Grain Free Nut Free Chocolate Chip Coconut Cookies

Grain Free Nut Free Chocolate Chip Coconut Cookies

Ingredients

  • 1 cup Ottos cassava flour
  • 1 cup organic Tigernut flour
  • 1 cup organic gf/df chocolate chips
  • 1/2 cup organic coconut shreds
  • 1 1/2 cups coconut sugar (for sugar free you can sub with 100 percent monk fruit with no fillers)
  • 2 pastured eggs
  • 1/3 – 1/2 cup ghee, melted
  • 1 Tbsp pure vanilla (alcohol free)
  • Pinch sea salt

Procedure

  1. Preheat oven to 325F
  2. Gather a large mixing bowl and combine all the dry ingredients.
  3. Add the wet ingredients and using your hands, knead dough until all ingredients have been combined. (you want a dry batter to prevent cookies from spreading while cooking)
  4. Line a baking tray with parchment paper and form dough into small balls. Spread out evenly on your baking tray and press down with a wet fork.
  5. Bake for 10 min or until golden. Let cool before transferring to a glass storage container. These cookies can be frozen for up to 2 months.

Nutrition Tip

Ottos cassava flour is a godsend if you are someone following a low histamine, MCAS friendly diet. Ottos cassava flour is the only cassava flour that I have found that is NOT fermented. Crazy huh? Who would have thought that a root vegetable flour would need to be fermented! Cassava is an excellent source of carbohydrates, fibre, vitamin C, thiamine, riboflavin, and niacin. This delicious root vegetable also contains 25 percent protein! No wonder this satiating food is a staple in so many parts of the world.

If you are looking for a sweet treat while following a therapeutic diet, look no further than these nutrient dense, flavourful cookies!

Mast Cell Activation Syndrome and Excipients

Mast Cell Activation Syndrome and Excipients

Mast cell activation syndrome (MCAS) is a complex disease that I’ve previously written about at length. It’s a multi-faceted condition that can often be frustrating and difficult to manage for both the patient and the provider.

Mast cells are immune cells that function to help your body get rid of what they deem to be harmful compounds. In the presence of a harmful substance, the mast cells release mediators such as histamine, leukotrienes and prostaglandins which help your body to expel the invader.

However, in certain individuals, mast cells can be oversensitive and release large amounts of mediators in response to certain triggers. These include heat, cold, sunlight, certain medications, and certain foods, among other things. These reactions can cause a cascade of symptoms of varying severity, up to and including anaphylactic shock.

Treatment for MCAS involves identification and strict avoidance of your triggers, along with medication therapy and lifestyle changes. Medications that may help with the management of MCAS include H1 and H2 histamine blockers.

However, sometimes these changes alone aren’t enough to help you completely manage your MCAS. You may also struggle to identify what triggers your MCAS reactions.

MCAS is considered ‘idiopathic’ when triggers can’t be identified. If you’re struggling with idiopathic MCAS, this article will be of interest to you.

Common drugs known to trigger MCAS

  • Vancomycin is an antibiotic often used in C. Difficile treatment, which is known to cause ‘Red Man Syndrome’.
  • Morphine and other opiates, with fentanyl and Dilaudid being the opiates that are the most easily tolerated.
  • Aspirin and non-steroidal anti-inflammatories (NSIADS), like Motrin and Advil, are only sometimes a problem as in certain people they can actually act as mast cell inhibitors.
  • Angiotensin converting enzyme inhibitors, known as ACE inhibitors, are drugs used to treat hypertension and can increase bradykinin levels, which in turn activates mast cells.
  • Beta-blockers are used to treat hypertension, anxiety and tachycardia and lower the threshold for mast cell activation, interfering with the efficacy of epinephrine if this is needed for anaphylaxis. A glucagon pen can be used as an alternative if beta-blockers are necessary to treat other conditions.
  • Some local anesthetics, such as benzocaine, procaine, tetracaine, and chloroprocaine, can trigger mast cell activation, although lidocaine is usually well tolerated.
  • Some muscle relaxants like atracurium and succinylcholine can act as triggers, but vecuronium and pancuronium are usually well tolerated.

One relatively recent development in the treatment and management of MCAS involves considering drug and supplement excipients or inactive ingredients, rather than the actual drug itself. Drug formulations vary significantly between brands and there’s mounting evidence to suggest that many people with MCAS may have reactions to certain excipients found in their medications and/or supplements. The same drug or supplement made by different manufactures with different dyes, excipients, or fillers may provoke very different reactions in patients with MCAS. The active drug itself may not be the issue, but the excipients, dyes, and fillers may be the culprit.

In this article, you’ll learn:

  • What excipients are
  • How they can trigger mast cell responses
  • Some of the most common harmful excipients
  • How to tell if you’re having a reaction to an excipient
  • How to identify and avoid excipients that may worsen your MCAS

What are excipients?

Excipients are inactive ingredients found in over-the-counter and prescription medications, as well as in vaccines. These ingredients play a number of different roles in the proper delivery of the active ingredient to the body and many of these roles are absolutely necessary to facilitate the efficacy of the drug. (1)

In fact, most drugs are made mostly of excipients and the active ingredients represent only a small percentage of the drug by weight.

According to Dr. Jill Schofield of the Center for Multisystem Disease, excipients “are supposed to be ‘inert’ and ‘safe,’ but they may cause problematic reactivity in MCAS patients, including anaphylaxis.” (2)

Unfortunately, many excipients pose a risk of reactivity in people with MCAS, so it’s important to fully consider the impact of not only the active ingredients of a drug, but also its inactive ingredients when starting a new medication.

Types of excipients

There are over a thousand known drug excipients and the list grows almost daily, as researchers continue to develop new drugs and drug delivery systems.

Here are some of the main categories of excipients and their role in medications, according to Dr. Schofield:

  • Lubricants: These prevent pills from sticking together in storage, examples being silica and magnesium stearate
  • Binders and fillers: These provide volume to pills and bind ingredients together. Binders and fillers include cellulose and polyethylene glycol.
  • Coatings: These protect pills from damage, make them easier to swallow, and may provide ‘time-release’ or ‘extended-release’ function, examples being shellac and gelatin.
  • Dyes: As you’d expect, these alter the color of medications. Dyes used include FD&C red #5 and FD&C blue #2.
  • Flavourings: These alter the taste of the drug to mask bad-tasting ingredients and improve acceptance of the medication, especially in the case of children. Flavouring examples include sucralose and xylitol.
  • Preservatives:Substances such ascitric acid and retinol palmitate improve the shelf life of medications.

This is just a small sampling of some commonly used excipients. Not only are there hundreds more individual excipients, there are also many more categories of excipients that play different roles in medications.

How can excipients affect MCAS?

Dr. Schofield describes people with MCAS as “canaries in the coal mine.” If you’re unfamiliar with this turn of phrase, it refers to the canaries that were carried by miners deep into mines when they worked. If there were toxic levels of gases present in the mine, the canary would die well before the miners, serving as warning that they needed to get out of the mine.

People with MCAS, like the canaries in the coal mine, are profoundly more sensitive to the chemicals they’re exposed to than other people. Unfortunately, this means that many people with MCAS experience reactivity to one or more drug excipients. These reactions can manifest in the following ways:

  • Fatigue
  • Malaise
  • Gastrointestinal upset, such as abdominal pain, nausea, vomiting, or diarrhea
  • Skin rashes
  • Itchy skin
  • Hives
  • Headache
  • Anxiety
  • Flushing
  • Anaphylaxis
  • Headaches
  • Insomnia

However, this isn’t a complete list of symptoms of excipient reactivity. MCAS is such a complex and individualized disease and symptoms can differ vastly from person to person.

If you’ve been diagnosed with MCAS and have removed your known triggers but are still experiencing symptoms, it may be time to investigate drug and supplement excipients and how they may be affecting you.

What are some of the common harmful excipients?

Some of the most common excipients that people with MCAS are reactive to include alcohol, dyes, and povidone. In fact, according to Dr. Schofield, dyes and alcohol are a great starting point for determining excipient reactivity in MCAS patients, primarily because so many people are reactive to them.

Povidone

Povidone is an extremely common excipient, used as an ingredient in hundreds of drugs. (3) It’s a polymer that’s added to drugs to help disperse the active ingredient evenly throughout a liquid or powder solution. It’s also used as a binder and to help drugs in pill form disintegrate properly. It’s water-soluble, so it’s commonly used in liquid drug solutions as well as in tablets or capsules.

It’s an ingredient in betadine, an antiseptic iodine solution that’s used to prep the skin before medical procedures. According to Lawrence B. Afrin, M.D., if you’ve previously been diagnosed with a betadine allergy, it’s highly likely that you’re actually sensitive to povidone. (4) You see, iodine is absolutely vital for proper body functioning so it’s illogical, and emerging research suggests it’s impossible, to be allergic to iodine (5). Because the only ingredients in iodine solutions like betadine are often water, iodine, and povidone, and it’s highly unlikely that you are allergic to water or iodine, this leaves povidone as the likely culprit.

Dyes

Dyes are ubiquitous in medications, a very common MCAS trigger, and unfortunately serve no purpose beyond an aesthetic one.

Although you may find that you’re only sensitive to one or two dyes, it’s often best to avoid all FD&C dyes when possible. Ferric oxide red and yellow may be better tolerated by people with MCAS, according to Dr. Schofield.

You should note that even white tablets may contain dyes, so you’ll need to check the ingredient list for confirmation.Many drugs have dye-free formulations or, in the case of drugs in capsule form, you can discard the capsule. This is often the only portion of the drug containing the dye and you can then simply take the powder inside.

Alcohol

According to Dr. Schofield, alcohols are an extremely common trigger. They’re commonly added to liquid medications, IV medications, or topical medications, which are applied directly to the skin.

Alcohol has some antiseptic qualities, which is why it’s used to disinfect the skin prior to medical procedures, along with being used as the active ingredient in most hand sanitizers. It’s also used as a solvent, to help suspend the active ingredient evenly throughout a drug, and as a preservative, to extend the shelf life of a drug.

Luckily, tablet or capsule forms of alcohol-containing liquid or IV medications are often alcohol-free. This makes them a potential alternative that wouldn’t cause reactivity.

Although these are some of the most common excipients that MCAS sufferers may react to, theoretically you could have a reaction to any of the hundreds of excipients that are used in medications today. This is why an understanding of how to identify an excipient reaction is of the utmost importance for people with MCAS that suspect they have excipient triggers.

Adhesives

Many adhesives are based in glycerin, which is corn-derived. If people react to corn, they may have problems with standard adhesives. Standard tegaderm adhesive wound dressings may be replaced with Opsite 3000 and the IV 3000 line of adhesive products.

Another product is DuoDerm Extra Thin CGF Dressing. If adhesives can’t be used and a patient needs an IV line, this can be wrapped with guaze, on top of which tape is then fastened. All IV bags should be DEHO free to reduce the risks of mast cells reactions

How to tell if you’re reacting to an excipient

There are several ways to tell if you’re reacting to an excipient in a drug, according to Dr. Schofield.


First and foremost, you should suspect excipient reactivity if you have an unexpected reaction to a drug that you previously tolerated well. In this case, some questions you can ask are:

  • Did you get this from a different pharmacy than usual?
  • Is this drug from a different manufacturer than the one that was well tolerated?
  • Was there a risk for environmental contamination when this drug was compounded?

Next, you should suspect an excipient reaction if you have different reactions to two different medications that are in the same class of drug. For example, loratadine and fexofenadine are two over-the-counter antihistamines that function in similar ways to help manage allergies. If you react differently to these drugs, it may be because one contains an excipient that you’re reacting to.

Additionally, if you experience side effects that aren’t typical for a drug, these side effects may actually be a result of reactivity to one of the excipients in that particular formulation of the drug.

You should also consider an excipient reaction if you react to a drug or supplement within the first few doses of taking a new pill. 

Finally, if you’ve been diagnosed with multiple drug allergies or intolerances, you should strongly suspect excipient reactivity. Particularly if you’ve been diagnosed with an iodine or betadine allergy, this is a strong indicator that you may actually be sensitive to povidone. This is an excipient that’s commonly added to iodine solutions along with a variety of other medications, including those as seemingly harmless as over-the-counter pain medications.

Identifying and avoiding harmful excipients

Identification of excipients to which you’re sensitive will require collaboration between you, your physician, and your pharmacist.

According to Dr. Schofield, once you’re able to identify an excipient that you react to, it should be added to your allergy list. However, you shouldn’t add the medication in which it was found to that list, as it’s likely you’re only sensitive to the specific excipient and not the medication itself.

Luckily, due to the availability of different brands and formulations of drugs, it’s often easier than you expect to find a formulation of your needed medication that doesn’t contain any of your excipient triggers.

However, you’ll need to thoroughly review the ingredient list of all medications you’re prescribed, or purchased over-the-counter, to see if they include any excipients that you’re sensitive to. Dr. Schofield recommends using DailyMed, a service of the U.S. National Library of Medicine that provides detailed information about medication ingredients, including excipients.

You may need to get creative in your avoidance of your excipient triggers. For example, if the tablet form of a medication contains an excipient you’re sensitive to, check to see if there’s a capsule, liquid, or IV form that would be okay for you.

As I already mentioned, if you’re sensitive to dyes, you can often just discard the capsule that contains the dye and still use the powder inside the capsule. You can sprinkle it on top of yogurt or mix it into a drink.

