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Could Your Histamine Intolerance Really Be Mast Cell Activation Disorder?

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Reviewed by Laura Beth Schoenfeld, RD, MPH

Do you have trouble with histamine? Have you struggled to get a diagnosis? In Mast Cell Activation Disorder (MCAD), part of the innate immune system becomes hyperactive, releasing histamine and other chemicals that affect every organ system in the body. Read on to learn more about MCAD, and how you can address the root cause.

Histamine intolerance
Do you have trouble with histamine? Mast cell activation syndrome can contribute to the release of histamine. istock.com/Ugreen

Histamine intolerance has become a popular term in the natural health community.  Characterized by symptoms that appear to worsen with the intake of foods that are high in histamine or that stimulate the release of histamine, histamine intolerance is not really a diagnosis as much as it is a description of symptoms.

Most clinicians, including myself, now believe that Mast Cell Activation Disorder is a more accurate description of what patients with so-called “histamine intolerance” are suffering from. There are a number of factors that can contribute to, or cause, histamine intolerance, including excess histamine production, diamine oxidase (DAO) enzyme deficiency, HMNT mutation, and poor methylation in the liver; however, my experience has been that MCAD is responsible for a large number of cases of histamine intolerance. This article will serve as an introduction to MCAD – what it is, what causes it, and how to treat it.

Mast Cells: Sentinels of the Immune System

Mast cells are white blood cells found in all human tissues, especially at places where the body interfaces with the environment, like the gut and skin. Though best known for their role in allergies, mast cells are also involved in the formation of new blood cells, wound healing, the development of immune tolerance, defense against pathogens, and the maintenance of blood-brain barrier function. (1, 2)

Mast cells are the sentinels of the innate immune system, on the lookout for environmental changes or insults to the body. They respond by releasing mediator molecules that influence the behavior of other cells and tissues in an effort to maintain normalcy, or “homeostasis.”

There are over 200 of these mediators stored within the granules of mast cells, including tryptase, prostaglandins, leukotrienes, and histamine. (3)

Histamine often gets a particularly bad rap, but it has many important physiological functions in the body: acting as a neurotransmitter, regulating stomach acid secretion, and playing a role in the local and systemic immune response. (4) The key takeaway here is that we need mast cells and their mediators for normal body function. The issue arises when these cells become overactive, as they do in individuals with MCAD.

Mast Cell Activation Disorder: The Hidden Diagnosis

Mast cell activation disorder is characterized by the accumulation of mast cells that are genetically altered (mastocytosis) and/or the abnormal release of mast cell mediators (Mast Cell Activation Syndrome). Because mast cells are found in all human tissues, and mast cell mediator receptors are found on almost every cell in the body, MCAD has the potential to affect every organ system. (5)

MCAD presents clinically as a chronic, multisystem pathology of a generally allergic and inflammatory theme, and has been associated with obesity, diabetes, skin conditions, irritable bowel syndrome (IBS), depression, and more. (6) MCAD does have a genetic component, and tends to cluster in families (7), though related individuals may present with very different symptoms. (8)

Trouble with histamines? Get to the root of the problem.

MCAD is estimated to be more prevalent (9) than other diseases of mast cell dysfunction, but also more difficult to recognize. This is at least in part due to the fact that it often does not cause abnormalities in routine lab testing. MCAD was not named as a condition until 2007 (10) and diagnostic criteria weren’t proposed until 2010. (11)

Finding the Root Cause of MCAD

In the functional medicine model, we always seek to address the root cause of disease, as opposed to just treating symptoms. We still have a lot to learn about MCAD, but I believe it is likely the result of deeper pathologies, including:

Heavy metal toxicity: Heavy metals like aluminum and mercury have been shown to destabilize mast cells. This makes sense, as the very purpose of using these as vaccine adjuvants is to elicit a heightened inflammatory immune response. Lead, cadmium, and bismuth have also been found to activate mast cells and cause mast cell mediator release. (12)

Infections or gut dysbiosis: The gut is home to 70% of the immune system (13), including a large number of mast cells. Parasitic infections, bacterial/viral infections, or bacterial/fungal overgrowth activate mast cells. (14) Helminth parasites and Candida have been shown to be potent stimulators of mast cell activation. (15, 16) Mast cells regularly interact with microbes, and gut dysbiosis itself may lead to MCAD. (17)

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CIRS: Chronic Inflammatory Response Syndrome could also play a role. Those who are particularly susceptible to mold and have a reduced ability to clear mycotoxins from the body, which leads to a constant activation of mast cells.

