness that's supposed to cause random reactions to various substances, red rashes on the skin, allergy attacks...? Can a person have MCAD and only display symptoms of a sensitivity to a certain substance, and in the case of poisers, to sexual activity? Isn't it a dangerous disease that would have caused us serious problems by now?

Honestly, I'm worried and scared about how this is going to evolve in time. Back when I was a teenager I could never have imagined the magnitude of the symptoms I'm having now, so who know what is yet to come? Does MCAD pose any risk to the brain? That's what terrifies me the most, my entire life revolves around intellectual activities, am I going to lose it all because of a stupid random disease?

The disease (MCAS) can range from very mild (almost unnoticable) to extreme (shock). You can react randomly to various substances or only react consistent to one specific substance. The rashes and allergic attacks have the potential to be involved but they don't necessarily have to occur. Yes you can develop sensitivies to a certain substance, but the overal picture is that patients show multisystem symptoms which are non-specific. Pressure, low ambient temperatures and food are able to induce symptoms in you, which are, not suprisingly, known mast cell triggers. The step up in magnitude of the symptoms is also what you are seeing in MCAS. It is not considered a dangerous disease. Sometimes you can have moments where you think you are dying but you will recover from those (I had these moments myself).

And I have frequency of toilet visit only after orgasm and this condition lasts for almost 24 hours.

Serotonin release from intestinal mast cells?

Muon:
"Does histamine inhibit the mast cell? I'm confused, is this an error? Table 1:"
Neuroendocrinology of mast cells: Challenges and controversies (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)

Dr. Theoharides:
"Histamine could inhibit mast cells via activation of H3 receptors"
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 26, 2020, 02:38:59 PM
Interesting cortisol discussions. I just recently completed CT scans of my adrenal glands, found benign nodules/tumors which might explain my resistance to blood pressure control meds. Under supervision of a nephrologist. I also have high creatinine count. Kidney problems have been a mystery to me.

Communication between mast cells, testosterone and the kidney?:

Testosterone and Mast Cell Interactions in the Development of Kidney Fibrosis after Unilateral Ureteral Obstruction in Rats (https://www.jstage.jst.go.jp/article/bpb/41/8/41_b17-00829/_article/-char/ja/)

(https://www.jstage.jst.go.jp/pub/bpb/41/8/41_b17-00829/figure/41_b17-00829.png)

https://repository.kulib.kyoto-u.ac.jp/dspace/handle/2433/115281

Not POIS but still posting. I wonder if beta-hexosaminidase mediator release is involved in POIS, perhaps something for research:

Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics (https://www.jacionline.org/article/S0091-6749(14)00715-5/fulltext)
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on April 26, 2020, 07:37:49 PM
Interesting, Muon
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on April 27, 2020, 02:27:07 AM
Muon, what are your thoughts on anti-histamines to alleviate MCAS symptoms? Some say that overuse of anti-histamines can eventually cause the body to produce more histamine. E.g. this interview:

https://healinghistamine.com/dr-janice-joneja-histamine-intolerance-interview-pt2/

Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 27, 2020, 06:29:50 PM
Muon, what are your thoughts on anti-histamines to alleviate MCAS symptoms? Some say that overuse of anti-histamines can eventually cause the body to produce more histamine. E.g. this interview:

https://healinghistamine.com/dr-janice-joneja-histamine-intolerance-interview-pt2/
I have never heard of overuse. Patients are going through an exhaustive list of mast cell targeted therapy one by one starting with anti-histamines. MCs can release a wide variety of mediators. If it doesn't secrete histamine then anti-histamines are worthless. The wide range of symptoms seen in poisers could indicate different mediator release profiles from person to person. Plus meds that gave improvement in poisers are often able to interact with mast cells or indirectly counter mediator effects in one way or the other.

A paper has been published including a Mast Cell Mediator Release Syndrome Questionnaire:

Mast Cell Activation Syndrome: A Primer for the Gastroenterologist (https://sci-hub.tw/10.1007/s10620-020-06264-9)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 28, 2020, 12:13:54 PM
I recently posted an article about treatment of idiopathic infertility by the mast cell blocker tranilast (there are more cases in literature):

Appearance of spermatozoon after administration of mast cell blocker to a patient with azoospermia (https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/115281/1/40_541.pdf)

I just encountered this one on reddit:
https://www.reddit.com/r/POIS/comments/g9lp3y/hello_people_of_reddit_i_hope_youre_all_doing/

YemAli
"My symptoms include:

Intense brain fog.
Aggravated.
Emotionless.
Fever the next 2 days.
Face bloated.
Hand tremors.
Speech errors.
Cognitive difficulties.
Anxiety.
Ears and nose all get stuffed up.
Face & Neck warm.

Was 99.99% Infertile. Didn't know what the reason was. After finding a miracle doctor. I discussed my infertility and my symptoms i have after O. He prescribed to take DeltaCortil 4 hours before O and see what happens. That month, the first time i tried with the medicine, got my wife pregnant. So i went back to my doctor and he then diagnosed me with POIS. Infertility can be linked with this cursed disease. Luckily i got linked with an amazing doctor who saved my life from getting corrupted by this nuisance of a illness.
"

tyrone737
"So did this medication help your other symptoms or just your infertility?"

YemAli
"Both! It's reduced my symptoms by 70-80 percent. And I achieved pregnancy. Well not i 😜 My wife."

https://www.drugs.com/international/deltacortil.html

Contains Prednisolone which is used in mast cell disorders, see this discussion:

https://poiscenter.com/forums/index.php?topic=3202.msg33995#msg33995

POIS (MC trigger?) --> MC activation ---> MC mediators affecting sperm production?

argumentdesk
"Was there anything else traumatic happening during your teenage years at the same time POIS manifested? (Illness, life stress, toxin exposure, car wreck, abuse, etc)"

YemAli
"No illness. Little stress because i wasn't the most brightest student and studies were tough."

Stress is a trigger in MCAD. There are more poisers on this forum and in literature who had stress before or during the development of POIS. Is there a stress induced change in mast cell phenotype involved in POIS?
Title: Re: Mast Cell Activation Syndrome
Post by: millstone on April 28, 2020, 03:34:21 PM
Muon,

Thanks for linking these two forums together. I am ArgumentDesk over on Reddit.

I believe the chronic stress / chronic disease / MCAS ties into my overall thoughts on how POIS manifests. I did a full write-up on Reddit a few weeks ago:

https://www.reddit.com/r/POIS/comments/g27a8l/pois_a_unified_theory_of_everything_suggestions/

This is why I was digging in to better understand YemAli's underlying triggers and background, as I do believe chronic stress (whether physical, chemical, or emotional) is the catalyst and foundation for manifesting POIS as a chronic condition (like all other chronic conditions) and ultimately the limbic system is (incorrectly) imprinted with the auto-immune-like instructions to release inflammation / immune response triggered by the rising chemical hormonal changes during arousal / orgasm.

Stress = Mind/Body Imbalance = Dis-ease

The stress leads to downstream gene expression, in particular, modifications that seems to up regulate the mast cell immune response.
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on April 29, 2020, 03:40:42 AM
Just to add more anecdotal evidence to the stress link, some of the main themes around my personal case are:

* What seems like a mast cell disorder (currently being diagnosed)
* Extensive chronic gut problems (currently greatly alleviated by a MCAD-friendly diet)
* Chronic background stress/anxiety all adult life and possibly before. (Am now 40)
* Severe tension in PSOAS, with related symptoms such as lower-back pain

I'm working on my PSOAS tension, but it's tricky as exercise is a trigger for me. :( This PSOAS release program feels awesome but leaves me with symptoms the day after:

https://www.youtube.com/watch?v=x2DB_ABQMFg
Title: Re: Mast Cell Activation Syndrome
Post by: Aladin on April 29, 2020, 06:24:27 AM
the symptoms the day after are normal part of the exercise: i used to have nightmares the night after when i did them at first. The idea is that your body gets rid of the toxines piled up in your psoas muscle. Hence the importance of drinking lots of water afterwards.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 29, 2020, 06:53:08 AM
Thanks for linking these two forums together. I am ArgumentDesk over on Reddit
Ok Hi, I rarely visit reddit due to the board format btw.

I'm working on my PSOAS tension, but it's tricky as exercise is a trigger for me. :( This PSOAS release program feels awesome but leaves me with symptoms the day after:

I got spinal issues, I think it's the pressure activating inflammation in sinovial tissue (high temperature, stress and POIS induce similar behaviour). Big chunk of my life problems with back muscles. Prolonged local stress/tension in muscles can ignite an inflammatory cascade in me (I assume it's inflammation). My mother got problems with the PSOAS, not me. I did Fysiotherapy for years but these were not the proper exercises for me. Yes exercise can worsen things while you do need it though, weak muscles are more susceptible to stress. It's a difficult balancing act. The tension must be relieved.

I have never heard of a poiser going through a complete MCAD diagnostic workup as presented in papers by the way. Even when your case is not mast cell related you still may give this questionnaire to your endocrinologist for other patients.
Mast Cell Activation Syndrome: A Primer for the Gastroenterologist (https://sci-hub.tw/10.1007/s10620-020-06264-9)

I tried an SSRI for a day.  I experienced a very severe headache (the likes I have never seen), so I stopped.
Same here even on the lowest possible dose. Where inside your head do you feel the pain the most?
That headache I experienced was totally unique.  Extremely heavy, crushing pressure in the middle of my skull.  Maybe there is no relationship...
I had same headache and i dont toletate any serotonergic drug. They cause fogginess and headache

Yes I triggered the same spot by taking citalopram.

SSRIs high risk of mediator release:
Compilation of drugs associated with a high risk of release of mediators from mast cells and their therapeutic alternatives (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab12/)

~90% of brain mast cells are concentrated in the middle of your skull. Not sure where I did get that number from, perhaps it was in this video:
'Brain Allergy' and ASD - T. Theoharides, MD, PhD (https://www.youtube.com/watch?v=9QbZp3WcC1Q)

In my case high ambient temperature + arousal can trigger a headache in that same spot. These are also potential MC triggers.
Title: Re: Mast Cell Activation Syndrome
Post by: millstone on April 29, 2020, 10:59:52 AM
Some SSRIs work different from one another in terms of specific receptor-site targeting, as well as elimination half-life.

When prescribed back in February, I tried Lexapro 20mg and felt an immediate terrible reaction within 2 hours.

I switched to Prozac (fluoxetine) 10 mg which has a much longer half-life and is a lower dose. No real side effects for me and it's been great.

Aside from the 'on-label' effect of serotonin reuptake inhibition, SSRI's have been found to catalyze neurogenesis in brain cell recovery, which is likely why they say it takes "4 to 6 weeks to see full effect".

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360216/

For me, POIS reactions led to serious neuro-inflammation and damage, so brain tissue recovery is very welcomed. I now focus on daily supplementation of Fish Oil and Vitamin D to enhance neurogenesis / recovery as well.

As for headaches, the very center of the brain is the limbic system, which is the more ancient "mammalian" brain that controls the sympathetic nervous system (including stress & immune response).

Just stitching concepts for thought... but an immediate headache in the area which controls your stress / immune response may correlate limbic brain function with POIS.
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on April 29, 2020, 01:57:15 PM
Yes exercise can worsen things while you do need it though, weak muscles are more susceptible to stress. It's a difficult balancing act. The tension must be relieved.

Yeah, I'm working on the balance. It's tricky as I have a wife and an 8-year-old child, and I get a bit grumpy as part of my symptom set. I've done the PSOAS release exercise about 15 times by now, and it feels less tense. But definitely needs more work.

I have never heard of a poiser going through a complete MCAD diagnostic workup as presented in papers by the way. Even when your case is not mast cell related you still may give this questionnaire to your endocrinologist for other patients.

Yeah, about that: My tryptase was normal. My endocrinologist is well-meaning albeit pretty busy, and not quite up-to-date on mast cell disorders. But he seems determined to reach a proper diagnosis and he still suspects a mast cell disorder. He hadn't read the papers I sent him (two of the ones you suggested), but said he would when time allows. The next step is going to a dermatologist at the same specialist centre to do a skin biopsy of some of the infection-like sores I have here and there, which seem to be tied to the overall symptom picture. He did take a quick look at some of the blood tests in the table you mentioned, and said some of them weren't available, but that the University hospital does chromogranin A tests. But he said he'd like to get the biopsy results first.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T6/ (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T6/)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 29, 2020, 05:45:09 PM
Well...good luck reaching a proper diagnosis without a proper diagnostic workup. Factor VIII is another MC mediator that should be available. More mediators inside this thread: https://poiscenter.com/forums/index.php?topic=3236.0
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on April 30, 2020, 01:57:24 AM
Well...good luck reaching a proper diagnosis without a proper diagnostic workup.

Well, beggars can't be choosers unfortunately. :) We have an extensive healthcare system over here, but the competency around chronic (and especially rare) disorders seems to be a real wasteland. I've heard from the University hospital that we basically had a single MCAD expert and she retired last year. So I have to work with this guy and see what I can do.

