The following is a long summary that I put together by and for my own research. It is not meant to be medical advice, but rather an aggregation of resources and the self-experimentation I engaged during the long wait for a specialist appointment in this area.
I published the page initially because many other patients who had CSF leaks (as I have) asked me how they can tamp down on reactions following leak diagnostics or treatment. While having a CSF leak does not, of course, correlate to having a mast cell disorder, the patient cohort that I know are all complicated cases just like me. And in those complicated cases, many have a connective tissue disorder that makes their leak harder to seal. Anecdotally, with mast cells living in connective tissue, many of these patients have increased food and environmental reactivity, anaphylaxis, and systemic issues during the diagnosis and treatment of their leaks.
For me, the first glimmer of these issues was actually in childhood. I had a cough that would itchy my throat when trying to sleep, and was unable to sleep through the night for a long time. This itchy cough went away when I hit puberty, but came back when I got sick on the trans-Mongolian trains en route to Ulaanbaatar. Then, following dengue fever in Vietnam, more glimmers: itchy skin when I exercised, itching when I ate certain foods like blue cheese, or drank red wine, and a first foray into seasonal allergies during first spring in Oaxaca, Mexico. They were so bad that my eyelashes fell out.
I had no idea what was going on, of course, but ended up landing on mast cells as a cause after the spinal tap that gave me my CSF leak. I saw many leak patients dealing with very similar issues, read up on dengue and mast cells (who knew!) and then it all culminated in my going into anaphylaxis during my 4th blood and fibrin glue patch and needing an epinephrine jab on the table.
I have been working on managing my ‘angry’ mast cells since that fibrin glue patch in early 2018.
What started as a resource page for fellow CSF leakers has becoming a more in-depth look at the many ways that mast cells can affect the body. When the pandemic hit, research emerged about how mast cell dysfunction could be driving the cytokine storms, and also leading to long covid / PAS-C.
For reference, prior to starting the regimen below, I had 24/7 searing and burning pain in my skin, adrenaline dumps at night that kept me up until 5am with heart racing, shaking with cold and low blood pressure, hives, heart racing, gastro-intestinal distress, and many instances of anaphylaxis following certain foods or smells. Since using the protocol I’ve listed out below, those have all disappeared, save for occasional reactions to new foods or smells. The skin burning disappearing was especially a relief, as is my ability to sleep again.
I update this page often, and welcome corrections or additional research – please use the contact page on the menu bar above to send me an email. Since writing this page in 2019, I have seen a mast cell specialist / gotten laboratory tests, and have been diagnosed with mast cell activation syndrome (MCAS).
Written: August 2019
Last updated: September 2021
A SUMMARY OF IMPORTANT POINTS
The following are discussed in more detail on this (long!) page. A summary of some main points:
– Mast cells exist all over the body, and symptoms can therefore occur all over the body. I am celiac, but my MCAS does not manifest with many GI symptoms, perhaps because I’ve long had that aspect under control. Other patients I know are constantly in the bathroom. It will differ person-to-person, and one patient may have anaphylaxis that differs from another patient’s symptoms and reactions.
– For patients with “wonky tissue” aka those with Ehlers-Danlos Syndrome or another connective tissue disorder, significant periods of mast cell dysfunction may result in visible changes to skin. With abnormal mast cells and collagen synthesis, and with mast cells living in the body’s tissues, this is the most common comorbidity in the patient cohort.
– With 200 mediators released by mast cells, and tests yet to be developed to measure many of them, each patient’s symptoms will be different, usually with some overlap.
– This also means that triggers can be different for each patient, be it environmental triggers or food-related triggers. These include excipient ingredients (fillers) in pills, radiological dyes and even procedures that cause pain. It is important to premedicate for procedures and surgeries. See the recommendations under “triggers”, below. Some people even react to their own sweat, or to vibrations, or to sunlight. One common trigger for most patients is situations of trauma and stress. The many other triggers that exist will vary person to person.
– A mast cell flare is not the same as a “true” allergy. True allergies can be identified with blood tests. Mast cell reactions vary based on someone’s baseline, and will not be identifiable in the same way. See the bucket analogy, below.
– Many conditions are comorbid with mast cell disorders, some of which are set out in on this page.
– Diagnosing mast cell conditions is not simple. Many practitioners falsely believe that a normal tryptase is indicative of no mast cell disorder. Patients sometimes get diagnoses (MS, lupus, anxiety, interstitial cystitis and more) that reflect one arm of mast cell problems, only to find out later that treating MCAS goes a long way to mitigating those (and other) symptoms.
– Given how patients differ with respect to triggers, it makes sense that treatment is also very bioindividual. Baseline treatment is usually a combo of an H1 and an H2 taken 12 hours apart as a “histamine blockade”. Finding the brand that works best for you will involve testing different brands methodically until landing on one your body likes. In addition, many patients benefit from natural mast cell stabilizers like quercetin, as set out below in the “naturally” section.
– Treating mast cell activation syndrome with only natural products is a difficult ask. I started out hoping for the same, with many lifestyle changes including neural retraining, EMDR, and changes to diet and more. With an active CSF Leak, it proved to be impossible to sufficiently calm my mast cells and I hate uncontrolled inflammation. I have since had to add H1s/H2s, and ketotifen. But even many naturopathic and functional doctors discuss the need for pharmaceuticals over and above natural stabilizers and treatment.
– As of the science right now, MCAS does not have a cure. It can only be carefully managed. I do hope the science evolves to find a way to put the genie back in the bottle, so to speak, for mast cells behaving badly. But be wary of people (especially paid-courses!) that boast curing MCAS. For those without a full blown mast cell disorder, lifestyle changes like diet and supplements and more may resolve their issues. With MCAS and sister disorders, however, there is only management and temporary remission.
– Many patients with anxiety have found that treating mast cell activation goes a low way toward lowering their baseline anxiety levels. This is not everyone, but specialists have documented cases where patients who previously had panic attacks, prolonged insomnia, and even diagnoses of generalized anxiety disorder have watched those disappear with treatment for MCAS. In my case, I always had trouble sleeping and thought I had anxiety. Both of these problems went away now that. Ihave my mast cells under more control.
– With “long covid” / PASC in the mix during the pandemic, some mast cell specialists are seeing an explosion of MCAS in that cohort of patients. I do hope the seeming correlation between long covid and mast cell-mediated hyperinflammation leads to more research that would benefit us all.
STARTING AT THE BEGINNING: WHAT ARE MAST CELLS?
Mast cells are “sentinels” of the immune system, a type of white blood cell that helps control the immune processes in the body. They are called resident immune cells because they reside in tissues and not in our bloodstream. And they reside in tissues all over the body, from the connective tissue, to the endothelial cells, to the epithelial cells, and even in the brain.
Mast cells are immune system cells that live in the bone marrow and in body tissues, internal and external, such as the gastrointestinal tract, the lining of the airway, and the skin. Everyone has mast cells in their body, and they play many complex and critical roles in keeping us healthy. The positive roles that they play include protecting us from infection, and helping our body by participating in the inflammatory process. However, mast cells are also involved in allergic reactions, from the tiny swelling that appears after a mosquito bite to a life threatening, full-blown anaphylaxis.
-The Mastocytosis Society of the United States (TMS); Source.
They’re important – we need them! – but as with many conditions out there when they get out of balance, things go awry.
When our mast cells are hyperactive, they can lead to problems and symptoms. Since the mast cells reside all over the body, those symptoms are often systemic. And since each of us has a different immune system, the symptoms and manifestations of mast cell disease is not exactly the same patient to patient.
What is mast cell degranulation?
Mast cells are filled with tiny granules, as you can see in the screenshot of the video below. When they get “angry,” a destabilization process known as degranulation, they dump up to 200 different signalling chemicals – called mediators – into the bloodstream. Those mediators are inflammatory, and the degranulation process kicks up a cascade inflammation that can affect other workings in the body. Mast cells exist in organs and tissue throughout the body, and mediate allergic, immune, and inflammatory reactions.
We don’t want to eliminate the mast cell’s ability to degranulate. As the quote above illustrates, the degranulation response is part of the body’s natural defence when it senses invaders, and part of what helps keep us safe and healthy.
The problem is that in mast cell activation syndromes, that normal defence response goes off the rails. The mast cells get riled up* and mount a defence for innocuous things that would not otherwise be a threat. The immune system now thinks things that would not deserve an ATTACK! response for a ‘normal’ immune system now do.
Essentially, the normal mast cell process is altered and the mast cells are sensitized and degranulate with exposure to a variety of triggers, including excipients in medication, stress, and more. I go into the types of triggers below.
*Yes, I am anthropomorphizing mast cells. I find it helpful to think of them as friends I’m trying to negotiate with.
Below is a short video showing what happens when mast cells degranulate:
And here’s an image, for those who don’t have the bandwidth for video:
Mast cell degranulation can lead to feelings of increased anxiety
Mast cell degranulation can also increase anxiety, via the release of meditators like histamine at high levels into the bloodstream. A Psychology Today article even called for examining patients for mast cell dysfunction when they present with anxiety, depression, or brain fog, noting:
When patients consult their primary care doctor with many seemingly random dramatic complaints affecting unrelated organ symptoms, which often feature prominent psychiatric symptoms, they are often thought to be suffering from a psychosomatic condition and told “its all in your head.” They may be sent home with a prescription for an antidepressant or anti-anxiety medication, which not only is experienced as invalidating but does not address the root cause of their symptoms. Identifying MCAS as the source of symptoms has important treatment implications and can speed recovery.
