1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
The ePatient Revolution
Ryan Prior shares his experience and his thoughts from attending the Stanford Medicine X Conference as he contemplates the rising of the ePatient Revolution ...
Discuss the article on the Forums.

Mast Cell Activation Symptomatology

Discussion in 'Mast Cell Disorders/Mastocytosis' started by nanonug, Jul 4, 2012.

  1. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

    Messages:
    700
    Likes:
    239
    US
    I'd guess that the pain is from bradykinin, which is also involved in vasodilation and generally occurs after histamine release. For example, if a person suffers a blunt trauma that'd be followed by swelling which is part of healing - and also pain occurs in order to keep you from re-injuring the site with any more forceful contact.

    You don't happen to take an ACE Inhibitor, do you? (Those drugs increase bradykinin levels by inhibiting its breakdown.)
     
  2. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

    Messages:
    700
    Likes:
    239
    US
    Now here's another clue: some years ago, before I got sick, I found some old niacin tablets and took enough to provoke a strong flush. But I had no reaction, even after more than an hour. I figured the niacin was simply weakened too much over time. I then made a steak and within a few minutes after starting to eat it, I surprisingly flushed.

    I'd been having only chicken breast for some weeks at that time. My impression was that arachidonic acid in the steak was necessary for the inflammatory flush, being substrate for PGs. I then researched and found that the association was well known.

    So a person really intent on lowering PGs might switch from red meat to fish, to lessen AA and also to increase the omega 3s which compete for the same delta-6-desaturase enyzyme.
     
    August59 likes this.
  3. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

    Messages:
    700
    Likes:
    239
    US
    You reminded me that I used to feel very wiped out for many hours after taking diphenhydramine. But that doesn't happen so much since I got sick. I assume that I have higher chronic levels of (the alertness chemical) histamine now.


    P.S. I'll just mention that Benadryl/diphenhydramine is said to have led to the development of Prozac.

    Also another mention of an unusual fact: schizophrenics don't flush much from niacin.
     
  4. OverTheHills

    OverTheHills

    Messages:
    311
    Likes:
    278
    New Zealand
    If you are looking for more random histamine experiences:
    once I got M.E. my lifetime strong motion sickness has disappeared.When I took a course of immunovir it came back, along with lots of my missing energy. Unfortunately the effect was temporary. Energy went, motion sickness went. I also note that I can't tolerate antihistamines anymore. Before I got ME,as well as a lot of allergies, I used to get heat/pressure/unexplained urticarias.Anyone who has a brain can make sense of this picture?

    OTH
     
  5. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
    The only medication I take is Topamax 100mg against chronic daily nonstop headaches (since the age of 6)
    and 1/2 tablet of Zolpidem to sleep.
     
  6. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
    Can a family doctor order the tests?

     
  7. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
    After some reading on MCAS fora, I notice some patients have auto-immune antibodies as well. What a coincidence.

    I still don't understand the link between MCAS, adrenal exhaustion, methylation block, leaky gut, viral load, Lyme, ... which so many of us suffer from.
     
  8. nanonug

    nanonug Senior Member

    Messages:
    1,248
    Likes:
    385
    Virginia, USA
    Technically, yes, but will s/he know how to interpret? Besides, if tryptase is normal there are other tests that need to be attempted such as prostaglandin D2. If at all possible, I would suggest seeing a mast cell specialist. You could maybe ask Claude Dupont for a recommendation...
     
  9. nanonug

    nanonug Senior Member

    Messages:
    1,248
    Likes:
    385
    Virginia, USA
    Leaky gut is easy: mast cells release tryptase which increases intestinal permeability. See, for example: "Mast Cell Tryptase Controls Paracellular Permeability of the Intestine"
     
  10. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
  11. August59

    August59 Daughters High School Graduation

    Messages:
    1,480
    Likes:
    405
    Upstate SC, USA
    That is what I have been sort of wondering about as well. It makes me want to think that there is another step beyond Mast Cell Activation, but it is possible this could lead us to it. It would really be interesting if one of the other studies going on by Lipkin, Montoya, Natelson or Bariniuk lead to Mast Cell Activation via a pathogen of some sort.
     