Nutritional Deficiencies: Some nutrient deficiencies can trigger MCAD. Vitamin D is required to maintain the stability of mast cells, and a deficiency has been shown to activate them. (18) Zinc is involved in regulating mast-cell function, and there may be a link between magnesium deficiency and inflammation. (19, 20)

Treatment for MCAD

Conventional treatments for MCAD are pharmacological agents that block the action of mast cell mediators. While these may provide much-needed relief to patients, they are not a long-term solution and can have unwanted side effects. Safer short-term action steps that you can take to provide some relief include:

  • Adopting a low-histamine diet: For some people with MCAD, a low-histamine diet provides significant relief. Supplemental diamine oxidase can also help by increasing histamine breakdown.  But, it’s important to keep in mind that this is only reducing exogenous (outside) histamine, and not altering the amount produced by your mast cells endogenously (within the body). Histamine is also only one of many mediators produced during mast cell degranulation.
  • Focus on nutrients and foods known to stabilize mast cells: Many nutrients, including selenium (21) and vitamin C (22), have been shown to stabilize mast cells. A number of herbs and spices, like holy basil (23), peppermint (24), ginger (25), thyme (26), and turmeric (27) also have this effect. I have also seen good results with supplemental forms of quercetin (28), bromelain, nigella sativa (29), nettle (30), and butterbur. (31)
  • Reducing stress: Corticotropin hormone, released in response to physical or psychological stress, destabilizes mast cells and causes them to release their mediators. (32)
  • Entraining circadian rhythms: Mast cell activity closely mirrors circadian rhythms (33), so getting enough sleep and avoiding blue light at night is crucial.

Ultimately though, we need to address the root cause:

  • Remove heavy metals from your system: Chelating agents can help to remove heavy metals from your system. This is best done under the guidance of a healthcare practitioner. Removal of old mercury fillings by a trained professional can also reduce the burden of heavy metals in the body.
  • Treat infections: A comprehensive stool test can help identify parasites and other infections that could be contributing to mast cell activation.
  • Heal your gut: Remove inflammatory foods and focus on nutrient density. Include plenty of probiotic, prebiotic, and healing foods in your diet.

Did You Know?

Symptoms of histamine intolerance vary, but can include:

  • Itchy skin, eyes, ears, and nose
  • Hives
  • Eczema
  • Swelling of the soft tissues on the face, mouth, or throat (often described as “throat tightening”)
  • Nasal congestion
  • Red, watery eyes
  • Low blood pressure
  • Chest pain
  • Rapid heart rate
  • Feelings of panic or extreme anxiety
  • Fatigue, irritability, or confusion
  • Joint and muscle pain
  • Tinnitus (ringing in the ears)
  • Gastrointestinal distress

While the underlying cause of histamine intolerance should be addressed, adopting a low-histamine diet can help alleviate some of these symptoms. That can mean making significant lifestyle shifts, like avoiding food additives, prepared foods, certain spices, and alcohol.

As a health coach, you could offer the support needed to help someone adopt a new dietary approach like a low-histamine diet. Health coaches facilitate life changes and empower their clients to uncover their motivations and establish their own goals for their health.

Mastering those skills is part of what we teach in the ADAPT Health Coach Training Program. We also offer an in-depth education into Functional and ancestral health, covering topics like histamine intolerance, eating for gut health, environmental toxins, and more.

Find out more about the ADAPT Health Coach Training Program

345 Comments

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  1. Sounds possible that this is what is going on with my husband. After several years of intense stress in an extremely demanding job, he started responding to cold temperatures with extreme itching, hives and burning skin. He also cannot tolerate even a drop of alcohol without being in detox for a week. Other symptoms are chest pain, tiredness and dizziness. We’ve seen a functional doctor and he ran a lot of tests and everything came back normal 🙁 He has not gone though any kind of genetic, heavy metal or microbial testing. What is the best way to test for this disorder?

    • Did your husband get his blood tested for cryoglobuline? It may be positive and may be the reason for itching and hives when the temperature drops.

  2. This diagnosis appears to be the key to solving Asthma problems. Most of the sutritients recommended do work for Asthma.

    I have Chronic Lyme (30+ Years) and the MTHFR A1298c mutation. The key issue is fighting the inflammation that is causing brain swelling and severe 24/7 headaches. Could the brain inflammation be MCAD? What is the best approach to control MCAD for people with these types of conditions?

    Thank you for this new insight into our medical conditions. Anita

  3. Thank you for raising awareness of this, we need to get MCAS onto the radar of more doctors and health professionals. In the UK there are only a handful of doctors who treat MCAS, i.e. A dermatologist, urologist ( some interstitial cystitis is mcas related), gastro, few allergists or immunologists…). But knowing that mcas is now thought to be quite common and linked to IBS, anxiety, depression, IC, etc etc this is so important.
    As in some areas holistic professionals are rare, and not everyone can afford it,?information on what tests would be very useful…i.e. How do U test fir metals?