Furthermore, a 2017 case study entitled “Mast cell activation disorder masquerading as a nervous breakdown,” notes that a patient who presented with severe psychiatric symptoms was actually found to have MCAS, and his neuro-psych symptoms dissipated once the mast cells were stabilized. That same paper states that “although rare, some patients can present with minor neurocognitive disturbances as well as frank psychotic behaviors.”
Anecdotally, several mast cell patients I’ve spoken with have said their anxiety levels plummeted once the mast cells were stabilized, including several who had a “feeling of doom” that accompanied extreme anxiety. For me, controlling mast cells help racing thoughts before bed; it turns out it wasn’t stress or anxiety after all.
BASICS OF MAST CELL DYSFUNCTION: BEYOND HISTAMINE INTOLERANCE
All mast cell diseases are caused by the proliferation and accumulation of sensitized/altered mast cells or the inappropriate release of mast cell mediators, creating symptoms in multiple organ systems. There are a few main forms of mast cell diseases: mast cell activation syndrome, mastocytosis, and the newer Hereditary Alpha Tryptasemia Syndrome (HATs). Mastocytosis is further broken down into different subtypes.
Mast cell diseases can cause tremendous suffering and disability due to symptomatology from daily mast cell mediator release, and/or symptoms arising from infiltration and accumulation of mast cells in major organ systems. Although systemic mastocytosis is a rare disease, those suffering with MCAS have recently been increasingly recognized and diagnosed. As a result, patients with MCAS appear to represent a growing proportion of the mast cell disease patient population. It is important to note that the process of mast cell activation can occur in anyone, even without a mast cell disease, as well as in patients with both mastocytosis and MCAS.
– The Mastocytosis Society of the United States
MCAS, Mastocytosis, and Histamine Intolerance
The focus on this page is mast cell activation disorder (MCAS), which is when the mast cells are hyperactive and degranulate easily, and too frequently). An April 2020 study estimates that “this disease that could affect up to 17% of the population on a spectrum from very mild to debilitating symptoms. MCAS is often either misdiagnosed or the diagnosis is greatly delayed due to a lack of provider awareness.” MCAS is often a lifelong issue, like my glimmers from childhood, that gets fast-tracked by trauma, viruses, and more.
As noted above, there is also also mastocytosis, where a patient has too many mast cells and they are often also prone to easy degranulation. Mastocytosis, of which there are several varieties, is often confirmed with a bone marrow biopsy that looks for a KIT-gene mutation. Mastocytosis also often has a sudden onset or precipitating event.
There are several different variants of mastocytosis, but most common are cutaneous mastocytosis, and systemic mastocytosis. Diagnosis for mastocytosis happens as follows:
- Cutaneous mastocytosis is diagnosed by the presence of typical skin lesions and a positive skin biopsy demonstrating characteristic clusters of mast cells.
- Systemic mastocytosis is diagnosed usually via bone marrow biopsy. The WHO has established criteria for diagnosing it, which includes a major criteria of a specific density of mast cells plus minor criteria that include a KIT D816V mutation, serum total tryptase, and more.
Then there is Histamine Intolerance, which my mast cell specialist believes it is essentially a milder case of MCAS. Other practitioners believe it may be rooted in microbiome or gut issues, or genetic issues that create a lack of DAO in the body, which is an enzyme that helps break down histamine. The DAO and HMT pathways are both implicated in histamine intolerance, and certain medications and foods can deplete DAO in the body as well.
Per expert Dr. Joneja, taking supplemental DAO and going on a low histamine diet can help these patients (see my recommendations in the “treating naturally” section below). If you believe that your issue is histamine intolerance and not MCAS, please see Dr. Joneja’s PDF primer about it here.
That said, mast cell diseases are transcend histamine alone; with 200 mediators released by the mast cells, histamine is but one of them. For those where DAO and low histamine diets are insufficient, you may want to think about in-depth mast cell testing.
This image below from a January 2020 study “Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery,” is also a helpful pictorial demonstration of the many conditions that can arise when the normal mast cell process gets dysfunctional.
From the study, with full citations here:
This figure schematically illustrates the wide spectrum of pathophysiological conditions in which mast cells and their mediators have been implicated. For several decades mast cells were considered to play mainly proinflammatory roles in several allergic disorders, such as bronchial asthma, allergic rhinitis, urticaria, food allergy, anaphylaxis, atopic dermatitis, and angioedema.
During the last years, it became evident that mast cells represent an important cell during bacterial, fungal, viral, and helminth infections. Elegant studies have demonstrated that mast cell-derived mediators can play protective roles against several venoms. Mast cells and their mediators can be involved in several aspects of tumor initiation and growth, presumably through the production of several angiogenic and lymphangiogenic factors. Systemic mastocytosis is a clonal disease associated with a somatic gain-of-function KIT mutation. Mast cells, strategically located in different sections of the human heart and atherosclerotic plaque, are involved in different phases of atherosclerosis and myocardial infarction. These cells can be involved in several autoimmune disorders, such as rheumatoid arthritis, coeliac disease, multiple sclerosis, and bullous dermatoses.
Mast cell–nerve communications are involved in stress, pain, pruritus, and in inflammatory bowel diseases.
Mast Cells and Nerves
There’s a lot of science discussing the association between mast cells and nerves in most tissues, including studies that suggest the mast cells are constantly providing information to the nervous system. Mast cells are also widely distributed in both connective tissue and mucosal surfaces, and interact with their environment locally in very different ways. They’ve got a load of different functions, too – they’re thought to play a major role in resistance to infection, and are involved in inflammation and the tissue repair that follows initial inflammation during an injury. They also are involved in hair follicles!
And that’s just the tip of the iceberg. They’re involved in so much of the body’s processes that patients go to different specialists with seemingly no commonalities within their symptom profile—only to later find out that the mast cells, located all over the body, are the culprit.
Mast cells are capable of the synthesis of a large number of pro- and anti-inflammatory mediators, including cytokines, growth factors and products of arachidonic acid metabolism. Pre-stored mediators, such as histamine, serine proteases, proteoglycans, sulphatases, and tumour necrosis factor (TNF), are released within minutes after degranulation of the cell.”
Full study/explanation of mediators in Significance of Conversation between Mast Cells and Nerves.
EXPLAINING MCAS TO FAMILY AND FRIENDS
One of the challenges in having a systemic, complex disease is how you communicate your needs and/or explain the condition to family and friends.
Most people are familiar with traditional allergies, which are described below and consistent of an allergen that is a constant trigger, often worsening each time you are exposed. Given the systemic aspect of mast cell disease, it’s less binary and less “I’m going to die if I come into contact with this thing” — though there are mast cell patients who also have IgE allergies. For example, I am allergic to bee venom and have an EpiPen for it. This is a non-changing allergy that is very severe in its anaphylaxis and I have to be vigilant.
The Bucket Analogy in Mast Cell Activation Syndrome
I also have mast cell activation syndrome, which leads to reactions all over my body–sometimes culminating in anaphylaxis–but depends on a variety of factors all funneling into my immune system. Many people use a bucket analogy.
Here’s how I use it to describe what’s going on:
Imagine a bucket where many things cause water to flow into it. Most people have a drain that works and is fully open in it. I have two problems: my drain is pretty clogged up, and I have a lot of water flowing into the bucket. When the bucket is super full, even a drop of extra water will cause the bucket to overflow.
Overflow can be gastro symptoms, itching, nausea, bone pain, and much more.
So my goal is to keep my water levels as low as possible. To do that, I go on a low histamine diet (helps less water flow into my bucket), I take mast cell stabilizers and antihistamines (which do the same), take DAO (an enzyme that breaks down histamine) with meals, which helps clear the drain a little bit.
But it takes constant calibration and also a calculus to try and make sure you keep the water low, and the drain as clear as possible.
Unlike IgE allergies, living with MCAS feels like using an abacus all day long. Can you eat this thing? Well, how stressed are you right now. How much pollen is in the air? How many mast cell stabilizers are you taking? It’s a lot of spinning plates to keep track of, but once you stop trying to make binary rules and let yourself explore the triggers you may have with curiosity instead of resentment, it becomes a lot easier to keep track of. Some things may always cause a reaction, but others may be only something you react to in tandem with how full your “bucket” is.
I highly, highly recommend getting a notebook to keep track of what you eat, supplements or medication you’re taking, what you’ve changed in your environment, and your symptoms to better allow you to narrow down on what your specific triggers are.
I built this “bucket” infographic to help summarize the idea and to list out what’s worked for me and many other patients:
SYMPTOMS AND TRIGGERS OF MAST CELL ACTIVATION SYNDROME
What are the Symptoms of Mast Cell Activation Disorder?