  12. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
    Link between histamine and methylation block

    Over-methylator and Under-methylator
    The Pfeiffer Treatment Center identifies two different supplement regimes depending on if you are an "over-methylator" or an "under- methylator." These are VERY rough estimations and nothing concrete...they may not be accurate either; further research is needed.
    Q: How can you find out if you are over or under?
    A: Histamine levels may be a good indicator of whether someone is an over or under-methylator.
    Low histamine points to over-methylator: If your histamine level is low you are probably an over-methylator (according to Pfeiffer research). This means that many supplements would be detrimental to him (those containing methyl). These would include taurine, GABA [both precursors to methyl activity in the brain], folic acid, B12, B6, DMG, TMG (and SAMe) - to name a few.
    Q: What test checks histamine levels?
    A: There is a blood test to measure histamine. Your pediatrician can do it.
    Q: How can I lower the histamine level, and the results of a histamine reaction?
    A: Some people who have trouble converting sulfur to sulfate (PST issue), and who have a sensitivity to certain foods and chemicals because of this, often times develop a high histamine level. My son develops a runny nose as a reaction to this problem. Benadryl helps my son with this, and anything else that lowers histamine would help him, also. I think the Feingold Diet, No-Fenol, or avoiding certain phenolic and high salicylate foods may help the sulfation problem and subsequently lower the high histamine level. Benadryl and Pepcid AC are histamine blockers. This might explain why Pepcid AC is so effective on some kids. A few parents have reported that a histamine reaction with certain foods did not happen when No-Fenol was given with those foods. MSM or Epsom salts also supply sulfur to the system and may be helpful. Some people cannot convert the sulfur in MSM to the needed sulfate form although other people can. Epsom salts supply sulfur in the sulfate form directly. Taking MSM or Epsom salts may alleviate a histamine reaction.
    Q: What amount of B6 is considered "high"?
    A: From the site http://www.methylmagic.com/faq.html
    Some supplements have lots of B6 (e.g. 100mg) and the author usually aims for between 20 and 50mg per day of B6. Excess niacin (B3) is metabolized by methylation and thus uses up methyl groups. Also aim for 50 mg or less. These values are likely for an adult so a child needs much less.
    According to Pfeiffer, "Actually excess niacin (B3) is metabolized by methylation and thus uses up methyl groups." So if you are an over-methylator, meaning you have extra, then B3 is good because it uses them up, but if you are an under-methylator, meaning deficient, then giving extra B3 is bad because it drains an already poor supply.


    http://www.enzymestuff.com/methylation.htm
     
  13. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    756
    Hi, Marlene.

    Here's a speculation. I won't dignify it by calling it a hypothesis :):

    As I think you know, I believe that the core of the pathophysiology of ME/CFS is the vicious circle mechanism that involves a partial block in the methylation cycle and glutathione depletion.

    The adrenal exhaustion is really a problem higher up in the HPA axis for most PWMEs: glutathione depletion in the pituitary interferes with the amount and diurnal variation of the ACTH secretion, and this causes the low and poorly regulated cortisol output from the adrenals.

    Leaky gut is caused by bacterial dysbiosis in the intestine. This could have come before the onset of ME/CFS, such as from the use of antibiotics without probiotics. It could also be caused by the vicious circle mechanism, by a variety of pathogenetic pathways: Low glutathione removes protection of the gut from oxidative stress, pathogens and toxins. Low folates interfere with formation of new DNA to make cells to replace those that are sloughed off. The lifetime of enterocytes is only a few days. Usually there is low secretory IgA, which may be caused by the cortisol abnormality, which in turn is caused by low glutathione.

    The viral load is a consequence of dysfunction of cell-mediated immunity, which in turn is caused by glutathione depletion, which prevents proper formation of perforin in the NK and killer T cells.

    Lyme disease is likely the first cause of the illness in many cases, and others may be exposed to tick bites after the onset of ME/CFS. Lyme and its coinfections lead into ME/CFS in those who are genetically predisposed, because they cause oxidative stress (in some of the infections directly, such as Babesiosis, and in others by the inflammatory response of the immune system to them, and Borrelia take cysteine from their host, which is the rate-limiting amino acid for making glutathione.

    Now, the mast cells are a new feature that I have not thought much about yet. Here's the speculation: We know that mast cells make histamine,among other things. Histamine is made from the amino acid histidine. Normally, a lot of the histidine is converted to formiminoglutamate and is then metabolized by reacting with tetrahydrofolate. If folate is depleted, as in the vicious circle mechanism I have described, the breakdown of histidine is partially blocked. Presumably this would raise the level of histidine, and that might cause more histamine to be produced. In addition, there are two reactions tha normallybreak down histamine. One is inside the cells, and it requires methylation, which is partially blocked when the vicious circle is operating. The other is diamine oxidase, which operates outside the cells. This requires B2 and B6 as well as copper. For various reasons, PWMEs tend to go low in B2 and/or B6, probably mainly because they have to use it a lot for amino acids transaminase reactions, because they burn more amino acids for fuel than normal, again because glutathione depletion blocks use of carbs and fats at normal rates.

    So probably more histamine is being made, and the reactions to break it down are working less rapidly.. This leads to high histamine. Now, histamine is known to be a neurotransmitter, and mast cells are known to be located near nerves. What if the histamine stimulates the nerves, producing hypersensitivity to pain, and then the neurons produce more substance P or other neuropeptides, which in turn are known to stimulate mast cells? Then we would have a dirty little vicious circle mechanism that would cause the pain sensitivity and the skin rashes, and it all comes back to the GD-MCB vicious circle mechanism.