If you find that you’re profoundly sensitive to a certain excipient, you may need to have your medications especially compounded in a ‘clean room’ that poses minimal risk for cross-contamination with your triggers. Your local compounding pharmacist should be intimately involved with the challenges of MCAS and the potential risks of excipient reactivity. Sourcing of the pure powder ingredient in a medication may be necessary. Compounding pharmacies should be accredited with their parent organization, the Pharmacy Compounding Accreditation Board (PCAB).Established in 2007 by eight of the nation’s leading pharmacy organizations, PCAB offers the most comprehensive compliance solution in the industry. This includes the combining, mixing, or altering of drug ingredients to create a medication pursuant to a prescription order for an individually identified patient.

In Canada, most of the compounding pharmacies will use microcrystalline cellulose, known as Avicel, as a filler. This compound is derived from wood pulp and contains strings of glucose molecules strung together. It’s commonly used a texturizer, an anti-caking agent, a fat substitute, an emulsifier, an extender, and a bulking agent in food production.The most common form is used in vitamin supplements or tablets or as an alternative binder in compounding medications. Some people may also not tolerate gelatin capsules and are given vegicaps as a substitute. These are composed of hypromellose, short for hydroxypropyl mMethylcellulose (HPMC), a substance that’s prepared from cellulose, which is the main polysaccharide and constituent of wood and all plant structures.

Additionally, excipients aren’t only found in medications. If you’re sensitive to an excipient, you’ll also need to check foods, supplements, cleaning products, cosmetics, and body care products to see if they contain any of your excipient triggers.

Please reach out to me or my team if you need help managing your MCAS or identifying potential triggers or excipient reactivity. My team is extremely experienced with the management of MCAS, and we can help you formulate a plan to identify your potential triggers and remove them so that you can have some relief.

References:

  1. Abrantes CG, Duarte D, Reis CP. An Overview of Pharmaceutical Excipients: Safe or Not Safe? J Pharm Sci. 2016;105(7):2019‐2026. doi:10.1016/j.xphs.2016.03.019 Abstract: https://pubmed.ncbi.nlm.nih.gov/27262205/
  2. Schofield J. The Problem of Excipient Reactivity in MCAS Patients. Lecture from The Center for Multisystem Disease, n.d.
  3. National Center for Biotechnology Information. PubChem Database. Povidone, CID=131751496, https://pubchem.ncbi.nlm.nih.gov/compound/povidone (accessed on May 31, 2020)
  4. Afrin LB. Re: [MASTerMinds] Precautions for Oral Surgeons doing Wisdom tooth extractions in CCI patients? #cci #mcas #dental. Email communication from MASTerMinds listserv. 2020 May 8.
  5. Dewachter P, Mouton-Faivre C. Allergie aux médicaments et aliments iodés : la séquence allergénique n’est pas l’iode [Allergy to iodinated drugs and to foods rich in iodine: Iodine is not the allergenic determinant]. Presse Med. 2015;44(11):1136‐1145. doi:10.1016/j.lpm.2014.12.008

Diagnosis of Mast Cell Activation Syndrome – A Global Consensus 2

Diagnosis of Mast Cell Activation Syndrome - A Global Consensus

Please take a look at this newly published peer-reviewed article by Dr. Lawrence Afrin of which I was a co-author, on the revised criteria for the diagnosis of mast cell activation syndrome (MCAS):

Diagnosis of mast cell activation syndrome: a global “consensus-2”

One of the most common difficulties patients seem to face after they have been to our clinic and given a diagnosis of mast cell activation syndrome is when they return to their GP’s or specialists with a description of this syndrome. Traditional medicine is well-schooled in the diagnosis of systemic mastocytosis, a condition characterized by an increased number of mast cells as opposed to MCAS which is a diagnosis arrived at due to the increased activity of mast cells (and not an increase in the actual numbers).

Systemic mastocytosis is most often diagnosed by using a biomarker called tryptase, whereas the diagnosis of MCAS has much broader diagnostic criteria as this article will outline.

For a much more in-depth description of MCAS, please see my treatment page and the following articles:

  1. Treating Mast Cell Activation Syndrome (MCAS)
  2. Mast Cell Activation Syndrome: When You Immune System Runs Rampant
  3. Natural Treatments For Mast Cell Activation Syndrome
  4. Your Ultimate Guide to the Low-Histamine Diet

Podcast: Mast Cell Activation Syndrome With Dr Bruce Hoffman

I was recently interviewed for The Dr. Hedberg Show, where we spoke about mast cell activation syndrome and how exactly the condition is diagnosed. In this podcast, we reviewed the similarities that exist among certain conditions (fatigue, brain fog, and GERD to name a few) and how they may be indicative of mast cell activation syndrome.

 

Dr. Hedberg: Well, welcome everyone to “Functional Medicine Research.” I’m Dr. Hedberg. And I’m really looking forward to today’s conversation with Dr. Bruce Hoffman. He’s a board-certified physician, and he has a Fellowship in Anti-Aging Medicine, as well as a Master’s Degree in Clinical Nutrition. He’s a certified functional medicine practitioner. And, one of the really interesting things about him is that, in addition to his clinical training, he studied with many of the leading mind-body and spiritual healers of our time. People like Deepak Chopra, Paul Lowe, Osho, Ramesh Balsekar, and one of my favorites, Jon Kabat-Zinn.

So, Dr. Hoffman, you shared the stage with Dr. Deepak Chopra and Dr. John Demartini. And he continues to spread his inspiring vision of healing and wellness with audiences and patients around the world. So, Dr. Hoffman, welcome to the show.

Dr. Hoffman: Thanks very much, Nikolas. I’m glad to be here. Thank you.

Dr. Hedberg: Great. So I’m really looking forward to this discussion on mast cell activation syndrome. It’s something I haven’t seen a lot of in my practice. I have heard a number of lectures on this and read quite a bit about it. And it seems to be an area of your expertise. So why don’t we jump right in and just talk about what mast cell activation is, and how is this condition diagnosed?

Dr. Hoffman: Sure. I first got interested in mast cell activation syndrome when I started to work with a cancer patient advocate by the name of Dr. Mark Renneker out of San Francisco. And he alerted me to the connection between cancer and mast cell activation syndrome, particularly in gynecological cancers. And then put me in touch with Dr. Lawrence Afrin, who leads one of the major sort of advocacy groups for mast cell activation syndrome as opposed to systemic mastocytosis, which I’ll explain in a bit.

And so, I’ve been for the last three to four years working with Dr. Lawrence Afrin’s group and learning to understand the implications of mast cell activation syndrome in most of the patients that we see. Which are chronic multisystem, multisymptom patients who, as you know, have been everywhere and remain frustrated with the one disease, one drug paradigm that we learned at medical school. So, what I learned over time was how to separate between two specific conditions, one called systemic mastocytosis and the other called mast cell activation syndrome.

Mast CellBut before I begin with that, I’d like to say that mast cells are part of, they’re produced in our bone marrow, and they’re part of our immune system. And they make up a very small percentage of it. And they act as defense structures against incoming invading pathogens. So, anything that comes into our environment or into our biome, mast cells are often at the first line of defense. And they were actually discovered a long time ago, 1878, I believe, by Paul Ehrlich. And he called them mast cells because they were fat and puffy.

And the word mast in Greek means breast or the German means masticate. So, this is how the name mast cell got generated. Just for your North American readers, I say mast, and most people don’t know what I’m saying. So, it is mast in North America. People often don’t know mast cells, what I’m saying.

So, these were originally discovered by Paul Ehrlich when he developed specific staining for them. And since then, they sort of lingered on in the literature. They were linked early on to cancer, but that sort of faded out of the picture until it was resuscitated by some Italian researchers who now are doing massive amounts of work on mast cell activation syndrome and cancers. And then it really sort of resurfaced in the 1990s and didn’t really gather steam until about 2007, when two, you know, researchers and clinicians put together sort of a consensus statement on what constitutes MCAS.

There are two different schools of thought and they do tend to conflict with each other in terms of the diagnostic criteria. But basically, mast cells being part of the immune system, and regulating many of the incoming so-called antigens or toxins tend to be distributed in almost all tissues, but nowhere quite as much as on mucosal surfaces: so eyes, mouth, skin, GI tract, bladder, etc. They’re also found in other tissues, you know, lungs and heart tissues, and brain, many mast cells are activated in the brain.

And so, when they get triggered, they do tend to release many, many mediators of inflammation. And it was estimated that there were over 200 mediators of inflammation that get released by these mast cells. But Dr. Afrin in a very recent post, as of last night, said that he’s now changing his opinion that he believes there are over 1,000 mediators released by mast cells. All these inflammatory mediators like histamine, like proteases, prostaglandins, leukotrienes, all these inflammatory mediators that then set up this multisystem, inflammatory response, which can confuse diagnosticians particularly if you have been trained in single organ, you know, specialties.

So that leads to the sort of difficulty with the diagnosis as people present with many different symptoms. And unless you have an understanding of mast cell activation syndrome, and a method of sort of sifting through the multiple systems they can present, you can often get very confused and misled. So, the recent, you know, people speaking about mast cell activation syndrome is an attempt to bring some coherence to this somewhat disorganized field. And hence, establishing criteria for the diagnosis, lab tests, and then treatment protocols. So now it’s coming into its own and I think you’re going to hear a lot about it in the years to come.

Dr. Hedberg: Mm-hmm, so we’re talking about illnesses that may be so-called mystery illnesses, and multifactorial presentations like gut issues, skin, brain, and things like that. Can you just let everyone know some of the overlap that you see in various conditions in your practice that would specifically indicate mast cell activation syndrome?

Dr. Hoffman: Yeah. So, mast cells, when they release the inflammatory mediators, can present locally or systemically. So, a local condition would be something like hives, urticaria, or interstitial cystitis. Or it can be systemically like people can present with cognitive symptoms. So, they’ll have fatigue and brain fog, and associated GI symptoms, like GERD. GERD is a potentially very big diagnostic category for mast cell activation syndrome or, you know, the irritable bowel syndrome. Even the autoimmune diseases of Crohn’s disease and ulcerative colitis have been linked to mast cell activation syndrome.

Asthma is another one. Asthma, you know, if you analyze all the triggers of an asthma response, and you identify them, like, for instance, mold, allergy or mold inflammation, which are two different criteria, and you remove the trigger and downregulate the mast cell activation potential, I can’t tell you how many cases of asthma have been absolutely shut down when you treat the mast cell activation. It’s very rewarding. The same goes for GERD, the same goes for irritable bowel syndrome. The same goes for anxiety and cognitive decline. When you target the triggers and downregulate the mast cell activation, it’s very rewarding to treat these patients, and they’re very grateful. Angioedema, another one, canker sores another one, there’s many, many symptoms in all the organs that can present with this syndrome.

Afrin has written a chapter in a book. The book is called “Mast Cells,” the editor is David Murray. The chapter is chapter…I think it’s chapter 6, and it’s called Presentation, Diagnosis and Management of Mast Cell Activation Syndrome. And at the back, he gives a long, long list of every organ that can be affected from ophthalmic, to lymphatic, to pulmonary, to cardiovascular, and just goes through all the systems. Even fibromyalgia, even osteoporosis, headache, all the mood disorders, dysmenorrhea, endometriosis, many of the hematological conditions, the immunological conditions. There’s a huge long list of different organ systems that can be affected that present as isolated diagnoses to specialists, but often they miss the overriding pathophysiological basis to the condition.

And our training as MDs makes us very aware of what is called systemic mastocytosis, which is when the mast cell from a clonal perspective within the bone marrow becomes amplified. There’s actually a mutation of the KIT gene. And the mast cells become very high in numbers. So, there’s increased numbers of mast cells, which is systemic mastocytosis, which is very different from mast cell activation syndrome, which is an abnormal reaction of the mast cells, not an increased number.

So, I can’t tell you how many patients come back to me after having got the diagnosis of mast cell activation syndrome by myself with the criteria I use, go to the specialties, go to the hematologist, go to the gastroenterologist, or pulmonologist, who then does a serum tryptase and even sometimes go as far as do a bone marrow biopsy, and then come back and say, “Oh, that diagnosis is incorrect, he doesn’t or she doesn’t have systemic mastocytosis.” Systemic mastocytosis is a very rare condition, I’ve never seen one in my life. But I see almost twice a day, mast cell activation syndrome. Dr. Afrin believes that probably about 30% of the population gets affected to some degree or the other.

Dr. Hedberg: And are there any theories at this point about why mast cells become so overactive in an individual’s body. Any good research out there on that?

Dr. Hoffman: Well, there’s lots of speculation. And the most common hypothesis is that we do live in a much more sort of, you know…we’re inundated, so to speak, with multiple stressors far more than our capacity to withstand them. Our immune system, it just gets triggered because of multiple stressors. And there are many triggers for mast cell activation. Poor sleep. Stress is one of the biggest triggers. Food, I mean, food is incredible in its ability to trigger the mast cells that are in the mucosal surfaces of the mouth through to the anus.

So, we believe that our ability to…..we can no longer withstand the onslaught of our ongoing multiple stressors, whether they be environmental, emotional, nutritional. We just are in this constant state of over reactivity if you’re genetically predisposed. Now, Dr. Afrin doesn’t believe it’s necessarily a genetic condition that is transmitted through the germline. But he believes there are mutations in some of the mast cell production. And Dr. Molderings, who’s published a lot of papers with Dr. Afrin, has done a lot of research on the so-called KIT mutation, not in the bone marrow, but within the mast cells themselves, and has shown that they are these sporadic and spontaneous mutations that occur. Why those occur? I can’t say. I don’t know the answer to that. Yeah.