Because mast cells exist in so much of the body’s tissues and systems, when they degranulate a large range of symptoms throughout the body may occur.
- Flushing of the face, neck, and chest Itching, +/- rash
- Hives, skin rashes – see TMS’ “visual guide to skin lesions” for more, here.
- Atopic dermatitis and eczema (see here, and here.)
- Angioedema (swelling)
- Nasal itching and congestion
- Wheezing and shortness of breath
- Throat itching and swelling
- Brain fog and cognitive dysfunction, accompanied with anxiety or depression
- Diarrhea, nausea, vomiting, abdominal pain, bloating, gastroesophageal reflux disease (GERD)
- Bone/muscle pain, osteosclerosis, osteopenia, osteoporosis
- Light-headedness, syncope/fainting
- Rapid heart rate, chest pain
- Low blood pressure, high blood pressure at the start of a reaction
- of a reaction, blood pressure instability
- Uterine cramps or bleeding
- Tinnitus / ear ringing
- Dermatographism (can write on your skin leaving a red welt where you traced something with fingernail or blunt object – more here.)
- Edema (fluid accumulation in different parts of body)
- Decreased wound healing
- Interstitial cystitis
- Deterioration in dentin and teeth
- Often liver enzymes that are wonky (High bilirubin, elevated liver enzymes, and high cholesterol)
- Brain fog
- Coagulation issues and blood disorders (Clots, deep vein thrombosis, easy bruising, heavy periods, nosebleeds and/or cuts that won’t seal up easily)
The specific mast cell mediator that gets dumped into your bloodstream, plus possible effects:
Histamine: Flushing, itching, diarrhea, hypotension, panic attacks/anxiety
Leukotrienes: Shortness of breath
Prostaglandins: Flushing, bone pain, brain fog, cramping
Tryptase: Osteoporosis, skin lesions
Interleukins: Fatigue, weight loss, enlarged lymph nodes
Heparin: Osteoporosis, problems with clotting/ bleeding
Tumor Necrosis Factor-α: Fatigue, headaches, body aches
What are Some Triggers in Mast Cell Activation Syndrome?
Triggers for mast cell degranulation are all across the map, from food to activity to environmental exposure and trauma. It’s difficult to imagine just how such disparate and seemingly innocuous things (vibration?!) can degranulate mast cells, but here we are.
The list below is cobbled together from the The Mastocytosis Society, the Canadian Mastocytosis Society, and blogs:
- Intense exercise
- Heat, cold or sudden temperature changes
- Stress, trauma, loss, emotional pain, family problems
- Physical triggers, including pain, accidents, dental procedures, radiological dyes, surgeries, and other medical procedures. Both the Canadian and American Mastocytosis Societies recommend premedicating before any such procedures or dyes are administered. Radiation can also trigger mast cell issues. I had no problems with MRIs previously, but now have to premedicate even for non contrast MRIs. For medical procedures, radiological procedures, dental surgeries, and more see this 2021 PDF guide to bring to hospital with you that discusses mast cell disorders, plus stages of anaphylaxis and triggers.)
- Environmental (weather changes, pollution, pollen, pet dander, mold, gas leaks)
- Food or beverages higher in histamine. See diet lists below under TREATING MCAS for more details. A big problem for people trying to get well is that many of the “no” list for histamine is actually recommended heavily for autoimmune diets – eg. fermented foods/natural probiotics, spinach, etc which will make MCAS symptoms worse for many patients.
- Dairy (especially fermented dairy like kefir, blue cheeses, or aged dairy like Parmesan cheese)
- Fermented foods (especially sauerkraut, kombucha, miso, kimchi, fish sauce, and soy sauce – anything that gives food a wonderful umami taste, basically)
- Cured and smoked meats and fish
- Citrus fruits
- Overripe fruit and vegetables
- Leftovers (I can tolerate dinner food the next day at lunch but that’s it. Usually, I will just freeze it right away and defrost to eat, so it stops the aging/histamine degradation process.
- Berries, especially strawberries
- Chocolate other than pure dark chocolate
- Some food additives (see here for more)
- A surprising amount of medications. The ‘avoid’ list includes some of the below. A longer list is here, and here. The latter list also includes meditation that may work to calm mast cells.
- Dextromethorphan (cough suppressant)
- Dipyridamole (Persantine)
- Fungal infection drugs
- Local anesthetics: lidocaine,etc.(any amino amide-type)
- Neuromuscular blocking agents (all):eg. Dexamethonium, Gallamine triethiodide
- NSAIDs (Non-steroidal anti-inflammatories: Advil,Motrin,etc)
- Most opiates (Codeine, Morphine, Percocet/Oxycodone, etc.)
- Thiamine hydrochloride (A form of vitamin B1)
- Tolazoline hydrochloride
- Trimethaphan and Trimethaphan
- Contrast dyes used in MRIs, CTs etc
- Mechanical irritation (rubbing/chafing) or friction
- Natural odours (strong natural scents like essential oils, environmental smells)
- Strong odours (cleaning products, for example, or perfumes)
- Infections (viral, bacterial or fungal infections can make MCAS worse and should be addressed carefully with help of your doctor – see below for how that works, including the image I included)
- Venom (bees, wasps, spiders, snakes, etc.)
- Diesel fuel (smell)
Viruses Can Sometimes Lead to Mast Cell Problems
Mast cells are involved in the body’s normal efforts to clear a virus, but prolonged infection or interaction with other aspects of the immune system can cause sustained mast cell problems, including with COVID-19 (see below).
For example, what kicked everything off for me as an adult was getting dengue fever from a mosquito on my travels. There are quite a few studies looking at the role of mast cells in dengue infections, including one that notes:
Immune cells called mast cells can hinder rather than help the body’s response to dengue virus, which suggests that mast cell products could be used as biomarkers to identify severe forms of the disease.
As the caption to the (ADORABLE) image notes, mast cells can be a double-edged sword in viruses, because we want them to do their job and clear out a virus, but when they are dysfunctional, they overdo it. (And in non-MCAS patients, trying to tamp down on the response may, the study notes, prevent them from doing their job in clearing the virus altogether).
Studies relating to influenza also note that tamping down on mast cell activation can be beneficial. A study “Mast Cell-Induced Lung Injury in Mice Infected with H5N1 Influenza Virus” in mice notes,
A combination of ketotifen and the neuraminidase inhibitor oseltamivir protected 100% of the mice from death postinfection. In conclusion, our data suggest that mast cells play a crucial role in the early stages of H5N1 influenza virus infection and provide a new approach to combat highly pathogenic influenza virus infection.
So, all this to say: if you have a virus like COVID-19, dengue fever, influenza, and more, this too can be a trigger to activate mast cells. If you are genetically pre-disposed to mast cell problems, this may complicated your recovery. And treating mast cell activation can thus potentially mitigate severity of viruses, though we wouldn’t want to overshoot (at least in dengue).
DIAGNOSIS OF MAST CELL ACTIVATION SYNDROME
As I wrote above, diagnosis of mast cell activation syndrome (or a sister disorder like mastocytosis or HATs) is often delayed due to lack of awareness about the nature of the condition and/or some practitioners testing only a narrow selection of meditators or only testing igE allergies.
In addition, the lab tests required to diagnose MCAS must be handled with great care and kept chilled. Specimens for urine testing also need to be kept cold at all times. The result is that several rounds of testing may be needed to confirm the lab results–which can be quite frustrating.
A differential diagnosis analysis is usually applied by the practitioner to rule out other inflammatory immune conditions or mimics of a mast cell disorder. Symptoms are so bio-individual, too, that it’s a lot harder to pin down a diagnosis than (say) a condition where it’s a simple gene test. The labs below test for some mast cell meditators to ascertain their ranges, but the experts have noted there are hundreds mediators released by the mast cells in total, but only a few have lab tests to measure them.
For those in Canada, doctors often don’t run (or can’t order) many mediator tests as they are expensive and not covered by provincial healthcare. Some private mast cell practitioners will cover them, as will mast cell specialists in the United States.
What Labs Are Needed for Mast Cell Activation Syndrome Testing?
Standard testing for MCAS includes both urine and serum (blood) tests. It can sometimes involve biopsies of the GI tract or colon. As stated earlier, samples can degrade really quickly at room temperature, and must be handled properly or else they will become corrupt. The mast cell doctor I saw said that laboratory or patient handling mistakes accounts for a lot of the false negative testing he sees, and he only works with specific labs that he knows he can trust to properly chill the samples.
Here were the tests the specialist order for me in order to assess whether or not I had mast cell activation syndrome:
Specific Blood Tests for MCAS
- Histamine, blood
- Histamine, plasma (chilled)
- PGD2, plasma (chilled)
- Comprehensive Metabolic Panel
- Plasma prostaglandin D2 assay
- PT + PTT
- Heparin assay
- Plasma heparin level Anti-Xa (anti-Xa for unfractionated heparin, chilled)
- Tryptase, Serum
- Chronic Urticaria Index
- Anti-IgE antibodies
Specific Urine tests for MCAS
- Chilled Histamine, 24hr Urine
- Histamine, Random Urine (then chilled)
- Random urinary prostaglandin D2 (then chilled)
- Chilled 24-hour urinary prostaglandin D2
- Random urinary 2,3-dinor-11-beta-prostaglandin-F2-alpha (then chilled)
- Chilled 24-hour urinary 2,3-dinor-11-beta-prostaglandin-F2-alpha
- Random urinary N-methylhistamine (then chilled)
- Chilled 24-hour urinary N-methylhistamine
- Random urinary leukotriene E4 (then chilled)
- Chilled 24-hour urinary leukotriene E4
- Autoinflammatory Syndromes Genotypings Panel (from Invitae)
Notes about mast cell testing: read before testing!