Factor VIII is another MC mediator that should be available. More mediators inside this thread: https://poiscenter.com/forums/index.php?topic=3236.0

Thanks, that's very helpful! Given that the attention span of this guy is stretched, what would you say are the very first things that should be checked? In case he's missing something obvious.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 30, 2020, 08:37:49 AM
Yes but you are narrowing your chances if you skip most of the diagnostic parameters. Aside from the ones mentioned in the table, the next in line would be the Leukotrienes preferably LTE4 (24h urine). Chromogranin A > Leukotrienes (E4 or C4) > Factor VIII
You want as much mediators tested as possible because these cells can behave in many different ways releasing selective groups.

On top of what was mentioned above; Theoharides proposes this additional selection of serum measurements: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/figure/F1/

Comorbid testing: Scan for osteoporosis and lactulose breathing test (hydrogen+methane, 30% of MCAS patients vs 10% healthy controls test positive)

If stress is triggering you often then VEGF is something to look at. For cardiovascular symptoms one could take a look at PAF.

Secondly a response to mast cell targeted therapy is part of diagnostic criteria, thus therapy is being applied before diagnosis has been established.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on April 30, 2020, 09:24:08 AM

The guy needs to do his goddamn job, do a proper investigation or leave it alone, stop with the half-baked stuff.


In our non-medical suggestive roles here (we’re not research or medical professionals), is this strong-armed approach really necessary?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on April 30, 2020, 09:48:44 AM
Ok fair enough, deleted the comment.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 01, 2020, 06:24:35 AM
Potential mast cell related symptoms:

https://poiscenter.com/forums/index.php?topic=3283.msg34142#msg34142
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 04, 2020, 02:53:01 AM
Yes but you are narrowing your chances if you skip most of the diagnostic parameters.

Hey Muon. Thanks again for your invaluable input here. I saw your deleted comment that demo quoted. ;) And I 100% feel you, and I feel the same anger and frustration at having to struggle to be believed (by some), and to get help. However I've got to play the hand I'm dealt here. Regardless of this doctor's potential shortcomings, bursting in there and telling him how to do his job is not going to work. He currently suspects Mastocytosis (as do I), and I think my best bet is to let him try to diagnose it his way, but if he fails to come up with anything, be politely insistent that he look at MCAS etc, and point to relevant research.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 04, 2020, 10:57:40 AM
To get a feel for relative numbers here are some rough estimates. Let's compare the MCAD subtypes Mastocytosis and MCAS.

For Mastocytosis, in western Europe , the prevalence is ~5-13/100,000 (Epidemiology (https://sci-hub.tw/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231))

Let us take 10 for easy calculation: (10/100,000)*100% = 0.01%

Recent papers have estimated a potential prevalence of MCAS within the 10% - 19% range. Let's take 10%. Ref (https://europepmc.org/article/med/32282570)

The estimated prevalence of the two MCAD disease types differs, roughly, by a factor of ~1000.

Take a look at this diagram again: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/figure/F1/

The green box with the text 'MCMD without elevated tryptase or MC profileration'. That one is more prevalent than diagnoses depicted by the other colored boxes. And not by a small margin but by a huge one. This algorithmic pathway is being skipped in healthcare while it is your most important one based on prevalency.

I think the reason he made that specific selection of supportive serum measurements (IL-6, IL-31, CCL2, CXCL8) is to cover a wide range of MC activation pathways which are involved in selective mediator release, like these: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/table/T3/ .There are tons of them.
Title: Re: Mast Cell Activation Syndrome
Post by: aswinpras06 on May 04, 2020, 09:34:07 PM
Hi everyone
The past 6 months have been really hard for me.  I am 42 now and I don't know how long I can tolerate  this dreadful disease.  My lungs are almost damaged now and very soon I will be on oxygen for breathing everyday.  All these years I have been an idiot and never thought seriously about my breathing problems and always thought they were caused by pois.  I never did a detailed investigation of my lungs and I now have end stage bronchiectasis.

But at last I have found the reason for my lung damage and probably for my pois. Mast cell activation disorder.  This was found by my pulmonologist after 6 months of many therapies which never worked for me due to my abnormal mast cell activation. At first he never accepted my theory about mast cells but later ordered seum tryptase test which was high.  But a baseline value could not be found because it was always high due to my constant triggers like fan air,showers, lack of sleep due to my lung problems.  Now he has recommended for omalizumab therapy.  But due to the covid ,19 I could not get admitted and try omalizumab which requires close monitoring. Hope I can get the therapy within a few months.  Will update once I get my anti-ige therapy.

Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 05, 2020, 01:51:09 AM
The green box with the text 'MCMD without elevated tryptase or MC profileration'. That one is more prevalent than diagnoses depicted by the other colored boxes. And not by a small margin but by a huge one. This algorithmic pathway is being skipped in healthcare while it is your most important one based on prevalency.

That's super interesting, thanks Muon. To be fair I don't think my doctor is rushing to a conclusion here, and in fact he's technically following that algorithm so far. He first tested tryptase, which was normal. I've got a lot of unexplained skin lesions, so the next step is a skin biopsy. So we're following that rightmost branch there at the moment. This graph is great to have as a reference.

I think the reason he made that specific selection of supportive serum measurements (IL-6, IL-31, CCL2, CXCL8) is to cover a wide range of MC activation pathways which are involved in selective mediator release, like these: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/table/T3/ .There are tons of them.

OK, that's good to know, thanks. I'll report back after the skin biopsy in a month or so!

In the meantime I'm making lifestyle changes to experiment. I've employed an MCAD-friendly diet and skin products, started intermittent fasting, and avoided orgasm and hard exercise in the last few weeks. Oh and also I'm doing Psoas exercises and Wim Hof breathing. My digestion has felt amazing apart from occasional light constipation. Brain fog and irritability have been consistently low. Other symptoms like skin lesions and extreme cold sensitivity have been the same as before. I tried an orgasm on Sunday. Noticeably less visible inflammation signs than the last time a month back or so. I felt normal cognitively yesterday (day 1 after), but my excrement was loose and slimy again, after consistently being healthy for weeks. Today it's the morning of day 2 which is when my POIS symptoms usually peak. Feel OK so far.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 06, 2020, 09:53:59 AM
At first he never accepted my theory about mast cells but later ordered seum tryptase test which was high.  But a baseline value could not be found because it was always high due to my constant triggers like fan air,showers, lack of sleep due to my lung problems.

Hi Aswinpras,
Sorry to hear about your situation. You are lucky Tryptase is elevated, then it's quite clear you are dealing with MCAD. What value did they measure? Generally speaking, increase in event-related tryptase is harder to capture than the baseline. What you have measured may actually be your baseline. Tryptase is correlated to mast cell load and not with disease activity which means that you may have MC infiltrates somewhere in your body (I will not be surprised when you have higher MC numbers in lung tissue).

Give this paper to your doctor:
Pharmacological treatment options for mast cell activation disease (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/)

This graph is great to have as a reference.
Here is another one See Figure 2 (https://sci-hub.tw/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231).

Sexual-related activity could be placed inside the box at the top of this diagram (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/figure/F1/) as well. POIS may be a manifestation of MCAD in a subgroup of poisers. There is probably no golden bullet to treat it due to individual phenotypes, therapy is personalized.

(https://www.ncbi.nlm.nih.gov/corecgi/tileshop/tileshop.fcgi?p=PMC3&id=173554&s=61&r=1&c=1)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 06, 2020, 05:54:44 PM
Steroid hormones during a flare:
CORTISOL *688.000 nmol/l 133.00 - 537.00
Aldosterone SERUM/PLASMA * 2210 pmol/l 61 - 970

Contributions of ACE and mast cell chymase to endogenous angiotensin II generation and leucocyte recruitment in vivo (https://academic.oup.com/cardiovascres/article/92/1/48/538626)

"Conclusion
In vivo, Ang II is primarily generated by ACE under basal conditions, but in inflammatory conditions, the release of MCP amplifies local Ang II concentrations and the associated inflammatory process. Thus, AT1 receptor antagonists may be more effective than ACE inhibitors for treating ongoing Ang II-mediated vascular inflammation."


(https://upload.wikimedia.org/wikipedia/commons/a/a2/Renin-angiotensin-aldosterone_system.png)

POIS ---> MC activation ---> Release of Chymase ---> Ang II-mediated vascular inflammation?
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on May 06, 2020, 06:29:38 PM
Muon what do you think a valid treatment for POIS is if anti-histamines do not work? There doesn't seem to be many option for therapy and therefor we may never actually be able to ascertain any anecdotal proof?
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on May 07, 2020, 11:33:27 AM
Has anyone tried Ketotifen? I'm thinking of asking my doctor for a prescription. It's a mast cell stabilizer and anti-histamine. I don't want to take sodium cromolyn daily and am looking for something to take only before O.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on May 07, 2020, 03:40:29 PM
Has anyone tried Ketotifen? I'm thinking of asking my doctor for a prescription. It's a mast cell stabilizer and anti-histamine. I don't want to take sodium cromolyn daily and am looking for something to take only before O.
I've tried ketotifen, didn't do much. Also Chromolyn Sodium cannot be absorbed into the blood stream, so I don't see how it can help us with brain symptoms.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 08, 2020, 02:36:52 PM
Muon what do you think a valid treatment for POIS is if anti-histamines do not work? There doesn't seem to be many option for therapy and therefor we may never actually be able to ascertain any anecdotal proof?

If there was validated treatment for POIS then you would not ask this question. My best guess is to interact with receptors on mast cells one by one. Like playing piano finding the right tone or combination of tones which may differ from person to person. But this is based on the assumption of mast cell involvement, that in itself may be part of a much wider spectrum.

If you want proof you will need to measure MC mediators via research in poisers vs healthy controls and I don't see that happening. I don't have a better answer for you. Here are some options: https://poiscenter.com/forums/index.php?topic=3236.msg33462#msg33462
Title: Re: Mast Cell Activation Syndrome
Post by: Labyrinth on May 09, 2020, 02:17:14 PM
That headache I experienced was totally unique.  Extremely heavy, crushing pressure in the middle of my skull.  Maybe there is no relationship...[/quote]

Yes I triggered the same spot by taking citalopram.

SSRIs high risk of mediator release:
Compilation of drugs associated with a high risk of release of mediators from mast cells and their therapeutic alternatives (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab12/)

~90% of brain mast cells are concentrated in the middle of your skull. Not sure where I did get that number from, perhaps it was in this video:
'Brain Allergy' and ASD - T. Theoharides, MD, PhD (https://www.youtube.com/watch?v=9QbZp3WcC1Q)

In my case high ambient temperature + arousal can trigger a headache in that same spot. These are also potential MC triggers.
[/quote]

that makes sense , may be  it is all related to mast cells and inflammator mediators

what meds can stop these ast cells from running crazy ?!
Title: Re: Mast Cell Activation Syndrome
Post by: Labyrinth on May 09, 2020, 02:26:11 PM
Muon what do you think a valid treatment for POIS is if anti-histamines do not work? There doesn't seem to be many option for therapy and therefor we may never actually be able to ascertain any anecdotal proof?

If there was validated treatment for POIS then you would not ask this question. My best guess is to interact with receptors on mast cells one by one. Like playing piano finding the right tone or combination of tones which may differ from person to person. But this is based on the assumption of mast cell involvement, that in itself may be part of a much wider spectrum.

If you want proof you will need to measure MC mediators via research in poisers vs healthy controls and I don't see that happening. I don't have a better answer for you. Here are some options: https://poiscenter.com/forums/index.php?topic=3236.msg33462#msg33462

I have high histamine levels , skin wheels and flares , easily deramtitis and eczema , all goes with high inflammatory mediators in blood
Title: Re: Mast Cell Activation Syndrome
Post by: aswinpras06 on May 11, 2020, 05:36:07 AM
Dear friends

I am going to start omalizumab therapy from june15 for mastcell disease.  I am in a very bad state now with my lungs totally destroyed and on oxygen due to a rare lung disease called bronchiectasis which was probably caused by mast cell disorder.

If I get relief I will post the details of the therapy which most likely to work for pois too

In case you do not hear from me assume that it has not worked and probably I am in critical state or have passed away.  This forum is of immense help for me in understanding what is wrong with my health.  I have learnt a lot and received some excellent advices from many members.  But unfortunately it is too late and I missed my lung damage.

Thanks once again to all members and the admin of this great forum .  Muon  I thank you specifically for your great help and concern.  God bless you all.
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 11, 2020, 06:06:27 AM
aswinpras06, I wish you the best! Will be thinking of you and hoping for a successful therapy!
Title: Re: Mast Cell Activation Syndrome
Post by: Hopeoneday on May 11, 2020, 11:24:47 AM
Hold on Aswinp... did you tryed pine nedles syrup or with hony? This is the first line for
bronchitis in my country... i dont know is it safe for you try and get some relief.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on May 11, 2020, 04:05:30 PM
Dear friends

I am going to start omalizumab therapy from june15 for mastcell disease.  I am in a very bad state now with my lungs totally destroyed and on oxygen due to a rare lung disease called bronchiectasis which was probably caused by mast cell disorder.

If I get relief I will post the details of the therapy which most likely to work for pois too

In case you do not hear from me assume that it has not worked and probably I am in critical state or have passed away.  This forum is of immense help for me in understanding what is wrong with my health.  I have learnt a lot and received some excellent advices from many members.  But unfortunately it is too late and I missed my lung damage.

