HISTAMINE INTOLERANCE EDUCATION
Updated: Oct 12
Histamine intolerance and MCAS come up together in our groups all the time, and they are easy to mix up. They are related, but doctors describe them in different ways, so each one has its own post. This post is about histamine intolerance and how it compares with MCAS. Doctors do not all agree on the details, so here is what the doctors and research I trust say. Always take your own questions to your doctor.
WHAT IS HISTAMINE INTOLERANCE?
Histamine is a chemical messenger made by many cells in the body. According to Dr. Tania Dempsey, mast cells and basophils are the main places it is stored. She says trouble starts when too much histamine is made or released, or when the body's clearing systems are not working well. Histamine intolerance may develop when the amount of histamine in the body is more than it can clear.
The body has two main ways to clear histamine:
-DAO (diamine oxidase) is an enzyme in the gut. Dr. Dempsey says it breaks down histamine that comes from food or is released by mast cells.
-HNMT changes histamine so the body can get rid of it. Dr. Dempsey says it needs methyl groups to do this.
A 2025 case report from NCBI (Takashi Nakamura and colleagues) describes histamine intolerance as a lowered ability of the gut to break down histamine. It says the cause is DAO that is impaired from birth or becomes impaired later in life.
COMMON SIGNS AND SYMPTOMS
Dr. Dempsey lists these as possible symptoms: itching, redness, hives, swelling, sneezing or coughing, asthma-like symptoms, blood pressure changes, palpitations, headache or migraine, dizziness, chronic fatigue, sleep problems, anxiety or depression, cramps, bloating, gas, and diarrhea or constipation. She says symptoms can come and go, so finding triggers is often needed.
The 2025 case report says symptoms are varied and not specific to one condition. It says they can involve the skin, breathing, gut, heart and circulation, and nervous system. It names bloating, diarrhea and belly pain as the most common gut symptoms, and says headache is more common than in allergy.
WHAT MAY CAUSE IT?
Dr. Dempsey lists these contributing factors: genetics, MCAS, altered histamine receptors, nutritional deficiencies, a diet high in histamine foods, and certain medications and supplements. She says DAO levels can be lowered by certain medications, supplements, medical conditions and genetics. She says HNMT can be affected by a genetic mutation, nutritional deficiencies, and other methylation genes.
HOW IS IT DIFFERENT FROM MCAS?
-The 2025 case report says histamine intolerance involves too much histamine action without too much mast cell activation. It also says allergy blood tests (specific IgE) are typically normal in histamine intolerance.
-Dr. Bruce Hoffman says MCAS is an overactive part of the innate immune system where mast cells release many chemicals, with histamine being only one of them. He describes histamine intolerance as a subset of MCAS.
-Dr. Dempsey lists MCAS as one thing that can affect how well the body handles histamine. She notes that mast cells can release over 1,000 chemicals, so gut symptoms that look like histamine intolerance may come from a chemical other than histamine. She says that in that case, lowering histamine may not control the symptoms.
-In a February 2023 article, Dr. Jill Carnahan says it has been widely assumed that histamine intolerance and MCAS simply go hand in hand. She says the histamine released by mast cells is only a small part of the story, because mast cells also release other chemicals.
The doctors describe the connection in different ways, which is one reason these two topics get mixed up.
HOW ARE THEY CONNECTED?
The June 2026 MCAS review by Dr. Lawrence Afrin, with Dr. Tania Dempsey and Dr. Leonard Weinstock among the co-authors, lists histamine-rich foods among the possible triggers to be cautious with in MCAS. It also says MCAS often causes various food intolerances.
Dr. Carnahan's February 2023 article says MCAS can certainly be a major contributing factor in histamine intolerance.
In a May 2026 article about MCAS symptoms in perimenopause and menopause, Dr. Carnahan describes DAO as the main enzyme that breaks down histamine in the gut and bloodstream. She also says many symptoms can have both a hormonal cause and a histamine cause, and that the two are not mutually exclusive.
Dr. Hoffman advises that anyone diagnosed with histamine intolerance be tested for MCAS by a doctor who specializes in it.
WHAT ABOUT MOLD?
In her February 2023 article, Dr. Carnahan answers yes to the question of whether mold can trigger MCAS. She says that when mold spores release their toxins, the immune system becomes activated and mast cells release their contents in a large burst. She says cutting down mold exposure is the key.
HOW DO DOCTORS FIGURE IT OUT?
The 2025 case report says there are no agreed diagnostic criteria for histamine intolerance. It says doctors rely on the patient's history, a trial of treatment to see what happens, and extra tests.
Dr. Dempsey describes a low histamine diet as a way to find out whether histamine is involved. She says people usually know within the first few days to weeks if it helps.
WHAT DOES DR. DEMPSEY SAY ABOUT THE LOW HISTAMINE DIET?
-She says there is no right answer on how to start. You can remove the most obvious high histamine foods first, or begin a strict elimination diet.
-She says it is "not usually a miracle cure" and that completely removing histamine from the diet is not possible.
-She says fresher food is better, because histamine builds up in food during storage.
-She lists these among the higher histamine foods: shellfish, canned and smoked fish, fermented foods such as fermented vegetables, soy sauce and miso, most aged cheeses, foods with vinegar, cocoa and chocolate, and alcohol.
-She says the diet can be hard to keep up, histamine levels in food vary with storage and preparation, and histamine may not be the real problem.
-She does not encourage people to self-treat if they think they have histamine intolerance.
WHERE TO READ MORE
Dr. Dempsey on the low histamine diet (Sept 2022):
Dr. Hoffman on histamine intolerance vs MCAS (March 2024):
Dr. Carnahan on mold and MCAS (Feb 2023):
Dr. Carnahan on histamine, DAO and hormones (May 2026):
Histamine intolerance case report on NCBI (2025):
MCAS consensus-2 criteria at six years (June 2026):
RELATED POSTS
Our MCAS education post:
Our MCAS possible solutions post:
Disclaimer: Rise Above Lyme makes no claims about any possible benefit of using any product mentioned within this site. Always consult with your doctor before adding anything. The information shared is based on personal experience, years of accumulated researched resources from Lyme Literate doctors and polls conducted within Lyme groups from actual patient experience using these solution ideas.
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