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Histamine intolerance and mast cell activation syndrome (MCAS) are both popular topics these days and something I’m frequently asked about.
What I see is some patients are already on an autoimmune diet yet develop histamine intolerance.
Symptoms of histamine intolerance include:
- Skin urticaria (hives)
- Nasal congestion
- Wheezing and respiratory issues
- Chronic gut issues
- Migraines
- Cognitive changes
- Mood changes
If you have chronic health issues and go online, you may end up feeling convinced you have histamine intolerance and MCAS.
The best way to know for sure is to take an antihistamine. If it significantly reduces symptoms, this is a strong clue of histamine intolerance.
What is a histamine reaction?
When you have a reaction to a food, you can have different immune responses. An allergy is an immediate IgE antibody response.
A food sensitivity is a delayed IgG or IgM antibody response.
A histamine intolerance works through the immediate IgE pathway. When IgE is activated, immune cells called mast cells release chemical mediators, one of which is histamine. Because we have histamine receptors throughout the body, symptoms will vary depending on the person.
For instance, histamine receptors in the gut are involved with the smooth muscle contractions and intestinal motility, and stomach acid and pancreatic enzyme release. Therefore, a histamine intolerance can disrupt gastrointestinal (GI) function.
Histamine receptors in the brain are involved with neurotransmitter activity and intolerance can cause cognitive issues or mood changes.
Occasional histamine responses are common, such as to pollen or pet dander. But it becomes a chronic health issue when people are living with ongoing sinus, respiratory, gut, mood, pain, or cognitive symptoms.
Look for triggers of chronic histamine intolerance
When histamine intolerance continues unchecked, it can turn into mast cell activation syndrome (MCAS). This happens when the immune system over produces pro-inflammatory immune cells called mast cells.
True MCAS is typically accompanied by IgE allergy responses such as anaphylaxis and other severe responses, as well as chronic and severe immune activation. This is much different than occasional symptoms in response to a trigger.
In the case of chronic histamine and mast cell responses—as opposed to occasional responses when exposed to a trigger—you have to look for what is triggering it.
A common trigger is mold toxicity. Studies show that the immune systems of people who are constantly in a damp moldy building shift from a delayed IgG reaction to a chronic and permanent IgE reaction. As the immune system becomes hyper reactive, this opens the door to developing additional abnormal immune reactions.
Studies show Lyme disease and parasite infections can also trigger chronic histamine responses.
These are examples of possible triggers that are not related to diet.
A therapy called low-dose antigen therapy (LDA) involves giving the patient a very small dose of the triggering antigen over a period of time to improve immune resilience and may help those with chronic histamine intolerance.
Can you clear histamines from your body?
Another factor that contributes to histamine intolerance is whether your body can clear histamines.
Two enzymes necessary to break down enzymes and clear them from the body are:
- Diamine oxidase (DAO), which can be measured in a blood test, though the accuracy of that test is controversial. You can take a DAO supplement to support this system.
- Histidine methyltransferase. This pathway is dependent on methyl donors and healthy methylation. Supplements that act as methyl donors (such as methyl B vitamins or trimethylglycine) can support this system. Genetic variations and/or certain medications can inhibit methylation.
Amplification of the immune response in histamine intolerance and MCAS
Another factor contributing to chronic histamine intolerance issues is “amplification of the immune response,” the immunological term for an exaggerated immune response to an antigen.
The prostaglandin pathway is involved with mast cell activation and is significantly impacted by diet.
Prostaglandins can be pro-inflammatory or anti-inflammatory and typically shift into a proinflammatory state if your diet is too high in animal products, fried foods, and vegetable oils. A shift towards an anti-inflammatory state requires plenty of omega 3 fatty acids. Fish oils and flaxseed oil can support anti-inflammatory prostaglandin pathways.
The other part of an amplified immune response relates to loss of immune tolerance. I developed an online program called the 3D Immune Tolerance Program, which explains the various immune cells involved in immune tolerance and oral tolerance, or the ability to tolerate foods.
Working with histamine intolerance
Many people become frustrated trying one supplement after another for histamine intolerance. They say, “I tried DAO and it didn’t work. So now what do I do?”
The goal with histamine intolerance is finding the triggering antigens, supporting clearance, and addressing mechanisms causing amplification of the immune response.
In a clinical setting, you may need to treat leaky gut, leaky lungs, low vitamin D levels, and environmental and food triggers. Additionally, you may need low-dose antigen therapy.
In other words, there is no one remedy or magic bullet. Chronic health conditions require methodically working through a list of underlying mechanisms until you find the one(s) that apply to you.
In the meantime, following a low-histamine diet will take the burden off your immune system and allow you to function with reduced symptoms.
Do you really have Mast Cell Activation Syndrome (MCAS)?
Mast cell activation syndrome (MCAS) is the most aggressive form of histamine reaction. MCAS occurs when too many mast cells are being produced and they are highly activated.
Many people have been diagnosed with MCAS inappropriately, or they have self-diagnosed based on internet articles. However, true MCAS must meet certain criteria for diagnosis:
- Histamine reaction symptoms in two or more organs.
- A 20% increase of serum tryptase levels measured from baseline.
- A positive response to histamine blockers, leukotriene blockers, and immune suppressors.
For someone with genuine MCAS, appropriate pharmacology can make a big difference in quality of life and allow better function.
Someone with true MCAS should also identify whether it is primary, secondary (to an infection, etc.), or idiopathic. Gene testing and biopsies can help determine this.