Thanks once again to all members and the admin of this great forum .  Muon  I thank you specifically for your great help and concern.  God bless you all.
Stay strong Aswinpras! You can do it! There are many MCAS remedies for lungs and I have faith that Docotros will figure something our for you!
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on May 11, 2020, 05:24:06 PM
Best wishes, aswinpras!
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on May 11, 2020, 06:54:09 PM
aswinpras, do you happen to have IBS as well or any digestive problems? I wish you all the best.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 12, 2020, 03:53:23 AM
I wish you much strength aswinpras. Perhaps, in the meantime, your doctor could give you a lighter medicine to try which is readily available to win you some time until june. I'm sorry you have such a hard life.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 18, 2020, 12:42:05 PM
Postorgasmic illness syndrome: potential new treatment options for a rare disorder (https://sci-hub.tw/10.1080/21681805.2019.1704861)

"The patient has a history of irritable bowel syndrome (IBS) well-controlled on loperamide."

IBS is often seen in MCAD patients. Also I found this regarding loperamide:
"Associated diarrhea can be treated with an oral histamine 2 receptor antagonist and loperamide. Ranitidine was administered to diminish the effects of her small-bowel mast cell burden, and loperamide, an opioid agonist, was administered to decrease the activity of the myenteric plexus, thereby slowing gastrointestinal transit." Ref (https://www.mayoclinicproceedings.org/article/S0025-6196(15)00061-0/pdf)

"He is otherwise in excellent health with an unremarkable physical examination."

That's what you will see in MCAD patients, they appear healthier than would be expected from their litanies of complaints.

"...and gastrointestinal symptoms beginning immediately after orgasm."

POIS could trigger activation of GI mast cells resulting in GI symptoms.

"A trial of antihistamine had good effect on his gastrointestinal symptoms"

Again, an indication that he could be dealing with mast cell activation in his GI tract.

"We also hypothesize that symptoms in this patient were related to sympathetic dysregulation, a new theory for potential pathogenesis of this disease."

I don't see many autonomic related symptoms in this patient. Other patients that do express relatively more autonomic symptoms could be explained by mast cell mediators interacting with autonomic nerve endings since mast cells abut neurons.

"...and alpha-blocker administration resulted in marked improvement of almost all symptoms."

α1-Adrenergic Receptor Blockade by Prazosin Synergistically Stabilizes Rat Peritoneal Mast Cells (https://www.hindawi.com/journals/bmri/2020/3214186/)

"This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors."
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on May 19, 2020, 03:23:03 PM
I assume you saw the old MCA reply by the researchers at the reddit forum?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 19, 2020, 03:53:45 PM
I assume you saw the old MCA reply by the researchers at the reddit forum?

If you mean the reply below then yes.

Tyrone737:
"Do you happen to know if this study will be looking at mast cell activation as a potential element in POIS?"

POIS_Scientist:
"We cannot disclose the specifics of what we are collecting, as this could influence participant responses. This may sound strange given that this is a biomarker, but even the expectation of having a system measured can change that system. Of course, we absolutely tell you all the things that we will ask you to do prior to asking you to come in for the study itself...no surprises!...but some of the specifics about what we are testing we should not disclose to avoid reactivity. Thanks for your question."

Dumping some papers here which I will take a look at later:

Immunocompetence, mast cells and sexual behaviour (https://sci-hub.tw/10.1111/j.1474-919X.1996.tb04316.x)

GnRH, brain mast cells and behavior (https://sci-hub.tw/10.1016/s0079-6123(02)41102-8)

Brain mast cells link the immune system to anxiety-like behavior (https://sci-hub.tw/10.1073/pnas.0809479105)
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on May 19, 2020, 04:23:56 PM
Yes, that’s it, good. Just wanted to make sure you saw it.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 22, 2020, 03:34:15 PM
The Gene Food Podcast: Episode 15 - Featuring Dr. Theoharis Theoharides:

Mast Cells, Autism, and the Immune System with Dr. Theoharis Theoharides (https://www.youtube.com/watch?v=37GtfXOP8dw)

Below are some snippets from the video link above.

https://youtu.be/37GtfXOP8dw?t=765

Dr. Theoharides:

"And then what happens is some of the molecules that we don't commonly discuss that are secreted from the mast cells act back on the mast cells. For instance, Corticotropin-releasing hormone is the main hormone released under stress from the hypothalamus in the brain. Yet, we published that human mast cells release more CRH than even the brain. And what happens is we also published that the mast cells have high affinity, very strong receptors for CRH. So if CRH is released after the mast cells have actually been activated, it will be released it will act back on the mast cells. So what happens is the mast cell grows even more receptors for CRH. So the mast cells now are much more susceptible to stress"

"And in fact, we publish papers where we measured CRH the stress hormone in the blood with patients to whom were given some decongestant State-Trait Anxiety Inventory, that within 34 questions are so gives you an idea how stressed individuals are. And CRH was very high in the blood and it was a very strong correlation with anxiety. So we know that. Therefore, any type of stress by definition is likely to stimulate the mast cells directly or make them more responsive either to new triggers or whatever triggers a patient might have had to begin with."

"We published a paper a long time ago that stress meaning CRH we add CRH to human mast cells they become much more responsive to Mercury, for instance, okay. And this is an area that just not being discussed, that the mast cells must have some threshold that is being reset. Because I have so many patients who basically say, "Something happened, and all of a sudden I'm allergic or I respond to everything"

Reminds me of some members who had stress prior to their POIS like Animus and suddenly develop POIS.
Title: Re: Mast Cell Activation Syndrome
Post by: Spartak on May 22, 2020, 06:38:31 PM
Scientific part about Mast Cell is way above my understanding of medicine, but seems like a subject that should not be ignored in any of the future POIS studies.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 23, 2020, 01:48:48 PM
I get a bit of "stuck feeling" and tightness in lower back too when stressed.

Yep me too. I think it correlates with some of my cognitive symptoms as well. E.g.: If I play a hectic videogame for a couple of hours, my lower back (probably psoas), hamstrings and glutes are all tight and aching, and my articulation and OCD get a bit worse.

"Computer-induced stress enhanced allergen specific responses with concomitant increase in plasma SP levels in patients with AD [182]. Similar findings with increased plasma levels of SP, VIP and NGF, along with a switch to a Th2 cytokine pattern, was reported in patients with AD playing video games [183]. " Mast cells and inflammation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 24, 2020, 07:53:11 AM
Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE-Mediated Allergy to Semen (https://sci-hub.se/https://www.sciencedirect.com/science/article/pii/S1743609515309632)

Mast cell related problems are all over the place in this paper.

"A 61-year-old male visited our allergy department complaining of flu-like symptoms after ejaculation (including spontaneous ejaculations, masturbation, and intercourse) over 40 years. The symptoms began 60 minutes after ejaculation and were ranged from severe to moderate, mainly including extreme fatigue and exhaustion, feelings of extreme dryness-heat inside the body (particularly in the lower right back region), perspiration, muscle tension in the lower limbs, difficulty concentrating, general irritability, memory problems, foggy feeling in the head, nasal congestion, sneezing and running nose, sore throat, itching eyes, and photophobia."

The combination of these multisystem symptoms expose potential involvement of mast cell activation/release. Nothing mysterious about it when you consider MCAD.

"Waldinger et al. [5], 26 (58%) reported an atopic constitution, similar to other reported cases [4]."

Atopy points to mast cell problems.

"The relationship between POIS and mental disorders has not been defined."

Mast cells may bridge those two.

" Difference in the skin reactions to seminal fluid may be explained by the different grading systems and skin test procedures used."

Or due to different mast cell phenotypes and/or different (normal) mast cell reactivity.

"Human seminal plasma has a variety of inflammatory cytokines and chemokines including TGFβ1, CXCL8 (ex-IL-8), GRO (CXCL1/Th17), monocyte chemotactic protein 1 (MCP-1), IL-13, and IL-17 [11], some of which can activate basophils or mast cells; for example, Conti et al. [12] showed that MCP-1 has chemotactic activity for mast cells and plays a fundamental role in the release of histamine."

RED ALERT! They might be heading in the right direction here. Someone needs to give these guys a push in that direction. Also there are tons of potential triggers in seminal fluid which may activate mast cells like neuropeptides. If mast cell chemotactic activity is at work here you would expect mast cell infiltrates in the mucosal layer of the genitourinary system. The increased prevalence of POIS in men relative to women may be explained by the extra amount of potential mast cell triggers which reside in seminal fluid.

There are multiple POIS case reports where patients have rhinitis:
"Neurotrophins like NGF represent prime candidates in upper airway pathophysiology in allergic rhinitis" Ref (https://onlinelibrary.wiley.com/doi/full/10.1111/imm.12717)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 24, 2020, 02:22:44 PM
Personally, I have an inflamed/painful mouth feeling one day(?) after O.

Independant of that I also have diagnosed peridontal disease without pain (and bleeding gums if I don't take care).

Table 1: Oral/oropharyngeal---> pain and dental decay. Ref (https://sci-hub.tw/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231)

https://youtu.be/lrKqlv6VK_w?t=3388

If pain is burning:

Neuropeptides in Saliva of Subjects With Burning Mouth Syndrome: A Pilot Study (https://pubmed.ncbi.nlm.nih.gov/20233324/)

"NGF peptide and tryptase activity were shown to be significantly and persistently higher in saliva of BMS subjects, with respect to control values."
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 25, 2020, 05:25:48 AM
"Computer-induced stress enhanced allergen specific responses with concomitant increase in plasma SP levels in patients with AD [182]. Similar findings with increased plasma levels of SP, VIP and NGF, along with a switch to a Th2 cytokine pattern, was reported in patients with AD playing video games [183]. " Mast cells and inflammation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/)

Wow, that's very interesting! I do have itchy rashes here and there that may be atopic dermatitis. I'm waiting for a biopsy of these, should be interesting.

A bit saddening to know as I love video games, and it's a good way to stay in touch with remote friends during the pandemic. But ultimately always good to know more. Thanks Muon. :)
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 25, 2020, 07:16:42 AM
Found this study which compares the effectiveness of Quercetin and Cromolyn Sodium in blocking mast cell cytokine release:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314669/

Quercetin sounds really promising for symptom management, any thoughts on this Muon?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 25, 2020, 09:39:53 AM
Some members are using Quercetin. I've haven't read that paper but I have read some comments about it in other papers. But they think Cromolyn can calm down nerve fibers as well and could have additional indirect ways of inhibiting the mast cells in humans. As far as mast cell inhibitory properties go it's like this, starting with the best one:

Tetramethoxyluteolin (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0091674914015747) >> Luteolin > Quercetin > Cromolyn

The problem with the first one is that it doesn't get absorbed by the body. They haven't found a way yet. The author of that paper helped making supplements. Scroll down to the algonot link: https://poiscenter.com/forums/index.php?topic=3236.msg33462#msg33462

Tetramethoxyluteolin is only being used in the Gentlederm (https://www.gentlederm.com/) product for skin problems. That one might also be useful to Dermatologists when other products fail. The other products are liposomal formulations. Similar products on the internet don't state the purity of the active ingredients and they are full of fillers.

A new one is coming up: "A new dietary supplement to be available soon combines luteolin, quercetin, and eriodictyol (ViralProtek, proprietary formulation, patent pending) to achieve the maximal benefit of these flavonoids." Ref (http://mastcellmaster.com/PDF/COVID-19-mast-cells-cytokines-luteolin-BioFactors-2020.pdf)

Hmm didn't know the hydroxyl groups at the structure with the two carbon rings made the difference (at the end of the paper you posted).

(https://ars.els-cdn.com/content/image/1-s2.0-S0091674914015747-fx1.jpg)

Quercetin:
(https://upload.wikimedia.org/wikipedia/commons/thumb/8/81/Quercetin.svg/250px-Quercetin.svg.png)

Eriodictyol:
(https://upload.wikimedia.org/wikipedia/commons/thumb/d/d3/Eriodictyol.png/200px-Eriodictyol.png)

There is also a problem with getting sufficient Luteolin into the brain.

(https://www.eurekaselect.com/images/graphical-abstract/ctmc/18/21/002.jpg)

More properties of flavonoids:

The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function (https://sci-hub.tw/https://www.ingentaconnect.com/content/ben/iadt/2010/00000009/00000004/art00006)

Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood (https://sci-hub.tw/https://link.springer.com/article/10.1007/s10753-014-9995-x)

"IFN- is an important cytokine that has been implicated in the pathogenesis of a variety of autoimmune and chronic inflammatory conditions systemic lupus erythematosus, type I diabetes mellitus, adjuvant-induced arthritis [1]. All the selected flavonoids were effective inhibitors of the IFN- production, percentages higher than 60 %, for 25 μM. Luteolin 4e was the best one inhibiting the production almost completely (Fig. 4). Once more, the presence of OH groups in A ring appeared as an important feature to the activity as flavonoid 1d was once more the less active."

"In accordance with the literature, in this work, luteolin 4e was the most active flavonoid in the inhibition of almost all cytokines, IL-6, IFN- , and TNF-α, which makes this flavonoid a promise in the modulation of the inflammatory process."
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 26, 2020, 01:28:12 AM
Some members are using Quercetin. I've haven't read that paper but I have read some comments about it in other papers. But they think Cromolyn can calm down nerve fibers as well and could have additional indirect ways of inhibiting the mast cells in humans. As far as mast cell inhibitory properties go it's like this, starting with the best one:

Tetramethoxyluteolin (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S0091674914015747) >> Luteolin > Quercetin > Cromolyn

That is super helpful Muon, thank you yet again for your advice and citations!