LAB TESTS

Lab Tests

Dr. Hedberg: So, there’s a number of functional medicine practitioners listening to this, so let’s just talk a little bit about lab tests, and some of the ones that you’re using and the ones that are beneficial. Obviously, CBC might be beneficial with elevated eosinophils, basophil, or possibly those are normal, histamine testing and things like that. What are some of the top tests you’re doing in your practice to identify this?

Dr. Hoffman: So yes, we do all the normal standard CBC and electrolytes, and liver function, etc., but those don’t usually yield what you’re looking for. And one of the challenges is that the lab testing positive results fluctuate depending on whether the symptoms are being expressed or not.

So, the first thing is you want to try and catch a person in a flare. Well, that’s difficult you know. So that’s the first challenge. And many of these tests need to be repeated over and over again until you get what Dr. Afrin likes to identify as two positive lab tests, which I’ll explain in a second. The second challenge is that you have to process a lot of these labs on ice. You have to have a refrigerated centrifuge to get accurate results. And it took me two years to get a refrigerated centrifuge. And as soon as I was able to, the positive rate of my lab has skyrocketed. Many of these lab specimens are very poorly handled. And, you know, they sit around for days and you’ll get these false positives for sure, false negatives, I mean. Sorry.

And also, a lot of the mast cell activation syndrome people or patients, they don’t always cause these abnormalities in the lab tests. Positive lab work is only obtained around 20% of the time. So, it’s quite frustrating, you know. But if you want to get lab work tests, I use sort of the minor and the major criteria. There are 10 major lab tests that we do. And then depending on the budget, we do the top 5 or 10, if we can.

And the tests that I recommend are plasma histamine, has to be chilled. And you should catch a person who’s in a flare. If they’re not in a flare, it will very often be negative. And you’ve also got to stop some of the inhibitors of histamine for five days prior to the test. Otherwise, you will get suppression of the histamine response. If people are on, you know, H1 or H2 blockers, you won’t get a positive test. And many people do take them intermittently you know.

Then we look for N-methylhistamine, which is a 24-hour urine also needs to be chilled. And then probably the one test that I get the most positives out of is the prostaglandin D2 plasma test, also must be chilled. And for that test, patients need to be off of all nonsteroidal anti-inflammatories, Motrin, Advil, or aspirin, or salicylate-containing foods. They can’t have a high salicylate diet. Anything containing aspirin for up to five days.

And then the one that is also done is the prostaglandin D2, 24-hour urine, also must be chilled with the same criteria of having to be off of all these medications. And then the last one is chromogranin A, and for that test you have to be off proton pump inhibitors and H2 blockers like famotidine. So, if you do go on proton pump inhibitors and so forth, they can falsely elevate chromogranin A.

And then after that, we’ve got prostaglandins 11 beta F2 alpha, a 24-hour urine, also must be chilled. And then the one that most MDs know about, which is serum tryptase. But this is rarely elevated in mast cell activation syndrome. It’s very important that every doctor who wishes to sort of work with mast cell patients knows this to be true. Because if the tryptase comes back normal, very often, the entire sort of clinical diagnostic differential gets thrown out, “Oh, they don’t have mast cell activation syndrome.” Big mistake, big, big, big mistake.

One of the criteria, one of the two different schools of the consensus criteria, they say that you have to have the serum tryptase elevated over 20% of baseline, or have a baseline greater than 15 nanograms per mil. But Dr. Afrin, who’s somewhat opposed to the consensus statement put out by Aiken and others, he highly disputes this finding and he doesn’t agree entirely that this is one of the main criteria to make the diagnosis. And I tend to agree with him.

Leukotriene E4, a 24-hour urine. Plasma heparin because heparin gets secreted by mast cells. And then a blood clotting profile, thrombin, PTT and INR is often done. And those are the top 10 and then after that, there’s many others; anti-IgE receptor antibodies, pheochromocytoma workup. We often do factor VIII deficiency workup, we do urinary metanephrines often. We almost always get an immunoglobulin profile IgG, IgA, IgE, and IgM. You might see IgE elevated or not. Often you won’t have an elevated IgE. So many people think “Oh, if a high IgE, then it can’t be this.” But that’s not true you can get a non-IgE-mediated mast cell activation. People then do bone marrow biopsies. People can do gastrin, serum gastrin levels. And then as you mentioned, the CBC with eosinophils and basophils can sometimes are elevated. Antiphospholipid antibodies are also often done.

And one test I like to do in the functional world is the Dunwoody Lab test for zonulin, histamine, and the DAO enzyme activity because that’s the diamine oxidase enzyme that sits on the villi that can be genetically compromised. Or because the villi are compromised, you cannot produce enough diamine oxidase. And that’s when you start to put people on low histamine diets and use the HistDAO enzyme to help break down any remaining histamine in food.

But I can tell you the one test that I tend to rely on more than any other right now, apart from the serum and urine test, is to get restaining of any gastric biopsies people have done. This has been overwhelmingly sort of helpful to some of my chronic GI tract patients in particular. So they would have gone, you know, to a GI specialist, they would have had the normal Giemsa tissue stain, and they comment on lymphocytosis. But they don’t actually comment on mast cell activation. And unless they get what’s called the CD117 stain, you won’t isolate the mast cells.

And almost 90% of people that I’ve clinically suspected of having mast cell activation syndrome turn up once they have their biopsies restained of having over 20 cells per high-power field being positive for mast cells. Which is the cut-off criteria that’s been agreed upon by numerous researchers, highly contested, by the way, by some pathologists and gastroenterologists. But we use a cut-off point of greater than 20 mast cells per high-power field to make a diagnosis of mast cell activation syndrome, particularly in the GI tract. The mast cells are very rich in the GI tract, particularly in the duodenum, not so much in the gastric tissue, but particularly in the duodenum.

So, if they ever had a biopsy in the duodenum, phone up the pathologist or write a letter and say, “Please will you restain for the CD117 stain.” And as I said, probably 9 out of 10 come back positive, very helpful. And then the patient sees that and the penny drops then they start reading up all the literature. And then they get on board for the treatment protocols which are, you know, quite…it can be onerous, and they can be extensive. But they’re very clearly delineated with multiple challenges along the way. Because people react to the medications and/or the supplements that you give them because that’s the nature of the condition.

EXCIPIENTS

pills

So, they’ll come back and say, “I can’t take the H1 blocker because I got worse.” Well, most of the time, it’s because it’s the excipient, the additive, the filler, or dye inside the medication that triggered the mast cell syndrome and it’s not the actual problem. You know, they’re not reactive to the supplement, they’re reactive to the excipient within the supplement or the drug. So those are some thoughts.

TREATMENTS

Doctors in meeting

Dr. Hedberg: Right. So once you’ve identified that someone has this syndrome, let’s talk about some of the natural treatments. You just mentioned that some of them are very difficult to follow. And some of these patients are…there’s probably a fair amount of trial and error with some of these patients figuring out what works for them. So, can you just talk a little bit about some of the treatments you’re using?

Dr. Hoffman: Sure. One of the hallmarks of this condition and one of the setups in my interaction with patients is a description of the complexity of the diagnosis and the challenges. And if you don’t have that conversation, you’ll often get a frustrated patient because they’ll come back with flare-ups and they understand it. So, I encourage that all your practitioners who wish to dive into this field really wont understand how patients can flare and how they

may have multiple triggers at any given time. And that the treatment may need to change, and that they mustn’t become frustrated, they must just stay for the long course. And they are sort of part of the team of trying to work out these multiple moving targets.

So the education is number one. I have two handouts, where I’ve described mast cell activation syndrome and mast cell activation syndrome treatment. I make sure they’ve read that. If they’re more interested, I give them Dr. Afrin’s book, “Never Bet Against Occam.” There are many patients who love to read because it’s filled with case histories. So once they get sort of an insight into other cases of complex presentation, they get encouraged to push on. So, education is first.

Second is to try and identify the triggers that trigger their mast cell activation. And this is one of the greatest challenges because there are many triggers from, you know, hot, too much heat, too much cold, stress, poor sleep, as mentioned. And then we get into the more obvious triggers, chemicals, heavy metals, dietary antigens, and then infections or inflammatory triggers like mold.

So, part of the process of working up mast cell patient is not just diagnosing the syndrome, but also trying to work up the triggers. So, in most patients, I do multiple food sensitivity profiles. I don’t just do IgG. I do IgG, IgG4, I do the so-called LEAP test. I do…am I allowed to mentioned lab names on your podcast?

Dr. Hedberg: Yes, definitely.

Dr. Hoffman: Okay. I do the lymphocyte sensitivity tests, the LEAP test. I do, as I said, IgE testing, IgG, IgG4. And I do Cyrex Lab food, I do the 10x, I think it is, with all three panels looking for dietary antigens. So, the Cyrex panel is different from the Meridian Valley food panel. Meridian Valley says it’s an IgG, IgE panel, but I disputed that once, and I’m not too sure there’s much IgE in the Meridian Valley panel. I think it’s more IgG. Whereas the Cyrex panel is more IgG and IgA. And you’ll often get contradictory findings. They’re very frustrating. That’s part of why allergists like to just throw them out, they say, “Don’t bring me this nonsense.”

But once you’ve been doing functional medicine for a long time and you have an understanding of the different complexities of dietary triggers, you can look at these profiles and you can sort of pull out the relevant data. And I encourage those of you who may be new practitioners is not to take each test literally. So, if they have a high say a banana on the one test and it’s not on the other, you want to look at the general profile of the dietary antigen testing. You don’t want to be too specific because if you get too specific, most people will have nothing left to eat. So, I’d look at the dietary antigens and most of the time, but not all the time, controversially or not, I tend to put people on the Paleo, autoimmune, low histamine diet for the first month or two. And I can’t tell you how many people immediately settle down just on that one intervention.

And I take out the high histaminic foods, and that is a very important part of it. And one of the great crazes right now is to use all these fermented foods to heal gut permeability, but it’s a disaster for the mast cell person. So, I’m always pulling people off sauerkraut, and kombuchas, and bone broth, it’s a huge trigger. So, all the fermented foods, and then all the leftover foods. As foods break down, then the proteins, the histamine gets broken down by bacteria that releases histamine. So, leftovers are no, no. We also ask people to, once they’ve cooked a meal, to put in the freezer and then to take it out and unfreeze it, but not to leave it sitting in the fridge for days.

And then things like tuna fish, huge triggers, the nightshades (tomato, potato, eggplant, peppers), huge triggers in many people. And even amongst, you know, some of the vegetable kingdom, you know, peas and beans can be triggers of mast cell activation. And so, you have to be careful when you look at the testing, you’re going to sort of see… when I look at particularly the Meridian Valley test, you can often see a mast cell patient, they’ll show up, all the legumes will be positive, all the histaminic fruits will be positive. Candida will often be positive.

And there’s like a trend you can see it and then immediately, you know this is a mast cell activation profile for food antigens. So, we remove the foods, we always treat gut dysbiosis as you know. I use two different labs for gut analysis. I use the Genova GI Effects, and I use the Diagnostic Laboratory Solution’s GI-MAPs. They contradict each other all the time, you know, one will have a zonulin of 700, the other one has zonulin as normal.

But then you just got to use your clinical acumen and your experience and correlate the labs against the symptom profile of the patient and do the best thing. I do tend to use Dunwoody Labs for the zonulin, the DAO, and histamine, as I mentioned. And then the second page of that test is all the LPS, the lipopolysaccharides, to see if there’s been any endotoxemia. And if there’s been any bacterial endotoxemia, you start entering into a whole new world of immune upregulation, which, you know, you have to down regulate in your treatment protocols and heal the leaky gut, etc. which I’m sure your listeners are very well aware of.

PHARMACEUTICALS

Stethescope sitting on open book

So A. is education, B. is testing, C. is removing the histaminic foods and downregulating inflammation in general. And then we get to specific treatments. And I differentiate between pharmaceuticals and botanicals. I tend to preferentially go to the pharmaceuticals to start with because they work quickly, if they’re going to work. And I tend to secondly, add botanicals. But I tend to be an MD, you know, it’s just my preference. I’m sure many naturopaths would go the other way. And many patients refuse to do pharmaceuticals and then I just have to use botanicals.

Pharmaceutical perspective, they must be compounded, you can’t get over-the-counter. Although paradoxically, some people do better on the over-the-counter than they do on the compounded. This is one of the challenges is what you think is going to work doesn’t work. This is why try, try, and try again, you know.

So, first thing, H1 blockers. Histamine 1 blockers, and I tend to use levocetirizine in a dose of 5 milligrams going up to 7.5, even 10 milligrams. And I think the trick to using H1 blockers is you have to dose it round the clock. You know on the box it will say “24-hour relief” that’s not true. You need to dose it at least 12 hourly and sometimes 8 hourly to create full round the clock mast cell blockade. And you’ve got your H1 blockers, you’ve got your first-generation and your second-generation. The first-generation H1 blockers like Benadryl, or ketotifen, cross the blood-brain barrier and have a sedating effect so those are often given at night.

I love to use ketotifen, I use lots of it on a dose ranging from 0.25mg, which is a homeopathic dose almost, right up 2 to 3 milligrams at night. And if there’s any issues with insomnia, it works like a dream. It’s absolutely spectacular for sedation. The problem is sometimes they over sedate when you have to lower the dose. But it also downregulates mast cell activity at night. So first-generation H1 blockers, I prefer ketotifen over Benadryl. Second-generation H1 blockers, I use levocetirizine as my preferred go-to H1 blocker.

