ME/CFS is a mast cell disorder (hypothesis)

[alex3619]

I was on a tricyclic (I don't recall which one) for a short while in the late 1980s. I had moderate to severe IBS. It went away. Since then I have had gut issues off and on, but not continuously.

 

[adreno]

I thought doxepin had alot stronger antihistamine properties then other tricyclics and possibly modulate the immune system in other ways??

Yes, doxepin has the strongest antihistamine action of all the tricyclics. And it is also a mast cell inhibitor. Tricyclics have several actions, hence the label "dirty drugs". You can see the binding profiles of the tricyclics here:

http://en.wikipedia.org/wiki/Tricyclic_antidepressant#Binding_profiles

H1 is histamine, the lower the number, the higher the binding = stronger effect.

 

[heapsreal]

Doxepin or Sinequan is a member of the tricyclic antidepressant class of drugs but at low doses typically used in CFS, Doxepin acts more as an immunomodulator through its actions as a very potent Histamine-2 (H2) blocker and is highly sedating, even at very low doses ( 1-2 mg). It is used in CFS for its properties of sleep maintenance, especially in combination with Klonopin. It can also be used in CFS relapse as an immunomodulator and softens immune activation symptoms, especially sore throat, swollen glands and congestion.

A copy and paste from Cheney's web site above. I find it interesting that he finds it useful for relapses, i may try this if i have a relapse/crash.
Alex i think doxepin is used for IBS.
I think it being a 'dirty' drug means its helpful for many indications.
I found it initially excellent for sleep but it wore off after a years or so and it does make one fall in love with food, thats the 'dirty' part.

 

[adreno]

A dirty drug is an informal term used in pharmacology to describe drugs that may bind to many different molecular targets or receptors in the body, and so tend to have a wide range of effects and possibly negative side effects.

http://en.wikipedia.org/wiki/Dirty_drug

 

[RustyJ]

I'm not sure of doxepin's effectiveness as a mast cell stabilizer. Wouldn't it be better to take ketotifen which is a recognized MCS.

 

[adreno]

Right, ketotifen is likely a more effective MCS. But I guess there is no reason why you couldn't combine them, if you wanted to.

 

[xchocoholic]

Klonopin is touted as a mast cell stabilizer too but as someone who takes it and mast cell meds I haven't seen
it work on this. It does a great job in my seizures and nocturnal myoclonus tho. Mast cell meds work on
my allergy symptoms.

I never felt right on anti depressants. I don't even know how to describe the feeling. Possessed maybe ? Lol

fwiw, my oi is either there or it's not. My biggest sign that it's there is when I lay down blood rushes into my head like
a damn has been opened up. When I first started zyrtec in sept 2012, my oi disappeared. It came back intermitently (sp?) and I've yet to find a pattern for when it's not there. I've had 4 whiplashes, 2 concussions and had ataxia so I'm not sure there aren't some nerves involved in mine. I get horrible
mind numbing headaches if I sleep in the wrong position.

Anyone seen nano ?

Tc ... X

 

[xchocoholic]

When I had h pylori and parasites my oi was the worst it had ever been. I could barely stand up.
I thought I was a goner. Lol. After treating my oi went back to my pre h pylori and parasite level.

I haven't tried any long term antibiotic or parasite treatments but haven't ruled it out either. The last treatment
made me tied to the throne and mostly couchbound so I'm anxious about trying it. Getting to the root of my mast
cell problems would be great but I'm not sure I'm up to it.

Tc .. X

 

[RustyJ]

When I had h pylori and parasites my oi was the worst it had ever been. I could barely stand up.
I thought I was a goner. Lol. After treating my oi went back to my pre h pylori and parasite level.

I haven't tried any long term antibiotic or parasite treatments but haven't ruled it out either. The last treatment
made me tied to the throne and mostly couchbound so I'm anxious about trying it. Getting to the root of my mast
cell problems would be great but I'm not sure I'm up to it.

Tc .. X

I have not noticed any side effects, other than weight gain, with ketotifen. It is regarded as pretty side-effect free and one of the best MCS around. PS not selling ketotifen lol.

With the weight gain, I am not sure if this is a side-effect or just my body re-balancing. There is some suggestion keto increases appetite, thus leading to increased weight. I am not sure I have increased my intake all that much. I have a little, due to increased appetite, but not enough to account for the weight. Previously I could eat a pig and not put on an ounce.

I am still not overweight. Also I am pretty sure that by regulating my diet I could keep the weight gain under control.

 

[soulfeast]

According to Theoharides, the rutin in NeuroProtek is directed at the gut, to help with intestinal hyperpermeability, and luteolin is directed at the brain to deal with neurological symptoms. The quercetin is there as a decoy to keep the liver "busy" and prevent degradation of luteolin.

Quercetin is a COMT inhibitor. Luetolin is a substrate of COMT.. metabolized through COMT. So, the quercetin by slowing COMT activity, keeps luteolin from metaoblizing sooner and it stays in system longer.

The problem here is the phase I detox issue mentioned by Sushi and also the fact that some of us are COMT+ or ++ and already have very slow COMT activity. Slowing COMT activity even further would lead to even slower breakdown of estrogens, some drugs-herbs, and certain toxins.

Also a slower metabolism of adrenaline, which paradoxically is a mast cell activator.

 

[camas]

Quercetin is a COMT inhibitor. Luetolin is a substrate of COMT.. metabolized through COMT. So, the quercetin by slowing COMT activity, keeps luteolin from metaoblizing sooner and it stays in system longer.

The problem here is the phase I detox issue mentioned by Sushi and also the fact that some of us are COMT+ or ++ and already have very slow COMT activity. Slowing COMT activity even further would lead to even slower breakdown of estrogens, some drugs-herbs, and certain toxins.