Part of the reason I was excited about Quercetin is that I can obtain it myself at a reasonable cost with no prescription etc. Whereas Cromolyn will be a hurdle I think.

Excited to learn about Luteolin as well. The only supplement I found that ships to Norway was Swanson Luteolin Complex (https://www.swansonvitamins.com/swanson-ultra-luteolin-complex-100-mg-30-veg-caps#product-details). It's 50 mg Luteolin and 50 mg Rutin per serving. The Rutin is supposed to help the bioavailability of the Lutelin according to the manufacturer. Any thoughts on this?

Also I saw you can get Quercetin Phytosome (https://www.thorne.com/products/dp/quercetin-phytosome) now, which ostensibly has much better bioavailability.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on May 26, 2020, 02:26:44 AM
Some members are using Quercetin. I've haven't read that paper but I have read some comments about it in other papers. But they think Cromolyn can calm down nerve fibers as well and could have additional indirect ways of inhibiting the mast cells in humans.
The problem with Chromolyn, just like with Tetramethoxyluteolin, that it can not be absorbed in the blood stream, regardless of actually passing through the Blood-Brain barrier and reaching the nerves.
I've tried Quercetine and luteolin, both, multiple times and they didn't even make a dent. You'd think they'd at least have x percent effect but not at all. If Mast Cells are indeed involved, there must be a therapeutic proof and until now I haven't had success with any.
Title: Re: Mast Cell Activation Syndrome
Post by: berlin1984 on May 26, 2020, 04:21:17 AM
There seem to be (supplement) forms of quercentin that claim to improve absorbtion..

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418071/

https://www.google.com/search?client=firefox-b-d&q=increase+quercetin+absorption
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 26, 2020, 04:24:30 AM
I've tried Quercetine and luteolin, both, multiple times and they didn't even make a dent. You'd think they'd at least have x percent effect but not at all. If Mast Cells are indeed involved, there must be a therapeutic proof and until now I haven't had success with any.

OK. Even though I'm about 80% certain I've got some sort of mast-cell-related disorder/disease, it might not be the same one you have, and I've heard reports from others seeing improvement with flavonoids, so I'll continue experimenting.

Did you try Cromolyn as well btw?

There seem to be (supplement) forms of quercentin that claim to improve absorbtion..

Yep, that's the one I mentioned as well berlin1984. Sounds promising, has anyone tried it?
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on May 26, 2020, 04:45:09 AM
Did you try Cromolyn as well btw?
I haven't but I mostly suffer from brain symptoms so they're not gonna help even if I tried.
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on May 26, 2020, 06:27:21 AM
I haven't but I mostly suffer from brain symptoms so they're not gonna help even if I tried.

OK, what do you base that on though? Not saying you're wrong, just curious. FYI there was someone on the forum, can't remember which thread, who said his brain fog was massively reduced by Cromolyn.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 26, 2020, 08:01:11 AM
The only supplement I found that ships to Norway was Swanson Luteolin Complex (https://www.swansonvitamins.com/swanson-ultra-luteolin-complex-100-mg-30-veg-caps#product-details). It's 50 mg Luteolin and 50 mg Rutin per serving. The Rutin is supposed to help the bioavailability of the Lutelin according to the manufacturer. Any thoughts on this?

Also I saw you can get Quercetin Phytosome (https://www.thorne.com/products/dp/quercetin-phytosome) now, which ostensibly has much better bioavailability.

It's actually the quercetin that helps with the bioavailability of Luteolin. Rutin is Quercetin bound to sugar. It will be cleaved in the gut by certain microbes. I remembered that it keeps enzymes/microbes busy metabolizing Rutin/Que while most of the Luteolin can slip passed them.

Quercetin:
(https://upload.wikimedia.org/wikipedia/commons/thumb/8/81/Quercetin.svg/250px-Quercetin.svg.png)
Rutin:
(https://upload.wikimedia.org/wikipedia/commons/thumb/0/09/Rutin_structure.svg/250px-Rutin_structure.svg.png)

1)The Swanson product doesn't seem to state in what form the luteolin comes along.
2)It doesn't state the purity of the active ingredients
3)It isn't hypo-allergenic
4)It's relatively cheap because they use peanut shells as source.

Neuroprotek (https://www.mastcellmaster.com/dietary-supplements/NeuroProtek-Frequently-Asked-Questions-Pg-2.pdf) gives more product information but is quite expensive. I didn't know about the phytosome formulation, thanks for sharing.

These flavonoids are meant for long term use by the way.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418071/
Thanks

Very nice reference, I like the way they compare different flavanols.  Quercetin AND Luteolin (specially) has a nice effect on me, whereas Fisetin (also cited in this research) somehow has an oppositely negative effect on me.  I get induced into temporary POIS for about 24 hrs after taking one dosage only.  Anyone else has this effect from Fisetin?

The Role of Quercetin, Flavonols and Flavones in Modulating Inflammatory Cell Function (https://sci-hub.tw/https://www.ingentaconnect.com/content/ben/iadt/2010/00000009/00000004/art00006)
I have never tried Fisetin. It could also be a bad reaction to the fillers.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 27, 2020, 08:57:50 AM
Posted this before and will post it again:

Intimate Contact Could Be Dangerous for Your Health (https://sci-hub.se/10.1016/j.clinthera.2019.04.010)

"Mast cells are unique immune cells responsible for hypersensitivity reactions through secretion of many mediators that may have both proinflammatory and anti-inflammatory effects. Mast cells may affect sexual function, depending on the mediators secreted, especially because mast cells respond to neurohormonal triggers. Mast cells are found in the genitourinary organs and in seminal plasma of infertile men, but the function of mast cells in these instances remains vague."

"Moreover, sensitive patients should be evaluated for atopic diathesis, especially the presence of conditions such as mast cell activation syndrome or multiple chemical sensitivity syndrome..."

POIS patients aren't being evaluated for MCAS that's the problem, and if one is being evaluated it's being done through an incomplete procedure.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 30, 2020, 11:16:19 AM
I was about 2 weeks out from my last O (4 times in 2 days before an MRI to purposely be as sick as possible before the scan).  Since then I abstained but had mini-POIS recurring every day (buzzing, light head, red eyes, anxiety, confusion, joint pain, nausea) despite the usual supplement regimen.  In any event, on Friday I had an O and felt moderately bad yesterday, but today feel quite good :D.  Which got me to thinking whether any of you believe that in addition to abstaining as the primary POIS avoidance, that it is also important for POIS maintenance from a symptom perspective to periodically release.  Insight or opinion appreciated!

Could be explained by the release of additional mast cell anti-inflammatory mediators (IL-10 for example). Also a mast cell can secrete mediators which inhibit its own cell in an autocrine manner, see autocrine triggers/blockers below (Ref (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/)):

(https://ars.els-cdn.com/content/image/1-s2.0-S0925443910002929-gr2.jpg)

I can have these events myself sometimes. It makes sense. In most cases the left side of autocrine triggers is what may keep the POIS reaction ongoing, however in some rare occasions the right blue box may take the overhand. Which also means that mediators inside the orange oval may be potential markers for POIS. We already discussed some of them like CRH, IL-33, SP and to some extent TSLP.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on May 31, 2020, 05:39:48 PM
Strashny's POIS survey (Ref (https://sci-hub.tw/10.1038/s41443-019-0154-7)):

"The most common symptom cluster from the criteria, involving fatigue, irritation, and concentration difficulties, is
always experienced by 80% of respondents
"

Afrin's MCAD findings (Ref (https://sci-hub.tw/https://www.tandfonline.com/doi/abs/10.3109/07853890.2016.1161231)), table 1 constitutional: Fatigue (83%)
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on June 02, 2020, 03:42:43 AM
I haven't but I mostly suffer from brain symptoms so they're not gonna help even if I tried.

OK, what do you base that on though? Not saying you're wrong, just curious. FYI there was someone on the forum, can't remember which thread, who said his brain fog was massively reduced by Cromolyn.
Based on that Chromolyn can not be absorbed into the blood stream. I also was looking into trying it, but it wasn't available in here anyway.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on June 02, 2020, 03:52:04 AM
I wonder if all it takes to increase the bioavailability of Quercitin is just to mix it with olive oil before intake? Is that a reasonable assumption?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 02, 2020, 04:49:36 AM
I haven't but I mostly suffer from brain symptoms so they're not gonna help even if I tried.

OK, what do you base that on though? Not saying you're wrong, just curious. FYI there was someone on the forum, can't remember which thread, who said his brain fog was massively reduced by Cromolyn.
Based on that Chromolyn can not be absorbed into the blood stream. I also was looking into trying it, but it wasn't available in here anyway.

You are refering to this thread: https://poiscenter.com/forums/index.php?topic=3216.0

"...while stimulation of brain and nasal MC leads to activation of the hypothalamic‐pituitary‐adrenal (HPA ) axis." Ref (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)

It seems from the above that there is some kind of communication between nasal MCs and the brain in animals.

I wonder whether stimulation of genitourinary MCs by the constituents of the ejaculate leads to HPA activation. MCs have the ability to interact with distant MCs by their paracrine/endocrine-like properties. With endocrine function is meant that mediators can reach circulation, not that their mediators are meant for the puropose of targeting specific organs as in endocrine glands.

I wonder if all it takes to increase the bioavailability of Quercitin is just to mix it with olive oil before intake? Is that a reasonable assumption?

Algonot uses olive kernel oil (OKO). Oil from squashed olive seeds. I believe they use sonification to stimulate sonochemical reactions. The phytosome formula could even have a better bioavailability. You could consult literature to compare numbers.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on June 02, 2020, 06:31:47 AM
I wonder if all it takes to increase the bioavailability of Quercitin is just to mix it with olive oil before intake? Is that a reasonable assumption?
Well, no, probably. I just mixed a Quercetin pill with olive oil and consumed it, waited an hour and orgasmed. Still had symptoms.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 02, 2020, 06:47:20 AM
Flavonoids are being used daily for the long term (a few months minimum) with an intake that should not exceed far more than 1 g per day. They are not being used for immediate short term gain as far as I know. 
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on June 02, 2020, 07:54:21 AM
Flavonoids are being used daily for the long term (a few months minimum) with an intake that should not exceed far more than 1 g per day. They are not being used for immediate short term gain as far as I know.
That's a lot of Quercetin lol
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 03, 2020, 10:18:12 AM
Pepto Bismol removed symptoms completely (https://poiscenter.com/forums/index.php?topic=3316.0)

Review article: microscopic colitis - lymphocytic, collagenous and 'mast cell' colitis (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2036.2011.04686.x)

Pepto-bismol:
"bismuth subsalicylate at a dose of two or three tablets (262 mg each) 3-4 times per day for several weeks may be beneficial"

(https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcT1ir5Sa9fiL_vFcEmq94R9wIEhcjxF421_u0FARmB9KiSejarn&s)
(https://ars.els-cdn.com/content/image/1-s2.0-S0091674914015747-fx1.jpg)

Looks a bit like the flavone backbone
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 04, 2020, 06:47:15 AM
TL;DR Had POIS since puberty, tried many things, Hydroxyzine by far has helped eliminate POIS for me.

It's medication for Mast Cell Activation Disorders:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/table/T9/

Hello!

I've been lurking here for a long time. But I had to join this site to give you some amazing news!!

I have found something that completely cures my POIS! All I have to do is eat a red apple before I orgasm! PLEASE don't try eating a green apple, it can make your symptoms worse :(

I tried all kinds of other things that didn't help:

Bananas
Oranges (with the seeds removed)
Watermelons
Kiwi Fruit
Ramen noodles
Pears

I hope somebody will find this useful. Red apples have changed my life forever!

Red delicious, 30 minutes before. It's amazing!

http://medcraveonline.com/MOJFPT/MOJFPT-06-00149.pdf

" Apples contain a range of flavonoids compounds within the peel, which contains procyanidins, catechin, epicatechin, chlorogenic acid, phloridzin and quercetin conjugates. The apple flesh also contains similar compounds but lower in concentrations. Clinical studies proved that quercetin rich apples significantly improve vascular function. Flavonoid content varies widely between apple varieties and even within the types of fruit tissues. Flavonoids tend to be higher in the peel rather than the flesh of apples. Research studies revealed that flavonoids content is higher in the darker, redder and bluer coloured apples. New Western Australian apple variety call -Bravo- was developed after many attempts and was selected over many years to ensure to obtain all required qualities such as has higher flavonoids content than other commercial apple varieties."

