Mast Cell Activation Syndrome (MCAS) vs Histamine Intolerance
Dr. Hoffman explains how histamine intolerance differs from mast cell activation syndrome, why it is considered a subset of MCAS, and which associated conditions make an MCAS diagnosis more likely.
Dr. Bruce HoffmanMSc, MBChB, FAARM, IFMCP · Integrative medicine educator
March 4, 2024March 4, 2024Updated October 21, 20263 min read
Are you wondering if your histamine intolerance or allergic reactions are actually an issue with your mast cells? Or maybe you’ve experienced chronic symptoms that seem like allergies for as long as you can remember?
In one paragraph: histamine intolerance is considered present when there is more histamine in the body than it can cope with, often because of a DAO deficiency in the gut or an HNMT deficiency in the liver, with dietary histamine adding to the load. In MCAS, mast cells secrete many inflammatory mediators, not just histamine, so histamine intolerance is regarded as a subset of MCAS, and anyone diagnosed with it should also be tested for MCAS.
Histamine is an important but potentially dangerous mast cell mediator and part of the immune system response. Histamine is secreted by mast cells into surrounding connective tissues when there’s an exposure to an allergen.
Mast cells release histamine works by increasing the permeability of blood vessels and allowing white blood cells and proteins to access affected tissues more easily.
Histamine intolerance is a condition that’s growing in recognition.
However, it is mostly considered a part of a much wider problem which is defined as Mast Cell Activation Syndrome (MCAS), a situation in which part of the innate immune system becomes hyperactive and as a immune response releases multiple inflammatory mediators, of which histamine is one.
Histamine intolerance is considered to be present when there is just too much histamine in your body for it to cope.
This is further exacerbated by the fact that histamine is also present in many foods and so a person’s histamine burden may be further amplified by their diet.
This histamine isn’t broken down due to a DAO gut enzyme deficiency, or a HNMT deficiency in the liver.
A comprehensive guide regarding the low-histamine diet can be found here.
How MCAS differs from histamine intolerance
Mast Cell Activation Syndrome is often confused for histamine intolerance. The difference between the two is that when a person has MCAS, their mast cells secrete many mediators, not just histamine.
Though, histamine release is still a major component of MCAS it’s only a piece of the puzzle.
Histamine intolerance is actually a subset of MCAS. If you’ve discovered you’re histamine intolerant or recently received a diagnosis, you should also be tested for MCAS.
Conditions associated with MCAS
Because MCAS is a multisystem condition throughout the body with inflammation at it’s core, it’s been associated with a number of other conditions including:
Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
Obesity
Diabetes
Asthma and allergies
Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
Candida overgrowth
Celiac disease
Parasite infections
Skin conditions such as eczema and psoriasis
Food intolerances and allergies
Gastroesophageal reflux (GERD)
Infertility and endometriosis
Postural orthostatic hypotension (POTS)
If you’ve been diagnosed with one of these associated conditions, it could mean that being diagnosed with MCAS is more likely.
Make an appointment with a doctor who specializes in MCAS treatments and begin the diagnostic process.
It can be somewhat of a journey, but once you know you have MCAS there’s a lot that can be done to relieve your symptoms (like using Mast cell stabilizers) and improve your life.
For a comprehensive guide on Mast Cell Activation Syndrome, you can read my in-depth article, Mast Cell Activation Syndrome and Mast Cell Histamine: When Your Immune System Runs Rampant.
What is the difference between histamine intolerance and MCAS?
In MCAS, mast cells secrete many mediators, not just histamine. Histamine release is a major component of MCAS but only one piece of the puzzle, and histamine intolerance is considered a subset of MCAS.
What causes histamine intolerance?
Histamine intolerance is considered present when there is too much histamine in the body for it to cope. The histamine is not broken down because of a DAO enzyme deficiency in the gut or an HNMT deficiency in the liver, and histamine in many foods can add to the burden.
Should someone with histamine intolerance be tested for MCAS?
Yes. Dr. Hoffman states that because histamine intolerance is a subset of MCAS, anyone who has discovered they are histamine intolerant or has recently been diagnosed should also be tested for MCAS.
What conditions are associated with MCAS?
Associated conditions include CIRS, irritable bowel syndrome, gut dysbiosis, obesity, diabetes, asthma and allergies, autoimmune diseases such as lupus, rheumatoid arthritis and Hashimoto's, candida overgrowth, celiac disease, parasite infections, eczema, psoriasis, food intolerances, GERD, infertility, endometriosis and POTS. Having one of these may make an MCAS diagnosis more likely.
What does histamine do in the body?
Histamine is a mast cell mediator and part of the immune response, secreted into surrounding connective tissues on exposure to an allergen. It increases the permeability of blood vessels so white blood cells and proteins can reach affected tissues more easily.
Do mast cells release histamine?
Yes. According to the article, histamine is secreted by mast cells into surrounding connective tissues when there is exposure to an allergen. In Mast Cell Activation Syndrome, histamine is only one of multiple inflammatory mediators that mast cells release, although it remains a major component.
What is mast cell activation syndrome?
Mast Cell Activation Syndrome (MCAS) is a situation in which part of the innate immune system becomes hyperactive and releases multiple inflammatory mediators, of which histamine is one. It is a multisystem condition throughout the body and is often confused with histamine intolerance, which is considered a subset of MCAS.
Does mast cell activation syndrome cause inflammation?
Yes. The article describes MCAS as a multisystem condition throughout the body with inflammation at its core, in which a hyperactive part of the innate immune system releases multiple inflammatory mediators. Because of this, MCAS has been associated with conditions such as CIRS, autoimmune diseases, gut dysbiosis and asthma.
More on MCAS & POTS
Everything Dr. Hoffman has written on mast cell activation syndrome, histamine and POTS: what it is, how it is tested, what triggers it and how it is treated, from the co-author of the global MCAS consensus-2 paper.