Author Topic: Mast Cell Activation Syndrome  (Read 55192 times)

hurray

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Re: Mast Cell Activation Syndrome
« Reply #280 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?

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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:

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

Elevated levels of norepinephrine are common in POTS suffers:

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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).

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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

Muon

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Re: Mast Cell Activation Syndrome
« Reply #281 on: September 21, 2020, 03:51:21 PM »
Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome (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.
« Last Edit: September 21, 2020, 04:01:25 PM by Muon »

hurray

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Re: Mast Cell Activation Syndrome
« Reply #282 on: September 21, 2020, 04:42:08 PM »
Evidence of Mast Cell Activation Disorder in Postural Tachycardia Syndrome (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):

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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.

Prospero

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Re: Mast Cell Activation Syndrome
« Reply #283 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 ?

Muon

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Re: Mast Cell Activation Syndrome
« Reply #284 on: September 22, 2020, 05:39:22 PM »
Role of inflammation in the pathogenesis and treatment of fibromyalgia

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



Glial cells

"Furthermore, astrocytes release gliotransmitters such as glutamate"
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.
« Last Edit: September 23, 2020, 08:56:09 AM by Muon »

Muon

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Re: Mast Cell Activation Syndrome
« Reply #285 on: September 23, 2020, 08:30:03 AM »
Anatomy and Physiology of Erection, Ejaculation, and Orgasm

"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=
« Last Edit: September 23, 2020, 08:34:19 AM by Muon »

Journey

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Re: Mast Cell Activation Syndrome
« Reply #286 on: September 23, 2020, 11:20:41 AM »
Anatomy and Physiology of Erection, Ejaculation, and Orgasm

"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?

Muon

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Re: Mast Cell Activation Syndrome
« Reply #287 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.

hurray

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Re: Mast Cell Activation Syndrome
« Reply #288 on: September 23, 2020, 05:07:58 PM »
Role of inflammation in the pathogenesis and treatment of fibromyalgia

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

Glial cells

"Furthermore, astrocytes release gliotransmitters such as glutamate"
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.

Muon

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Re: Mast Cell Activation Syndrome
« Reply #289 on: September 24, 2020, 06:18:42 AM »
Role of inflammation in the pathogenesis and treatment of fibromyalgia

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

Glial cells

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

Muon

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Re: Mast Cell Activation Syndrome
« Reply #290 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.

Muon

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Re: Mast Cell Activation Syndrome
« Reply #291 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/
« Last Edit: October 04, 2020, 02:34:26 PM by Muon »

Vandemolen

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Re: Mast Cell Activation Syndrome
« Reply #292 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.
POIS since 2000. Very bad since 2008. I knew that I have POIS since June 2010. Desensitization since March 2011. I stopped with desens in July 2016. I have 50% less POIS. And only 1 day of POIS. Purified CBD works for me, but I am allergic for CBD.

Muon

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Re: Mast Cell Activation Syndrome
« Reply #293 on: October 09, 2020, 07:27:18 AM »
« Last Edit: October 13, 2020, 02:18:43 PM by Muon »

Muon

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Re: Mast Cell Activation Syndrome
« Reply #294 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

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 )  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 )

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
« Last Edit: October 17, 2020, 01:41:51 PM by Muon »

Muon

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Re: Mast Cell Activation Syndrome
« Reply #295 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


Muon

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Re: Mast Cell Activation Syndrome
« Reply #296 on: November 28, 2020, 07:36:19 AM »
Mold and mycotoxins can cause most symptoms of Pois by activating mast cells.  I have at last found the root cause of of my deadly lung problem  allergic aspergilloses.  I have been living in a moldy home with high humidity and little ventilation. mycotoxins from mold can cause havoc in the human body affecting brain and liver the most apart from lungs.  I am very much annoyed that my pulmonologist had found this only now.  I am now in a very critical stage and now planning to move to a new location by next month.  The dietary advice for me is avoid sugar and carbohydrates as far as possible and have only fat and protein based free range meat or fresh seafood.  I think many of us should be having mold allergy and if it is treated it will greatly reduce the pois by preventing mast cell activation during ejaculation.

Table 2: Specific IgE against mold. House dust mite allergy pops up in more than one paper. Did you manage to get your hands on Omalizumab?

Muon

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Re: Mast Cell Activation Syndrome
« Reply #297 on: November 28, 2020, 10:20:09 AM »
A focus on neurotransmitters. Dumped this one in the POIS paper archive thread.

Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review

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Re: Mast Cell Activation Syndrome
« Reply #298 on: November 28, 2020, 11:02:38 PM »
Thanks muon.  My pulmonologist  thinks Omalizumab is too risky during covid and has given oral itraconazole for aspergilloses.

Muon

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Re: Mast Cell Activation Syndrome
« Reply #299 on: November 29, 2020, 03:32:10 PM »
I remember a case of a Russian POISer who developed POIS when he moved into a new apartment. Not sure if I have read this on this forum, reddit or the russian poiscenter.