They also contain allergens and significant amount of FODMAPS.
Title: Re: Mast Cell Activation Syndrome
Post by: berlin1984 on June 05, 2020, 03:54:02 PM
Sorry if this site was mentioned already, but I found it quite interesting:
https://www.mastzellaktivierung.info/en/introduction.html (at least the probably more verbose German version)

Seems to be the sister site of histaminintoleranz.ch (https://poiscenter.com/forums/index.php?topic=820.msg34735#msg34735)

Somewhere else in this forum there was a theory that POIS is more prevalent in dutch people, now I wonder if mast cell / histamine things are more prevalent in Swiss people? (assuming now they are non-related, no matter if they are or not)

And I wonder why is there not more discussion on this forum here about potentials for a low histamine diet (instead of popping pills..at least to nail down the issue more)
https://www.mastzellaktivierung.info/en/symptoms.html#triggers
Low histamine thread: https://poiscenter.com/forums/index.php?topic=820
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 05, 2020, 04:53:00 PM
Sorry if this site was mentioned already, but I found it quite interesting:
https://www.mastzellaktivierung.info/en/introduction.html
No this hasn't been mentioned yet. I know the site from years ago, it seems they have updated it a lot. Great site worth a mention. Perhaps I will put it in the MCAD thread later.

"Hunger due to omitted or delayed meals can also increase the symptoms. However, it is unclear whether a state of hunger activates the mast cells or whether only a temporary undersupply of vitamins, minerals or energy leads to a reduced degradation of the mediators."

This is actually what I got. I can tell you right away that it's a kind of stress the hunger induces. Skipping meals makes me feel better, too much time without food gives stress.

What is even more problematic right now is pressure on my spine acting as a trigger just from gravity.

Wasn't aware of this one:
Mast cell activation disease: An underappreciated cause of neurologic and psychiatric symptoms and diseases (https://www.sciencedirect.com/science/article/abs/pii/S0889159115002366?via%3Dihub)

My brother has a lot of neuropsychiatric symptoms. Doctors don't know how to deal with it. Probably mast cells firing inside his brain.

Cytokines and chemokines are often involved in MCAD more so than Histamine. (Can't remember where I read that.)

I think you meant caucasian instead of Swiss people. This ethnic group is the most prevalent one in MCAD but that could have to do with western life style. We have a poll for that:
https://poiscenter.com/forums/index.php?topic=151.0
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 07, 2020, 11:50:46 AM
Hello everyone,

I had low hemoglobin.

I'm taking iron since january 11 th 2020 (200 mg elemental iron a day)

I started Vit C 1000 mg a day a week ago.

Brainfog is gone. (i had this brainfog daily since 2008) ,i'm living the 3 rd day without it.

Anemia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T5/

Brain fog typical MCAS symptom.

Vitamin C: Increased degradation of histamine; decrease of histamine formation by inhibition of histidine decarboxylase.
Title: Re: Mast Cell Activation Syndrome
Post by: Nas on June 07, 2020, 12:58:34 PM

Anemia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T5/

Brain fog typical MCAS symptom.

Vitamin C: Increased degradation of histamine; decrease of histamine formation by inhibition of histidine decarboxylase.
I find it difficult to believe that histamine is what's causing the brain fog.
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on June 08, 2020, 04:34:59 AM

Anemia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T5/

Brain fog typical MCAS symptom.

Vitamin C: Increased degradation of histamine; decrease of histamine formation by inhibition of histidine decarboxylase.
I find it difficult to believe that histamine is what's causing the brain fog.

https://psychology.wikia.org/wiki/Histamine
 (https://psychology.wikia.org/wiki/Histamine)

H3 histamine receptor    Found on central nervous system and to a lesser extent peripheral nervous system tissue    Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 08, 2020, 07:20:19 AM
 Note for the table I have posted above:

"Pct - percentage of the study population showing the indicated abnormality at least once prior to MCAS diagnosis"

Be aware that this is not your typical one time measurement in a cohort of patients. It may take decades before diagnosis has been made. The data is the result of collecting results of patient's entire past prior to diagnosis.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 09, 2020, 05:44:04 AM
Quotation from https://www.mastzellaktivierung.info/en/therapy_triggers.html

MCAD patients often mistakenly have the feeling that they have a "weak immune system". In reality it is not weak, but on the contrary over-stimulated by overactive mast cells. As a result, it no longer functions properly (high susceptibility to infections). Many then fatally resort to immune-strengthening agents, which make the condition even worse. On the contrary, one would rather have to suppress the immune system (immuno-suppressants), e.g. with corticosteroids (which can also have side effects).
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 16, 2020, 01:50:33 AM
Is there a possibility that we have MCAS, just triggered in different POISers through different ways?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 17, 2020, 05:43:11 AM
(Mast cell inhibition in %, Ref (https://youtu.be/6gfTFwJgIVQ?t=5669)):

Tetramethoxyluteolin (90-100%) > Luteolin (75%) > Quercetin (55%) > Cromolyn (15%)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 18, 2020, 12:34:30 PM
Recognizable:

https://www.youtube.com/watch?v=7oVK7NwLM14
Title: Re: Mast Cell Activation Syndrome
Post by: swell on June 18, 2020, 01:50:59 PM
Great info Muon, though wondering on a different topic, whether mast-cell inhibition might not be good for Covid - since we need Innate immune system well optimized?

Recognizable:

https://www.youtube.com/watch?v=7oVK7NwLM14
Title: Re: Mast Cell Activation Syndrome
Post by: Clues on June 19, 2020, 10:31:50 AM
Thanks for that video Muon, might show that to family members if/when I get a diagnosis.

Btw, I got my skin biopsy taken today by a dermatologist. I was really pleasantly surprised how much he knew about mast cell issues. He said based on my skin lesions he suspects it's not Mastocytosis, but that we'll know more or less for sure after we get the results. If it's not Mastocytosis we'll look into MCAS.

Waiting time for my endochrinologist is long, and it's even longer for this specialised dermatologist. So diagnosis might take a while, but they seem pretty determined to get there.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 19, 2020, 05:27:13 PM
though wondering on a different topic, whether mast-cell inhibition might not be good for Covid - since we need Innate immune system well optimized?

Covid-19 activates pulmonary mast cells. You want to inhibit mast cells. I would not be surprised when Covid-19 induces additonal POIS symptoms in POISers.
Title: Re: Mast Cell Activation Syndrome
Post by: aswinpras06 on June 19, 2020, 10:53:48 PM
Very frustrating, my omalizumab therapy postponed due to covid.  My lung condition is getting more worse and I think omalizumab therapy will be of little help for me.  But if it works it will be great news for all other poisers.  Hope god gives me at least that privilege.
Title: Re: Mast Cell Activation Syndrome
Post by: Iwillbeatthis on June 23, 2020, 03:55:48 PM
https://youtu.be/9QbZp3WcC1Q?t=1884

I haven't watched any videos of this doctor until today but Dr T. Theoharides understands MCAS and autism perfectly, he would be the best suited person to study POIS, its a shame he declined Muons request. He hits the nail on the head about brain allergy mast cell issues and autistic symptoms and I resonate deeply with his words. It's also a shame I live in a country like UK, which is supposed to be a developed country, where I've heard Mast cell doctors have stopped seeing MCAS patients because they find it too complicated to diagnose. The patient has no power in the UK because everything is government owned so it's impossible to get any kind of treatment or make any progress with the GPs and so called specialists. The licensing here means that doctors aren't allowed to prescribe anything unless its licensed to give for a specific condition and they only prescribe based on evidence. But if they don't recognise MCAS or POIS then they are unable to prescribe anything.

I have a hunch that prostaglandin is the mediator thats causing my problems as asprin helps my symptoms from showers  and POIS and I also have interstitial cystitis
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 24, 2020, 03:20:51 PM
Dr T. Theoharides understands MCAS and autism perfectly, he would be the best suited person to study POIS, its a shame he declined Muons request.

People can sign up and try their luck here:

https://poiscenter.com/forums/index.php?topic=3328.0
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 27, 2020, 04:38:45 AM
Very frustrating, my omalizumab therapy postponed due to covid.  My lung condition is getting more worse and I think omalizumab therapy will be of little help for me.  But if it works it will be great news for all other poisers.  Hope god gives me at least that privilege.

Send Quantum a message when it helps for POIS. Stumbled upon some alternatives for pulmonary mast cell activity:

"In the present study we have investigated an alternative approach for tryptase regulation. We show that the heparin antagonists Polybrene and protamine are potent inhibitors of both human lung tryptase and of recombinant mouse tryptase (mouse mast cell protease 6)."

Heparin Antagonists Are Potent Inhibitors of Mast Cell Tryptase (https://pubs.acs.org/doi/abs/10.1021/bi001988c)

An Anti‐Siglec‐8 Antibody Depletes Sputum Eosinophils from Asthmatic Subjects and Inhibits Lung Mast Cells (https://onlinelibrary.wiley.com/doi/abs/10.1111/cea.13681)

"As reported by other studies, tryptase does not seem to parallel clinical response, although omalizumab reduces the potential reactivity of mast cells"

Timing of response and long term efficacy of Omalizumab in non-clonal Mast Cell Activation Syndrome: A case series (https://www.ejinme.com/article/S0953-6205(19)30397-8/fulltext)

There are more papers where MCAS patients benefit from (low dose) omalizumab, here is one, response rate is quite high. It could be a potential option for POISers to try under supervision when everything else fails:

"The overall response rate was 78.2% with a very favorable safety profile."

Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS (https://sci-hub.se/https://www.sciencedirect.com/science/article/abs/pii/S2213219819303228)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 27, 2020, 05:55:33 AM
Short fragment about Covid-19:

Dr.Theoharides of Tufts University speaks to Yanna Darilis about his latest research on COVID19 (https://youtu.be/FSPwp2AjVsk?t=963)

This combination will be present in a new product called Viralprotek.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on June 28, 2020, 05:35:04 AM
Also a 20 day antidepressant (visited a psychiatrist) course before that which I believe did no good and only worsened it, I was testing this as it works for many people here. To my horror, I got the most severe POIS symptoms. Severe headache, fatigue, blackouts. I don't have any body pains or any physical symptoms.
I've seen more people on this board with adverse reactions than people who benefit from antidepressants.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab12/
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on June 28, 2020, 07:20:58 PM
Also a 20 day antidepressant (visited a psychiatrist) course before that which I believe did no good and only worsened it, I was testing this as it works for many people here. To my horror, I got the most severe POIS symptoms. Severe headache, fatigue, blackouts. I don't have any body pains or any physical symptoms.
I've seen more people on this board with adverse reactions than people who benefit from antidepressants.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/table/Tab12/


Your link only mentions SSRIs. There are several different kinds of antidepressants.

I've seen plenty of people on this board who benefit from antidepressants. Also, I thought SSRIs suppressed mast cell function?

https://www.jimmunol.org/content/200/1_Supplement/105.8
https://grantome.com/grant/NIH/R21-AI138494-01A1
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on June 28, 2020, 10:18:36 PM

Your link only mentions SSRIs. There are several different kinds of antidepressants.


Correct.

I was on SNRI’s for a while.

Lexapro works for me today.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 02, 2020, 07:57:53 AM
https://www.reddit.com/r/POIS/comments/hj9ddl/do_i_have_pois/

"The above are the main symptoms but other symptoms include: headache (which paracetamol does not improve), flushed face, sensitivity to heat/sweating and anxiety/worrying."

https://youtu.be/6gfTFwJgIVQ?t=1777

Antihistamines/NSAIDs:

https://www.reddit.com/r/POIS/comments/hjgzo0/treament_update/

https://www.reddit.com/r/POIS/comments/hj9135/antihistamines/
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 03, 2020, 02:59:19 PM
https://www.reddit.com/r/POIS/comments/hkic2q/is_pois_caused_by_pathogens/

aquantiV:

"doesn't check out for me. My symptoms emerged when I was otherwise healthy. I was under a ton of social and school stress though at that time, so I wondered and sometimes still wonder if it is psychosomatic. But the evidence stacks against that too (thank god)"

Animus, did you experience any stress or were you in a stressful situation just prior to your development of POIS symptoms?

Hi Muon,
Great question... thank you for asking. Short answer: YES.  Lots of stress at the time when I developed POIS.
I was stressed out with life in New York City, and wanting to leave.  Also intense physical stress I think. What really triggered it for me, was when I took some herbal "male enhancement pills". They were designed to give more powerful erections, and more volume ejaculations. They also caused my testicles to grow twice their size, seriously.  They had a very bad effect on me for some reason.

So, as to your question, I don't know if you mean physical or mental stress. But at the time, I certainly had both.

Dr. Theoharides:

" Therefore, any type of stress by definition is likely to stimulate the mast cells directly or make them more responsive either to new triggers or whatever triggers a patient might have had to begin with."

"We published a paper a long time ago that stress meaning CRH we add CRH to human mast cells they become much more responsive to Mercury, for instance, okay. And this is an area that just not being discussed, that the mast cells must have some threshold that is being reset. Because I have so many patients who basically say, "Something happened, and all of a sudden I'm allergic or I respond to everything"
Ref (https://youtu.be/37GtfXOP8dw?t=765)

https://www.reddit.com/r/POIS/comments/gau9qf/did_you_exprience_any_changes_n_life_when_you/

POISFIGHTER:

"I'll say this. When I had surgery in May 2019 due to abdominal abscess and appendicitis, I was given loads of antibiotics and they checked my blood count and realised that by red blood cell count was very low. I was treated with Trihemic for a few weeks. During the time in the hospital, I also refrained from ejaculation, probably for about 3 weeks. When I left the hospital, I was able to ejaculate for 3-4 times per week with just slight body weakness after ejaculation. No other POIS symptoms were present. My POIS returned 8 months after."