    Now pure fibromyalgia is different. It's beginning to look like the mast cell-nerve interaction is going on there, too. But possibly something else kicks it off, other than the GD-MCB vicious circle that we find in ME/CFS. Once it gets going, it is a vicious circle itself, and I think it could account for the chronic nature of fibromyalgia. I would like to know more about pure fibro, because it affects a lot of people. It looks like some good things are happening in fibro research these days.

    Again, I am just speculating and don't have a lot to back this up with.


    Best regards,

    Rich
     
    katim likes this.
  14. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

    Messages:
    700
    Likes:
    239
    US
    Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms
    I began CFS in 10/2008. I believe I had high histamine from MTHFR long, long before that. But my really high histamine symptoms (burning eyes and horrible insomnia plus nocturia) didn't begin until 3/2012. I think that allergy or a viral infection stirs it up more, occasionally. (Plus conversely, 3/2012 was around the time that my enlarged submandibular nodes started to go down after over 3 years of being the same size. I haven't had much fatigue since then, except due to lack of sleep.)

    I could not sleep more than 4 hours straight most nights since March. But for two nights this week, 500mg quercetin gave me 6 straight hours or more. Last night I took no quercetin and went right back to waking after 4 hours, plus the nocturia was back. Quercetin gives me similar results to diphenhydramine.

    In the past, I'd thought that the burning eyes and nocturia were symptoms of excess endogenous interferon. Since recombinant interferon is used to treat hepatitis, it's easy to find the side effects listed online. Maybe interferon still plays some role, but that wouldn't explain the benefit from taking anti-histamine measures, such as the diphenhydramine and quercetin.

    I don't believe that I have any genetic defect in mast cells per se. My guess is that high chronic histamine makes my mast cells unstable. Basophils might play a role. Basophils have histamine receptors.

    Regarding my insomnia and temperature dysregulation: the hypothalamus has H4 receptors.

    Yet despite the abundance of mast cells in the gut, I haven't personally had any leaky gut effects for a while.

    Why the varying effects in different body parts, not to mention in different people? I began looking into whether degranulation is all-or-nothing, and also whether MC contents are homogenous or heterogenous.

    "it is not clear whether these granules are homogenous or whether there is heterogeneity within the secretory granule population in mast cells", from:
    http://www.pnas.org/content/105/7/2580.full
    "Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms"
    Their conclusion IIRC is that different granule subsets can exocytose, it's not all or nothing. I'd also bet that at any given time, my MCs from my lungs have different composition from those e.g. in my skin.


    But I'm mostly in burnout more again now and didn't pursue further for the time being.
     
    August59 likes this.
  15. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

    Messages:
    700
    Likes:
    239
    US
    you can also easily find the association between MTHFR and over-reaction to hymenoptera stings
     
  16. August59

    August59 Daughters High School Graduation

    Messages:
    1,480
    Likes:
    405
    Upstate SC, USA
    As many times I've been to a doctor and all the lab work that has been done. My histamine levels have never been checked. I'll see him in a few weeks and I'm going to push him to check it.
     
  17. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

    Messages:
    700
    Likes:
    239
    US
    While in the mood for posting, let me add this, regarding alcohol intolerance (which is likely in my opinion due to acetaldehyde, the primary metabolite of ethanol) and exercise intolerance (malondialdehyde is often used as a marker for exercise induced oxidative stress) and thus how aldehydes can tie in:

    Acetaldehyde Induces Histamine Release from Human Airway Mast Cells to Cause Bronchoconstriction
    http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=IAA2004134003233 2004
    "Conclusions: The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine..."
     
  18. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
    I have a teenage son who is very allergic to everything, sneezing from morning till evening, acne all over, asthma-like breath, anaphalaxis-shock once after intake of ibuprofen, painful and red eyes, achy bones and backpain once a week but he feels fine in general. Good condition overall. He tries gluten free for the moment and we're considering anti-histamine to see if it makes the "acne" go away and keeping a list of what make trigger it.

    His bloodwork - and I keep a close look at at - only shows low zinc and white bloodcells. Extra zinc has improved his skin condition.

    But, when he was born, he was in intensive care because of very low B12 and folic acid as well as sepsis due to bacterial infection of unknown origin.

    I liked the analogy with the nitrogen wagon earlier in the thread.
     
  19. Marlène

    Marlène Senior Member

    Messages:
    441
    Likes:
    211
    Edegem, Belgium
    Thank you very much Rich for your time and explanation.
     
  20. EMilo

    EMilo Elizabethmilo.com

    Messages:
    188
    Likes:
    125
    Seattle, WA
    I've never heard of anyone else having idiopathic anaphylaxis. 6 times in the ER. They never figured out what was happening and I've lived in fear for years. I'd love to know how they treated you if they couldn't find the cause!
     

See more popular forum discussions.

Share This Page