- You should not be asked to go off your antihistamines for testing. In Canada, some doctors do require this. In the United States, the main mast cell specialists absolutely do not. The consensus from mast cell experts is that antihistamines will not affect the results of serum and urine tests, since they only block the body’s receptors.
- Some doctors do require you to get off mast cell stabilizers for testing. I went off quercetin, PEA, Vitamin E, and the other stabilizers listed above one week prior to testing, as well as anything that affected inflammation.
- If you take NSAIDs like Advil, you are generally asked to stop 5 days prior to your testing.
- If you take PPIs (proton pump inhibitors) you are generally asked to stop 5 days prior to your testing.
- A note about tryptase: most mast cell patients with MCAS (not mastocytosis) test normally for tryptase, even during flares. This is why providers should be testing for multiple mediators. However! If your tryptase is elevated, you might want to also do a gene test for HATs, hereditary alpha tryptasemia syndrome, which is newer in the mast cell disorders world. It is an easier condition to rule in or out, because it requires a saliva gene panel that can be ordered online by Gene By Gene.
- Tryptase is elevated in both mastocytosis (but not all cases of it) and in HATs. Since MCAS is a fairly new disease, some allergists or immunologists will test tryptase and, if it’s negative, say it’s not MCAS. That does not appear to be reflective of the data mast cell experts, even those who include tryptase in the requirements for diagnosis. Tryptase testing alone is not sufficient to rule out MCAS.
- Among the mast cell experts, there are currently two ‘consensuses’ of diagnosis, with both of them accepted by the World Health Organization. One group consists of Drs. Afrin, Molderings, and more, here. The second group consists of Drs. Valent, Akin, and more, here. The second group that focuses more on tryptase, whereas Dr. Afrin’s group does not**. Both groups believe they are correct.
- A note about IgG vs. IgE reactions: There’s often confusion about testing for food allergies or allergies using IgG and IgE testing. They are related to the functioning of mast cells, but not an accurate test for mast cell activation. So: yes, IgE allergens can lead to mast cell degranulation. But no, IgE testing (traditionally done by an allergist) is not used for diagnosis of MCAS. You can have no IgE allergies and still have MCAS. Conversely, many mast cell patients have issues with skin-writing, called dermatographism. I can easily write my name out on my skin and it’ll glow puffy and red for a long time. Skin IgE testing may just show reactions to the scratches and not necessarily the allergen; it’s not accurate for MCAS.
- Mast cells have receptors for both IgE or IgG on them, and both types of antibodies can result in higher histamine levels or higher levels of other meditators, as well as triggering degranulation itself.
- IgG reactions the calmer of the two, though they are still capable of producing anaphylaxis-like symptoms. These antibodies are common not only for pathogens we are affected by, but also food issues when we have issues with GI permeability (leaky gut and more).
- IgE reactions, in contrast, are usually sharp and immediate — like when we are stung by something we are allergic to. It’s a fast-paced degranulation response by the sentinels of the immune system to try and protect from something significant. While not part of MCAS testing per se, they can be useful. It’s important to use IgG antigen testing if you are testing IgG, and then phase out those foods for several months to see if that makes a big difference, then try to reintroduce with nutritionist support.
**Drs. Afrin and Dempsey responded to comments about why tryptase should not be a reliable / gold standard marker for diagnosis mast cell activation syndrome, as follows, but the disagreement between experts continues:
- In our combined clinical experience now across many thousands of MCAS patients, we (Dr. Dempsey and Dr. Afrin) have not seen a rise in tryptase to be a reliable marker of mast cell activation. Again, a persistently elevated tryptase may be a reliable marker of an increased number of mast cells in a person, and a clear, brief spike in the tryptase level over some lower, stable baseline level of tryptase probably represents a brief flare of mast cell activation, but such a spike it is not a reliable marker of mast cell activation. In fact, it appears that mast cells can become activated via so many different routes, releasing so many different mediators under different circumstances, that it is difficult to imagine how a spike (by any amount) in just one mast cell mediator could be a truly reliable marker of mast cell activation detectable in most activation events in most people. We have even seen many patients whose tryptase levels have gone *down* during events of flagrant mast cell activation, such as anaphylaxis. And we have seen that in patients whose symptoms are suggestive of mast cell activation, it almost always is the case that elevated levels of mast-cell-specific mediators other than tryptase can be found in the blood and/or urine.
BRIEF SUMMARY OF HOW I GOT MY MAST CELLS UNDER CONTROL
The level of pain I was with the CSF leak and the (unknown to me at the time) mast cell dysfunction was debilitating. It got to a point where I simply sobbed in bed all day long. When my research led me to suspect a mast cell disorder, I implemented the following steps. They sharply reduced my pain levels while I waited for specialist testing.
** This is just what has worked for me so far and is not medical advice. **
FIRST, I identified triggers and removed them from my environment, like strongly-scented home cleaning products, non-natural cosmetic products or shampoos or face washes (see below for what brands I use), and more.
SECOND, I went on a strict low histamine diet for two weeks, removing things like alcohol, cold cuts and smoked/cured meats, canned fish, anything pickled or fermented, aged cheese, overripe produce, gluten (already done because I’m celiac), citrus fruit, spinach, yeast, soy, and tomatoes. I also stopped eating leftovers more than one day old, freezing anything I cooked after making it for future consumption. See the diet list below for the full list of items to remove. I then slowly added in some of the medium histamine foods.
THIRD, I added natural mast cell stabilizers like quercetin and PEA. See the protocol below for what I used.
FOURTH, additional lifestyle changes: a) cutting down on inflammatory foods and starting DAO, the enzyme listed below, 15 mins prior to eating higher-histamine meals, and b) reducing stress by implementing a meditation practice. Lowering stress can reduce levels of corticotropin hormone (CRH), a potent mast cell degranulator.
FIFTH, started experimenting with H1 antihistamines to see what helps. If an H1 didn’t work or make a big difference after two weeks, I stopped it and tried a different one. The standard dosing regimen for MCAS every 12 hours to create a “histamine blockade”, which is more often than H1s are usually taken for non-MCAS patients.
SIXTH, started experimenting with H2 antihistamines after I landed on “my” H1. As with H1s, these are meant to be dosed every 12 hours. I haven’t gotten to one that works for me yet, but still trying.
SEVENTH, to ensure some of my mast cell issues weren’t being fuelled by parasites or viruses, I did a stool test and specialist blood tests. I realize not everyone has access to this testing.
For each of these, it was important to go low and slow when onboarding new supplements or medication. Know that it’s very hard to know what is a material/substance you react to sometimes. I now have a long chart where I write in the stuff that works for me and its fillers, because the experts have made clear that excipients/fillers in medication are often what mast cell patients react to and not necessarily the medication itself. (Here’s more on excipients in fillers: Recognition and Management of Medication Excipient Reactivity in Patients With Mast Cell Activation Syndrome, a 2019 review article.)
It wasn’t fun or easy, but with no access to knowledgeable medical care, it really helped me stay afloat until I could get to a mast cell specialist.
TREATING MAST CELL ACTIVATION NATURALLY
Reducing Histamine via Elimination of Triggers
Reduction of triggers includes whatever triggers you from the long list I shared earlier. This means removing not only environmental triggers like shampoos and soaps, but also eating a lower histamine diet to potentially lower circulating levels of histamine in the body. While some doctors do not recommend a low histamine diet, I know that without sharply limiting the food I intake, I cannot stay on top of my reactions and symptoms.
(My lab testing also showed a very high level of circulating histamine–one of the highest my practitioner had seen; always an overachiever here, eh?)
Note that for many vibration is a trigger, so car rides, electric toothbrushes, and more can degranulate mast cells. For many essential oils are also too strong a scent and will cause symptoms.
Low Histamine Diet and Other Diets That may Help in MCAS
Few mast cell patients I’ve spoken with eat a normal diet. As a former food/travel writer, this part is hard. I joke that I’m the worst food writer ever, but the truth is after wrapping my head around celiac disease 20 years ago, cutting things out strictly and systematically is not new to me. I just didn’t ever think I’d have to cut out so much!
Being on a low histamine diet can help reduce the overall burden on your body because it reduces the amount of histamine floating around. For non-MCAS patients, it can also sometimes help itching or asthma.
In addition to low histamine, there is low oxalate (especially for patients with pelvic inflammation or interstitial cystitis), and low FODMAP.
Some diet plans from around the web:
- Low Histamine: Swiss SIGHI lists. Elimination diet recommendations here. Food lists for histamine: a long PDF of graded histamine levels in foods/additives, etc here.
