Histamine Intolerance, MCAD / MCAS and How Dietary Changes Help

INTRODUCTION: In the previous article about milk intolerance related to a novel beta casein protein found in commercial cow’s milk, I mentioned both histamine intolerance and Mast Cell Activation Disorder (MCAD) — which is also called MCAS (Mast Cell Activation Syndrome).  Quite a few people with these disorders reached out to me on social media, looking for articles I may have written about them and as I hadn’t yet, I decided to write this one.

Adverse reactions to food or components of food can be divided into food allergy and food intolerance.

A food allergy is an IgE antibody-mediated immune reaction and can range from mild skin itching or hives, to full-blown anaphylactic attack where a person is unable to breathe. Specific IgE-mediated antibodies can be assessed and quantified by a blood test for an allergen, or assessed via skin scratch test with a small amount of the allergen.

A food intolerance is a non-immune reaction to a food or food component that can result in a disturbance of enzymes of the gastrointestinal (GI) tract. Lactose intolerance is probably the best known food intolerance, where people have a disturbance of the enzyme lactase in the GI tract, which makes them unable to properly digest the sugar in milk.

Histamine intolerance, like tyramine intolerance is a food intolerance and while rarely life-threatening, it can makes people’s lives quite miserable.

What are Histamines

Most people know that term ‘antihistamine‘ as medications that people take when they have seasonal allergies, such as trees and grasses or ragweed (“hay fever”), but what are histamines?

Histamine is a chemical that performs many helpful functions in the body such as stimulating the production of stomach acid (via the H2 receptors), but in this context, the interest is in histamine’s role in the immune system.

As it is intended to, histamine is released in response to exposure to an allergen, in the body’s attempt to protect you against something that it perceives as a threat. If you have breathed in some pollen that you you are allergic to for example, a signal is sent to your mast cells to release histamine in the body.  These histamines result in inflammation; a condition which signals the immune system to respond. That response could make you sneeze or make your nose run in order to help get rid of the offending allergen — or in cases with people with IgE mediated allergies it can be a very serious reaction that causes your blood pressure to suddenly drop very low, and you find it very difficult to breathe (anaphylaxis).

In histamine intolerance or mast cell activation disorder, histamine is either not broken down properly so it builds up in the body or is released by the mast cells inappropriately, such as when there is no allergen present. In these people, histamine becomes like gluten to a celiac, or regular milk to someone with lactase deficiency — only worse.

Some foods are high in an amino acid called histidine; which converts to histamine during digestion (via a carboxylation reaction mediated L-histidine decarboxylase).

Foods high in histamine include aged and fermented foods such as cheese, yogurt, pickled foods such as kimchi or saurkraut, and smoked fish. Other foods include dried fruit, specific vegetables, some nuts, well as alcohol.

There are also foods that are histamine-liberators, such as chocolate, milk and tomatoes (just to name a few) that need to be considered to minimize the symptoms of histamine intolerance, as well as certain food additives [1].

Finally, foods high in histidine, which is converted to histamine upon digestion, aslo need to be factored in to the diet of someone with histamine intolerance or mast cell activation disorder.

People with mastocytosis, mast cell activation disorder (MCAD) or histamine intolerance react to foods high in histadine / histamine as well as to foods that liberate histamine from mast cells. While these are separate disorders, they all involve problems with histamine.

Mastocytosis is condition where there are too many mast cells. This can be limited to just the skin or can be systemic (all over the body) and occurs due to a mutation in a specific gene.

Mast Cell Activation Disorder (MCAD) – sometimes called Mast Cell Activation Syndrome (MCAS) is where the mast cells ‘degranulate’ (spill their contents, including histamine) at an inappropriate time.  That is, they release histamine when there is no allergen present.

Histamine Intolerance is where the rate of histamine accumulation in the body is greater than the rate at which histamine degrades. The analogy of histamine intolerance is that of an overflowing “bucket”.

Histamine Intolerance

Normally, histamine is stored in the mast cells, or is rapidly degraded by one of two enzymes; either by diamine oxidase (DAO) or histamine-N-methyltransferase (HNMT) upon release, so it doesn’t accumulate.  Disfunction in these enzymes can

DAO primarily functions in the small intestine, ascending colon (a section of the large intestine), as well as kidney [1]. The primary function of DAO is the elimination of excess histamine, as well as controlling the amount of histamine in the body, coming from the digestive tract [1].

HNMT is primarily functions at the level of the histamine receptors themselves, where it deactivates histamine. This enzyme is active in a wide range of body tissues; but greatest in the kidney and liver, followed by the spleen, colon (large intestine), reproductive organs (prostate, ovary), spinal cord cells and parts of the lungs (bronchi, trachea).

