Mast Cell Activation Syndrome

[Muon]

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.

[demografx]

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

[hurray]

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.

[demografx]

I was thinking more in terms of [“the treasure trove of”] evidence that we currently have.

Same here.

[Vandemolen]

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

Cannabinomimetic Control of Mast Cell Mediator Release: New Perspective in Chronic Inflammation

Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells

Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.

Differential Roles of CB1 and CB2 Cannabinoid Receptors in Mast Cells

Cannabinoid receptor 1 controls human mucosal-type mast cell degranulation and maturation in situ

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.

[Vandemolen]

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.

[Mushnikk]

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.

[Muon]

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

[drop247]

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.

[Vandemolen]

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

[Quantum]

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):

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

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.

[Nas]

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? 

[Nas]

Also another question is: If mast cell activation does not include degranulation then how do mast cell stabilizers help?

[Mushnikk]

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

[Nas]

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?

[hurray]

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:

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.

[drop247]

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.

[drop247]

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.

[hurray]

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 

[hurray]

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