Also a slower metabolism of adrenaline, which paradoxically is a mast cell activator.

Hi soulfeast,

What kind of response did you have to neuroprotek? I think Quercetone worked better for me until it built up in my system and made me feel much too wired. I don't have problems with COMT, but may have some other methylation issues according to my 23andMe results. I see that some others are looking at combining methylation and mast cell treatments and am following their comments with great interest.

 

[soulfeast]

Hi soulfeast,

What kind of response did you have to neuroprotek? I think Quercetone worked better for me until it built up in my system and made me feel much too wired. I don't have problems with COMT, but may have some other methylation issues according to my 23andMe results. I see that some others are looking at combining methylation and mast cell treatments and am following their comments with great interest.

I can's say for sure. My symptoms also coincided with the beginning of my menstrual cycle and ended at day 14. But day 14 was right after I stopped taking the NP. It was RSD like intense body pain. It was awful. This past month's cycle, I only had 1 day of intense pain. I was not taking NP. It would make sense (in my mind) that the quercetin would if it slows COMT make someone who already has a very slow COMT (++) have problems one way or another.

 

[camas]

I can's say for sure. My symptoms also coincided with the beginning of my menstrual cycle and ended at day 14. But day 14 was right after I stopped taking the NP. It was RSD like intense body pain. It was awful. This past month's cycle, I only had 1 day of intense pain. I was not taking NP. It would make sense (in my mind) that the quercetin would if it slows COMT make someone who already has a very slow COMT (++) have problems one way or another.

That's interesting. I've had increased bone pain on NP. I'm not sure how much longer to continue my trial as I don't feel like I'm seeing much, if any, improvement and it's a bit on the pricey side.

 

[xrayspex]

Camas I am curious about the "bone pain" you mention
I get that, bad burning pain that feels like its in my bones, sometimes my teeth hurt too (and they are generally not in bad shape, have gotten primo dental over the years)
that is why I don't relate to fibromyalgia completely as I dont think its as much a muscle pain as bone pain altho sometimes I get both

anyhoo, if I take anti-virals, natural or synthetic I get horrific pain flares, almost seems like how I would imagine chemo to be
a bit of dilemma, if it seems good to kill "bugs" but yet its not like I ever get thru to other side to make it worth putting up with the pain from those sort of supps/meds

what have you found most helpful?

 

[camas]

Camas I am curious about the "bone pain" you mention. I get that, bad burning pain that feels like its in my bones, sometimes my teeth hurt too (and they are generally not in bad shape, have gotten primo dental over the years) that is why I don't relate to fibromyalgia completely as I dont think its as much a muscle pain as bone pain altho sometimes I get both

anyhoo, if I take anti-virals, natural or synthetic I get horrific pain flares, almost seems like how I would imagine chemo to be a bit of dilemma, if it seems good to kill "bugs" but yet its not like I ever get thru to other side to make it worth putting up with the pain from those sort of supps/meds. what have you found most helpful?

My pain is mostly in my shins and a little in my left thigh. It kind of feels like a low level toothache and there is some burning, too. They say mast cells issues usually affect the long bones, so that makes sense, but I also have chronic pain in my upper spine. I take gabapentin for fibro pain, but it doesn't seem to have any effect on the bone pain. The only other pain killer I can tolerate is tylenol and it does seem to make a small dent in the bone pain.

It's funny because looking back I've had this pain since high school. I used to run track and my coach said it was shin splints and just had me tape my legs. You would have thought that some adult in my life might have been concerned that after every race I threw up, nearly passed out (did black out once), and had bad bone pain. I quit after my first year despite pressure to continue.

I have no idea why antivirals would make your bone pain worse, but a lot of drugs can cause mast cells to degranulate and then lead to bone pain.

 

[Mya Symons]

Hello. Thanks for the information. I have had some strange blood tests in the past. When they separate the B-Cells and the T-Cells, I have too little T-Cells and too many B-Cells. However, most of the B-Cells are immature. It's seems the older B-Cells are quickly dying off. This fits with Mass Cell Disorder, doesn't it. I found this article
http://www.ncbi.nlm.nih.gov/pubmed/20101023

What do you think?

 

[camas]

Hello. Thanks for the information. I have had some strange blood tests in the past. When they separate the B-Cells and the T-Cells, I have too little T-Cells and too many B-Cells. However, most of the B-Cells are immature. It's seems the older B-Cells are quickly dying off. This fits with Mass Cell Disorder, doesn't it. I found this article
http://www.ncbi.nlm.nih.gov/pubmed/20101023

What do you think?

Hi Mya,

I have no idea as this is way over my head. Maybe someone else here will have a better understanding of how mast cells affect T and B cells.

Are you on facebook? The nurses from the Mastocytosis Society are great at answering these kinds of questions in their group at: https://www.facebook.com/groups/155824303735/

 

[MNC]

I got part of my MCAS test results but nanoung seems to have quit the forum.

Is he/she officially gone?

 

[camas]

I got part of my MCAS test results but nanoung seems to have quit the forum.

Is he/she officially gone?

He disappeared around Thanksgiving. I hope he's okay and comes back. We could really use his input. Did you learn anything interesting from your results?

 

[MNC]

He disappeared around Thanksgiving. I hope he's okay and comes back. We could really use his input. Did you learn anything interesting from your results?

Negative, but I still miss one of them and besides my Internist says I should repeat the n-methylhistamine one because they made a wrong one at the lab (testing for just histamine instead of methylhistamine). I got quite angry after so much effort, time and money I put on it. I will let you know if something interesting comes out, but doesn't look very promising.