I lost count how many times I encountered people on these boards having a history of some kind of anemia:

Common abnormalities in routine hematologic and serum chemistry tests found in the study population. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/table/T5/)

Squiggyzz

"I was exposed to mold since I used to live in section 8 housing. Had an allergy panel done last year and somehow I'm allergic to damn near everything. Like a bunch of trees, grass, corn, wheat, dogs, cats, dust mites, and etc. Surprisingly, no allergies to mold which also surprised the doctor. Also I wasn't allergic to all those things before, so something happened.

I was on antibiotics for awhile, but this was after I had pois symptoms already. Was on it long term because I had very bad acne when I was younger. Additionally I was getting frequent infections too, so was prescribed for those reasons as well.

I also have a history of asthma, bronchitis, and mild allergies (now my allergies are bad) . I remember going to the doctor as a kid and getting weekly shots. I still don't know what it was to this day. I do remember my mom telling me it was allergy shots. But wtf is allergy shots back in the early 90s? When I think back, I think these shots might have been what triggered it because I took them before I ever got pois.
"

Mast cells can activate the immune system leading to a hyperactive immune system which is unable to act optimally to infections. Below is another one:

https://www.reddit.com/r/POIS/comments/f8iuf4/severe_illness_following_ejaculation/

Timur_1332:

"Hi Guys, wonder if any of you have every observed this sequence of events.
Youre in a new place, or situation, lots of stressors.
You have been exposed to some infections but have no symptoms because of strong immunity.
You ejaculate.
You add a final stressor such as an intense gym work out.
BAM you come down with 2 degree fever and full symptoms of the infection you were exposed to.
"

meatball4u:

"Never had that happen to me. But stress is part of how I developed POIS."
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 04, 2020, 05:07:35 PM
ajs (https://www.thenakedscientists.com/forum/index.php?topic=6576.msg416323;topicseen#msg416323)

"I'm a woman and I have pois so I personally know it has nothing to do with allergy to seamen....I have been reading since the beginning and I remember that girlwind was very irritated by the moderater and I agree his ego and wanting to be right all the time was annoying and I really wish she did not leave...my pois turned into chronic fatigue and fibromyalgia and I could not digest anything and went to get food tested and my back welted up to everything but my blood work showed no allergies to food...I do know that my pois started after getting shingles....all the testing I've done and the only thing they have found were very high levels of antibodies to three different viruses."

Conditions Often Comorbid With Mast Cell Diseases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/table/T2/)
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on July 04, 2020, 06:49:39 PM
ajs (https://www.thenakedscientists.com/forum/index.php?topic=6576.msg416323;topicseen#msg416323)

"I'm a woman and I have pois so I personally know it has nothing to do with allergy to seamen....I have been reading since the beginning and I remember that girlwind was very irritated by the moderater and I agree his ego and wanting to be right all the time was annoying and I really wish she did not leave...my pois turned into chronic fatigue and fibromyalgia and I could not digest anything and went to get food tested and my back welted up to everything but my blood work showed no allergies to food...I do know that my pois started after getting shingles....all the testing I've done and the only thing they have found were very high levels of antibodies to three different viruses."

Conditions Often Comorbid With Mast Cell Diseases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/table/T2/)

Interesting that she mentions fibromyalgia. A drug specifically designed to help fibromyaglia sufferers has helped me to get rid of my POIS.

https://poiscenter.com/forums/index.php?topic=3312.0

Quote
Drugs that deal with brain fog in fibromyalgia - milnacipran

We recommend milnacipran as the first-line medication for FMS patients who rate Fatigue and/or Fibrofog as the symptoms that are most limiting for them. This recommendation is based on our clinical experience and the fact that milnacipran is the only FDA approved FMS treatment shown to improve symptoms of fatigue and cognitive dysfunction in phase 3 clinical trials

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004654/
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on July 06, 2020, 12:55:59 PM

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.
My POIS doctor gave me Nalcrom for two months. I hope it will help.
Title: Re: Mast Cell Activation Syndrome
Post by: demografx on July 06, 2020, 07:01:47 PM
Good luck, Van!
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on July 07, 2020, 03:03:08 PM
Thanks! There is delay because all the Dutch pharmacies do not have Nalcrom for at least two weeks. I do not know why.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 22, 2020, 07:01:31 AM
Interesting that she mentions fibromyalgia. A drug specifically designed to help fibromyaglia sufferers has helped me to get rid of my POIS.

Milnacipran increases bioavailability of norepinephrine in the brain which can inhibit mast cells.

The mast cell can be manipulated by giving them neurohormonal triggers (Ref (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)). One may drive the MCs away from a stimulatory state towards a more calmer/inhibitory state by shifting the 'balance' of the parameters below, that is, increasing parameters with a downward arrow next to them and/or decrease parameters that have an upward arrow next to them.

↑ = Mast cell stimulation
↓ = Mast cell inhibition

Trigger   Effect

Circadian hormones

Melatonin   ↓

Growth factors

BDNF   ↑
Insulin‐like growth factor‐1   ↑
Neurotrophin‐3   ↑
NGF   ↑
PDGF   ↑
SCF   ↑

Metabolic hormones

Leptin   ↑

Neuropeptides

Adrenomedullin   ↑
CGRP   ↑
Hemokinin‐A   ↑
Neurotensin   ↑
PACAP   ↑
PTH   ↑
Somatostatin   ↓
SP   ↑

Neurotransmitters

Acetylcholine   ↑
Dopamine   ?
Epinephrine   ↓
GABA   ↓
Histamine   ↓
Norepinephrine   ↓
Serotonin   ?

Pheromones

Oxytocin   ?

Pain peptides

Enkephalins   ↑
β‐Endorphin   ↑

Sex hormones

Oestrogen   ↑
Gonadotrophins   ↑
Progesterone   ↓
Testosterone   ↓

Stress hormones

ACTH   ?
CRH   ↑
Cortisone   ↓
Urocortin   ↑

Vascular peptides

Endothelin   ↑
VEGF   ?
VIP   ↑
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 22, 2020, 08:42:37 AM
This drug is for treatment of Fibromyalgia. I can't help but notice the similarities between Fibromyalgia symptoms and POIS. I wonder if we are suffering from a similar or even the same ailment.
Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome (https://www.frontiersin.org/articles/10.3389/fncel.2019.00353/full)

"Increased levels of the pro-inflammatory chemokine IL-8 (CXCL8) have been reported in the serum and CSF in patients with FMS"

https://poiscenter.com/forums/index.php?topic=2545.msg32239#msg32239

It was quite a hot day when it was measured. Combine it with the previous post, it could drop due to orgasm only for the short term by rise in (nor)epi: Specificity of the neuroendocrine response to orgasm during sexual arousal in men (https://www.researchgate.net/profile/Tillmann_Kruger/publication/277549555_Specificity_of_the_neuroendocrine_response_to_orgasm_during_sexual_arousal_in_men/links/56606a4808ae4931cd5976fe.pdf).

Then there could be negative ejaculatory effects from MC activation due to interaction between urogenital MCs and potential triggers in seminal fluid doing other things.

Bluesbrother's TNF - alpha (https://poiscenter.com/forums/index.php?topic=2684.msg32284#msg32284) going down as well post-orgasm from 32.6 pg/ml to normal range (reference range <12.0 pg/ml).

Anti-inflammatory effect of β2-agonists: Inhibition of TNF-α release from human mast cells (https://www.sciencedirect.com/science/article/abs/pii/S009167499770280X)

Off-topic: #males vs #females in POIS regarding sex hormones and Th1/Th2 function. TESTOSTERONE AND ESTROGEN DIFFERENTLY EFFECT TH1 AND TH2 CYTOKINE RELEASE FOLLOWING TRAUMA-HAEMORRHAGE (https://www.sciencedirect.com/science/article/abs/pii/S1043466601909457)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 22, 2020, 10:55:16 AM
The difference in absorption between unformulated Quercetin and Quercetin Phytosome is huge:

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418071/bin/13318_2018_517_Fig2_HTML.jpg)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418071/

https://www.thorne.com/products/dp/quercetin-phytosome
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 22, 2020, 07:06:00 PM
Mallory (https://www.thenakedscientists.com/forum/index.php?PHPSESSID=ptq3bd0gu41qvcoq6e09uoddq5&topic=14697.msg177763#msg177763):

"I am so glad to have found this... .trust me you are not the only woman with this problem!  I am 27 and have been experiencing the very same problem for the last few years.  During and immediately after orgasm, from intercourse or masturbation, I get  body and joint aches, neck stiffness, throbbing headache and nausea. This also happens when I perform oral sex on my husband, that does not result in an orgasm on my end.   It's the worst for several hours but the flu like symptoms will last for days. I have been gluten and dairy free for 4 years now, so it isn't allergies.  I have recently been diagnosed with fibromyalgia  and a tentative  MS dx, but still need a spinal tap.  Do you have any other illness, nerve pain, or odd symptoms..... do you get the same feeling with intense exercise?  I exercise frequently but get a similar headache only when I go running for some reason.. minus the flu symptoms though.  I have a normal body weight and BMI, and have normal blood pressure and blood work.  My doc has be taking 400 mg of riboflavin daily, which is apparently for migraines, although I never really get headaches at any other time"

Oral sex: Non-IgE mediated activation of mucosal mast cells?
Fibromyalgia: Often comorbid with MCAD
Multisystem symptoms and odd symptoms induced by triggers: Typical MCAD
Exercise: potential mast cell trigger

Many women have CFS on the TNS forum which is also often seen comorbid with MCAD.
Title: Re: Mast Cell Activation Syndrome
Post by: drop247 on July 23, 2020, 10:20:10 AM
Muon do you take daily quercetin?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 23, 2020, 01:10:06 PM
Muon do you take daily quercetin?

No, I do not take it, was thinking about pumping Luteolin into my system but may put that on hold. Had some hope doctors would prescribe me some mast cell stabilizers last year to save money, like cromolyn, but to no avail. Right now I'm thinking about saving the money for a spine MRI scan instead of spending it to supplements. Not entirely sure where to go from here. 
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on July 23, 2020, 02:37:26 PM

Interesting that she mentions fibromyalgia. A drug specifically designed to help fibromyaglia sufferers has helped me to get rid of my POIS.

Milnacipran increases bioavailability of norepinephrine in the brain which can inhibit mast cells.

The mast cell can be manipulated by giving them neurohormonal triggers (Ref (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)). One may drive the MCs away from a stimulatory state towards a more calmer/inhibitory state by shifting the 'balance' of the parameters below, that is, increasing parameters with a downward arrow next to them and/or decrease parameters that have an upward arrow next to them.


That's a good theory, and could be the correct one. Although it does lead me to wonder why milnacipran worked, but the various other NRIs I have tried did not? Theoretically they should all have increased the bioavailability of norepinephrine.

Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 23, 2020, 03:03:01 PM
That's a good theory, and could be the correct one. Although it does lead me to wonder why milnacipran worked, but the various other NRIs I have tried did not? Theoretically they should all have increased the bioavailability of norepinephrine.

That's the part I don't get. It must have additional properties then, like these:
Anti-inflammatory and anti-hyperalgesic effects of milnacipran in inflamed rats: involvement of myeloperoxidase activity, cytokines and oxidative/nitrosative stress (https://link.springer.com/article/10.1007/s10787-020-00726-2)

Now some of these cytokines are elevated during brain inflammation leading to brain fog. If other SNRIs don't work then it may have nothing to do with the reuptake of serotonin or norepi. You might just be suppressing pro-inflammatory cytokines inside your brain reducing inflammation and thus reversing brain fog. Some of these cytokines are elevated in Fibro:

Fibromyalgia and cytokines (https://www.sciencedirect.com/science/article/abs/pii/S0165247814000133)

If mast cells were the culprit then the other SNRI's should affect the AB2R as well unless this med acts on different receptors. With other words the source of cytokines might be something else. Perhaps microglia.
Title: Re: Mast Cell Activation Syndrome
Post by: berlin1984 on July 23, 2020, 04:11:25 PM
That's a good theory, and could be the correct one. Although it does lead me to wonder why milnacipran worked, but the various other NRIs I have tried did not? Theoretically they should all have increased the bioavailability of norepinephrine.

My take:

...
HOWEVER, since I buy into the theory that POIS is virus-caused, maybe the main reason people on the forum have success with anti depressants is because of the effect on some viruses?
(Of course, certain effects on serotonine might also help with the general POIS associated feelings)
...
(Clic the date to expand to full post)
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on July 23, 2020, 06:45:42 PM
That's a good theory, and could be the correct one. Although it does lead me to wonder why milnacipran worked, but the various other NRIs I have tried did not? Theoretically they should all have increased the bioavailability of norepinephrine.

My take:

...
HOWEVER, since I buy into the theory that POIS is virus-caused, maybe the main reason people on the forum have success with anti depressants is because of the effect on some viruses?
(Of course, certain effects on serotonine might also help with the general POIS associated feelings)
...
(Clic the date to expand to full post)

It's an interesting possibility. It doesn't feel quite right in my case - I have taken several different kinds of anti-depressants in the last 10 years (SSRIs and SNRIs). 1 of them consistently eliminates my brain fog, all the rest of them did absolutely nothing for my brain fog :)

Most of them did have the side-effect of making me feel more comfortable about my POIS, but that doesn't help when you're trying to hold down a job that involves talking to people :)
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on July 23, 2020, 07:15:49 PM
That's a good theory, and could be the correct one. Although it does lead me to wonder why milnacipran worked, but the various other NRIs I have tried did not? Theoretically they should all have increased the bioavailability of norepinephrine.