Histamine Receptors

There are 4 types of histamine receptors that bind histamine and cause mast cells to release histamine. The binding of histamine with these receptors result in different types of allergic reactions.

from [1] Baily N, Histamine Intolerance, Igennus Healthcare Nutrition, https://www.slideshare.net/igennus/managing-histamine-intolerance-80982438

H1 Receptors

H1 receptors are primarily involved in allergic rhinitis symptoms (sneezing, blowing ones nose), broncho-constriction such as what occurs in allergy-induced asthma, as well as systemic vasodilation (enlarging of the blood vessels)[2].

H2 Receptors

H2 receptors stimulate the stomach to release HCL acid, and inhibit the body from making antibodies, as well as activate the immune system response, including T-cell proliferation and the production of cytokines[2].

H3 Receptors

H3 receptors change neurotransmitter release in the central nervous system, including serotonin and norepinephrine (noradrenaline)[2].

H4 Receptors

H4 receptors are found mostly in bone marrow and white blood cells and are also expressed in the colon (large intestine), small intestine, spleen, tonsils and trachea (wind-pipe)[2].

Symptoms of Histamine Intolerance

People with histamine intolerance display a wide variety of symptoms, affecting different parts of the body.  Some people have many symptoms in different parts of the body, whereas others have a few symptoms clustered in specific parts.  Those with histamine intolerance may have chronic reactions and others may have them seemingly ‘randomly’.

That said, the most frequently observed symptoms are acute (sudden) or chronic (long term) gasto-intestinal GI symptoms [2] and can easily  be mistaken for ‘food poisoning’ (acute symptoms) or irritable bowel syndrome (chronic symptoms). That said, there are individuals with MCAD that have anaphylactic-type reactions. 

Gastro-intestinal symptoms often take place several hours after ingestion of the offending food or food component, because the food itself has to be digested (which takes time) for its histamine to be liberated and bind with the histamine receptors.

In other cases, the reaction is faster; especially when eating aged or leftover food or other foods with high histamine content. These foods may trigger abdominal cramps or diarrhea within 15-30 minutes[2].

Other non-GI related symptoms common with histamine intolerance and mast cell activation disorder (MCAD) are skin rashes, hives (with or without itchiness), facial and chest flushing (getting red and ‘hot’ feeling), faster or slower heartbeat (arrhythmia) or low blood pressure or extreme fatigue. Some people also experience mood changes, including inattentiveness or something described as a ‘brain fog’, as well as sleep disturbances [3,4].

Getting Diagnosed

Histamine intolerance and mast cell activation disorder are difficult to diagnose, firstly because people themselves don’t think wide range of symptoms are related, so they often don’t seek medical help. Another challenge is that the very fact that the symptoms are diverse may result in them be discounted by some physicians as being related to stress/anxiety or depression.

Mast cell activation disorder (MCAD) takes on average 14 years to be diagnosed [4] and often only occurs once the person finally gets a referral to an immunologist or allergist knowledgeable in the condition. I can assist in helping people get that referral, as well as provide support once they know they have either MCAD or histamine intolerance.

You may be interested in this article about similar condition called tyramine intolerance, especially if you suffer from migraine headaches.

More Info?

If you have been diagnosed with histamine-intolerance or mast cell activation disorder (MCAD) or suspect you may have one of these, I can help.

I can assess your symptoms to see if may meet the criteria for MCAD and if so, can put together the documentation required to obtain a referral to an experienced immunologist who can either rule out or make a diagnosis. If it seems you may have histamine intolerance or you have been diagnosed as such, I can provide you with the nutrition education in making the needed dietary changes in an effort to minimize your symptoms.

You can find out more about the packages and hourly consultations I offer by clicking here and if you would like additional information, please send me a note using the Contact Me form above and I will reply as soon as I can.

To your good health!


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  1. Baily N, Histamine Intolerance, Igennus Healthcare Nutrition, https://www.slideshare.net/igennus/managing-histamine-intolerance-80982438
  2. Jernigan D, Histamine Intolerance Syndrome, Hansa Center for Optimal Health, Bimed Network, https://www.marioninstitute.org/histamine-intolerance-syndrome/
  3. Molderings GJ, Brettner S, Homann J et al, 2011, Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options, J of Hemat and Onc 4 (10)
  4. Hamilton MJ et al, 2011, Mast cell activation syndrome: A newly recognized disorder with systemic clinical manifestations. J of Allergy and Clin Immunology Vol 28 (1), p. 147-153