- Low Histamine: Alison Vickery. Here is her DIET PDF. She uses a functional approach that combines naturopathic and allopathic medicine, and cites her sources fully. Of all the low histamine diet lists, this one has most matched how my body reacts to different foods.
- Beyond low histamine: some people with Ehlers Danlos variations or auto-immune issues such as Crohns or colitis also have trouble digesting foods beyond the low histamine varieties. See this page about those additional restrictions, including a low histamine diet suggestion list for people who need to mindful of other categories.
- These categories include lectins, oxalates, salicylates, sulfur, and FODMAPs, which – depending on the body — can affect MCAS as well. Note that if oxalates are an issue, higher-doses of Vitamin C will be a problem. It is important to keep track of data related to food and supplements to ensure you can pin down triggers.
- Lectins are proteins found in some plants, and preliminary research suggests that they may activate mast cells also. For a low-lectin diet list, see here.
- Oxalates are found in Vitamin C, which is an issue as high-dose vitamin C is helpful for mast cell stabilization, and for collagen synthesis. I have had to lower oxalate intake, which I did not realize was causing worse symptoms for me. There are many oxalate food lists out there, but you can start here.
- Speaking of FODMAPS: a low FODMAP diet can also reduce circulating histamine.
- From study: “Controversies and Recent Developments of the Low-FODMAP Diet” – “Mechanistically, dietary FODMAPs have very limited effects on the consistency of bowel actions but seem to suppress the release of histamine”
- And from study FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial.“Histamine, a measure of immune activation, was reduced eightfold in the low FODMAP group (p<0.05)”
- NOTE: would need low histamine AND low FODMAP for this to work, as a few of the low FODMAP foods are high in histamine.
- Some helpful apps for mobile use: Baliza is a German company that has developed several apps that are useful for the low histamine diet, and both are updated as new data and studies come out.
- Food Intolerances: The app is very thorough and allows you to sort by different food intolerances or allergies. Includes measurements for histamine, fructose, sorbitol, gluten, lactose, and FODMAPs.
Apple here; Play store here.
- OxiPur: Measures foods by oxalate and soluble oxalate, searchable, sortable by food category, and includes some measurements related to oxalate content, like calcium in each food. Apple only, here.
- Histamine Info: App that uses the Sighi list above, and is updated frequently. Apple only, here.
- Food Intolerances: The app is very thorough and allows you to sort by different food intolerances or allergies. Includes measurements for histamine, fructose, sorbitol, gluten, lactose, and FODMAPs.
Supplements For Mast Cell Activation Syndrome
(Studies supporting why I take each of these products are below.)
- Seeking Health DAO: DAO is an enzyme naturally produced in the body that helps break down histamine from food intake. Some people have genetic mutations that lower their DAO production, some people eating diets rich in products that lower DAO, and some people just need the extra DAO to help them mitigate the effects of high levels of circulating histamine. There are two products on the market that are trustworthy for DAO (in my opinion), and I use the Seeking Health version as the other one (Umbrellux) changed their formulation and it now does not work as well for me. This DAO is derived from porcine sources, and should be taken within 10-15 minutes of a meal high in histamine.
- Vitamin C Nutribiotic Ascorbic Acid Powder (non-gmo, pharmaceutical grade) –
- Vitamin C Nutribiotic Sodium Ascorbate (non-gmo, pharmaceutical grade). There is some evidence that sodium ascorbate also helps the extracellular matrix, so I include that in my supplements / total Vitamin C count.
- Camu Camu, organic and freeze dried. My preferred vehicle for vitamin C. Note that if you have an oxalate issue, you will need to limit your vitamin C intake. This is unfortunate, since Vitamin C can help reduce histamine and also stabilize in other ways, but mast cell issues are truly an onion of catch-22s.
- Non-GMO MicroIngredients Quercetin from Sephora Japonica buds If you prefer capsules, Jarrow Formulas Quercetin, Cardiovascular Support, 500 mg. Quercetin should be taken with fat to help it absorb. A more bioavailable version of Quercetin is the Thorne Quercetin Phytosome. The phytosome formulation, in this case bound with sunflower lecithin, helps the quercetin absorb better.
- Zeolite: Functional medicine doctors believe that zeolite can help clear histamine from the body because it acts as a binder for the histamine itself. Zeolite is also used as a binder for metals for some.
- NasalChrom: Useful for seasonal-type allergies, food reactions that include nose running/itching in face. Sodium cromlyn is a mast cell stabilizer.
- Zatidor eye drops: These are ketotifen fumarate, potent mast cell stabilizer – if you can’t access pills or compounded ketotifen, eye drops may help with oral symptoms considerably.
- PEA: Palmitoylethanolamide, pure and from a reputable source. Two companies I trust are PeaCure and Vitalitus. PeaCure has been out of stock for some time, but Vitalitus is currently in stock and ships to Canada as well. When choosing a brand, it is important to make sure the supplement has been micronized to small diameters; this is the form the studies used that showed it was effective. PeaCure is the smallest diameter (they are ultra-micronized), and Vitalitus is micronized to less than 5 micrometers, and are a good second option.
- Magnesium L– Threonate is the type of magnesium I use. Doublewood’s brand has caused no reactions, and is available in USA and Canada.
- The best Curcumin for mast cell patients that I’ve found is Thorne Soy Free Meriva. It has sunflower lecithin to help with bioavailabilty, and is soy-free. It is also made just from curcumin, so it does not have the higher-oxalate turmeric in it. The many other supplements in this category contain black pepper extract to help with bioavailability, but this is a mast cell degranulator. Meriva is a great option for those who want to try this.
- LutiMax luteolin plus Rutin powder (NOTE- not Lutein! Must be luteolin. Another option for luteolin, rutin, and quercetin is Neuroprotek – this is Dr. Theoharides supplement from his Algonot company, and profits fund further studies)
- Mirica® – Pea (Palmitoylethanolamide) and Luteolin – Natural Pain Relief – Made with OptiPEA® from The Netherlands, if you wanted to combine the two (Luteolin and PEA). I don’t do so, but it’s an option. The PEA is micronized, not ultra-micronized.
- Amazing Herbs Premium Black Seed Oil, Organic and Cold Pressed.
- Culturelle without Inulin (LGG strain) is has been shown to help stabilize mast cells.
- If too sensitive for Culturelle – Custom Probiotics D-lactate free probiotic with histamine-reducing strains.
- For a cheaper low-histamine d-lactate free option with similar strains, see Lifted Natural’s new Mood Probiotic, which contains LGG as well as a few Bifo strains.
- Vital Nutrients Vitamin E 400 (with Mixed Tocopherols) (NOT soy free) OR, Healthy Origins Tocomin SupraBio (Tocotrienols) 50 mg – if like me you don’t just want one of the tocopherol but rather tocotrienols too. (Soy free. 1 in AM and 1 in PM)
** Note that the links above for Amazon are affiliate links, as with the others on Legal Nomads (see the footer for more), where I get a small commission on some purchases.
MY CURRENT PROTOCOL
- 5mg H1 twice a day, 10am and 10pm (levocetirizine). In Canada, this is not over the counter so I have had to get it compounded. It’s the best H1 for me, but each person is different. Also, many patients react to excipients in medication and thus require compounding regardless. The most popular compounding is with Avicel, a hypoallergenic filler, or with rice flour or baking soda. Check with a compounding pharmacy near you to learn about options.
- MicroIngredients pure powdered Quercetin – 1 scoop 500mg, 1x a day
- 0.5mg ketotifen with lunch
- Quercetin phytosome – 2 capsules with dinner
- PEA (PeaCure or Vitalitus brand), 1x AM, 1x with lunch
- Vitamin C 250mg 1x per day (camu-camu is what I use most)
- Luteolin/Rutin powder – 1 scoop (150mg of each in 1 scoop) before bed, as needed
- DAO, 1x with lunch and 1x with dinner
- Magnesium L-Threonate – 2 capsules in late afternoon
- 1 Vitamin E with lunch and 1 with dinner
- 1 Vitamin D (1000mg) in AM
Studies and Science Behind Natural Mast Cell Stabilizers
- Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. (Study – Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin). The same study also notes that luteolin protects against histamine release from mast cells
- Palmitoylethanolamide (works on the endocannabanoid system)
- “The ability of PEA to control MC degranulation, via a CB1 ⁄ CB2 independent mechanism, has paved the way for its therapeutic use in both animals and humans. The PEA-mediated stabilisation of MCs has proven to be useful in the treatment of atopic and irritative dermatitis. In conclusion, we can hypothesise that cannabinomimetic compounds, including PEA and its congeners, act to control MC activation and degranulation early during the inflammatory response, thus leading to a swift resolution and preventing the development of chronic inflammatory disease.” (Study)
- Palmitoylethanolamide is a potent mast cell stabilizer and pain reliever (Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator – study)
- For those with other issues a potent neuroinflammation reducer too, acting synergistically within the endocannabenoid system. Overview /meta analysis, and neuroinflammation study: N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution.
- And luteolin PLUS Palmitoylethanolamide = even more stabilization. Study: PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia. (This is the Mirica product above).