That's the part I don't get. It must have additional properties then, like these:
Anti-inflammatory and anti-hyperalgesic effects of milnacipran in inflamed rats: involvement of myeloperoxidase activity, cytokines and oxidative/nitrosative stress (https://link.springer.com/article/10.1007/s10787-020-00726-2)

Now some of these cytokines are elevated during brain inflammation leading to brain fog. If other SNRIs don't work then it may have nothing to do with the reuptake of serotonin or norepi. You might just be suppressing pro-inflammatory cytokines inside your brain reducing inflammation and thus reversing brain fog. Some of these cytokines are elevated in Fibro:

Fibromyalgia and cytokines (https://www.sciencedirect.com/science/article/abs/pii/S0165247814000133)

If mast cells were the culprit then the other SNRI's should affect the AB2R as well unless this med acts on different receptors. With other words the source of cytokines might be something else. Perhaps microglia.

You give some good reasons as to why milnacipran could be considered to fit within the MCAS theory of POIS. A combination of theory and experimentation could be what we need to beat POIS  :)
Title: Re: Mast Cell Activation Syndrome
Post by: Iwillbeatthis on July 27, 2020, 11:09:14 AM
Need some advice guys
I am planning to purchase either Neuro Protek or Histaquel, was just wondering if NeuroProtek contains quercetin phytosome or if it only has quercitin.
Histaquel has double the amount but serving size is two capusles, and its hard to compare the amounts in both products.

Histaquel has no rutin either but does have quercetin phytosome:

https://www.researchednutritionals.com/product/histaquel/?doing_wp_cron=1595866058.4130389690399169921875

https://www.amazon.com/Algonot-NeuroProtek-1-Bottle/dp/B0045JB858

Thanks
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 27, 2020, 11:41:47 AM
Neuroprotek doesn't contain Quercetin phytosome but Quercetin lipsome. Absorption from best to worst: Quercetin Phytosome > Quercetin liposome > Quercetin (it could be liposome or just powder, they never mention this on the supplement facts). I can't compare them because HistaQuel doesn't state the amount per ingredient.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on July 28, 2020, 06:08:22 AM
Wasn't there someone who used Manuka honey for POIS? Quality seems to matter:

Medical-grade Manuka honey inhibits mast cell degranulation by downregulating protein kinase-B (Akt) phosphorylation: Potential role as intravesical agent in interstitial cystitis/bladder pain syndrome (https://www.eu-openscience.europeanurology.com/article/S2666-1683(20)32900-1/pdf)

Pseudoephedrine alleviates atopic dermatitis-like inflammatory responses in vivo and in vitro (https://www.sciencedirect.com/science/article/abs/pii/S0024320520308900)

Adding these to the MCAD thread (https://poiscenter.com/forums/index.php?topic=3236.msg33462#msg33462) under potential treatment.
Title: Re: Mast Cell Activation Syndrome
Post by: Iwillbeatthis on August 15, 2020, 10:19:07 AM
Update I have been using histaquel for over two weeks now and haven't seen any difference, for me personally I have doubts now that my issues are mast cell related.

I think Nanna's immune deficiency theory is whats going wrong with me. I have started amitriptyline as of two days ago, I have tried it in the past at a tiny dose (1/4 of 10mg) as advised by my doctor and combined it with piracetam and alpha gpc (I think this is also what caused my severe reactions to showers when i stopped). The trouble was I was still experiencing immune and infectious symptoms back then so I stopped the amitriptyline.

Now I have cleared the infectious symptoms mainly I am trying it again at the full dose of 10mg, as I still have adrenal issues eg: reactions to showers. In a organic acids test it said I had a high HVA/VMA ratio which meant my body was having difficulty converting dopamine into noradrenaline. I have tried co factors for noradrenaline like vitamin c and copper but they aren't strong enough. This also explains why I react badly to bupropion a dopamine antagonist and n acetyl tyrosine.

The test recommends droxidopa - Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine. Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier. However I am unable to get this in the Uk as its not licensed here or on any online eu pharmacys.
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on August 22, 2020, 06:07:44 AM

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.
My POIS doctor gave me Nalcrom for two months. I hope it will help.
Nalcrom did not help me.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on August 27, 2020, 04:03:57 PM
This guy went to Mayoclinic but didn't test for MCAS? What a missed opportunity.

https://www.reddit.com/r/POIS/comments/ihh66g/do_you_think_people_on_nofap_actually_have_pois/
Title: Re: Mast Cell Activation Syndrome
Post by: Iwillbeatthis on August 28, 2020, 05:32:45 AM
Finished the whole bottle of Histaquel now and it hasn't helped me.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 10, 2020, 02:27:39 PM
"Combination of triggers is more important than individual ones as they can lower the stimulation threshold of mast cells and ‘prime’ them for additional triggers." Ref (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003574/)

Lower activation threshold due to decreased expression/function of inhibitory molecules/pathways.
Intracellular
PTEN
Chondroitin sulfate
Sergylin
Spermine/spermidine
TGF beta
Extracellular
Deflisinc
IL-10
IL-37
IL-38
TGF beta
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 14, 2020, 02:44:57 PM
Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be Rooted in Mast Cell Activation Syndrome (https://www.sciencedirect.com/science/article/pii/S1201971220307323)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 15, 2020, 07:34:13 AM
While I like flavonoids, but they yet have to eradicate my 3-4 warts (on foot sole).  I think they are due to HPV.  Any method to get permanently get rid of HPV?
I just saw a otolaryngologist (ear, nose and throat doctor) about a growth on the uvula in my throat. He said that the growth was a benign papilloma (wart) and that it was probably caused by viral infection of the uvula. No test were done, but the otolaryngologist seemed confident that the growth was caused by human papillomavirus (HPV). I did not suggest any cause, he came up with this diagnosis on his own after examination of my uvula.

More: https://poiscenter.com/forums/index.php?topic=2301.msg34026#msg34026

Finally I took Diazepam (Valium) the day after O, while in POIS, and it completely removed my brain fog and anxiety.

Mast cells express benzo receptors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/table/T1/

Some subtypes of adenosine receptors have affinity for benzodiazepines if I'm not mistaken (I could be wrong about that).
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on September 21, 2020, 02:57:57 PM
I found an interesting paper called "Postural Tachycardia Syndrome (POTS) - Satish R. Raj".

Mast Cell Activation triggered by sexual intercourse?

Quote
Some patients with POTS present with episodic flushing associated with surges in tachycardia and have coexistent mast cell activation
There are many triggers for the flushing, including prolonged standing, exercise, premenstrual cycle, meals, and sexual intercourse.

Mental clouding:

Quote
Many patients are also greatly troubled by mental clouding or troubles concentrating.

Elevated levels of norepinephrine are common in POTS suffers:

Quote
Many patients with POTS have elevated levels of plasma norepinephrine, suggestive of a hyperadrenergic state. This is most commonly secondary to a partial dysautonomia or hypovolemia. In a small subgroup of patients, the primary underlying problem seems to be excessive sympathetic discharge. These patients often have extremely high levels of upright plasma norepinephrine (>1000 pg/mL and occasionally >2000 pg/mL, with an upper limit of normal of 475 pg/mL in our clinical laboratory).

Quote
Norepinephrine Transporter Deficiency and Blockers

A specific genetic abnormality has been identified in a kindred with hyperadrenergic POTS.11 These individuals have a single point mutation causing loss of function in the norepinephrine transporter. The resultant diminished norepinephrine clearance leads to a hyperadrenergic state in response sympathetic nerve activation.

Although functional norepinephrine transporter mutations might be infrequent, many antidepressant and attention deficit medications work at least in part through inhibition of norepinephrine transporter. This includes traditional drugs such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine, or milnacipran), or purer norepinephrine transporter inhibitors (eg, atomoxetine or reboxetine).

https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.112.144501
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 21, 2020, 03:51:21 PM
Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome (P1.277) (https://n.neurology.org/content/84/14_Supplement/P1.277)

"Urinary 11-beta-prostaglandin F2 levels were elevated in 50[percnt], urinary N-methylhistamine levels increase in 16[percnt], while serum tryptase was not elevated in any of the PoTs + MCAD patients."

Urinary 11-beta-prostaglandin F2 alpha is also the one I found being elevated. Norepi has been measured but only in flat position which was normal. There is a paper about a point mutation under atopic dermatitits in the paper thread (receptor not transporter though). Milnacipran could tackle multiple issues at once, catecholamine/dysautonomia related and cytokine/inflammation related symptoms.

My brother doesn't have POTS but he told me recently that he had a spontaneous POTS-like attack where blood suddenly pooled in the legs and didn't go properly to the brain. He said he underestimated these kind of symptoms. He also tried SNRIs in the past with no benefit I believe, not sure what meds he tried.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on September 21, 2020, 04:42:08 PM
Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome (P1.277) (https://n.neurology.org/content/84/14_Supplement/P1.277)

"Urinary 11-beta-prostaglandin F2 levels were elevated in 50[percnt], urinary N-methylhistamine levels increase in 16[percnt], while serum tryptase was not elevated in any of the PoTs + MCAD patients."

Urinary 11-beta-prostaglandin F2 alpha is also the one I found being elevated. Norepi has been measured but only in flat position which was normal. There is a paper about a point mutation under atopic dermatitits in the paper thread (receptor not transporter though). Milnacipran could tackle multiple issues at once, catecholamine/dysautonomia related and cytokine/inflammation related symptoms.

My brother doesn't have POTS but he told me recently that he had a spontaneous POTS-like attack where blood suddenly pooled in the legs and didn't go properly to the brain. He said he underestimated these kind of symptoms. He also tried SNRIs in the past with no benefit I believe, not sure what meds he tried.

Milnacipran could tackle multiple issues at once, catecholamine/dysautonomia related and cytokine/inflammation related symptoms.

Good insight Muon - I think you are right.

re cytokine/inflammation (from the milnacipran thread):

Quote
milnacipran analgesic and anti-inflammatory effects were at least in part exerted through its suppression of MPO activity and inflammatory mediators, such as IL-1?, IL-6 and TNF-?. Carrageenan triggers neutrophil recruitment and MPO activity, and activates the cytokines production, including IL-1?, IL-6 and TNF-?, which are accountable for inflammation and pain

https://sci-hub.tw/10.1007/s10787-020-00726-2

The most common SNRIs are venlafaxine and duloxetine - I tried them both and they were of no benefit to me either.
Title: Re: Mast Cell Activation Syndrome
Post by: Prospero on September 22, 2020, 10:48:30 AM
Quote
Norepinephrine Transporter Deficiency and Blockers

A specific genetic abnormality has been identified in a kindred with hyperadrenergic POTS.11 These individuals have a single point mutation causing loss of function in the norepinephrine transporter. The resultant diminished norepinephrine clearance leads to a hyperadrenergic state in response sympathetic nerve activation.

Although functional norepinephrine transporter mutations might be infrequent, many antidepressant and attention deficit medications work at least in part through inhibition of norepinephrine transporter. This includes traditional drugs such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine, or milnacipran), or purer norepinephrine transporter inhibitors (eg, atomoxetine or reboxetine).

https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.112.144501

I don't understand this. Dysfunctional norepinephrine transporter -> bad NOR clearance -> too much NOR -> POTS (or POIS), presumably.
If Milnacipran inhibits NOR transporter, it should increase NOR levels, which are believed to be already too high, and thus it should worsen POTS/POIS... What did I get wrong ?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 22, 2020, 05:39:22 PM
Role of inflammation in the pathogenesis and treatment of fibromyalgia (https://sci-hub.se/10.1007/s00296-019-04251-6)

" Milnacipran, a dual reuptake inhibitor, acts its therapeutic effect partly by targeting glial activation and thereby inhibiting neuroinflammation."

(https://media.giphy.com/media/MPLpvJcsWvrkk/giphy.gif)

Glial cells (https://en.wikipedia.org/wiki/Glia)

"Furthermore, astrocytes release gliotransmitters such as glutamate (https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter))"
Milnacipran blocks NMDA receptors. Glutamate receptor activation leads to mechanisms related to intracellular calcium concentration. Also I'm not surprised if (micro)glia crosstalk with mast cells in POIS.

Check education and intelligence polls:
"Recent publications have proposed that the number of glial cells in the brain is correlated with the intelligence of a species."

(https://upload.wikimedia.org/wikipedia/commons/5/56/Human_astrocyte.png)

There might be a link with testosterone somewhere in this story. Mast cells respond to T so that may shutdown communication or it affects glia directly somehow. I haven't looked into literature for the neuroendocrinology of glial cells.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 23, 2020, 08:30:03 AM
Anatomy and Physiology of Erection, Ejaculation, and Orgasm (https://sci-hub.se/10.1007/978-1-4939-3100-2_5)

"Through activation of specific protein kinases, protein phosphorylation leads to opening of potassium channels, closing of calcium channels".