And then I use H2 blockers, and I use famotidine in a dose of 20 milligrams twice a day, sometimes going up to three times a day. And this tends to downregulate all the mast cell activation activity in the GI tract.

One of the little tricks of the trade I’ve picked up over time is if you do the Genova GI Effects, you’ll often see that eosinophil protein X marker a little high, that’s almost a slam dunk for mast cell activation…not always because there’s other things that trigger that. But if you see that with a constellation of other positives, you follow that marker closely because when that starts to downregulate, you know, you’ve got your mast cell activity under control. So those are my first two go-to medications H1 and H2 blockers.

Probably my next is cromolyn. Cromolyn is a mast cell stabilizer particularly for people who are very food sensitive. You take it before meals. I give it along with the HistDAO enzyme. And that dose you can take it from 100 to 300 milligrams, and that can also be a major game-changer in many people’s lives. You have to play with the dose, you have to play with the different companies that make it. It’s a bit of a tricky thing, but it can really have a huge effect on downregulation of mast cell activation.

And then the fourth drug that I use, and many patients have come back to me with this fourth drug, Singulair, montelukast. This downregulates leukotrienes, which are one of the thousand mediators of inflammation. One of the things that we’ve noticed in mast cell syndrome is that when you think a patient has an upregulated leukotriene pathway, which is typical for asthma, you give the montelukast or the Singulair and the asthma is managed.

Well, it so happens that one can’t predict which class of drugs is going to work on which mediator. So, if you give a mast cell stabilizer for food sensitivities, guess what? The asthma may go away. Or if you give Singulair for asthma symptoms, the hives go away. So, thereis crosstalk amongst many of the mediators. And it’s a great mystery as to why that occurs, nobody’s worked it out yet. Dr. Afrin said he doesn’t know. He doesn’t know why this happens and he’s going to keep researching till he works it out. So those are the four drugs I use, probably the top four drugs I use over and over again.

SUPPLEMENTS

supplements

Nutraceuticals, of course, Quercetin, tops the list, no question about it. There’s a product called Natural D-Hist made by Ortho Molecular, that’s my go-to supplement over and over again. Two, three times a day seems to be the magic dose. And then using HistDAO one to two before each meal that seems to be the number one nutraceutical.

Number two would be vitamin C, either orally or intravenously, sometimes can have a huge benefit as well. Green tea has an effect. Turmeric or curcumin can have an effect but some people react to it. If you see on the food sensitivity profile, if you see that it’s positive in at least one or two tests, you can use it, but you want to be cautious because it can sometimes activate mast cell activation. You got to be careful with turmeric. Resveratrol is another one. And chamomile tea has some calming effects. So those are my sort of…they’re called the A team of my nutraceutical approach.

And the B team is sort of…there are many others like luteolin, Ginkgo biloba, Pycnogenol. Pycnogenol is a great one too I use quite a lot of Pycnogenol. Feverfew works. There are many things that can work. So, I pick and choose and go through them and change them. I ask everybody to first identify the triggers, if they can, and then to start rotating the pharmaceuticals and/or nutraceuticals and see which has the biggest blockade effect. And people soon work it out, you know. You’ve got to get a good compounding pharmacist on your side. And you got to make sure that they don’t fill the compounded pharmaceuticals with lots of fillers and dyes because some people react to that.

And then one of the other challenges…I just had a very seriously ill patient present to a hospital with anaphylaxis and she was on polypharmacy. She was on 10 different drugs. And many of the drugs she was on were triggers for her mast cell activation. And those were never identified as triggers by her medical team. And so, we asked the pharmacist to go through each drug and look for the additives. Many of them had iodine in them, many of them, there was soy extract base, and those had to be changed accordingly. And she settled down. So those are some of the challenges I have.

Dr. Hedberg: And one of the drugs that wasn’t mentioned was LDN, low-dose naltrexone, I know some practitioners are using that for this. Have you tried that or used it?

Dr. Hoffman: I do use low-dose naltrexone. It’s part of the many other…there’s many other alpha-lipoic, and so forth. And LDN is definitely part of it. And LDN has an effect particularly on autoimmune responses and downregulation of an inflammatory response. It’s not my first drug though, I don’t go to LDN as my first line. I use it if there’s autoimmunity and lots of gut permeability then I bring in LDN. And LDN is challenging because people give it at night but it can be very activating. Just yesterday, I saw a patient who since she started LDN hasn’t slept a wink. We changed it to morning.

Dr. Hedberg: Right. So how do you deal with the psychoneuroimmunology aspects of this condition? You know, some people, they develop a deep identification with their illness, and then they develop a lot of beliefs about things that they’re sensitive to. And we’re not saying that it’s all in their head, but we do know from the PNI research that what we believe, and what we emphasize, and think about, and focus on can affect the immune system and our biochemistry. So, are you using any kind of cognitive behavioral therapy or things like that, that could help some of these patients who are so focused on their condition and their hypersensitivities?

Dr. Hoffman: Yeah, because this opens up a huge area of the work that I’ve been forced to look at over time and for which I use quite a complex algorithm to sort of diagnose and treat. I’ve studied Ayurveda for years and I use the Ayurvedic model of layers and levels of healing. And when a person presents with specific belief systems around their condition, I have to sort of look through the layers and levels of what may be playing a role in that belief system.

Just very briefly, I tend to look at these diagnostic criteria. I look at the family system to see what family system they were born into and what beliefs the family system carried. Because I can’t tell you how many cases get resolved when we do what’s called family constellation therapy and look at the entanglements of the forefathers and ancestors, and how those epigenetically got transferred down to the offspring. Very profound piece of work, I cannot emphasize it enough. And I encourage all functional medicine practitioners to get a very sound footing on the epigenetic transfer of family system trauma and the entanglements that can be inherited, completely silently, unknown consciously to the patient, only uncovered through work in family constellation therapy whereby certain methodology is employed to determine what these factors may be. So that’s number one.

Number two, I look at early developmental trauma patterns, and ego strength, and defense systems of a patient. And I employ a number of ways to identify that. The number one system that I look at is looking at defense structures of the patient and the ego strength. And you can tell after, you know, half an hour, is this person…do they have good ego strength? Are they resilient or they do have a fragile ego structure? And I send people for quite a lot of psychometric testing to establish some of these criteria.

I have a psychologist I work with who is able to help me with some of the psychometrics. And we even do, you know, some of the simple psychometrics testing, and even the Burns Inventory, the ACE Questionnaire. When we do qEEGs, we do the in-depth psychological assessment that’s provided by the CNS Vital Signs software to look at which of their psychological profiles are most dominant. Is it anxiety, OCD, is it depression, etc.?

So we look at that level of their development, the ego strength and their defenses. And then we look at early developmental trauma. And as you know from literature, people who have early developmental trauma have very different brain structures. They have, you know, very often this hugely enlarged anterior cingulate gyrus. They have in their beta, their fast brainwaves, there’s two to three standard deviations above normal. Their capacity to inhibit the sort of reptilian, limbic brain is diminished. And those are challenging patients, very challenging, and you have to address that level of healing.

This is not a biological intervention. There’s not much you can do biologically unless you identify what the core ego strength resilience of the patient is. How much projection of will the patient has? Many patients will sit in front of you, project the will to heal on you. And that’s a slippery slope. If they are not invested in sort of figuring it out on their own with you, you have a problem on your hands, you know. And patients will often project their early developmental trauma of parents on to you, whether it’s positive or negative. Best to have a positive projection in the beginning. But if you are the evil father that you get projected onto you, you’re in trouble.

So it behooves all of us as functional medicine practitioners to kind of try and identify, who is this person sitting in front of me, what did they inherit, how was the early developmental life? And then what defenses are they employing to keep away feelings they don’t want to feel? And I use a psychological technique called ISTDP. And I refer that out to somebody who’s specialized in it. That person I use is also very well versed in CBT. But CBT, without the underpinnings of the complexity of the presentation, can sometimes not stick. It can be very helpful to some, but for those who are fragile with projection of will, CBT will not hold. You can’t use CBT, it washes off them, you know, they won’t be able to hold that.

The next thing I do, I do NeuroQuant MRIs on everybody as well as a qEEG. And I look at the brain patterns and I can’t tell you how helpful that is. If you’ve got this high beta brainwave, and you’ve got maybe high theta brainwaves with not enough alpha, you’ve got work to do. And then you correlate that with the NeuroQuant MRI, and we look particularly for the amygdala upregulation. Many of these people with anxiety, OCD, and belief systems around the illness, who are multiple chemically sensitive and environmentally sensitive and are triggered by everything, will have a very…..the amygdala will be 2 standard deviations above normal, being like in the 97th percentile. The thalamus will be in the 97th percentile.

Hand holding image of brain

And the thalamus is rich in mast cells. So, when the thalamus is high, the amygdala is high, you want to ask about mast cell activation, and you want to ask about early developmental trauma. Because the amygdala gets increased in size when there’s repeated stresses on the fear-based part of the limbic brain. And if I see that, I often start inquiring about other techniques to downregulate the amygdala. And that we use DNRS, as you’re probably aware of the Dynamic Neural Retraining System.

We do refer people to that, we do neurofeedback, we do biofeedback, we do vagal tone stimulation. And we start to bring in the Porges polyvagal theory of, you know, sympathetic, parasympathetic dorsal vagal shutdown. And we try to work out where in this constellation of symptoms is this patient presenting? Are they in dorsal vagal shutdown with a rigid defense and sort of no will to get better? Are they getting secondary gain? That’s a very different patient from the one who’s, you know, loved by the parents, no developmental trauma, is loved and seen by a mother, develop appropriate right prefrontal cortex to self-regulate, has financial resources, is loved by the husband, the kids are doing well, they have a home to go to. This is how it works.

And we have to work out who are we sitting in front of when it comes to addressing some of these complex beliefs about, you know, is this a biological overreactive reactive mast cell syndrome, or is this a psychologically overreactive amygdala? Or is this person highly defended? Do they have the ego structure to take on what I’m about to tell them? It’s complex, as you know. I think that…

Dr. Hedberg: Right. And it’s a difficult situation for everyone because, you know, we don’t really get a lot of training, if at all, in all these things you just mentioned. So, we have to learn these things on our own, learn how to incorporate them. And then at the same time, present these to the patient in a way that isn’t telling them that you know, “This is just all in your head” or helping them understand that some of this could be due to your childhood and the way that your parents treated you, and all these kinds of things that happen. And I have done a few podcasts with some experts on adverse childhood experiences and things like that.

So, it’s refreshing to hear you talk about all these things, and it just creates a very complex picture on how to put it all together. And you know, like you said, they come to see you and they put all the burden on you for the healing. And then, you know, you come back with recommendations that, “Well, we need to work on your childhood trauma or your relationships,” and things like that. So, this is a very difficult, you know, condition to take on as a practitioner. I mean its massive amount of mental and emotional output that you have to take on.

Dr. Hoffman: Yes, one of the commonest words I see in the referrals back from specialists is this so-called, awful term, somatization disorder. And it’s just not true 90% of one of the most stressful diagnoses for one of these patients to get is the so-called somatization disorder but it’s often handed out. You know, and, “Yeah, it’s all in your head,” this is so awful. There may be a component that is filtered through the neurological pathways and then synapses. And they may tend to have an upregulated sensory system that processes things somatically. But it doesn’t mean to say that we have to discard this as all psychological, which is very often the insurance companies like to do things like that and some of the specialties too.

I recently referred a patient to a psychiatrist for insurance purposes and I sent five articles plus a written response. “Please do not diagnose this patient as being psychiatric, he has the following conditions.” And then we listed the mast cell activation, the mold sensitivities, electromagnetic sensitivities, etc. And I sent him five papers in support of the validity of this diagnosis. I haven’t heard back yet; I’m waiting to see what the response is. We often have to advocate for our patients in this way because they do present with neuropsychiatric manifestations, but it’s as a consequence, it’s not the cause. Although there may be some issues which provoked, you know, an expression of a mast cell disorder, but you can’t separate you know, mind-body, you’ve got to work with the whole continuum.

Dr. Hedberg: Exactly. Well, this has been really excellent. How would you like people to find you online, what’s your website and contact information?

Dr. Hoffman: The website is hoffmancentre.com. And the phone number here is 403-206-2333. That’s the phone number for my clinic. I do have a number of blogs on my website, and I post to Facebook and Instagram. But my website has a lot of the histaminic articles as blogs, so they can access them on there.

Dr. Hedberg: Excellent. So, to all the listeners, I have created a transcript of this conversation, which will be on drhedberg.com. So just search for Dr. Hoffman and you’ll be able to get the entire transcript there in case you missed anything. Well, thanks for tuning in, everyone. Talk to you next time. This is Dr. Hedberg, and take care.

Natural Treatments for Mast Cell Activation Syndrome

I have recently returned from a most stimulating conference/think tank with Dr. Afrin and 30 other leading clinicians on Mast Cell Activation Syndrome (MCAS) at Commonweal—a cancer retreat centre in northern California.

MCAS is a type of mast cell activation disorder (MCAD) characterised by an abnormal activation of mast cells resulting in chronic multisystem polymorbidity of a general inflammatory nature, with or without an allergic nature. Mast cells are white blood cells that are concentrated at the entrances to body tissues (ears, ears, nose throat, skin, genitalia, rectum), and when activated, they release over 200 signalling chemicals (e.g. histamine, prostaglandins, leukotrienes, cytokines and chemokines). These chemical mediators trigger inflammation in response to the invasion of foreign toxins, infections or chemicals, resulting in a range of chronic symptoms. With MCAS, this function becomes upregulated and chronic, occurring at inappropriate times in response to substances that are not necessary a threat. This can lead to widespread symptoms in many different body organs and systems.

