Mast Cell Activation Syndrome (MCAS)

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As early as the first century BC, the Roman poet and philosopher Lucretius (c. 99 BC – 55 BC) had noted that

“..what is food to one man is bitter poison to others....”

And it is fairly certain that he was refering to allergic, and possibly anaphylactic reactions. See Wikipedia link on Lucretius

But, this is another clinical picture which seems to be becoming increasingly common. It is important to realise that this is not a diagnosis but a clinical picture. A proper diagnosis gives us the mechanism of the clinical picture and that has obvious implications for management.

What is MCAS?

This occurs when the allergy and mast cells release mediators such as interleukins, histamine, leukotrienes, prostaglandin, heparin and enzymes such as tryptase. These can produce many symptoms.

The diagnosis is best made on clinical grounds and the clues are:

1- From the symptoms

Mediators - any or all of these can be released in MCAS Possible symptoms associated with....
Interleukins Fatigue, weight loss, nausea, enlarged lymph nodes
Histamine Anaphylaxis, flushing, itching, hives, sneezing, diarrhoea, hypotension
Leukotrienes Shortness of breath due to asthma
Prostaglandins Flushing, bone pain, brain fog, cramping
Tryptase Osteoporosis, skin lesions
Heparin Osteoporosis, problems with clotting/bleeding

2- From the history

Potential triggers Possible mechanisms Action
Heat, cold or sudden temperature changes, weather changes. Sun/sunlight Mast cells are known to respond to several mechanical irritants – one example is cold urticaria Make them less irritant with Magnesium, Vitamin D, Vitamin C (in high doses this has an anti-histamine effect BUT it also kills microbes and so may produce a Herxheimer reaction)
Mechanical irritation, friction, vibration Ditto above eg Dermographism Ditto
Infections (viral, bacterial or fungal) MCAS is part of the natural defences against infection Identify and treat the infection
Exercise, stress: emotional, physical including pain. Severe fatigue Immune system does not have the energy to respond appropriately Improve energy delivery mechanisms - See Overview of CFS/ME protocol including energy delivery mechanisms
High carbohydrate diet Makes for a fermenting gut - see Fermentation in the gut and CFS PK diet and Vitamin C to bowel tolerance. See The Paleo Ketogenic Diet - this is a diet which we all should follow
Alcohol, NSAIs, (Non-steroidal anti-inflammatory drugs) opioids Make for Leaky Gut Avoid
Drugs, NSAIDs, and some local anaesthetics) and contrast dyes Destabilise cell membranes Avoid
Foods, Pollen, pet dander, etc Venoms (bee, wasp, mixed vespids, spiders, fire ants, jelly fish, snakes, biting insects, such as flies, mosquitos and fleas, etc.) Allergy Avoid

At the first sign of any bite, apply topical Lugol’s iodine 15% to the bite. This gets rid of swelling and itch within seconds! In the garden I carry this with me at all times!

Antibiotics Herxheimer reactions) See Diet, Detox and Die-off Reactions
Natural odours, chemical odours, perfumes and scents. Pollution Multiple chemical sensitivity- - triggers degranulation probably by destabilising cell membranes See Chemical Poisoning and Multiple Chemical Sensitivity (MCS) - how to reduce your daily exposures , Multiple Chemical Sensitivity (MCS) - a common problem and often triggered by exposure to chemicals and Multiple Chemical Sensitivity (MCS) - Principles of Treatment
Possibly electromagnetic pollution eg 4G, 5G We know this affects calcium influx and so destabilises cell membranes
Poor hydration may be part of membrane destabilisation To be hydrated you need FAT and SALT and WATER

What are the mechanisms that produce Mast cell reactions?

What Where Notes
Gram negative bacteria such as E coli, pseudomonas, klebsiella, haemophilus influenzae, Citrobacter freundii, proteus, H pylori, Rickettsia and many others

Fungi and yeast - -S cerevisiae

Gut Many of these microbes can be seen in tests such as a Comprehensive Digestive Stool Analysis.

Some appear in probiotics

Klebsiella, mycoplasma, pseudomonas

Fungi – aspergillus fumigatus

Lungs May be picked up in sputum specimens.

Fungal infection often missed in sputum samples – urinary mycotoxins may be a helpful test. See Great Plains Lab Mycotoxin Test

Haemophilus influenzae Middle ear Consider if there is acute or chronic upper airways inflammation
Possibly viruses Depends on which virus!