- Binders, including zeolite, mentioned as a help for mopping up histamine here, and a specific post about how zeolite binds histamines here. See also Study – Histamine-binding capacities of different natural zeolites: a comparative study.
- Rosae multiflora fructus extract stops mast cell release of histamine (rat study – Rosae Multiflorae Fructus Hot Water Extract Inhibits a Murine Allergic Asthma Via the Suppression of Th2 Cytokine Production and Histamine Release from Mast Cells – Study
- Blocks histamine release due to chemotherapy drug. Study – Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1.
- Quercetin also generally works for a wide range of allergies. Quercetin and Its Anti-Allergic Immune Response – study.
- Quercetin works better than sodium cromlyn for stabilizing mast cells in certain conditions. Study: Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans.
- Quercetin phytosome increases availability and allows for more meditator stabilization and cytokine blocking. Study: “Significant improvements in both in vitro solubility and oral absorption (in terms of both exposure and maximum concentration achieved) by healthy volunteers in a human clinical study were obtained with the Quercetin Phytosome formulation as compared to unformulated quercetin.”
- Cannabinoid receptor agonists suppress mast cell release of histamine Study – Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model. Also in the study “Cannabinomimetic Control of Mast Cell Mediator Release: New Perspective in Chronic Inflammation,”
- Curcumin also acts as an antihistamine, and has been found to decrease mediator release by mast cells, when activated:
- Anti-inflammatory effect of curcumin on mast cell-mediated allergic responses in ovalbumin-induced allergic rhinitis mouse (study)
- Lipopolysaccharide (LPS) exposure differently affects allergic asthma exacerbations and its amelioration by intranasal curcumin in mice. (study)
- Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy. (study)
- Inhibitory eff ects of curcumin on passive cutaneous anaphylactoid response and compound 48/80-induced mast cell activation (study)
- Vitamin C: Helps stabilize mast cells
- Alison Vickery’s post about how Vitamin C can help increase DAO in the body, which then mops up histamine from food.
- Article: The relationship between Vitamin C, Mast Cells and Inflammation:
In the light of these studies, we found that vitamin C relieves most of the symptoms of diseases that involve activation of MCs and we can conclude that further research on the role of vitamin C and MCs is needed.”
- Article: Vitamin C Revisited: “In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury.”
- Nigella sativa (black cumin seed) blocks mast cell degranulation in rats (A study – “Effects of Nigella sativa seeds and certain species of fungi extracts on number and activation of dural mast cells in rats.”)
- Probiotics that may help:
- Vitamin E has been found to decrease mast cell degranulation in some studies. (study)
What Cosmetics, Laundry and Cleaning Products, and Toiletries are Safe with MCAS?
Because I’ve lived in both the USA and Canada with this condition, I’m listing out both products from Canada and the United States. This is what I’ve switched to, and this section came about from readers writing in for me to share what’s worked for me.
- I use Seventh Generation free and clear all purpose cleaner for cleaning products
- I use Oneka lavender and angelica shampoo and conditioners in Canada (they’re so great! I do fine with lavender but they also have fully unscented options), and Andalou Naturals lavender shampoo and conditioner in the USA.
- I use ECOS lavender laundry detergent in the USA, and EcoMax baby laundry detergent in Canada
- I use unscented Seventh Generation free and clear laundry drying sheets in both countries
- For sunscreen, I use Badger Baby SPF 30 Sensitive sunscreen in Canada, and Badger Baby SPF40 sunscreen in USA.
- For face and eye moisturizing: I switched to using Cliganic Organic Jojoba Oil for the face and eyes during the day, and Jojoba for the face plus a few drops of Cliganic Organic Rosehip Oil around my eyes at night. (These brands are available both in Canada and the US)
- For face wash, I use REN Clean Skincare Rosa Centifolia Cleansing Gel (the Amazon review is rubbish because someone got mad their face pump didn’t work, but you can check out the REN site for more. I’ve used this for years and love it. It does have xanthan gum in it, though very little, which might irritate some of you.
- For makeup, I’ve found Tarte Cosmetics to be the safest for my skin and eyes. I didn’t realize how much my makeup was impacting how I feel until I connected that it was my mascara making my eyes burn and run a lot more than usual. The tinted face cream I used to use also started to give me rashes as I continued on this mast cell journey. I use their Tarte Lights, Camera, Lashes mascara, their Face Tape Foundation, their Amazonian clay blush in Paaarty (I don’t make the names here), and their natural eyeshadow palette. I find their products last a long time, though they are costly. If you wanted to try them out, their website has a lot of mini sizes for you to sample at a lower cost.
- For pain, I can’t tolerate Voltaren gel so I use Soothamide from Vitalitus using pharmaceutical grade palmitoylethanolamide.
- Toothpaste is Hello Coconut and Mint toothpaste (the toothpaste has dyes, colours, flavours or SLS/Sulfates or parabens, but it does have fluoride. Some mast cell patients will avoid fluoride as it too can increase histamine levels (source), but as my teeth health has worsened due to MCAS, I do use a fluoride toothpaste.)
- Dishwashing soap is Live Clean Dish Soap in Canada, and ECOS hypoallergenic lavender dish soap in the USA.
- Hand soap is EcoMax hypoallergenic soap in Canada, and ECOS hypoallergenic lavender hand soap in the USA.
SUMMARY OF THIS NATURAL MCAS TREATMENT SECTION:
TREATING MAST CELLS PHARMACEUTICALLY
Generally: an H1/H2 “blockade”, taken every 12 hours. Plus mast cell stabilizers and occasionally pain medication.
- H1 blockers (Suggested to leave Benadryl for emergencies) – eg. Zyrtec, Xyzal, Claritin, Allegra, hydroxyzine, doxepin, loratadine, fexofenadine.
- H2 blockers Pepcid, Zantac, Tagamet, famotidine
- Leukotriene inhibitors: Montelukast/Singulair
- Prescription mast cell stabilizers (NOTE: per mast cell expert Doctor Theoharides, these are not full mast cell stabilizers as they do not block cytokine release, but have some mast cell stabilizing properties and mast cell doctors prescribe them as stabilizers often.)
- Cromolyn sodium
- Ketotifen (oral, compounded and by prescription in the United States. Teva makes a ketotifen oral tablet called Zatiden in Canada and other countries. Ketotifen oral tablets are also over the counter in many countries such as Mexico, Myanmar, India, and more. Zatidor eye drops are ketotifen as well, but fumarate form).
See the study Pharmacological treatment options for mast cell activation disease, as well as the suggestions in the Hoffman article from the overview section, here.
Further, the Mastocytosis Society has a list of pharmaceutical treatments that are common in mast cell disorders here.
MAST CELLS AND PAIN
Pain and mast cell activation, generally (includes tables with treatment options)
Throughout the entire pain communication network, mast cells are the gatekeepers of pain. Mast cells can communicate with neurons, glia cells, microglia, and vascular endothelial cells through mediators. They influence brain functions directly through histamine. Pain alone can thus increase mast cell degranulation. Mast cells and the nervous system influence each other’s responses through mediators and cytokines. In the periphery mediators can stimulate receptors, resulting in pain. This stimulates mast cell activation creating a feedback loop, resulting in neurogenic inflammation. Mast cells can recruit other immune cells, which release more mediators, boosting inflammation.
Extreme mast cell activation causes inappropriate mediator release and reactivity, causing an enormous range of reactions in all tissues and systems. Classical analgesics, most narcotics and nonsteroidal anti-inflammatory drugs (NSAIDS), can trigger MCAD and thus can be ineffective. (See chart 1 “TABLE 4” below)
Pain perception in mast cell dysfunction should be treated by addressing the mast cell mediator-related causes. But pain is also one of the biggest mast cell triggers – so lowering pain levels is important.
Mast cell stabilizers, avoiding inflammatory foods, meditation: these have all helped me, and may help others before stronger drug therapy if that’s what you prefer, especially since neuropathic pain is so hard to treat. (Personally, I went from 24/7 burning pain all over my body to none, unless I consume/am around something that angers mast cells.)
Neuropathic pain poorly (if at all) responsive to classical drug management in the case of mast cell activation, as shown in the table below. Moreover, some of those drugs may worsen the severity of symptoms by further increasing mast cell activity.
Mast cells and Pain in Fibromyalgia: a 2019 Study
A 2019 study concludes that mast cells are key players of neuroendocrine and painful disorders, including fibromyalgia, and that inhibiting mast cells would be a useful tool in treating fibromyalgia.
Natural molecules could include the flavonoids, luteolin and tetramethoxyluteolin, alone or in combination with other substances selected to reduce stress Other natural molecules could include palmitoylethanolamide, which apparently inhibits neuro-inflammation and reduces pain.” Source: “Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome“
Mast cells and Pain in IBS (Irritable Bowel Syndrome)
A 2021 study in Nature entitled “Local immune response to food antigens drives meal-induced abdominal pain” concludes that researchers have identified the biological mechanism that they think may explain why some people experience abdominal pain when they eat certain foods. The studies, from KU Leuven, were carried out in mice and in humans and point to local mast cell activation. This local immune response includes the release of histamine and other mediators (as set forth in this resource page) which lead to pain and discomfort. The researches feel that the findings could pave the way to the development of more efficient treatments for IBS and other food intolerances, and are currently pursuing a larger clinical trial of antihistamine treatments.
