Histamine intolerance (HIT) and Mast Cell Activation Syndrome (MCAS) are both caused from a build-up of histamine in the body (and additional chemicals in the case of mcas). HIT can develop from a deficiency in the DAO (diamine oxidase) enzyme, used to break down histamine in the body. Histamine intolerance can be triggered by eating foods that are high in histamine and consuming alcohol and drugs that block DAO or liberate histamine.

MCAS can develop when mast cells, or allergy cells, excessively release products called “mediators” (including histamine), resulting in symptoms that mimic an allergic response. MCAS is one type of mast cell activation disorder (MCAD) but unlike MCAD, where patients have an abnormally high number of mast cells, MCAS occurs when a normal number of mast cells are “hyperresponsive”.

Both conditions have similar symptoms so it can be difficult to distinguish between the two and often, patients may find that they have both conditions.

What makes histamine intolerance and mast cell activation syndrome difficult to identify

There are several factors that make these conditions challenging to identify. First, because histamine is involved in many different functions in the body (ranging from allergic responses to reproduction and stress), the symptoms of both HIT and MCAS are diverse and can seem unrelated. Second, different people may have different symptoms. As a result, there is no standard list of symptoms that makes HIT and MCAS easy to identify. Third, many doctors and General Physicians (GPs) are not familiar with the conditions so patients often find themselves visiting various specialists (for example allergists for hay fever and a dermatologist for eczema) before finding a doctor familiar with HIT and MCAS who can thoroughly evaluate patient history and provide a diagnosis.

Getting a diagnosis for histamine intolerance or mast cell activation syndrome

The first step towards getting a formal diagnosis and treatment is to educate yourself on HIT and MCAS and let your GP know that you suspect you may have one or both. Identify a list of specialists in your area who are familiar with the condition and ask for a referral from your GP to obtain an appointment (or contact the specialist directly if you have private health insurance). It is important that you see a medical practitioner who has knowledge of these conditions so that they may do a thorough historical analysis of your symptoms. This is a key step to getting diagnosed as your doctor will need to rule out other diseases which could account for your range of symptoms.

An elimination diet is the gold standard for determining whether a patient has HIT. There are many foods which are high in histamine (e.g. cured meats, alcohol, tomatoes, avocados, canned foods etc.) and people with HIT will likely have a reaction when consuming these foods. For 4-6 weeks, follow a low histamine diet and notice whether your symptoms have improved. For the most accurate results, it is important to completely eliminate high histamine foods from your diet during this period. After several weeks, slowly re-introduce any foods you suspect are causing a reaction to see how you fare. People with HIT will often react well to a low-histamine diet and may be able to eventually reintroduce high histamine foods (an elimination diet will not determine if you have MCAS as MCAS is not caused by consuming high-histamine foods).

There is no universal test that will definitively diagnose a patient with MCAS or HIT but there are several laboratory tests that can be used in conjunction with a full analysis of a patient’s medical history:

  1. Testing for serum DAO activity – DAO is the enzyme that breaks down histamine in the body. People with HIT, can have low levels of DAO in their body. Laboratories that perform this test are not readily available so this may be a difficult one to perform, depending on where you live.
  2. Testing for serum tryptase – Tryptase is a mast cell mediator and elevated levels of serum tryptase may indicate that a patient has MCAS.
  3. 24-hour urine test for other mast cell mediators – a rise in other mediators (urinary n-methyl histamine, prostaglandin-D2, or its metabolite, 11β-prostaglandin-F2α) are also considered indicators for MCAS. Though there are many mast cell mediators, unfortunately there are only commercial tests in the US for less than five.

Laboratory tests, together with an examination of a patient’s medical history, can help your doctor to determine whether you have one or both of these conditions.


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