Mast Cell Activation Syndrome + It’s Relationship To Histamine Intolerance: A Functional Medicine Overview


As a functional medicine practitioner, symptoms are not always so obvious and I have to do a little digging to get to the bottom of someone’s health problem. That’s especially true in the case of histamine intolerance and mast cell activation syndrome - two conditions that mirror each other in symptoms and having no known single cause.

Both of these issues are not that uncommon, but can be miserable to live with until you uncover exactly what you are going through. Let’s uncover what exactly these conditions are, how they can affect you, and what you can do to overcome these troublesome health problems.


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What is mast cell activation syndrome?

As part of your immune system, mast cells are a type of white blood cells that are responsible for fighting off infection and play a role in allergic reactions. For example, if you come across an allergen, mast cells release chemicals known as mediators to protect your body.

However, in mast cell activation syndrome (MCAS) these mediators can be released regardless of whether or not an allergen is present and can be triggered by things as simple as exercise, stress, certain medications, and food. This can make it very difficult for those with MCAS to pinpoint the cause of their symptoms and why they are in a constant state of “allergy-season” when it comes to their symptoms and how they feel. 

The difference between MCAS and histamine intolerance

As a response to allergens, your mast cells release mediators as part of a normal, healthy inflammatory-immune response. Histamines are just one type of these mediators.

Histamine intolerance happens when there is a deficiency or dysfunction of the enzymes - histamine N-methyltransferase (HNMT) and diamine oxidase (DAO) - responsible for breaking down histamine. If your body doesn’t have enough of these enzymes, histamine will continue to build up in your body leading to a cascade of health problems.

Ultimately, histamine intolerance is known as a “pseudoallergy” where one experiences an allergic reaction without having to be triggered by an allergen. Therefore, symptoms can mimic allergic reactions and include a few others such as:

Histamine intolerance and MCAS often get confused for one another since mast cells do play a role in histamine intolerance. However, in MCAS, mast cells release multiple different types of mediators - not just histamine - whereas in histamine intolerance, it’s only histamine.

While not everyone who has histamine intolerance has MCAS, it can be an indicator of this condition. Since symptoms of both can mirror a lot of other health problems, I always recommend additional testing to look at levels of histamine, tryptase, and prostaglandins to determine if either one of these conditions is a factor in your health case.

A Functional Medicine Approach

Researchers don’t fully understand what causes MCAS or histamine intolerance. However, they have seen that both of these conditions are linked to other health problems which can give us a clue to any overlooked factors that might be contributing to these conditions.

 1. Run a comprehensive health history

Since histamine intolerance and MCAS are linked to the following conditions, running specific labs can be extremely beneficial in knowing whether or not any of these are a factor in someone’s health to give us insight on how to treat each of these problems. 

We also look at what medications someone is taking, specifically antihistamines and other mediator-blocking medications. If someone’s symptoms improve after using these types of medications, chances are very likely that they have either histamine intolerance or MCAS.

     2. Change your diet

Since many foods naturally contain histamine, or trigger the release of histamine in the body, eliminating your intake of high-histamine foods is going to help alleviate any reactions:

  • Alcohol (including wine)
  • Bone broth
  • Canned food
  • Cheese
  • Chocolate
  • Eggplant
  • Fermented food (kefir, kimchi, yogurt, sauerkraut)
  • Legumes (soybeans, chickpeas, peanuts)
  • Mushrooms
  • Nuts
  • Processed foods
  • Smoked meat products (bacon, salami, salmon, ham)
  • Shellfish
  • Spinach
  • Vinegar

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

  • Avocados
  • Bananas
  • Citrus fruits (kiwi, lemon, lime, papayas, pineapple, plums)
  • Strawberries
  • Tomatoes

Some foods can also block the enzyme diamine Oxidase (DAO) that controls histamine.

  • Alcohol
  • Energy drinks
  • 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. (15) These include:

  • Coconut milk
  • Egg yolk
  • Fresh wild-caught fish
  • Fresh organic meat
  • Fresh vegetables (except eggplants, tomatoes, and spinach)
  • Gluten-free grains (rice, corn)
  • Herbal teas
  • Non-citrus fresh fruits
  • Rice milk

Remember, what works for someone else won’t always work for you. A functional medicine practitioner can walk you through an elimination diet and run food sensitivity labs to determine what foods are actually causing a problem for you.

3. Heal your gut

Researchers may have found the correlation between leaky gut syndrome, SIBO, and histamine intolerance/MCAS. Studies have shown that if you have histamine intolerance you also are more likely to have one of these digestive problems as they can lead to a deficiency in the enzyme DAO causing histamine to not be absorbed properly in the digestive tract. (16)

Again, since little is known about exactly what causes MCAS, researchers are continuing to look at the correlation between MCAS and other health problems like leaky gut and SIBO for example. More research needs to be done to further investigate how these underlying health problems play a role in both MCAS and histamine intolerance to better come up with a plan of care for addressing these conditions along with specific testing to definitively diagnose someone with either one, or both, of these conditions.

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  1. Rosell-Camps, Antonio et al. “Histamine intolerance as a cause of chronic digestive complaints in pediatric patients.” Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva vol. 105,4 (2013): 201-6. doi:10.4321/s1130-01082013000400004
  2. Theoharides TC, Stewart JM, Hatziagelaki E and Kolaitis G (2015) Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Front. Neurosci. 9:225. doi: 10.3389/fnins.2015.00225
  3. Zierau, Oliver et al. “Role of female sex hormones, estradiol and progesterone, in mast cell behavior.” Frontiers in immunology vol. 3 169. 19 Jun. 2012, doi:10.3389/fimmu.2012.00169
  4. Rosell-Camps, Antonio et al. “Histamine intolerance as a cause of chronic digestive complaints in pediatric patients.” Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva vol. 105,4 (2013): 201-6. doi:10.4321/s1130-01082013000400004
  5. Clejan, Sanda et al. “Blood histamine is associated with coronary artery disease, cardiac events and severity of inflammation and atherosclerosis.” Journal of cellular and molecular medicine vol. 6,4 (2002): 583-92. doi:10.1111/j.1582-4934.2002.tb00456.x
  6. Yuan, Hsiangkuo, and Stephen D Silberstein. “Histamine and Migraine.” Headache vol. 58,1 (2018): 184-193. doi:10.1111/head.13164
  7. Schaper-Gerhardt, Katrin et al. “The role of the histamine H4 receptor in atopic dermatitis and psoriasis.” British journal of pharmacology vol. 177,3 (2020): 490-502. doi:10.1111/bph.14550

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Dr. Will Cole, DNM, IFMCP, DC is a leading functional medicine expert who consults people around the globe, starting one of the first functional medicine telehealth centers in the world. Named one of the top 50 functional and integrative doctors in the nation, Dr. Will Cole provides a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is the host of the popular The Art Of Being Well podcast and the New York Times bestselling author of Intuitive Fasting, Ketotarian, The Inflammation Spectrum and the brand new book Gut Feelings: Healing the Shame-Fueled Relationship Between What You Eat and How You Feel.

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