Histamine Intolerance and Mast Cell Activation Syndrome Otesanya David March 31, 2022

Histamine Intolerance and Mast Cell Activation Syndrome

Histamine Intolerance and Mast Cell Activation Syndrome


Histamine Intolerance and Mast Cell Activation Syndrome

Histamine Intolerance and Mast Cell Activation Syndrome

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Photo courtesy of Melissa Marshall

Histamine Intolerance and Mast Cell Activation Syndrome

Will Cole

Functional medicine practitioner Will Cole says that histamine intolerance and mast cell activation syndrome (MCAS) are two related conditions that are often-overlooked pieces of a larger health puzzle. “Because the symptoms of histamine intolerance and MCAS can be similar to a lot of other health problems, it’s not always obvious that a person is struggling with them,” Cole says. He takes us through symptoms, how histamine intolerance and MCAS are diagnosed, and different approaches to treatment.

A Q&A with Will Cole, IFMCP, DNM, DC

What is mast cell activation syndrome?

Mast cells are a type of white blood cells that are a major part of your immune system. They help you fight infections and play a role in allergic reactions: If you come in contact with an allergen or an allergic substance, mast cells release chemicals known as mediators. Histamines are one type of mediator released by your mast cells during the inflammatory immune response to allergens.

In a healthy individual, these mediators help protect and heal your body. Mast cell activation syndrome, on the other hand, is when histamines are in hyperdrive. This excess release of histamines can be triggered by food, stress, trauma, medications, and even exercise.

What is histamine intolerance?

Your mast cells releasing histamines is part of a healthy, balanced immune system. Many foods naturally contain histamine or trigger the release of histamine in the body.

Problems occur, however, when there is a dysfunction or deficiency of the enzymes that break down histamine. Those enzymes are called histamine N-methyltransferase (HNMT) and diamine oxidase (DAO). Without the enzymes to effectively get rid of excess histamine, you could experience a histamine overflow, which can cause a lot of problems. This is histamine intolerance.

Because histamine intolerance is basically an allergic reaction without the allergen—also called a pseudoallergy—symptoms can be similar to allergic reactions (like a rash, runny nose, or trouble breathing). But I often see other symptoms in patients with histamine intolerance that have also been documented in scientific literature:

  1. Brain fog

  2. Digestive problems

  3. Skin problems like eczema and psoriasis

  4. Hormone imbalances

  5. Cardiovascular problems

  6. Migraines

  7. Nausea and vomiting

Because histamine intolerance involves the mast cells, it is often confused with mast cell activation. The difference, however, is that with MCAS, mast cells secrete multiple mediators in addition to histamine—whereas in histamine intolerance, the mast cells release only histamines and nothing else.

Ultimately, histamine intolerance can be an indicator of MCAS, but that doesn’t necessarily mean you have MCAS if you have histamine intolerance. By getting a comprehensive health history and lab testing, I am able to explore the extent of someone’s histamine intolerance and immune system as a whole.

How do you diagnose MCAS and histamine intolerance?

If I suspect either one of these conditions, I typically run labs to measure levels of histamine and the histamine enzyme DAO. Additionally, if someone notices their symptoms getting better after using antihistamine medications or other mediator-blocking medications, that’s a sign that we are likely dealing with MCAS and/or histamine intolerance.

What are the different approaches to treatment?

In functional medicine, we look at the many facets of someone’s health in order to uncover often-overlooked pieces of the puzzle that might be contributing to MCAS and/or histamine intolerance.

1. Get to the root of the problem.

MCAS and histamine intolerance have been directly linked to a variety of different conditions such as leaky gut syndrome, small intestinal bacterial overgrowth (SIBO), gluten intolerance, deficiencies of nutrients like vitamin D, medications (NSAIDs and pain medications, among others), methylation gene variants, mold exposure/toxicity, and chronic stress.

I find it is typically a confluence of some of these factors for most people struggling with histamine intolerance and MCAS. When I explore their health history thoroughly and run microbiome labs, food reactivity tests, nutrient panels, and genetic tests (some methylation gene variants can predispose some people to histamine intolerance), we are able to better determine if someone is dealing with any of these contributing factors and make a plan to address each one of them individually.