    Also I know dysbyosis can lead to overproduction of histamine but how does it relate to overactive mast cells? Thanks!

    • Hello Anastasia,

      Would you please point me in the direction of some of the doctors in the UK? I am trying to get a diagnosis of the dozens of symptoms I have going on, and my GP is kindly condescending and not helpful.

      Thank you.

      • If you join the Mast cell activation uk group on facebook they have s great list in their files…plus is great group!

  4. Hi Chris,
    I have been searching for better ways to treat MCAD. I was diagnosed with Crohn’s disease in my early 20s but have suspected it was more allergic. About 10 years ago I had “an episode” that has been diagnosed as heart problems, anxiety, allergies, brucellosis exposure, asthma, and many other things. I finally found an allergist willing to think outside the box who mentioned MCAD. She started me on many antihistamines and a drinkable mast cell inhibitor called Cromolyn, and I have found some relief, most particularly in my Crohn’s symptoms and anaphylactic responses. Unfortunately, I also get to deal with extreme fatigue among other side effects of so many antihistamines. I would love any and all information you have on this topic. My goal is to get off all of the medication and treat this naturally if possible.

    • I was excited to learn about cromolyn liquid, so I quiclkly logged-on to my prescription coverage plan’s website to see how much it costs. Too rich for my pockets! Depending on brand or generic, it is between $2,600 – $3,360 for a 90 day supply, and it’s all out of pocket. So sad!

      • Look into Enteragam. I am finding it helpful and am replacing the expensive Cromolyn with it (and it tastes much better!!). Foundation Care along with my insurance reduces the cost of Enteragam to $25/month!! Cromolyn was $145/month for me, but still expensive along with my other supplements, and thyroid hormone (which is costing me a arm and a leg!!). I have SIBO, hypothroid and a histamine issue.

  5. Wonderful to read this article! The more exposure this “rare” disease gets the more people will be helped.
    I’m one of the “lucky” who has a diagnosis of Mast Cell Activation Syndrome and have received a great deal of help from specific foods, supplements, probiotics and avoiding triggers. I also take one medication that is actually a mast cell stabilizer in addition to being an antihistamine. As Chris mentions there can be side effects, long term issues, etc. But it improved my quality of life tremendously.
    Be prepared to be your best advocate. Learn all you can about the disease if you seriously think you have it because your doctor (I have seen regular and functional) more than likely will not know it exists.

      • Test for serum tryptase, prostaglandins, leukotrienes, chromagranin A, heparin, and then possible tissue and/or bone marrow biopsies and aspirations. A very detailed health history of your entire life is also important.

  6. I was diagnosed with Mast Cell Activation Syndrome four years ago. My symptoms have improved since beginning treatment with antihistamines, mast cell stabilizers (oral Cromolyn and Ketotifen) and following a low histamine diet. Keeping a journal of foods and symptoms helps to identify triggers (odors/food/heat) and strategies to reduce mast cell degranulation. Mast cell disorder research is advancing and the Mastocytosis Society helps keep us up to date.

  7. I have Histamine Intolerance for sure. I assumed that it was basically the same thing as the Mast Cell Activation Disorder. Either way, I’m generally doing better, it presents on my chest. BUT, I also have been suffering with “seasonal allergies” all year long for the past year and a half. I defiantly think that the two presentations are connected. How to I reverse the condition? Just diet and nutrients aren’t doing it.

  8. I do know for a fact that if you get the trash foods out of your system and feed your body healthy foods and exercise at least 30 minutes EVERY day, you will see a huge improvement in how your body feels. This includes allergies, digestion problems, achy joints and arthritis. Eat three meals a day, small portions, lots of color, you can still have your dark chocolate in small portions, nuts and fruit become your go to snacks, drink plenty of water. Tea and coffee are ok too. I switched to decaf coffee over two years ago and have never gone back. The caffiene is out of my system and I feel much better than I used to. I know that everybody cannot do all this, but if I can I believe almost anybody can. I quit smoking 17 years ago and I feel like I never smoked at all. This lifestyle is different for me, it is a constant daily challenge and I face it every day knowing the changes I am making show me the results I have been looking for.

    • exercise can actually be a problem for people with mast cell and histamine problems. Unless you mean gentle yoga or walking. Probably best to just speak for yourself

        • Me too. I have always gotten “heat stroke”, and migraines from heat. Now I know why. Too vigorous of exercise makes me feel ill and depleted. Also, I have to be careful on beach vacations. I will feel worse on vacation because of the heat and because of more alcohol :(. Oh the alcohol. It was so sad to say goodbye to wine!!