Mast cells are located throughout your body in many different tissues, primarily including dermatological, gastrointestinal, neurological and respiratory tissues.  While we need mast cells to protect us from threats, they become a problem when they are overactive and hyper-responsive and will not ‘turn off’. Dr. Afrin, a leading mast cell researcher, believes that between 15 and 20% of the North American population may be affected  by MCAS. The symptoms of MCAS vary greatly. As a result, many people spend years, even decades, in search of a correct diagnosis, visiting many different subspecialists. What is more frustrating for patients is that many doctors are not familiar with the multiple ways in which MCAS may manifest.

MCAS is often found in individuals with hypermobility syndromes (Ehlers–Danlos syndrome), postural orthostatic hypotension (POTS) as well as chronic inflammatory response syndrome (CIRS) and tick-borne illnesses (Lyme disease and co-infections).

The most common symptoms of MCAS include:

  1. Feeling as though you have been sick forever
  2. Trouble with allergies and asthma
  3. Overreaction to insect bites, bee stings and chemical intolerances
  4. Facial and chest flushing
  5. Skin rashes that come and go, including hives and angioedema
  6. Itchiness and a burning feeling
  7. Brain fog and headaches
  8. Poor wound healing and easy bruising
  9. Waxing and waning of symptoms

The condition may be mild in some people and only exacerbate in response to a significant life stressor, which may be either physical or psychological in nature (divorce, bankruptcy, loss of job, travel, infection, death of a loved one, exposure to novel infections, occupying a water damaged building, exposure to cold or heat). In others, symptoms may develop from a young age and slowly become worse over time. People with MCAS are likely to experience a few of the most common symptoms. Because mast cells are located throughout the body, symptoms can affect the eyes, nose, ears, throat, skin, heart, blood, lungs, gastrointestinal tract and the nervous, endocrine and musculoskeletal systems.

The symptoms of MCAS are often confusing. For a long time, many people with MCAS have been told that their condition was psychosomatic or ‘in their head’. Fortunately, awareness of this frustrating and debilitating condition is spreading. Testing for MCAS is somewhat complex and confusing, as positive biomarkers may only be observed when a patient has a flare up. Incorrect collection of specimens may also lead to false negative testing. Many specimens need to be chilled with a refrigerated centrifuge, which is not available in every lab or doctors’ office.

If you need a comprehensive overview MCAS, I encourage you to read my article: Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

The most common drugs that are prescribed for treating MCAS include:

  • Histamine 1 blockers – Hydroxyzine (Atarax), Doxepin (Silenor), Cyproheptadine (Periactin), Loratadine (Claritin), Fexofenadine (Allegra), Diphenhydramine (Benadryl), Ketotifen (Zaditen) and Cetirizine (Zyrtec, Reactine).
  • Histamine 2 blockers – Famotidine (Pepcid, Pepcid AC), Cimetidine (Tagamet, Tagamet HB) and Ranitidine (Zantac). Famotidine is chosen most often because it has fewer drug interactions than Tagamet.
  • Mast Cell Stabilisers – Cromolyn (Cromolyn Sodium, Gastrocom—oral form, Nasalcrom—nasal spray, Opticrom—eye drops, and there is a nebulised form and a cream can be made from a bottle of Nasalcrom and Eucerin or DMSO cream), Ketotifen (both a mast cell stabiliser and an H1 blocker) and Hydroxyurea (Hydrea).
  • Mast Cell Inhibitors – Montelukast (Singulair), Zafirlukast (Accolate) and Zileuton (Zyflo). Pentosan (Elmiron) is used in the genitourinary tract for perineal pain and interstitial cystitis.
  • Antibody neutralisers – Omalizumab (Xolair).
  • Tyrosine Kinase Inhibitor – Imatinib (Gleevac).
  • Stimulants – Mixed salts amphetamine (Adderall XR), Methylphenidate (Ritalin) and Ephedrine (Epipen provides an acute rescue injection when experiencing an anaphylactic episode).
  • Non-steroidal anti-inflammatory (NSAIDS) – Helpful in some, a trigger in others.  Aspirin is the most commonly used NSAID. COX 2 selective NSAIDs—Celecoxib (Celebrex)—are also used.
  • Low-dose Naltrexone (LDN) – Used in a step-up dosing at night.
  • Cannabinoids – Drobaninol downregulates neurons and mast cells via inhibitory cell-surface cannabinoid receptors (not available in Canada). CBD is more helpful than THC.
  • Benzodiazepenes – Addresses the inhibitory mast cell benzodiazepine receptors. Use short-acting varieties. Lorazepam (Ativan) and Clonazepam (Klonopin, Rivotril) are best when used three times daily. Valium and Midazolam are also sometimes used.
  • Selective Serotonin Reuptake Inhibitors – may occasionally be of benefit.
  • IV Immune Globulin (IVIG) – this treatment is sometimes used in MCAS.

While your doctor may prescribe you some of these mast cell stabilizer drugs to help your symptoms, there are also several natural treatment options. A benefit of using natural treatments for MCAS is that you can take these on your own and they do not require a prescription. However, because most patients with MCAS present differently, it is a good idea to implement these with the guidance of a functional medical doctor who is experienced in MCAS.

Although there is a good possibility that you will eventually find the right therapeutic combination of treatments that will help alleviate many of your symptoms, the fact is that there are no specific biomarkers that will predict which therapy will be the most effective for your specific manifestation of this condition. Trial and error with both drug- and non-drug-based options is often the name of the game.

Also, if you opt for natural treatments for MCAS and mast cell activation disorder, always be sure to disclose everything you are taking to your doctor so he or she has a clear idea of what is going on. It is also important that you make only one change at a time when attempting different combinations of treatment options.

Advantages of Using Natural Treatments for Mast Cell Activation Syndrome

There are many advantages of using natural treatments for MCAS, including:

  1. Lower cost
  2. No need for a prescription
  3. MCAS patients are often sensitive to pharmaceuticals, particularly the excipients (bulking agents, binders, fillers, dyes) within the products. Patients will have to work closely with their compounding pharmacists to help identify a list of offending ingredients in drug formulations. If a patient has a strange reaction to medications (e.g. insomnia while using a typically sedating antihistamine), it is likely a flare up of mast cells in the CNS causing the problem and not the drug itself.
  4. Some drugs block DAO—an enzyme in the gut that breaks down histamine
  5. Many patients prefer natural treatments
  6. May have benefits beyond mast cell stabilisation

Disadvantages of Using Natural Treatments for Mast Cell Activation Syndrome

  1. Supplements are bioactive compounds that may have unacceptable effects
  2. They may interfere with known medications
  3. They still have to be processed through the same liver detoxification enzymes as pharmaceuticals and thus may have unacceptable side effects
  4. Supplements may also contain excipients that produce unacceptable side effects

Many of my patients find that these natural treatments are sufficient when it comes to treating their MCAS. For others, these natural treatments allow them to reduce the number or amount of drugs they need. When it comes to natural treatments for MCAS and mast cell activation disorder, the most effective work in the following ways:

  1. Stabilising mast cells
  2. Increasing histamine breakdown
  3. Reducing histamine levels
  4. Stabilising the immune system and reducing inflammation

With that in mind, here are some of the best natural treatments for MCAS according to the mechanisms they influence. These recommendations were presented at the think tank by Dr. Brian Bouch, a leading integrative medical doctor from California.

1. Stabilising Mast Cells

One of the best things you can do for MCAS is add natural treatments that stabilise your mast cells. Such therapies work by inhibiting the inflammatory mediators mast cells release and can be broken down into three groups (A, B, and C) based on how helpful and potent they are.

The “A” Team:

  1. Quercetin  – 2000 mg daily, dose divided
  2. Green tea (EGCG, L-Theanine) – 2 to 3 cups daily. Supplement with 500 mg (175 mg of ECGC) twice daily
  3. Curcumin (Meriva is a common brand name) – 1 to 4 g daily, dose divided
  4. Chamomile tea (Apigenin, luteolin) – 1 to 2 cups before bed
  5. Resveratrol – 20 mg twice daily
  6. Diamine oxidase enzymes (DAO) – 2 capsules with each meal
  7. Vitamin C – may need a non-citrus source such as rose hips – 1 to 3 g daily

The “B” Team:

  1. Luteolin – 100 mg twice daily
  2. Ginkgo biloba – 500 mg daily
  3. Silymarin – 500-1000 mg daily, doses divided
  4. Shea oil – 3 capsules daily
  5. Ellagic acid – 500 mg daily
  6. Pycnogenol – 500 to 1000 mg daily
  7. Magnolia/Honokiol – 200 to 250 mg twice daily
  8. Parthenolide (Feverfew) – 200 to 400 mg twice daily

The “C” Team:

  1. Fiestin – 100 mg twice daily
  2. Rutin – 200 mg daily
  3. Genistein (isoflavone)
  4. Mangostin (often taken as a juice) – 500 to 1000 mg daily
  5. Xanthium (dihydroleucodeine, also known as cocklebur) – 6 to 9 capsules daily
  6. Isatis (indoline) – 6 to 9 capsules daily

Here is some further information about select products that are used most often

Quercetin

  • Found naturally in stinging nettle, grapefruits, onions, apples, black tea, leafy green vegetables and beans
  • Downregulates the enzyme that converts the protein histidine to histamine—histidine decarboxylase
  • Inhibits the release of histamine, prostaglandins and leukotrienes— three of the most common inflammatory mediators found in MCAS
  • Decreases the production and release of inflammatory cytokines—the inflammatory mediators responsible for many of the symptoms of inflammation related to MCAS
  • Often used as a primary therapy—has been shown to be more effective than the pharmaceutical Cromolyn
  • Treats allergies, contact dermatitis, photosensitivity and inflammation
  • The dihydrate form has the best bioavailability
  • Dr. Theoharides, a top mast cell researcher, has produced a product called NeuroProtek, which contains quercetin, luteolin and rutin. At least 8 capsules must be taken daily for maximum effect.

Green Tea – EGCG

  • EGCG is the most common polyphenol found in green tea
  • Inhibits calcium influx into mast cells, thus preventing their degranulation
  • Inhibits mast cell production of inflammatory mediator leukotriene C4.
  • Has other benefits: improves brain function, improves dental health, lowers risk for cardiovascular disease, combats skin aging
  • Lowers risk for Alzheimer’s disease, Parkinson’s disease and diabetes mellitus

Curcumin 

  • Widely used in popular supplements for lowering inflammation
  • Best found in phospholipid forms such as Meriva
  • Has antiallergic activity—inhibits the degranulation of mast cells in a dose-dependent manner
  • Inhibits inflammatory molecules—interleukin-4 and tumour necrosis factor -?
  • Widely used in cancer and joint inflammation

Resveratrol

  • Found in grapes, berries and peanuts
  • Reduces the expression of inflammatory markers IL-6 and IL-8
  • Inhibits IgE allergy reactions

Vitamin C

  • Research has shown that when Vitamin C levels fall in the blood, histamine levels increase exponentially. When Vitamin C is reintroduced, histamine levels fall exponentially
  • There is very little evidence in the literature, however, to support its use as a natural antihistamine
  • It is frequently combined with quercetin in supplements—a popular supplement is Natural D-Hist by Ortho Molecular Products. Take 2 three times per day for maximum effect
  • Be careful of citrus-based Vitamin C and be aware that high does can cause diarrhoea. It is best to take smaller amounts more frequently
  • Slow-release formulations may be better

Silymarin

  • Silymarin, an extract of milk thistle, which has been shown to attenuate mast cell-mediated anaphylaxis-like reactions
  • It also prevents the release of proinflammatory cytokines such as tumour necrosis factor, interleukin 6 and nuclear factor–kappa B.
  • Also known to have hepatoprotective, anti-carcinogenic and anti-inflammatory effects. Widely used to protect against drug- and chemo-induced liver toxicity

Other supplements that have been used in MCAS:

  • Lipoic acid
  • N-acetylcysteine
  • Ashwagandha – an Ayurvedic remedy known as an adaptogenic herb that modulates the body’s response to stress. Withaferin A is a compound found in ashwagandha that has been shown to prevent mast cells from releasing histamine and other inflammatory mediators
  • Vitamin D – usually best at higher doses. Need to test blood levels

Important Caveat:

Both quercetin and green tea extracts may inhibit the COMT enzyme. If you have a COMT ++ enzyme (slow function) on your 23andme, be careful when using these two supplements. The COMT gene determines your ability to process catechols, oestrogen and the major neurotransmitters adrenaline, noradrenaline and dopamine. Your anxiety, insomnia and pain may increase due to further slowing down of the excretion of these excitatory chemicals plus the excitatory catechols, substances found in green and black tea, coffee, chocolate, green coffee-bean extracts and quercetin.