"While these are similar between genders, in men there is additional activation in the periaqueductal gray matter."

Additional activation may lead to additional activation of glia and may explain bias of gender aside from ejaculate/mast cell dynamics.

Ideas: https://scholar.google.com/scholar?hl=nl&as_sdt=0%2C5&q=+periaqueductal+gray+matter+glial&btnG=
Title: Re: Mast Cell Activation Syndrome
Post by: Journey on September 23, 2020, 11:20:41 AM
Anatomy and Physiology of Erection, Ejaculation, and Orgasm (https://sci-hub.se/10.1007/978-1-4939-3100-2_5)

"Through activation of specific protein kinases, protein phosphorylation leads to opening of potassium channels, closing of calcium channels".

"While these are similar between genders, in men there is additional activation in the periaqueductal gray matter."

Additional activation may lead to additional activation of glia and may explain bias of gender aside from ejaculate/mast cell dynamics.

Ideas: https://scholar.google.com/scholar?hl=nl&as_sdt=0%2C5&q=+periaqueductal+gray+matter+glial&btnG=
U say it's why more men than women got POIS?
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 23, 2020, 11:32:36 AM
U say it's why more men than women got POIS?

Yes that's what I meant with bias of gender. I'm throwing ideas around, don't take them as fact.
Title: Re: Mast Cell Activation Syndrome
Post by: hurray on September 23, 2020, 05:07:58 PM
Role of inflammation in the pathogenesis and treatment of fibromyalgia (https://sci-hub.se/10.1007/s00296-019-04251-6)

" Milnacipran, a dual reuptake inhibitor, acts its therapeutic effect partly by targeting glial activation and thereby inhibiting neuroinflammation."

Glial cells (https://en.wikipedia.org/wiki/Glia)

"Furthermore, astrocytes release gliotransmitters such as glutamate (https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter))"
Milnacipran blocks NMDA receptors. Glutamate receptor activation leads to mechanisms related to intracellular calcium concentration. Also I'm not surprised if (micro)glia crosstalk with mast cells in POIS.

Check education and intelligence polls:
"Recent publications have proposed that the number of glial cells in the brain is correlated with the intelligence of a species."

There might be a link with testosterone somewhere in this story. Mast cells respond to T so that may shutdown communication or it affects glia directly somehow. I haven't looked into literature for the neuroendocrinology of glial cells.

That's an interesting chain of thought, Muon. Milnacipran's inhibition of NMDA receptors could help to explain why milnacipran works as it does.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 24, 2020, 06:18:42 AM
Role of inflammation in the pathogenesis and treatment of fibromyalgia (https://sci-hub.se/10.1007/s00296-019-04251-6)

" Milnacipran, a dual reuptake inhibitor, acts its therapeutic effect partly by targeting glial activation and thereby inhibiting neuroinflammation."

Glial cells (https://en.wikipedia.org/wiki/Glia)

Thanks for that Muon, that's more evidence showing that milnacipran can play an anti-inflammatory role.

"Mast cells, glia and neuroinflammation: partners in crime?"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930370/

More stuff here:
https://scholar.google.nl/scholar?start=0&q=mast+cells+glia&hl=nl&as_sdt=0,5
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 24, 2020, 06:39:24 AM

My excellent doctor found a POIS study using Cromolyn on Pubmed. He said it was only 4 patients and the drug helped only half of them. He prescribed Nalcrom to me to try for a month. I had to have the pharmacy order it because it's not commonly used in Canada. I'll have it in the next day or two to try out and I'll report back. It's very expensive too but luckily my insurance covered it. A 4 week supply was over $400.
My POIS doctor gave me Nalcrom for two months. I hope it will help.
Nalcrom did not help me.

You could try palmitoylethanolamide (PEA) since CBD helped you.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on September 24, 2020, 10:05:27 AM
Food for thought:

Is POIS a subtype of MCAD that activates glia? Or is POIS some sort of glia activation disorder which may be primary or secondary and crosstalk with mast cells leading to secondary MCAD?

https://www.reddit.com/r/POIS/comments/j4jej1/research_papers_and_articles/
Title: Re: Mast Cell Activation Syndrome
Post by: Vandemolen on October 08, 2020, 06:54:05 PM

You could try palmitoylethanolamide (PEA) since CBD helped you.
I already tried that years ago but it did not help me. But thanks.
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on October 09, 2020, 07:27:18 AM
I haven't posted anything in this thread related to hypoxia I believe. Mast cells release/secrete mediators under hypoxic conditions:

Mast Cell Survival and Mediator Secretion in Response to Hypoxia (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012360)

Mast cells mediate the microvascular inflammatory response to systemic hypoxia (https://journals.physiology.org/doi/full/10.1152/japplphysiol.00637.2002)

COVID-19 and Multisystem Inflammatory Syndrome, or is it Mast Cell Activation Syndrome? (https://pubmed.ncbi.nlm.nih.gov/33023287/)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on October 17, 2020, 10:24:39 AM
Scroll all the way down to table 1 and 2:
Cardiovascular symptoms in patients with systemic mast cell activation disease (https://sci-hub.se/10.1016/j.trsl.2015.12.012)

Demografx

Demo's open heart surgery:
Muon:"What kind of cardiac symptom(s) led up to this surgery?"
Clogged arteries, arrhythmia, chest pain.

Using table 2 above to look for potential candidates:

Atherosclerosis: Tryptase, Heparin, IL-8, CCL-5, IL-1b, IL-4, IL-6, CCL2, CCL3, CCL4, TNF-a, VEGF, FGF-2, FGF-7.
Atherosclerosis+heart failure: Tryptase, IL-4, IL-6, TNF-alpha, FGF-2, FGF-7.
Heart failure: Histamine, Tryptase, Chymase, Platelet activating factor, IL-4, IL-6, IL-10, TNF-alpha, FGF-2, FGF-7, TGF-b.

https://academic.oup.com/view-large/127906878
Correlation Between T Level and Inflammatory Markers in Hypogonadal Men, low T:
Adiposity: high CRP, IL-6
Metabolic: high CRP, insulin
Normal pop: high CRP, fibrinogen, oxidative stress
Investigation into cancer: high WBC
Hypogonadism: High TNF-a, CCL3, CCL4
Heart failure: High IL-1b, TNF-a, IL-6

https://academic.oup.com/view-large/127906879
Effect of T Administration on Inflammatory Markers:

Hi there,

I think i have a form of POIS. I can't diagnose it really and this would be a great place to talk about it...  I am a fit bloke, 25years old. I can be feeling energetic and after an erection i can lose all my energy. If i have an orgasm i can feel absolutely debilitated. I slept all through the night and woke up at 7am, had an orgasm and slept until 3pm. even after all that sleep(16+hrs) i feel exhausted and i feel light headed and feint if i exercise. i fear i will have a heart attack.

I try to abstain a lot. I can abstain for a week or 2 and feel great. exercise a lot and then if i have an orgasm i won't be able to play sport safely for a week. my heart feels like its tired all day. my heart rate escalates for the proceeding days(5-7) and i become exhausted so quickly. Mentally i feel ok except tired. a lot of the time after i get sick very easily. My immune system suffers.

i guess im just wanting to know if this is normal or not. my resting heart rate for the days after an orgasm is like 76-82bpm.. and during abstinence its like 72-76bpm..

Guess i just want an explanation and if anyone knows anything i can try to help out

heartPois

Feint if exercising = hypotension? Compensated by increased heart rate?

Two more people with hypotension, check full thread for context, meds could rule out mediators if hypotension is MC driven. If the hypotension isn't immediate then we could be dealing with De-novo formed mediators, which aren't stored but start being generated from scratch upon a trigger.


Do you notice any other health problems besides POIS? (Even with the great lab tests, of course)

Have you tried shaking up your gut around a bit (internet calls it cleanse or detox), for example by doing a 1-2 day fast with only water, coconut oil and minerals? (as an example).

Have you tried for a few days to not eat the eggs and try meat instead?
Or replace wheat grains with rice?
Remove casein/milk products for some time?

I have a tendency of having low blood pressure. I feel my blood pressure drops after an orgasm, which is responsible for my blackouts, headaches, and severe fatigue.

I can't really have meat. I am planning to go on a vegan diet but will continue to have wheat. If I see no improvement then also, I plan on cutting on wheat too. I haven't really tried fasting because I feel that taking more calories helps me reducing general weakness. Also coffee is the only thing which temporarily brings a little relief to me.

Hi Legendary Animal.

I read you have a tendency to hypotension.  This is the first objective symptoms that I have found for my own POIS attacks, years ago !  And not many members report to have it.  So I cannot tell you what to take, but I can share what works for me to normalize my blood pressure in POIS.  It is very important for me, since low blood pressure is one of my worst POIS symptoms - it causes me extreme fatigue, dizziness, severe exercise intolerance, major difficulty to be able to work for 2 or 3 days ( that was a living nightmare !),  heart palpitations, major irritability, and so on.

The first 2 things I have found,  about 25 years ago, were green tea and magnesium.

Green tea is helping me raise my blood pressure (BP) for 4 to 6 hours.  At first, I was drinking commercial iced tea.  But for years now, I use Green Tea extract capsules, because I have now a very healthy diet, which also helps with POIS, so I do not drink sugary drinks anymore. The green tea capsules I take are very effective and high quality, with standardized EGCG and standardized polyphenols, which are the antioxidants in it  ( I use the Jamieson ones - I have no commercial link with them - the one I use are these:  https://www.amazon.ca/Jamieson-Green-Tea-Phytosome-Complex/dp/B001Q8BBFS (https://www.amazon.ca/Jamieson-Green-Tea-Phytosome-Complex/dp/B001Q8BBFS) )  One green tea capsule every 6 hours or so is really helping me to raise my BP. 

Than, the magnesium is also very helping.  I take 50 to 100mg 3 times a day ( still in the jamieson brand - I like their preparation, it is a mix of several natural magnesium salts ).  It helps raise my BP too, and helps with other POIS symptoms too.  With years, I have found that all electrolytes are great to help raise my BP.  .  So I came to use table salt too, which is Sodium chloride. It is very effective to raise BP... I put 2,5 to 3 cc of salt ( 3 cc is the same as 3 ml) in a glass of water and drink it, and take my pressure 20 minutes after... it really helps (  About the salt quantity, here in Canada we use metric measures, and 2,5 to 3 cc, or ml, seems to be the same as 1/4 tbs, but different converters give different results....so I prefer to use ml and cc for accuracy ) .  It is better for me to take less salt, and take more later if needed, than to take too much salt.  But important to note, I have no kidneys issues, and no cardiac issues, and surely not high blood pressure problems, unless I would not take salted water like that, it would be contraindicated, and not safe.

Some potassium, some calcium helps too, but not as much as Sodium chloride and magnesium.  However, when I do physical exercise and sport, I take all of them after, because like in POIS, i get low pressure after, especially when I had sweat a lot.  I lookl like I lose much minerals through sweet ( mine has a very, very salty taste), so I must replenish my electrolytes after.  I take potassium, sodium chloride, magnesium, and calcium, after sport, so I recover much more faster.
During a POIS attack, I aim to get a BP at or over 110/70.   With time, I saw that even at 109/68, I do not feel well and have no energy.  At 112/71,  I am ok.    It usually take 15 to 20 minutes to see the effect of what I have taken on my BP.  I can take some more salty water and other electrolytes after that, if I did not reach my 110/70 mark.
Once my hypotension is under control, I would say that about 75% of my POIS is relieved... and I can live with the rest  ( However, now, my pre-pack take care of 80% to 100% of my symptoms, like explained at https://poiscenter.com/forums/index.php?topic=2090.msg16604#msg16604 (https://poiscenter.com/forums/index.php?topic=2090.msg16604#msg16604) )

For 5 years now,, I take my pre-pack before ejaculation, so I do not have hypotension problems anymore.  Green tea, magnesium and potassium are still part of this pre-pack, and I suppose that other components of it, like 5-HTP, helps keep my BP normal, too.

Also, apart from that, I keep in check my B12 and my Iron intake, because a low hemoglobin facilitates hypotension.

See with a health professional if a similar strategy as mine would be safe and useful for yourself.

Hello again. I have POIS with chronic muscle pain, uncomfort in the chest when I swallow food, difficulty tolerating intense exercise, and heat intolerance. All these problems involve palpitations that I can hear.  I’ve passed every blood test my doctor has thrown at me except for the vitamin d 25-hydroxy test. I’ve only gotten referrals for physical therapy and pain management. I requested a referral to see neurology, but my doctor and clinic denied it. It’s been quite difficult to put my focus on each problem individually while focusing on the rest of my life. Does any one know what could be wrong with me chronically aside from POIS?

https://poiscenter.com/forums/index.php?topic=976.0

There are probably more people with cardiovascular symptoms haven't digged much.

Risk of solid cancer:
Risk of solid cancer in patients with mast cell activation syndrome: Results from Germany and USA (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710302.1/)
Title: Re: Mast Cell Activation Syndrome
Post by: Muon on October 18, 2020, 11:18:04 AM
This one is interesting, Rupatadine is a PAF antagonist plus antihistamine. Has anyone tried this one?

https://en.wikipedia.org/wiki/Rupatadine
https://en.wikipedia.org/wiki/Platelet-activating_factor