    • You are an inspiration, I know I’m not willing to do all the changes you made at once, but I have made a list of what you did, and it’s all so realistic and simple (implementing will be not so simple 😉 ). Thank you for the down to earth reminder to take charge of health/lifestyle!

  9. Forgot to say that I frequently get itchy all over and have to take an anti histamine pill which quietens it somewhat but I will now try some natural remedies.
    Very interesting article the first time I have read about this condition.

  10. I have Hashimotos, celiac D, Candida overgrowth, and also have problems with contact dermatitis at the moment only occasionally, I thought it was hormone based but suppose it could be MCAD? My brother has lung fungus problems and asthma.

  11. I think I have histamine intolerance too, it started last year as a lumpy scratchy feeling in my throat which I was attributing to my hot yoga practice ,after a while I started to manifest dermatographism that is on and off depends on whatever.
    Sometimes I think is associated with stress sometimes can be food ,anyways its a mystery for me and am trying to understand it and to try to fix it but its a a tuff thing, the good side is that I am able to live with the symptoms once I understood that it’s not a big issue but it’s unpleasant and I hope at one point to be able to wake up one day without this condition.
    Also I think it may have been triggered by the flu vaccine that I took for the first time 2 years ago.

  12. This is interesting information. I have been diagnosed with dermatographia since I was ~13. I’ve been told it means the mast cells in my skin are “leaky” and will release their contents with just a light touch. Now I begin to think this is a systemic issue as I have migraines and digestive stress as well. Is there a test for this or just trial of diet changes and supplements?
    Thanks.

    • Low histamine chef has a whole post about testing if you Google. But they aren’t very accurate. A lot us diet supplement and med trials. Leaky cells is pretty much mcas!

  13. My daughter has histamime intolerance and MCAD. I have yet to find a stool test that accurately detects parasites. I’ve done Metametrics GI Effects on her several times and DRG lab stool test. Is there a different one you recommend Chris? Thank you!!

  14. I had histamine intolerance fairly severely for about two years. I couldn’t eat at a restaurant without flushing badly and had to limit my diet at home. I’m 42 years old, homozygous MTHFR C677T, and have some hetereozygous DAO mutations. I’ve been taking methylfolate/B vitamins along with trace minerals, vitamin c, etc., but the SINGLE thing that cured my histamine intolerance was avoidance of all cultured milk products, which contain the L. Casei strain of probiotic, (had to give up the morning yogurt!) plus an introduction of three probiotic/biophage products:

    1) Arthur Andrew Medical “Floraphage”
    2) Seeking Health “Bifido”
    3) Allergy Research Group “Lactobacillus plantarum / rhamnosus / salivarius”

    I have no intention of promoting these companies; only to tell fellow sufferers what worked for me because I know how awful it is to live with histamine intolerance. I took the three products every morning on an empty stomach before breakfast. Within two weeks, I saw a major improvement; and within a month or two I was back to eating anything and everything – red wine, parmesan, hurray!

  15. Very good article Chris. I have learned so much from you you’ll never know, thanks so much. I’m dealing with histamine issues. Working with a functional medicine doctor. Just got test results today, zonulin perfect, Dao optimum but histamine is high. So not sure what is going on at this point, but will see at my next appointment.

  16. So what probiotic foods can you eat? Most all low histamine food lists I have seen show most fermented foods as being high in histamine. And from personel experience I have had trouble with some fermented foods depending on my histamine and stress level.

  17. Could SIBO be a trigger for MCAD and histamine intolerance, and treating SIBO can be enough to treat MCAD?

    • In my experience, yes. I posted above that I was diagnosed with MCAD and then went to a naturopath who diagnosed SIBO and treated that with high-dose garlic (and, I’m remembering now, something else. I think it was neem maybe.) I have had very few symptoms for the last two years.

  18. Is this also related to Tyramine issues? I was told I have a SNP that makes me intolerant to high Tyramine foods.

    • Also I have taken antihistamines everyday for the last 35 years for nasal allergy symptoms and I have many food sensitivities, that result in migraines.

  19. I believe the major source of inflammation is aluminum. Check out the periodic table. Unlike every other heavy metals, which the body recognizes and strives to eliminate, aluminum is right in the middle of loads of essential minerals. Until about 80 years ago no one in the whole of evolutionary history was exposed to free aluminum. Now it is everywhere, it is highly reactive, and the body has no idea what it is or what to do with it. Unless we address our daily exposure I believe all kinds of inflammatory diseases will continue to increase. Check out the work of Dr. Christopher Exley.

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