Histamine Intolerance, Mast Cell Activation Syndrome, And Thyroid Health: What’s the Connection?

Thyroid conditions, including hypothyroidism, hyperthyroidism, and the autoimmune conditions Hashimoto’s and Graves’ disease (the leading causes of hypothyroidism and hyperthyroidism, respectively), are on the rise.


Not everyone responds to conventional or natural thyroid-focused treatments. Some may find that certain symptoms improve, but others remain, or even get worse. And even if symptoms do improve, most available therapies fall short of addressing the root cause of a thyroid hormone imbalance.


These and other issues might lead you to wonder if there’s a different kind of imbalance underlying your thyroid issues. Some research suggests that overactive mast cell activation or histamine intolerance may contribute to thyroid conditions.


Similarly, thyroid hormone imbalances may exacerbate issues with mast cell activation or histamine intolerance.


Understanding these potential relationships can help you to untangle the web and get to the bottom of your symptoms.


If thyroid medication has not relieved existing symptoms, it may be time to explore underlying issues, like the possibility of histamine intolerance or gut dysbiosis.


Untangling the Web: Histamine Intolerance, Mast Cell Activation Syndrome, and Thyroid Conditions


So what exactly is the relationship between histamine intolerance, mast cell activation, and the thyroid? Here are a few key points.


  • Mast cells can store thyroid hormones. When mast cells activate, they release more than just histamine. In addition to other inflammatory molecules, mast cells can actually store and release thyroid hormones. This means that if mast cell activation is dysregulated, thyroid hormone levels may be, too. The relationship between mast cells and the thyroid also seems to be bidirectional: mast cells can influence thyroid hormone release, and thyroid function can influence mast cell activation (1).

  • Certain thyroid issues may contribute to histamine intolerance. Low thyroid hormone levels can cause an increase in histamine production while high levels may create a heightened histamine response (2).

  • Histamine intolerance may contribute to thyroid conditions. High amounts of histamine can promote the development of thyroid-related autoimmune diseases.

  • Many common symptoms of thyroid disorders overlap with symptoms of MCAS and histamine intolerance. Fatigue, palpitations, heat or cold sensitivity, digestive disturbances, menstrual cycle changes, and sleep disturbances are a few examples of symptoms that are often attributed to thyroid conditions, but that are also hallmarks of MCAS and histamine intolerance.

  • In some cases, histamine intolerance and thyroid conditions may share a root cause related to imbalances in the gut. Gut health imbalances including SIBO (small intestinal bacterial overgrowth) and leaky gut have been linked to both thyroid conditions and histamine intolerance (3, 4, 5).



Is It Your Thyroid, Or Is It Mast Cell Activation or Histamine Intolerance?


Because thyroid conditions are so common, and because they’re known to lead to various symptoms affecting different areas of the body, “nonspecific” symptoms may end up being automatically associated with the thyroid, when something else is also going on.


Here’s a quick representation of some of the overlapping symptoms of MCAS, histamine intolerance, hypothyroidism, and hyperthyroidism (6, 7, 8).

Keep in mind that symptoms like fatigue and constipation can be signs of many different things, and that the symptoms of mast cell activation syndrome, histamine intolerance, and thyroid conditions vary person to person.


The key takeaway here is that if you haven’t yet been able to resolve symptoms of hypothyroidism or hyperthyroidism, there may be an underlying mast cell activation (or histamine intolerance) component -- and vice versa.


Does this mean you have mast cell activation syndrome and not a thyroid condition? No, not necessarily. Remember that everything that goes on in our bodies is connected, and that imbalances exist on a spectrum.


For example, you may have some degree of mast cell instability and chronic inflammation that is contributing to a thyroid hormone imbalance, but it’s most helpful to think of mast cell activation as an underlying process, and one that can be addressed.


The Role of Gut Health In Thyroid Conditions and Histamine Intolerance


In some cases, an underlying gut imbalance may be contributing to or causing both a thyroid condition and histamine intolerance.


Gut health imbalances including SIBO (small intestinal bacterial overgrowth) and leaky gut have been linked to both thyroid conditions and histamine intolerance as well as mast cell activation syndrome.


SIBO and dysbiosis can also lead to decreased production of DAO, increased amounts of histamine-producing gut bacteria, and increased mast cell activation.


If an imbalance within the gut microbiome is an underlying cause of both hypothyroidism and histamine issues, then treating that imbalance and healing the gut may help to resolve both.



What To Do Next


Understanding the connections between histamine intolerance, mast cell activation syndrome, and thyroid disorders can help you to get to the root cause of your symptoms and better manage your health.


Next Steps


  • Try a low histamine diet for 3-4 weeks. A low histamine diet involves eliminating foods and beverages that are naturally high in histamine and those that may trigger histamine release or block DAO. These include alcohol, aged cheeses and meats, fermented foods, processed foods, additives, dairy, gluten, and certain fruits and vegetables including avocados, spinach, and tomatoes. If a low histamine diet helps to improve your symptoms, it’s likely that you have some degree of impaired histamine metabolism, and you can move on to additional supportive measures while continuing to follow the diet.

  • Consider introducing supplements. Helpful supplements may include natural mast cell stabilizers like vitamin C, quercetin, and melatonin; the DAO enzyme; probiotics for gut support; and DAO cofactors like vitamin B6 and zinc.

  • Minimize mast cell triggers. Triggers of mast cell activation vary from person to person, but may include specific medications or their excipient ingredients (speak with your doctor before making any changes), extreme temperatures, excessive exercise, and stress.

  • Consider working with a Functional Medicine practitioner. A Functional Medicine practitioner who is knowledgeable in the area of histamine intolerance and MCAS can perform tests to better understand factors influencing your histamine levels as well as any genetic or environmental factors that may be impacting your gut health or thyroid function.



Understanding your unique triggers is key to finding relief for your symptoms and treating the root cause of these conditions. For a personalized treatment plan for histamine intolerance, mast cell activation syndrome, and/or thyroid disorders, request a consultation with Dr. Gannage.