Other things to consider in MCAS patients:

  1. Ensure you have sufficient magnesium levels, as a deficiency has been shown to induce the emergence of mast cells, particularly in the liver. Magnesium also has hundreds of other important functions in a healthy body.
  2. Zinc is another mineral you should ensure you’re getting enough of because it is important in appropriate mast cell signalling.
  3. Stress reduction is also important in stabilising mast cells. When you’re stressed, your body releases corticotropin-releasing hormone (CRH), which is associated with the activation of skin mast cells. Incorporate meditation, yoga, breathing exercises and other stress-reducing techniques into your daily life.
  4. Maintaining a schedule is a great way to help stabilise your mast cells because they exhibit circadian rhythm patterns. Try to wake up and go to sleep at the same time each day. Also, avoid electronic screens before bed or wear a pair of blue-blocking glasses for better hormone regulation.

2. Increasing Histamine Breakdown

Diamine oxidase (DAO) stabilises mast cells, but more importantly, it is the predominant enzyme that breaks down histamine. To increase your DAO levels, you can take DAO enzymes. I recommend taking two capsules with each meal. You can also increase your DAO levels with high doses of vitamin C.

You should also avoid anything that blocks the release of DAO. First and foremost, this includes any form of alcohol. Histamine and alcohol metabolic pathways share common enzymes—aldehyde oxidase and aldehyde dehydrogenase. When you drink alcohol, histamine is released from your mast cells and DAO is simultaneously inhibited. This can cause a runaway chain reaction, which results in greater sensitivity to alcohol and worsening histamine intolerance. Aged cheese and wine together may induce a major mast cell activation.

3. Reducing Histamine Levels

To reduce histamine levels in your body, you should adopt a low histamine diet. Avoid the following:

  • Alcohol
  • Smoked and cured meat
  • Seafood
  • Pickled foods
  • Fermented foods
  • Leftovers
  • Canned fish or meat
  • Berries, especially strawberries
  • Nightshades, including tomatoes and potatoes
  • Preservatives
  • Vinegar

Try to eat foods as fresh as possible, and stick to anti-inflammatory foods. Adding rosemary oil to fish reduces histamine formation as the fish ages.

For a comprehensive resource on low-histamine foods, diets and recipes, I recommend my guide on the Low Histamine Diet as well as Healing Histamine.

4. Stabilising the Immune System and Reducing Inflammation

Calming the immune system and reducing inflammation is a critical part of any MCAS protocol. The recommendations above mainly help to stabilise the immune system and reduce inflammation, though there are a few other effective methods:

  1. Check and treat any underlying infections – These can contribute to a widespread inflammatory response in the body if left untreated. These may include H. pylori, Epstein Barr and herpes simplex.
  2. Correct gut dysbiosis – Correcting the balance of your gut microbiome has been shown to reduce inflammation and improve immune system health. Specifically, there are certain strains of probiotics that have been shown to help breakdown histamine, including:

Many patients will need to experiment with various therapeutic options at different doses until they find the right combination of medications that helps with their particular symptoms. If unusual side effects are experienced with known medications, remember that the excipients contained within the medications may be the problem, not the medications themselves.

While there is no cure for MCAS, there is a lot you can do to minimise the condition’s impact on your life. The good news is that most of the natural treatments for MCAS are recommendations for a healthier life that anyone would benefit from. To read more about living with MCAS, check out 12 Tips for Living With Mast Cell Activation Syndrome.

With a chronic illness such as MCAS, it is possible to live a full life—the treatment just requires a careful, comprehensive approach. If you believe you have MCAS or have already received a diagnosis and need a functional medical doctor who specialises in MCAS in Calgary, Alberta, you can request an appointment here or call 403-206-2333.

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Resources:

https://hoffmancentre.com/2017/11/mast-cell-activation-syndrome-histamine-immune-system-runs-rampant/ https://www.ncbi.nlm.nih.gov/pubmed/22470478
https://www.ncbi.nlm.nih.gov/pubmed/24477254
https://www.ncbi.nlm.nih.gov/pubmed/28458279
https://www.ncbi.nlm.nih.gov/pubmed/9421440
https://www.nature.com/articles/srep39934
https://www.ncbi.nlm.nih.gov/pubmed/17490952
https://www.ncbi.nlm.nih.gov/pubmed/25095772
https://www.ncbi.nlm.nih.gov/pubmed/10344773
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/
https://www.ncbi.nlm.nih.gov/pubmed/12793960
https://www.ncbi.nlm.nih.gov/pubmed/21390145
https://hoffmancentre.com/2017/11/12-tips-living-mast-cell-activation-syndrome/

Is Your Histamine Intolerance Actually Mast Cell Activation Syndrome?

Are you wondering if your histamine intolerance or allergic reactions are actually an issue with your mast cells? Or maybe you’ve experienced chronic symptoms that seem like allergies for as long as you can remember?

Histamine is an important but potentially dangerous mast cell mediator and part of the immune system response. Histamine is secreted by mast cells into surrounding connective tissues when there’s an exposure to an allergen. Mast cell histamine works by increasing the permeability of blood vessels and allowing white blood cells and proteins to access affected tissues more easily.

Histamine intolerance is a condition that’s growing in recognition. However, it is mostly considered a part of a much wider problem which is defined as Mast Cell Activation Syndrome (MCAS); a situation in which part of the innate immune system becomes hyperactive and releases multiple inflammatory mediators, of which histamine is one.

Histamine intolerance is considered to be present when there is just too much histamine in your body for it to cope. This is further exacerbated by the fact that histamine is also present in many foods and so a person’s histamine burden may be further amplified by their diet. This histamine isn’t broken down due to a DAO gut enzyme deficiency, or a HNMT deficiency in the liver. A comprehensive guide regarding the low-histamine diet can be found here.

Histamine intolerance is a subset of MCAS

Mast Cell Activation Syndrome is often confused for histamine intolerance. The difference between the two is that when a person has MCAS, their mast cells secrete many mediators, not just histamine. Though, histamine is still a major component of MCAS it’s only a piece of the puzzle.

Histamine intolerance is actually a subset of MCAS. If you’ve discovered you’re histamine intolerant or recently received a diagnosis, you should also be tested for MCAS.

Conditions associated with MCAS

Because MCAS is a multisystem condition with inflammation at it’s core, it’s been associated with a number of other conditions including:

  • Chronic inflammatory response syndrome (CIRS)
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Postural orthostatic hypotension (POTS)

If you’ve been diagnosed with one of these associated conditions, it could mean that being diagnosed with MCAS is more likely. Make an appointment with a doctor who specializes in MCAS and begin the diagnostic process. It can be somewhat of a journey, but once you know you have MCAS there’s a lot that can be done to relieve your symptoms and improve your life.

For a comprehensive guide on Mast Cell Activation Syndrome, you can read my in-depth article, Mast Cell Activation Syndrome and Mast Cell Histamine: When Your Immune System Runs Rampant.

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Resources:

https://www.ncbi.nlm.nih.gov/pubmed/25773459

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507480/

https://www.ncbi.nlm.nih.gov/pubmed/15462834

12 Tips for Living With Mast Cell Activation Syndrome

Living with Mast Cell Activation Syndrome (MCAS) usually results in widespread mast cell activation syndrome symptoms that are seemingly unrelated. Unfortunately, most people go many years or even their whole life without a diagnosis.

If you’ve been diagnosed with MCAS or suspect you have this condition, the best course of action is making a series of lifestyle changes and working with your functional medicine doctor. Fortunately, many of the changes are easy to implement and you’ll see the benefits from implementing them fairly quickly.

Try not to get overwhelmed by this list, instead pick one or two items and incorporate them into your routine. Add a few items week by week, and soon enough you’ll have a comprehensive plan that has the potential to significantly improve your symptoms and your quality of life.

1. Adopt a low histamine diet

Avoid leftover foods, alcohol, cured meats, canned fish, pickled and fermented foods, berries, citrus, nuts, chocolate, dairy, yeast, soy sauce, tomatoes, vinegar, and preservatives. A comprehensive guide to a low histamine diet can be found here.

2. Avoid triggers of MCAS (non-food items)

Avoid temperature extremes, mold, emotional stress, insect bites, chemicals in personal products, medications that liberate histamine of block DAO, sodium benzoate (common food preservative), airborne chemicals, smoke, heavy metals and anesthetics.

3. Work on your gut health

Good gut health is a cornerstone of overall wellness and will help you get your MCAS under control. Cut back on food that damages the gut or causes inflammation. Take probiotics and a DAO enzyme (generic name Umbrellux DAO).

4. Stabilize mast cell mediator release

Stabilize mast cell release of histamine with quercetin and vitamin C.

5. Use H1 and H2 blockers every 12 hours

Try using 5 mg of levocetirizine twice daily and 20 mg of famotidine twice daily.

6. Block and reduce nighttime histamine release

You can block nighttime histamine release and get a better night’s sleep by taking 0.25 -1 mg of ketotifen or zaditen at night.

7. Treat existing infections

Treat any existing infections to help your body heal and reduce mast cell triggers. Get a thorough examination with your functional medicine doctor and test for any pathogens.

8. Identify and remove toxins and allergens

When you have MCAS, you’ll do your body a world of good by reducing its toxin burden. You can reduce your exposure to toxins in your daily life through cleaning up your personal care products and opting for natural solutions, using natural household cleaners, and removing mercury fillings.

9. Take helpful nutrients

Support your health with important nutrients that assist in treatment. Some of these include vitamin B6, alpha lipoic acid, vitamin C, selenium, omega-3s, N-acetylcysteine, methyl-folate, SAMe, and riboflavin.

10. Add supportive herbs

Take nigella sativa, butterbur, turmeric, ginger, and peppermint to support your MCAS treatment.

11. Get into a routine and stick to it

Try to stick to a routine because your body’s cycles are closely linked to your daily activities. This will also help you get high quality sleep, which is essential to reducing the impact of MCAS on your life.

12. Reduce stress

Stress can activate your mast cells and cause them to release mediators like histamine. Reducing stress is important for anyone living with MCAS.

For a comprehensive guide on Mast Cell Activation Syndrome, you can read my in-depth article, Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

Mast Cell Activation Syndrome Diet

Another great resource for dealing with histamine and MCAS using a mast cell activation syndrome diet and exercise is through Yasmina Ykelestam at Healing Histamine.

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How to Tell If You Have Mast Cell Activation Syndrome

If you’ve been searching for solutions to your mysterious health symptoms, they could be caused by Mast Cell Activation Syndrome.

Mast cell activation syndrome (MCAS) is an immunological condition where mast cells inappropriately secrete mast cell mediators. Mediators include but are not limited to histamine, which can cause widespread and chronic inflammation.

This mediator release can be excessive and/or chronic and result in long-lasting symptoms in almost any cell of the body where their receptors are found. This can potentially affect every organ system in the body.

Some experts believe as many as 14 to 17 percent of the US population have MCAS, which is one out of every six to seven people. It’s also been estimated to take up to 10 years to reach a mast cell activation syndrome diagnosis. This is mostly due to the lack of awareness surrounding MCAS.

Because mast cell activation syndrome goes unnoticed for years, I’d like to dig a bit deeper and uncover some of the symptoms and lab work available that can help with MCAS diagnosis.

Symptoms of MCAS

Patients who have MCAS typically have been struggling with inflammation-related symptoms over the years, which commonly include:

  • Having allergies as a toddler
  • Various rashes that came and went
  • Gut conditions (that may have been misdiagnosed)
  • Anxiety
  • Headaches
  • Insomnia
  • Poor wound healing

While these are common MCAS symptoms due to mast cell mediators occurring throughout the body, a person can be affected by symptoms that are more widespread. These can include, but are not limited to the following questions:

  • Feeling as though you’ve always been sick
  • Overreaction to bee stings and mosquito bites
  • Shortness of breath
  • Feeling lightheaded when you stand
  • Insomnia
  • Ringing of the ears
  • Facial and chest flushing
  • Frequent colds, infections or fevers
  • Food, chemical, and drug sensitivities and intolerances
  • Heat intolerance

You can also find a comprehensive list of MCAS symptoms in my in-depth article, Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

You have the option to get testing done with a doctor to help confirm the MCAS diagnosis. I recommend you have these tests done with a doctor who’s experienced in MCAS because it’s still largely unknown, even in the medical community.

Lab work for MCAS

Working with a doctor who specializes in MCAS is your best bet as you’ll need to get testing on multiple occasions since the symptoms of MCAS wax and wane. False negatives are a common occurrence with MCAS testing. In fact, positive lab work is only obtained 20 percent of the time. However, testing can still give you a lot of valuable information regarding your mast cell mediator status. Testing for MCAS is quite complex and requires specialized handling of tissue samples.

The most important MCAS tests are:

  • Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  • N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  • Prostaglandin D2 – plasma – must be immediately chilled and spun in a refrigerated centrifuge. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  • Prostaglandin D2 (PGD2) – 24-hour urine – specimen collection must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  • Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.

There are others you can have taken, which you can find in more detail in my in-depth article, Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant.

More information regarding a low-histamine diet may found found in my guide here.

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Resources:

20 Triggers of Mast Cell Activation Syndrome

In an effort to help you notice common triggers, below are 10 non-food and 10 food triggers that commonly provoke mediator release in those with MCAS.

