Posted 7/9/2016 7:47 AM (GMT 0)
A Relatively Complete List of Associated Symptoms I fit all these symptoms but don't find extreme fatigue on this list...which is my worst symptom...
◦hot flushing – described as a dry feeling of heat, rather than the sort of wet heat you experience when sweating
◦palpitations (irregular heartbeat)
◦lightheadedness
◦headache
◦shortness of breath
◦chest pain
◦nausea
◦diarrhoea
◦stomach pain caused by peptic ulcers
◦loss of appetite
◦weight loss
◦swelling of the liver, which can cause jaundice (yellowing of the skin and eyes) and make you feel lethargic
◦swelling of the spleen, which can cause abdominal (tummy) and shoulder pain
◦joint pain
◦swelling of the lymph nodes
◦weakness
◦fatigue
◦changes in mental state, such as confusion, irritability, poor attention span and impaired memory
◦urinary symptoms (needing to pass urine frequently, or pain when passing urine)
◦Low Blood Pressure (Hypotension)
◦dizziness
◦fainting (a sudden, temporary loss of consciousness)
◦blurred vision
◦general weakness
If you reach the state of anaphylaxis, you can even also have symptoms such as:
◦breathing difficulties
◦dizziness
◦swollen eyes, lips, genitals, hands, feet and other areas (called angio-oedema)
◦itchy skin or nettle rash (hives)
◦a strange metallic taste in the mouth
◦sore, red, itchy eyes
◦changes in heart rate
◦a sudden feeling of extreme anxiety
◦unconsciousness due to very low blood pressure
◦abdominal cramps, vomiting or diarrhoea
◦fever
While the NHS doesn’t mention hypertension, some patients may present with hypertension. Hyperadrenergic POTS can present in Mast Cell Activation Disorders. Hyperadrenergic POTS presents with orthostatic intolerance associated with an elevated heart rate (≥30 bpm within 5 minutes of standing) and hypertension (≥20 mm Hg increase in systolic blood pressure upon standing).
See Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders in the journal Hypertension.
Is There Research Connecting MCAD to Chronic Illness?
Ok, by now, you may be thinking, wow, I have many of the triggers and symptoms on this list, but is there research showing that this condition exists in various chronic illnesses? The answer to that question is yes. While there may not be a whole lot of research, Dr. Theoharides, the Director of the Molecular Immunopharmacology & Drug Discovery Laboratory, has put out quite a lot of research.
You can check out his huge amount of research here: http://www.mastcellmaster.com/publications.php
Treating Mast Cell Activation
While a lot of Dr. Theoharide’s research focuses on natural substances such as Luteolin for inhibiting mast-cell activation, and while he is the medical director of Algonot, it’s important to note that he receives no compensation from this company. I think it is important to note this fact because often when one has financial ties to companies or products, their research often becomes skewed or misleading. Algonot develops a supplement for MCAD called Neuroprotek that contains the bioflavonoids Luteolin, Quercetin, and Rutin.
There are pharmaceuticals for MCAD. Hydroxyzine preparations can be quite powerful, but usually require a prescription. Anecdotally, the combination of Zantac and Zyrtec (OTC at your local pharmacy) seems to work pretty well. Zyrtec is an H1 receptor inverse agonist and Zantac is a H2-receptor antagonist. However, even though these are over the counter, do not begin these medications without consulting with a qualified healthcare practitioner first.
Is MCAD connected to methylation?
This may be the million dollar question. There is not much information and MCAD and methylation, but I will end with a quote from the theory at mthfrheds.com.
MTHFR Polymorphism may be a predisposing factor to mast cell disease. 5-MTHF regulates biosynthesis of BH4. The A1298 mutation in the MTHFR enzyme effects the conversion of BH2 to BH4. Less amounts of BH4 inhibits NO formation resulting in increased mast cell degranulation. Inadequate BH4 formation also puts a strain on the conversion of tryptophan to serotonin and tyrosine to dopamine, leading to low levels of the neurotransmitters: dopamine, norepinephrine, serotonin and melatonin.