An open access piece that accompanies the study, called “Food for thought about the immune drivers of gut pain”, notes that while debilitating gut pain is common, the underlying cause is often unclear. This new mast cell study points to a localized immune response that cause normally innocuous foods to be perceived as harmful, leading to persistent pain.
The article notes that:
People with IBS had more mast cells in close proximity to nerve fibres compared with healthy individuals, suggesting more-effective transfer of information between the mast cells and nerve endings of the sensory neurons.
And suggests that as a result of the data provided by this study, treatments for IBS may in the future include:
- improving the gut permeability to reduce gut access to the intestinal immune system (what healing ‘leaky gut’ focuses on);
- targeting IgE antibodies that are specific to the food substance of interest;
- reducing mast-cell degranulation (the topic of this page!);
- targeting the specific molecules released by mast cells; and
- blocking the colonic sensory nerves that transmit information and cause pain.
HOW DO MAST CELLS INCREASE INFLAMMATION?
This section explains why low inflammation and low histamine diets can be useful.
- Dr Theoharides believes CRH stimulates the mast cells in the hypothalamus (and elsewhere) to produce something called vascular endothelial growth factor (VEGF), which then increases the permeability of the blood-brain barrier (BBB). That leaky BBB then allows more immune cell (e.g. mast cell) and perhaps pathogen infiltration into the brain and bingo, you have inflammation. Source: Could the Brain’s Mast Cells Be Causing Chronic Fatigue Syndrome (ME/CFS)?.
- Mast cells are both sensors and effectors communicating between the nervous, vascular, and immune systems. In the brain, they live in the “brain side” of the blood-brain-barrier, and there they interact with astrocytes, microglia, and blood vessels via their mediators and chemicals. They are first responders in the body, catalyzing reactions, amplifying responses in the body, and also recruiting OTHER immune responses once they’re activated. When dysregulated, this contributes to neuroinflammation. See also the next study.
“Mast cells both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotion. Mast cells may play a key role in treating systemic inflammation or blockade of signaling pathways from the periphery to the brain.”
Source: Mast Cells and Neuroinflammation“.
- Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Source: Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer’s Disease Pathogenesis.
- An enhanced interaction between mast cells and nerves can lead to neurogenic inflammation. Inflammatory models have shown a significant increase in the number of mast cells, resulting in the increased release of inflammatory mediators on degranulation.
“Inflammatory mast cell mediators may modulate sensory nerves through the activation of receptors on nerve terminals. […] Thus, mast cell activation can result in an increase in the excitability of sensory nerves and the production and secretion of neuropeptides.”
Source: Significance of Conversation between Mast Cells and Nerves“
- Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including Alzheimer’s disease. Mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of Alzheimer’s disease. “We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of Alzheimer’s disease.” Source: Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer’s Disease Pathogenesis
- Mast cell disorders: From infancy to maturity: “Mast cells are also establishing a new‐found importance in severe asthma, and in remodeling of blood vessels in cancer and atherosclerotic vascular disease. Furthermore, recent evidence suggests that mast cells sense changes in oxygen tension, particularly in neonates, and that subsequent degranulation may contribute to common lung, eye, and brain diseases of prematurity classically associated with hypoxic insults.” This article is a review of mast cell disorders and chronic inflammatory conditions that involve mast cell dysfunction.
MAST CELLS AND CELIAC DISEASE
- Mast cells associated with onset of celiac [study]. “We provide a description of the progressive stages of Celiac Disease, in which mast cells are the hallmark of the inflammatory process. Thus the view of Celiac Disease, should be revised, and the contribution of mast cells in the onset and progression of Celiac Disease, should be reconsidered in developing new therapeutic approaches.”
- Intestinal mast cell involvement with celiac disease [study].
- A review of studies that investigate the role of mast cells in the pathogenesis of coeliac disease, showing that these cells increase in number during the progression of the disease and contribute to define a pro-inflammatory microenvironment. [study] “In conclusion, it can be assumed that mast cells represent one of the main players of the intestinal damage in the onset of Celiac Disease. Hence, the pathogenesis of Celiac Disease should be revised and the contribution of mast cells in the onset and progression of the disease should be considered in the planning of new therapeutic approaches.”
- Mast cells also involved in dermatitis herpetiformis, a chronic, itchy, blistering skin condition that is a skin manifestation of celiac disease. Patients with dermatitis herpetiformis usually lack the gastrointestinal symptoms of traditional celiac disease, but it is nonetheless linked. Mast cells gone rogue will active inflammation excessively, causing tissue damage. Studies have found that this pattern directly contributes to conditions like dermatitis herpetiformis.
MAST CELLS AND EHLERS DANLOS SYNDROME (EDS)
Part of what led me to write this page was the staggering prevalence of mast cell issues within the leaker community. That community is primarily made up of “long haul” leakers like me, people with connective tissue dysfunction or some other genetic and/or pathogenetic reason that the body isn’t able to seal and heal the dura robustly, even with intervention.
It turns out that continuous mast cell degranulation can affect the connective tissue adversely, and for patients with connective tissue disorders that’s a double whammy. When mast cell degranulation happens it not only releases histamine but also proteases, which are enzymes that lead to the breakdown of proteins into smaller polypeptides or single amino acids. Since mast cells live all over the body in tissues, this can affect the integrity of that tissue over time.
EDS is a genetic connective tissue disorder caused by defects in collagen or other proteins that are part of the extracellular matrix (ECM). The ECM is a network that holds tissues together, so when mast cell degranulation comes in and breaks down that network, it can lead to permeability of, say, the gut lining — but also per studies lead to additional tissue laxity and/or hypermobility symptoms.
So mast cell disease can go beyond “just” the symptoms day to day but also the effects on the whole body’s connective tissue, especially if you have a pre-existing genetic disorder.
- Several investigators have noted a possible link between EDS and MCAD, primarily patients with the hypermobility type of EDS.” – this study examines whether the fact that mast cells live in connective tissue, combined with the “wonky” connective tissue of EDSers means that mast cell activation is more common because of the changes in structure of connective tissue in primarily hEDS patients. Full study here, by Doctor Maitland and Doctor Afrin.
- After being recruited to connective tissues, mast cells go through more change when they are influenced by surrounding cells. And many mast cells live in our connective tissues. This study looks into how dysregulation of the mast cells occurs in connective tissue disorders.
MAST CELLS AND MULTIPLE SCLEROSIS (MS)
- In a review article called Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?, the author discusses how many inflammatory diseases are fuelled by both internal and external stimuli, and begin as inflammation and then progress to a disease state following tissue damage and more. Many different cell types are involved depending on the disease, but mast cells are usually one of them (in both the acute inflammation and in the disease state). “Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a “nerve-mast cell-myofibroblast axis”, article notes, playing a big role in the inflammatory process that leads to disease.
Elevated levels of mast cell products have been detected in fluids from MS patients. These include mast cell tryptase in CSF from MS patients and histamine levels in CSF from MS patients. In spite of such evidence, the role of mast cells in MS is still somewhat controversial.
The article concludes based on what it discusses that targeting mast cells in both MS and endometriosis “may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions.”
- Another study from April 2019 called Mast Cells in Neurodegenerative Disease notes that neuroinflammation is well-established now as a primary pathological component of diseases such as multiple sclerosis, and is gaining acceptance as an underlying component of most, if not all, neurodegenerative diseases. Before, studies focused on the glial cells of the central nervous system, but now researches are looking at mast cells as well, since mast cells affect both their microenvironment and neighbouring cells including T cells, astrocytes, microglia, and neurons. And they can also disrupt and change the permeability of the blood brain barrier, which “has the potential for dramatically altering the neuroinflammatory state,” per the study.
- Role of Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis, from 2017, discusses how mast cells may act at the early stages of ME or EAE to promote demyelination. The study concludes that depleting or limiting mast cells could be a new promising therapeutic target for MS and EAE.
- Another study from 2020 reviews the relationship between mast cells and angiogenesis in multiple sclerosis.
- From 2016, a study called Important role of mast cells in multiple sclerosis Autoimmunity is a disease that occurs when the body tissue is attacked by its own immune system. Multiple sclerosis (MS) is an autoimmune illness which triggers neurological progressive and persistent functions. MS is associated with an abnormal B-cell response and upregulation of T-cell reactivity against a multitude of antigens. Mast cells are the first line of the innate immune system and act by degranulating and secreting chemical mediators and cytokines. Their participation on the central nervous system has been recognized since the beginning of the last century. They have an important role in autoimmune disease, including MS where they mediate inflammation and demyelinization by presenting myelin antigens to T cells or disrupting the blood-brain barrier and permitting entry of inflammatory cells and cytokines. The participation of mast cells in MS is demonstrated by gene overexpression of chemical mediators and inflammatory cytokines. Here we report the relationship and involvement between mast cells and multiple sclerosis.