2. Pay attention to what you eat.

If you are dealing with MCAS and/or histamine intolerance, eliminating or greatly reducing your intake of high-histamine and histamine-releasing foods (while you are dealing with the root reasons of why you have the problem in the first place) is going to help mitigate reactions while you are on your healing journey. According the American Journal of Clinical Nutrition, these foods can include:

  1. Alcohol (including wine)

  2. Bone broth

  3. Canned food

  4. Cheese

  5. Chocolate

  6. Eggplant

  7. Fermented foods (kefir, kimchi, yogurt, sauerkraut)

  8. Legumes (soybeans, chickpeas, peanuts)

  9. Mushrooms

  10. Nuts

  11. Processed foods

  12. Shellfish

  13. Smoked meat products (bacon, salami, salmon, ham)

  14. Spinach

  15. Vinegar

Additionally, certain foods can trigger the release of histamine and create problems for people with histamine intolerance:

  1. Avocados

  2. Bananas

  3. Citrus fruits

  4. Kiwi

  5. Papaya

  6. Pineapple

  7. Plums

  8. Tomatoes

Some foods can also block DAO, which controls histamine:

  1. Alcohol

  2. Energy drinks

  3. Teas (black, green, yerba)

Studies have shown that focusing on a diet of low-histamine-containing foods can be helpful in alleviating symptoms of histamine intolerance. These include:

  1. Coconut milk

  2. Egg yolk

  3. Fresh organic meat

  4. Fresh vegetables (except eggplants, tomatoes, and spinach)

  5. Fresh wild-caught fish

  6. Gluten-free grains (rice, corn)

  7. Herbal teas

  8. Non-citrus fresh fruits (except for those mentioned above)

  9. Rice milk

The goal here is not to necessarily decrease or remove foods entirely or forever, but to deal with the underlying drivers of what is triggering the histamine intolerance in the first place. Over time, as function is regained, we work on the reintroduction of foods and drinks that were temporarily avoided.

Ultimately, since every person’s biochemistry is uniquely different, what works for one person is not always going to work for the next. That is why I always advocate working with your doctor to determine the best course of action for your specific health case when it comes to diet.

3. Support gut health and stabilize the immune system.

Research has shown that a component of histamine intolerance can be a deficiency of DAO, causing histamine not to be absorbed properly in the digestive tract due to problems like leaky gut syndrome, dysbiosis, or SIBO.

Addressing the underlying gut microbiome problem can be key. A few studies show probiotics can be beneficial—two strains of bifidobacterium and Lactobacillus rhamnosus are able to suppress histamine receptors.

While we are improving gut health, supplementing with DAO as well as nutrients like quercetin and vitamin C can help support the immune system’s ability to handle the excess histamines.

Do functional medicine approaches to MCAS/histamine intolerance treatment diverge from more traditional biomedical approaches to treatment?

On the surface level, functional medicine and traditional treatment approaches are similar: Decrease food triggers and stress. However, whereas conventional medicine relies on medications like antihistamines to alleviate symptoms, functional medicine also aims to address the underlying issues that are triggering the problem in the first place.

This is typically done by working on gut health, detoxing from mold toxins (mycotoxins), and supporting any genetic variants that play a role in MCAS and histamine intolerance. By doing this, functional medicine aims to avoid, if possible, the excessive or chronic use of antihistamines. Now, sometimes these are absolutely necessary—it’s just that in functional medicine, we don’t want to necessarily rely on them for daily use, indefinitely, if there’s another option.


Will Cole, IFMCP, DNM, DC, is a functional medicine expert who consults with people via webcam and locally in Pittsburgh. Cole specializes in clinically investigating underlying factors of chronic disease and customizing a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is the bestselling author of Ketotarian, The Inflammation Spectrum, and his newest book, Intuitive Fasting. Cole also cohosted the podcast goopfellas, and he now hosts his own podcast, The Art of Being Well.

This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.

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