10 Non-Food Triggers of Mast Cell Activation Syndrome

If you’re struggling or suspect you have MCAS, it’s in your best interest to reduce your exposure to these triggers, including:

  1. Extreme temperatures – either hot or cold
  2. Exposure to mold or Lyme disease and co-infections
  3. Emotional stress
  4. Insect bites
  5. Chemicals in personal products
  6. Medications that liberate histamine or block DAO
  7. Sodium benzoate –a common food preservative
  8. Airborne smells from chemicals or smoke
  9. Heavy metal toxicity – aluminum, mercury, lead, cadmium, bismuth and arsenic are known to be mast cell destabilizers
  10. Anesthetics

10 High Histamine Foods that Should be Avoided

Studies have shown that eliminating foods high in histamine and other triggers can significantly improve symptoms. Ten of the highest histamine foods include:

  1. Yeast and alcohol
  2. Dairy (especially fermented dairy like kefir)
  3. Gluten
  4. Fermented foods, especially sauerkraut, kombucha, miso
  5. Cured and smoked meats and fish
  6. Shellfish
  7. Citrus foods – lemon, lime, orange
  8. Vinegar
  9. Leftover and aged food – especially if left in the refrigerator and not frozen immediately
  10. Berries – strawberries, blueberries, raspberries

More information about histamine containing foods and following a low-histamine diet can be found here.

Conditions Associated with Mast Cell Activation Syndrome

Because MCAS is a chronic, multi-system, multi-symptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:

  • Chronic inflammatory response syndrome
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autism
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Chemical and medication sensitivities
  • Postural orthostatic hypotension (POTS)
  • CIRS – exposure to mold mycotoxins is a potent stimulator of mast cell activation
  • Migraines
  • Depression
  • Fibromyalgia
  • Fungal infections
  • Tinnitus
  • Multiple Sclerosis
  • Cancer

In general, inflammation accompanies MCAS and most of its coinciding or associated illnesses. If you are struggling to get one of these illnesses under control, there’s a possibility MCAS could be causing further complications.

It’s a good idea to check for MCAS if you have any of the above conditions and vice versa.

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Mast Cell Activation Syndrome and Histamine: When Your Immune System Runs Rampant

There is undoubtedly an escalating epidemic of chronically unwell people in North America. The present method of looking at illness is geared toward a single organ, a single specialty, a single drug, and voila! – let’s hope for a cure. Often patients go from pillar to post to see various medical consultants according to specialty (gastroenterologists, dermatologists, etc.), only to discover there isn’t one underlying syndrome or root cause that explains all the assorted symptoms the patient is experiencing. Patients may be given multiple diagnoses with multiple treatment options or medications, often with conflicting interactions and side effects that are worse than the underlying condition they are meant to treat.

Recently, a number of new ways of looking at chronic multisystem, multisymptom diseases has emerged as pioneering physicians connect previously disconnected dots and make sense of disparate symptoms that were never understood as components of a single syndrome. The first is the trailblazing work of Dr. Ritchie Shoemaker on chronic inflammatory response syndrome (CIRS). This syndrome is induced primarily by mold biotoxins and the inflammagens of water-damaged buildings, ciguatera or pfiesteria infestations, or Lyme disease and co-infections. The second is the pioneering work of Dr. Lawrence Afrin on mast cell activation syndrome (MCAS). Dr. Afrin is a board-certified hematologist/oncologist who recently wrote a book, “Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity.”

Two important books that address the complex syndromes that may underlie many chronic, multisymptom, multisystem disease conditions are:

  • Surviving Mold: Life in the Era of Dangerous Buildings, by Ritchie C. Shoemaker, M.D.
  • Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity, by Lawrence B. Afrin, M.D.

What is Mast Cell Activation Syndrome?

What is MCAS? Mast cell activation syndrome (MCAS) refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release, often without causing abnormalities in routine laboratory or radiologic testing. Most people with MCAS have chronic and recurrent inflammation, with or without allergic symptoms. This occurs when an aspect of the innate immune system becomes overactive and releases a flood of inflammatory chemicals, which may affect every organ in the body. The symptoms of MCAS will wax and wane over time. Another way to think of this is the symptoms will flare up and go into remission, affecting different organs and body parts, over and over again throughout a person’s life, without a common unifying theme or established diagnoses to account for the patient’s presentation of symptoms.

MCAS can present subtly but may become more serious as an individual ages. If you were to chart the symptoms of MCAS on a timeline, beginning at birth you can often identify symptoms that began at a very young age.

For some, MCAS becomes a highly probable diagnosis when they notice that they have had various symptoms of an inflammatory nature over the years. Mast cell activation syndrome symptoms may include:

  • Allergies as a toddler
  • Various skin rashes that came and went
  • Disturbed gut function (possibly diagnosed as irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD) or small intestinal bacterial overgrowth (SIBO))
  • Unexplained anxiety
  • Headaches
  • Insomnia
  • Poor wound healing

Any of these symptoms could indicate MCAS.

You can take our Hoffman Centre for Integrative Medicine MCAS Questionnaire HERE.

Dr. Afrin believes that MCAS is an epidemic with as many as 14 to 17 percent of the US population having MCAS – one out of every six to seven individuals. It has been said that it may take up to 10 years and numerous doctor visits before someone is adequately diagnosed and treated by a knowledgeable physician—or the patient figures it out for themselves!

What are Mast Cells, Mast Cell Mediators, and Histamine?

Mast cells are types of white blood cells that release up to 200 signalling chemicals, or mast cell mediators, into the body as part of an immune system stabilizing defense response against foreign invaders (parasites, fungi, bacteria, or viruses), allergens and environmental toxins.
We need mast cells to protect us from infection, heal wounds, create new blood cells, and develop immune tolerance. However, in conditions in which these cells are dysfunctional or overactive, they can cause serious issues.

Mast cells are found in most tissues throughout your body. In particular, they are found in tissues that are in close contact with the environment such as your skin, airways, and gastrointestinal tract. Mast cells are also found in your cardiovascular, nervous, and reproductive systems.

Mast cell mediators are the preformed granules secreted by mast cells in response to an outside stimulus, which can occur very quickly, in milliseconds. Mast cell mediators include histamine, proteases, leukotrienes, prostaglandins, chemokines, and cytokines. Their job is to signal and guide other cells, tissues, and organs to respond to the hostile invaders. These mast cell mediators provoke potent inflammatory responses that can include urticaria (AKA hives—skin rash and swelling), angioedema (swelling beneath the skin surface), bronchoconstriction (airway constriction), diarrhea, vomiting, hypotension (low blood pressure), cardiovascular collapse, and death, all within a matter of minutes.

Detailed Symptoms of Mast Cell Activation Syndrome

Patients who come into my office with MCAS usually have multisystem, multisymptom inflammatory responses. These symptoms have often caused them to trudge from doctor to doctor, undergoing rounds of testing, causing them to feel extraordinarily confused as to what’s happening to their body. Because the symptoms of MCAS have so broad a reach and differ so considerably from person to person I’d like to break them down by nonspecific, general clues, and organ system signs.

See Keith Berndtson’s (http://havenmedical.com/) slide below: Permission to use slide given by author.

 

Mast Cells The Bad

 

Histamine Intolerance & Mast Cell Activation

 

Most Common General Symptoms:

  • “I’ve been sick for as long as I can remember”
  • “I overreact to bee stings, mosquito bites, penicillin and most medications”
  • “I can’t take a full breath”
  • “Whenever I stand up I get lightheaded”
  • Insomnia/sleep disorders starting early in life
  • Tinnitus/ringing in the ears from a young age
  • Vomiting as an infant
  • Abdominal pain as an infant
  • Facial and chest flushing ( a red flush when embarrassed or stressed)
  • Dermatographism—a red line appearing on the skin when scratched with a blunt object
  • Frequent infections, cold, viruses, gut viruses as an infant, adolescent or adult
  • Fatigue and malaise
  • Frequent fevers
  • Edema—“water” accumulation in different parts of body
  • Waxing and waning of symptoms
  • Food, drug, and chemical intolerances (especially fragrances). This is a very common symptom which may be exacerbated by phase 1 and phase II liver detoxification problems as identified by gene testing
  • Sense of being cold all the time
  • Decreased wound healing
  • Hypersensitivity to much in environment, including medications
  • Weight gain or loss
  • Heat intolerance
  • Frequent family history of cancer, especially intestinal or bone marrow (hematologic)
  • Generally feeling inflamed
  • Generalized lymphadenopathy (enlarged lymph nodes)

MCAS Symptoms by Organ System

Eyes – Red eyes, irritated eyes, dry eyes, burning eyes, difficulty focusing vision, and conjunctivitis (pink eye).

Nose – Nasal stuffiness, sinusitis, postnasal drip, hoarseness, laryngitis, nose bleeds (epistaxis), and intranasal sores.

Ears – Ringing in ears (tinnitus) and Eustachian tube dysfunction (blocked, popping ears).

Throat – Vocal cord dysfunction, throat swelling, sores on tongue/mouth, itchy throat, burning mouth, and difficulty swallowing

Skin – Hives, angioedema (swelling of the skin), skin flushing, itching, skin rashes, dermatographism (when scratched skin causes a red welt), chronic itching, urticarial pigmentosa (legion/hive-like spots on the skin), flushing, bruising easily, reddish or pale complexion, cherry angiomata (skin growths), patchy red rashes, red face in the morning, cuts that won’t heal, fungal skin infections, and lichen planus.

Cardiovascular – Fainting, fainting upon standing, increased pulse rate (tachycardia), palpitations, spikes and drops in blood pressure, high pulse or temperature, high triglycerides, lightheadedness, dizzy, hot flashes, and postural orthostatic hypotension syndrome (POTS).

Respiratory – Wheezing, asthma, shortness of breath, difficulty breathing deep, air hunger, dry cough, chronic obstructive pulmonary disease (COPD), and chronic interstitial fibrosis.

GI Tract – Left upper abdominal pain, splenomegaly (enlarged spleen) epigastric tenderness, nausea, vomiting, diarrhea and/or constipation, abdominal cramping, bloating, non-cardiac chest pain, malabsorption, GERD/acid reflux, cyclic vomiting syndrome, colonic polyps, and gastric polyps.

Liver – High bilirubin, elevated liver enzymes, and high cholesterol.

Neurological – Numbness and tingling (especially in the hands and feet), headaches, migraines tics, tremors, pseudo-seizures, true seizures, waxing and waning brain fog, memory loss, poor concentration, difficulty finding words, and spells of cataplexy (suddenly becoming disconnected from and unresponsive or unreactive to the world around).

Musculoskeletal – Muscle pain, fibromyalgia, increased osteopenia, osteoporosis, weakness, and migratory arthritis (joint pain).

Coagulation – History of clots, deep vein thrombosis, increased bruising, heavy menstrual bleeding, bleeding nose, and cuts that won’t stop bleeding.

Blood disorders – Anemia, increased white blood cell count, platelets, decreased white blood cell counts, decreased neutrophils, decreased lymphocytes, decreased platelets, reductions in CD4 helper lymphocytes, reductions in CD8 positive suppressor lymphocytes, reductions or excesses of IgA, IgG, IgM, IgE, a known condition called MGUS, myelodysplastic syndrome (reduced red cells, white cells, platelets), and increased MCV (mean corpuscular volume).

Psychiatry – Anxiety, panic, depression, obsessive compulsive disorder (OCD), decreased attention span, attention deficit/hyperactivity disorder (ADHD), forgetfulness, and insomnia.

Genitourinary – Interstitial cystitis, recurrent bladder infections, sterile bladder infections, and frequent urination.

Hormones – Decreased libido, painful periods, heavy periods, infertility, and decreased sperm counts.

Dental – Deteriorating teeth.

Anaphylaxis – Difficulty breathing, itchy hives, flushing or pale skin, feeling warm after exposure, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.

Illnesses Associated with MCAS

There are a number of illnesses and conditions that can exacerbate MCAS, including chronic inflammatory response syndrome (CIRS), poor methylation as determined by genetic MTHFR defects (leading to low SAMe, which degrades histamine intracellularly), deficiencies in histamine-N-methyltransferase enzyme (HNMT; degrades histamine in the liver) and deficiencies in the gut-based diamine oxidase (DAO) enzyme, which degrades histamine found in food. Histamine is one of the many inflammatory mediators released by individuals with MCAS. For those with healthy DAO levels, nearly all the histamine derived from food sources are broken down by their DAO enzymes.

But when there’s a lack of DAO, a DAO deficiency, histamine can assist in creating intestinal permeability and upregulated inflammation. If a person suffers from small bowel intestinal overgrowth (SIBO) or has significant small intestinal issues (called dysbiosis), the lining of the small intestine may be disrupted. This leads to even lower levels of the DAO enzyme and hence, intestinal permeability.

Here’s a relatively common situation:

A woman who struggles with chronic fatigue and malaise throughout her life gets pregnant and suddenly feels energetic and wonderful throughout her pregnancy. Studies suggest this could be because DAO levels are up to 500 times higher than normal during normal pregnancies.

Alternatively, a person who was previously quite healthy develops a bacterial infection, is prescribed a 10-day course of antibiotics and suddenly develops severe reactions to certain foods. When looked at closely, these foods are found to contain high histamine levels. The current fads of consuming bone broths and fermented foods such as sauerkraut and kombucha only help to exacerbate this condition.

Histamine can have a powerful effect on a person’s wellbeing, making it important to be aware of the symptoms that indicate MCAS.

Histamine Intolerance is a Subset of MCAS

Mast cell activation syndrome (also referred to as mast cell activation disorder (MCAD)) is sometimes confused with histamine intolerance. The major difference is that with MCAS and mast cell activation disorder, a person’s mast cells secrete many mediators of inflammation, such as leukotrienes and prostaglandins, not just histamine—although histamine is an important component. Histamine intolerance is considered a subset of MCAS where too much histamine is released from mast cells, too much histamine is taken in by consuming histamine-containing foods, histamine is not broken down in the gut because of DAO gut enzyme deficiency, or not broken down in the liver because of HNMT deficiency.