Low blood serotonin levels help define a sub-group of patients with mastocytosis that are more likely to present with neurological and gastrointestinal complaints. Human mast cells can express and be activated through multiple serotonin receptors, and synthesize and release serotonin. Low blood serotonin levels in such patients may be the result of low BH4 levels due to 5-MTHF deficiency, the result of long-term malabsorption from chronic inflammation of the gastrointestinal tract or both, as is the case with me.
BH4 is a critical factor in cellular activities such as cell proliferation, cell cycle regulation and differentiation. Could BH4 deficiency secondary to MTHFR polymorphism be one of the fundamental mechanisms that underlie mast cell proliferation?
So the question I am left with is what substances should we try, or how do we modify our methylation protocol when it seems that MCAD may play a large role in the clinical picture. In the absence of improvement of MCAD type symptoms (without taking antihistamines or Luteolin-based supplements), would taking BH4 directly help? Is BH4 deficiency really the issue?
If anyone has any comments on how to address MCAD with methylation supplements, or if they have tried taking BH4 directly, please comment.
By geneticgenie | January 31st, 2013 | Posted in Uncategorized |
123 Responses to “Mast Cell Activation Disorder (MCAD), Chronic Illness, and its Role in Methylation”
julie gregory Says:
February 4th, 2013 at 8:29 pm
Interesting. How about a variation of the MAO A R2974 gene (rs6323)? http://snpedia.com/index.php/Rs6323
It is also involved in dopamine, norepinephrine, serotonin and melatonin levels. I am DXed with MCAD and I have the TT allele.
julie gregory Says:
February 4th, 2013 at 8:46 pm
Aha, I found the BH4 connection via the MAO defect!
MAO A: Monoamine Oxidase A
Monoamine Oxidase A breaks down serotonin, a neurotransmitter that is generated from the dietary amino acid tryptophan, in a BH4 requiring reaction. Many anti-depressant drugs, including the SSRIs (Serotonin Selective Reuptake Inhibitors) work by blocking the breakdown of serotonin. Defects in serotonin metabolism have been associated with mood and neurological disorders. How best to address the MAO A R297R abnormality is not clear to me. As serotonin metabolism is adversely affected, individuals with the R297R defect should avoid large doses of high tryptophan foods (see appendix). High doses of St. John’s Wort, often taken to address depression, could lead to mood swings as serotonin levels fluctuate. Dr. Yasko recommends frequent dosing in small amounts of St. John’s Wort, 5HTP (a tryptophan metabolite), and the Mood S RNA formula if serotonin support is needed. If serotonin production is impaired on the basis of BH4 deficiency secondary to a Methyl Cycle abnormality, as the abnormality itself is addressed, BH4 levels should stabilize, hopefully normalizing serotonin production.
admin Says:
February 4th, 2013 at 9:34 pm
I have MAO-A homozygous and I can’t handle epinephrine at the dentist, SSRIs, etc. I have high norepinephrine as well. Stuck in fight or flight a lot, tachycardia, etc. In a bad mood almost all the time – sorry, can’t help it!
So I was searching for MAO-A agonist, and this is all I found. It’s called Respen-A. I think it’s a transdermal patch if I remember right.
http://www.respen-a.com/
I have never tried the RNA formulas because I never heard anybody using them and saying great things about them. Do they really work?
You can only get it from a few pharmacies as prescription. They call it homeopathic, but it looks more like a diluted version of Resperine to me as the “homeopathic” has the same side effects and method of action according to their data.
http://en.wikipedia.org/wiki/Reserpine
As far as fixing the problem. I can’t figure that one out.
I don’t understand the frequent doses of St. John’s Wort. Isn’t there too much Serotonin? SSRI’s either drive me up the walls or put me in the fetal position feeling like I am going to die.
I think the stress from being so sick made that MAO-A gene express itself in a bad way.
julie gregory Says:
February 5th, 2013 at 8:29 am
Or too little serotonin? MAO is involved in breaking it down. Perhaps it is present in great quantities, but we are unable to utilize it? Yasko’s