MAST CELLS, LONG COVID, AND COVID-19
I’m including this section because we are seeing a lot of write ups about long-COVID / PAS-C, and the impacts on the body. Some mast cell doctors believe that a chunk of long-COVID symptoms is due to dysfunctional mast cells. In a September 2020 study from doctors Afrin, Weinstock, and Molderings, the conclusion notes:
The prevalence of MCAS is similar to that of severe cases within the Covid-19-infected population. Much of Covid-19’s hyperinflammation is concordant with manners of inflammation which MC activation can drive. Drugs with activity against MCs or their mediators have preliminarily been observed to be helpful in Covid-19 patients. None of the authors’ treated MCAS patients with Covid-19 suffered severe infection, let alone mortality.
In addition, please see:
- Potential association of mast cells with coronavirus disease 2019, and
- Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome (discussing how both severe outcomes and PAS-C / long haulers may have unruly mast cells as the root of their hyperinflammation.
with a longstanding history of signs and symptoms, worrisome for a mast cell activation syndrome (MCAS), but never had laboratory confirmation of this non-clonal mast cell activation disorder, until she contracted COVID-19. This case illustrates the need to recognize the rate of mast cell activation in SARS-CoV-2 infection, not only to optimize anti-SARS-CoV-2 therapy, including the development of vaccine, but to potentially curb the risk of SARS CoV-2 triggered hyperinflammatory syndrome.
I will update this section with more info as it comes up.
OTHER CONDITIONS THAT STUDIES ARE LINKING TO MAST CELL DYSFUNCTION
I’ve shared studies linking mast cells to IBS and fibromyalgia pain, as well as to a few specific conditions. In addition, mast cells have been implicated in a variety of other conditions. This does not mean having those conditions means you have a mast cell issue so much as it working on suppressing mast cells may effectively provide relief of some symptoms involved in the disease. I’ve linked to some studies or review articles for some of those conditions below.
When you think about the fact that mast cells are found throughout the body and brain, it makes sense that they would have a critical impact on a variety of conditions that relate to the nervous system, immune system, or tissues. Among them:
- Vulvodynia – see here (also covers interstitial cystitis) and here.*
- Interstitial cystitis – see here and here.*
- Postural Orthostatic Tachycardia Syndrome – see here.
- Osteoarthritis – see here.
- Chronic hives / itching – see here.
- Restless Leg Syndrome – see here.
- Peripheral neuropathy – see here and here. (For bad flares, I often get painful tingling and burning in my hands and feet)
- Allergic diseases like asthma and atopic dermatitis (and others)- see here.
- Endometriosis – see the study from the MS section, above, and here.
- Arthritis – see here.
- Migraines – see here, with full study here.
- Trigeminal neuralgia – see here.
- Asthma specifically – see here.
*Per pelvic pain and vulvodynia foundations, patients with interstitial cystitis and/or vulvodynia may benefit from a low-oxalate diet. (See here) That diet is set out in the ‘treating mast cells naturally’ section above.
MAST CELLS, SLEEP, AND JET LAG
Does this page sound very familar to you, and you also have a terrible time with sleep? You’re not alone. Mast cell research has shown that the cells are controlled by their own “internal clock”, regulated by clock genes just like other organs in the body. This circadian clock regulates many things in the body, and since mast cells themselves have a circadian expression, it’s important to look at them when it comes to sleep as well.
Mast cells are controlled by their clock genes, but also by the factors I’ve set out in this article — things like diet, triggers, and also hormones. In addition, histamine also plays a role in the regulation of sleep phases. So mast cells are very involved in sleep and wakeful times.
My sleep was terrible for most of my life, until I got my mast cells under control. I would have racing thoughts before bed, keeping me awake well into the night. As my mast cell issues got worse during the onset of the CSF leak, attempts to fall asleep were futile until 4-5am in the morning. Prior to that, I would feel wide awake or if I started to doze off, I would gasp awake again physically jerking my body away from sleep. Of course, this was not done intentionally and I thought it was simply anxiety.
But it turns out the anxiety that I thought I had? It was vastly physiological. When I put the protocol I share above into place, I was able to sleep again. I was no longer dealing with the myoclonic jerks before sleep. I was no longer dealing with racing thoughts before bed. I was no longer waking up at 4am if I did manage to fall asleep.
It turns out it was mast cell issues all along. This makes sense, because histamine not only affects sleep/wake cycles but peaks around 3am. It also promotes wakefulness, so if it’s extra high in someone with a mast cell disorder where it’s insufficiently synthesized in the body or in levels of excess, it makes sense that insomnia (and a racing heartbeat, changes in temperature, blood pressure, and flushing) would follow.
For more see my long article about jet lag, mast cells, and immune cells, which includes a thorough jet lag protocol to minimize the circadian rhythm disruption both for day-t0-day life, and when traveling.
COVID-19 and Chronotherapy
Increasingly, scientists are looking to the circadian rhythm of the body to help manage the diseases of the present, and the treatments of the future.
“When we saw the controversy surrounding the use of ibuprofen, we wanted to fully understand why this drug was beneficial to some people, but having negative effects on others,” said Harry Karmouty-Quintana of University of Texas Health. In a report published in the British Journal of Pharmacology called The case for chronotherapy in Covid‐19‐induced acute respiratory distress syndrome, Harry’s team suggests providing anti-inflammatory medicine at specific times of the day, which would impact the body’s response to the medication without interfering with its fight against COVID-19.
“We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS, and thus, chronotherapy may be used to effectively manage ARDS in COVID‐19 patients,” notes the study – which dovetails well with the sections on mast cells, below. We know mast cells have their own circadian rhythm, and that they release cytokines when they degranulate (release inflammatory substances into the blood). It follows, per Harry’s team, that administering medication based on the schedule of that inflammatory flood could optimize the body’s attempts to heal.
Per the conclusion:
“This would mean that afternoon is the preferred time window for drug administration whereas intake at night should be avoided. This is particularly important when administering immune modulators where a single dose is usually given. Furthermore, the goal of chronotherapy in COVID‐19 is to avoid reaching steady‐state drug levels; as in the case of anti‐inflammatory therapy, these would dampen the inflammatory response directed towards the virus.”
Based on what doctors know about the circadian clock of immune cells, they think that time timing of anti-inflammatory agents are important. This is because the immune cells release cell signals associated with negative effects to the body during the mid-to-late afternoon, but release antiviral molecules during the night and into the early morning. A “therapeutic window” for medication would give the medication an opportunity tamp down on inflammation that harms, while also allowing immune cells to produce the inflammatory molecules needed to fight the virus at night.
LESS CONVENTIONAL TREATMENTS FOR CALMING MAST CELLS
- Breathing: pranayama breathing (PDF) or Butyeko breathing method (introduction here):
- Treatment of mast cells with carbon dioxide suppresses degranulation via a novel mechanism involving repression of increased intracellular calcium levels. [Study breathing increases Co2]
- Evidence-Based Role of Hypercapnia and Exhalation Phase in Vagus Nerve Stimulation: Insights into Hypercapnic Yoga Breathing Exercises [Study article – “Research has shown that vagal stimulation helps you not only in controlling the health of your organs and tissues, but it also determines the growth of your stem cells which, in turn, help body in repairing and replacing damaged cells”]
- Meditation: see my 10-week free course with guided tracks for beginners, if you’re just getting started.
- Dynamic Neural Retraining System. Some mast cell practitioners recommend DNRS as a means of reducing overall stress and reactivity to triggers, not to ‘cure’ MCAS (as it has no cure) but to help lower the overall level of burden on the body. This is a practice related to neuroplasticity, but is not without controversy.
- EMDR / trauma therapy or somatic experiencing therapy
- Intermittent fasting. Not recommended to try multi-day water fasts, as histamine levels start rising again with too much fasting. However, restricting eating to an 8-hour or 6-hour window does seem to benefit.
FURTHER READING: BOOKS, ARTICLES & VIDEO
- This thorough symptom list, Clinical Manifestations of Mast Cell Activation Syndrome By Organ Systems, by Dr. Lawrence Afrin and Dr. Tania Dempsey.
- Jill Carnahan’s overview of mast cell activation, When Histamine Goes Haywire.
- Hoffman Center: MCAS, When The Immune System Runs Rampant. Their MCAS questionnaire here.
- This PDF from the Mastocytosis Society, that differentiates between mastocytosis, cutaneous masto issues, and mast cell activation syndrome. (Link is to PDF in my Dropbox where you can download to your computer)
- This video “Living With Mast Cell Activation Syndrome” from Dr. Maitland, presented at the Ehlers Danlos Global Learning Conference in 2018:
The two most helpful books I’ve read about mast cells are:
- Mast Cells United: A Holistic Approach to Mast Cell Activation Syndrome, by Amber Walker The title notes that it’s a holistic approach, and I suppose this simply shows how non-holistic other approaches are because the treatment she uses includes antihistamines, ketotifen, cromlyn and other medication that are not simply holistic/flavonoids. But from worldwide travels to essentially being completely bed bound and incapacitated indefinitely, she has put together a remarkably thorough book. She’s in the medical field, though not a doctor, so the perspective as patient is also invaluable.
- Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity, by Lawrence Afrin MD The bible of mast cell activation syndrome by one of the foremost experts in the field.
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