MCAS is found in conjunction with Ehlers-Danlos Syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS).


  • EDS - there is poor quality connective tissue. If the connective tissue is poor then microbes start to leak through the gut wall and so leaky gut is more likely. See Leaky Gut Syndrome. Microbes come into greater contact with mast cells. MCAS may also be an appropriate reaction to these microbes trying to invade the body through the gut wall. Please see Ehlers Danlos Support UK charity website for more information.
  • POTS - this results where there are poor energy delivery mechanisms and so the immune system is under-powered. The point here is that MCAS may be an entirely appropriate reaction to chronic infection. If the immune system is under-powered then the usual front line fighters of lymphocytes and neutrophils do not have the energy to fight and so other cells are recruited – these include mast cells. Please see POTS UK charity website for more information.

The link between MCAS and POTS can be seen below in diagrammatic form -

Pots and mcas.png


The above mechanisms give us a logical approach to treatment:

Sort out the fermenting gut

As you can see, many of the triggers of MCAS come from the gut. Whilst the lower gut copes with them fine (it is supposed to be full of fibre fermenting friendlies), the upper gut does not - indeed the upper gut is meant to be a pretty much sterile digesting gut. First put in place interventions to treat the upper fermenting gut of which the most important are to starve the little wretches out with a PK diet AND to kill them with vitamin C to bowel tolerance. See The Paleo Ketogenic Diet - this is a diet which we all should follow

Identify and treat any chronic infection

The starting point here is to improve the immune defences with Groundhog Chronic interventions. See Groundhog CHRONIC

We then may need specific treatments for tackle those little wretches who are so comfortably ensconced in the body that we need a nuclear weapon to dislodge them. This many involve antibiotics for bacteria, antifungals for fungi and antivirals for viruses. Much more information see my book “The Infection Game - life is an arms race"

Identify any other triggers and avoid

We know antibiotics can trigger an MCAS attack BUT it is possible this is a Herxheimer reaction – ie short term pain long term gain. See Diet, Detox and Die-off Reactions.
NSAIs, alcohol and opioids make Leaky Gut worse and so can worsen MCAS

Mop up histamine and other mediators in the gut

With clays such such as Toxaprevent 3 grams at night on an empty stomach taken away from food and supplements

Break histamine down in the gut with Diamine Oxidase enzyme

Sometimes helps - suggest DAO 4.2mgs taken 5 mins before food. Here is one such product - 'Seeking Health' - Histamine Block - 4.2mg

The figure of 4.2mg is suggested because most available studies used doses of 4.2 mg of DAO at a time up to 2–3 times daily just before meals. See HealthLine Article - Diamine Oxidase Supplements Explained and also this study:

Reprogramme the immune system

It may be that the MCAS has become switched on, has adequately dealt with the infection, but has not been switched off. In this event we need to put in places interventions to reduce useless inflammation such as high dose vitamin D (up to 10,000iu daily is completely safe, and if on a PK diet, with no dairy products, then up to 20,000iu daily is safe, but if you take more than that, then serum calcium needs to be monitored with blood tests), Low Dose Naltrexone and possibly micro-immunotherapy 2L ALLERG - see Reprogram the immune system with micro-immunotherapy

Interventions to improve energy delivery mechanisms

See my book Diagnosis and Treatment of Chronic Fatigue Syndrome and Myalgic Encephalitis and Overview of CFS/ME protocol including energy delivery mechanisms

Interventions to improve the quality of connective tissue

Bone broth, The GAPS diet, Joint Mix, organic silica, minerals (as in Sunshine Salt).


Magnesium stabilises mast cells and so they degranulate more easily where there is a magnesium deficiency. Take Magnesium supplements - at least 300mgs of elemental Mg daily together with vitamin D as above (vitamin D is essential for the absorption of Mg)

CBD (Cannabidiol) Oil

Many people have found benefit from using CBD oil - please see this article - Medical Cannabis & Mast Cell Activation Syndrome.

Possibly use antihistamines, cromoglicate, quercetin and other such medications

I put this as a last resort because it is possible that MCAS is a vital defence to protect against infection and so using antihistamines and other such medications may be a case of symptom squashing. The interventions, as above, treat the mechanisms as identified, and are “sustainable” in that they reverse, not escalate, disease processes.

Related Articles

Related Tests

External Links

More Information

Please see Mast Cell Action charity website for more information.

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