However, histamine is not all bad; it serves useful functions as a neurotransmitter, helps to produce stomach acid, and is an important immune mediator when not in excess.

Diagnosis of Mast Cell Activation Syndrome

A proper diagnosis of mast cell disorder requires the presence of several symptoms from the above list. In addition, other disorders should be ruled out by a specialist in functional medicine.

MCAS is so difficult to diagnose because it may present in so many varied ways that traditional health care providers are not always trained to assess. There is a tremendous range of possible presentations, with local and remote effects which wax and wane over time.

If MCAS is suspected at our office, I send patients home with Chapter 6 of the book Mast Cells – Phenotypic Features, Biological Functions and Role in Immunity by David Murray. This chapter was written by Dr. Afrin, entitled Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome. It describes, system by system, most of the symptoms that can be attributed to this diagnosis. Patients then return the symptom check list, which we review together slowly in order to establish the clinical diagnosis. I then order the lab tests to prove its existence.

In Dr. Afrin’s own words, “The general presenting motif of MCAS is chronic multisystem polymorbidity, generally of an inflammatory theme and with assorted elements waxing and waning over time, sometimes in synchronization with one another but more often cycling with different periods and amplitudes. The range of mast cell mediators and their effects is so great that “unusual” presentations actually become de riguer.”

Lab tests can be done to check for mast cell mediators. Tryptase is one of the most common mediators released by mast cells in those with mastocytosis (abnormal numbers of mast cells), but not for those with MCAS (abnormal release of proinflammatory mediators by mast cells, but not an increased number, as in the much rarer mastocytosis). Lab tests can also check for other mediators, such as histamine and prostaglandins; however, most doctors and many labs, particularly those in Canada, will not run the tests that are required to make the diagnosis.

Sometimes patients are able to identify triggers of their MCAS. These may be food or non-food triggers. Pay close attention to what you’ve eaten and have been exposed to when symptoms worsen.

After symptoms have been identified, other conditions have been ruled out, lab tests have been analyzed, and some treatment techniques have proven to relieve symptoms, an official diagnosis of MCAS is made.

In an effort to help you notice common triggers, below are 10 non-food and 10 food triggers that commonly provoke mediator release in those with MCAS.

10 Non-Food Triggers of Mast Cell Activation Syndrome

If you’re struggling or suspect you have MCAS, it’s in your best interest to reduce your exposure to these triggers, including:

  1. Extreme temperatures – either hot or cold
  2. Exposure to mold or Lyme disease and coinfections
  3. Emotional stress
  4. Insect bites
  5. Chemicals in personal products
  6. Medications that liberate histamine or block DAO
  7. Sodium benzoate –a common food preservative
  8. Airborne smells from chemicals or smoke
  9. Heavy metal toxicity – aluminum, mercury, lead, cadmium, bismuth and arsenic are known to be mast cell destabilizers
  10. Anesthetics

10 High Histamine Foods that Should be Avoided

Studies have shown that eliminating foods high in histamine and other triggers can significantly improve symptoms. Ten of the highest histamine foods include:

  1. Yeast and alcohol
  2. Dairy (especially fermented dairy like kefir)
  3. Gluten
  4. Fermented foods, especially sauerkraut, kombucha, miso
  5. Cured and smoked meats and fish
  6. Shellfish
  7. Citrus foods – lemon, lime, orange
  8. Vinegar
  9. Leftover and aged food – especially if left in the refrigerator and not frozen immediately
  10. Berries – strawberries, blueberries, raspberries

Conditions Associated with Mast Cell Activation Syndrome

Because MCAS is a chronic, multisystem, multisymptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:

  • Chronic inflammatory response syndrome
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autism
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Chemical and medication sensitivities
  • Postural orthostatic hypotension (POTS)
  • CIRS – exposure to mold mycotoxins is a potent stimulator of mast cell activation
  • Migraines
  • Depression
  • Fibromyalgia
  • Fungal infections
  • Tinnitus
  • Multiple Sclerosis
  • Cancer

In general, inflammation accompanies MCAS and most of its coinciding or associated illnesses. If you are struggling to get one of these illnesses under control, there’s a possibility MCAS could be causing further complications.

It’s a good idea to check for MCAS if you have any of the above conditions and vice versa.

You can take our Hoffman Centre for Integrative Medicine MCAS Questionnaire HERE.

Ask Your Doctor for Lab Work

MCAS can be difficult to diagnose because lab test results may fluctuate as symptoms wax and wane. Many tests may need to be repeated during times of symptom flare-ups. Poor handling of specimens by the laboratory is also a real issue affecting results. Lab testing may thus result in false negatives despite a clinical history highly consistent with MCAS. Furthermore, MCAS doesn’t always cause abnormalities in lab work, adding to the complexity of diagnosis. Positive lab work is obtained only 20% of the time.

If you’re interested in getting lab work done to check for MCAS, I recommend the tests listed below. The top five, in bold, are the most important and necessary to establish a diagnosis:

  1. Histamine – plasma – Quest 36586 – must be chilled. Normal range – 28-51 ug/l.
  2. N-Methylhistamine – 24-hour urine – must be chilled. Normal range – less than 200 mcg/g.
  3. Prostaglandin D2 – plasma – must be chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  4. Prostaglandin D2 (PGD2) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  5. Chromogranin A – Quest 16379 – must be off proton pump inhibitors (PPIs) and H2 blockers (Pepcid and Zantac) for 5 days before tests, since they can falsely elevate chromogranin A.
  6. Prostaglandin 11-beta F2 Alpha (PGF2alpha) – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  7. Serum Tryptase – Quest 34484. Rarely elevated in MCAS. NR less than 11.5 ng/ml. Positive if increase over baseline of 20% or baseline greater than 15.
  8. Leukotriene E4 – 24-hour urine – chilled. Must be off NSAIDS (Motrin, Advil), aspirin, ASA, anything containing aspirin, for 5 days.
  9. Plasma heparin Anti-XA (must be off heparin products) – chilled. Degrades quickly.
  10. Blood clotting profile – Thrombin/PT/PTT/INR.
  11. Anti-IgE Receptor antibody.
  12. Neuron Specific Enolase – Quest 34476.
  13. Plasma pheochromocytoma workup.
  14. Porphyria workup.
  15. Factor VIII deficiency.
  16. Plasma free norepinephrine – Quest 37562.
  17. Urinary metanephrines – can b done in normal Calgary labs.
  18. Immunoglobulins – IgG, IgM, IgE, IgA
  19. Bone marrow biopsy looking for the following markers: CD117/CD25; CD117/CD2.
  20. Gastrin
  21. Ferritin
  22. CBC – eosinophils, basophils.
  23. Antiphospholipid antibodies.
  24. Genetic testing looking for Phase 1 and Phase II liver detox and methylation defects.
  25. Dunwoody Labs – test zonulin, histamine, DAO enzyme deficiency.

Many of these tests require specimens that are chilled by using a special centrifuge as the mast cell mediators are fleeting and degrade very quickly if not handled properly.

Further tests that may be of help:

  1. MTHFR gene mutations
  2. MAT gene mutations
  3. DAO gene mutations
  4. HNMT gene mutations. The liver plays a role in histamine intolerance. Histamine is not just disassembled in the gut by diamine oxidase (DAO). It is also disassembled in the liver, where it is in high concentrations, by HNMT.
  5. Glutathione levels. If glutathione levels are depleted, the inflammatory mediators released by mast cells may not be adequately neutralized by glutathione, the master antioxidant. This can lead to a vicious circle where oxidative stress results in mast-cells releasing inflammatory chemicals, which need to be detoxified by Phase 1 of the liver. If glutathione is low, the liver will be unable to neutralize them, resulting in further inflammation and oxidative stress.

These tests can help you identify whether MCAS is the cause of your mysterious and seemingly unrelated symptoms.

Treatments for Lowering Histamine and Reducing MCAS Symptoms

Now, you might be thinking, “Why can’t I just take an antihistamine?”

Antihistamines don’t actually reduce histamine release. They only block histamine receptors, preventing you from feeling the symptoms. You may need a round-the-clock blockade of the H1 and H2 receptors, every 12 hours.

If you want lasting relief for MCAS:

  • Histamine 1 blockers – hydroxyzine, doxepin, loratadine, fexofenadine, diphenhydramine, ketotifen, and cetirizine.
  • Histamine 2 blockers – famotidine (Pepcid, Pepcid AC), cimetidine (Tagamet, Tagamet HB), ranitidine (Zantac). Famotidine is chosen most often as it has fewer drug interactions than Tagamet).
  • Mast cell stabilizers – cromolyn, ketotifen (both a mast cell stabilizer and an H1 blocker), hydroxyurea, quercetin.
  • Leukotriene inhibitors – montelukast (Singulair), zafirlukast (Accolate)
  • Tyrosine kinase inhibitors.

H1 and H2 blockers must be taken every 12 hours for maximum effect. It may take up to 12 months to achieve maximum therapeutic effect. The doses may need to be increased to up to three times the recommended over-the-counter dosing.

Here is how I approach treatment with my MCAS patients:

  • Eat a low-histamine diet: Remove alcohol, smoked and cured meat, tinned fish, pickled and fermented foods, berries (strawberries being one of the worst culprits), citrus, nuts, chocolate, dairy, spinach, yeast, soy sauce, tomatoes and tomato products, preservatives, and vinegar. Stop eating leftover food. This will only reduce the incoming histamine and won’t affect the mast cell overactivity within the cells of the body. A comprehensive guide regarding the low-histamine diet can be found here.
  • Promote good gut health: Cut back on gut-damaging and inflammatory foods, and increase probiotics. Use a DAO enzyme, which goes under the generic name Umbrellux DAO – two tablets, 20 minutes before each meal.
  • Stabilize mast cell release of histamine with quercetin and vitamin C 500 mg – two tablets three times daily. We use a product called Natural-D Hist from Ortho Molecular Products.
  • Use H1 and H2 blockers every 12 hours – I use, on average, levocetirizine 5 mg twice daily and famotidine 20 mg twice daily.
  • Block nighttime histamine release with ketotifen or zaditen – 0.25–1 mg at night. Excellent sleep aid, mast cell stabilizer, H1 antihistamine. Excellent treatment for eosinophilic esophagitis.
  • Treat any existing infections: Have a thorough examination done to identify and treat any potential infections in the body which are powerful mast cell triggers. Stool testing by Genova labs and Cyrex Lab Pathogen Testing (array 12) can be of assistance in identifying pathogens.
  • Identify and remove toxins and allergens: This could be heavy metals, mercury fillings, cosmetics, and household cleaners.
  • Nutrients that assist in the treatment: This includes vitamin B6, alpha lipoic acid, vitamin C and E, selenium, omega-3s, N-acetylcysteine (NAC), methylation donors like methyl-folate, SAMe, and riboflavin.
  • Herbs: Nigella sativa, butterbur, turmeric, ginger and peppermint.
  • Get into a solid routine: Getting high quality sleep and staying on schedule helps keep mast cells in check.
  • Reduce stress: Stress, through the action of corticotropin hormone, can activate your mast cells and cause them to destabilize and release mediators.
  • One of the best resources for how to deal with histamine and mast cell activation through nutrition and supplementation is the website and Facebook posts by Yasmina Ykelenstam www.healinghistamine.com.

It can be incredibly discouraging to feel so sick for so long and not find any answers. It is my hope that we continue to learn more about multisystem conditions such as MCAS and spread useful information so it may end up in the hands of those suffering.

Share this article with friends and family to help spread the word about mast cell activation syndrome. They may discover it’s more than allergies that’s keeping them down.

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Resources

Yasmina Ykelenstam – excellent resource:  www.healinghistamine.com.

Dr. Afrin’s website – the main researcher:  www.mastcellresearch.com. Many links to mast cell information are available on this website.

Dr. Theoharides – another major researcher: http://www.mastcellmaster.com/

Hoffman Centre for Integrative Medicine MCAS Questionnaire: https://hoffmancentre.com/wp-content/uploads/2017/11/7.-Mast-Cell-Activation-Syndrome-Clinical-Questionniare-November-7-2017.pdf

https://www.youtube.com/watch?v=82dmZhCBuBo

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

https://ehlers-danlos.com/2014-annual-conference-files/Anne%20Maitland.pdf

https://tmsforacure.org/symptoms/symptoms-and-triggers-of-mast-cell-activation/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231949/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343118/

https://www.ncbi.nlm.nih.gov/pubmed/16931289

https://www.ncbi.nlm.nih.gov/pubmed/17587883

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/

https://www.ncbi.nlm.nih.gov/pubmed/22957768

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545645/

https://academic.oup.com/humupd/article/14/5/485/812106/Effects-of-histamine-and-diamine-oxidase

https://www.ncbi.nlm.nih.gov/pubmed/24098785

http://ajcn.nutrition.org/content/85/5/1185.long

https://link.springer.com/article/10.1007/BF01997363

https://www.ncbi.nlm.nih.gov/pubmed/25773459

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507480/

https://www.ncbi.nlm.nih.gov/pubmed/15462834

https://www.ncbi.nlm.nih.gov/pubmed/22562473

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374363/

https://www.ncbi.nlm.nih.gov/pubmed/21244748

https://www.ncbi.nlm.nih.gov/pubmed/23784732

https://www.ncbi.nlm.nih.gov/pubmed/18394691

https://www.ncbi.nlm.nih.gov/pubmed/24060274

https://www.ncbi.nlm.nih.gov/pubmed/10415589