Histamine Intolerance And Its Gut-Brain Connection

Histamine Intolerance And Its Gut-Brain Connection

Have you heard of histamine intolerance?

Histamine is a naturally occurring compound made within our body that is most commonly associated with being responsible for the symptoms we experience with allergies. However, it plays several vital roles, including regulating stomach acid, aiding in our immune response and influencing our mood. What’s becoming increasingly more common in some individuals, is an imbalance in how our bodies manage histamine, leading to a condition known as histamine intolerance

What is Histamine Intolerance?

Histamine intolerance can occur if your body has difficulty breaking down and processing histamine properly. When histamine levels accumulate beyond what your body can handle, it can lead to a wide range of symptoms, including:

  • Headaches
  • Hives or skin rashes
  • Digestive problems (such as diarrhoea, bloating, and abdominal pain)
  • Nasal congestion and sneezing
  • Fatigue
  • Irregular heart rate
  • Anxiety and mood changes
  • Dizziness
  • Nausea and vomiting

These symptoms can be confusing because many mimic those of allergies or other sensitivities. However, histamine intolerance itself is not an allergy; instead, it's related to how your body manages histamine. There is a range of reasons this might occur, from changes in genes that manage certain metabolic pathways to hypersensitive immune systems, nutrient deficiencies, or most commonly, problems with gut health or with the primary enzyme pathway responsible for breaking down histamine called diamine oxidase (DAO).

The Role of DAO Enzyme in Histamine Regulation

DAO is an enzyme found within your gut lining and other tissues. Its primary job is to break down excess histamine from the food you eat (yes! food can be a source of histamine), ensuring that your histamine levels remain balanced. When DAO isn't functioning correctly or is overwhelmed by a sudden influx of histamine, symptoms of histamine intolerance can occur.

To maintain optimal DAO activity, several cofactor nutrients are essential. These include vitamin B6, vitamin C, copper, and zinc. Ensuring you have an adequate intake of these nutrients through your diet or supplements can more effectively support your body's ability to break down histamine.

Conversely, some foods and nutrients can inhibit DAO activity, contributing to histamine excess, which can result in histamine intolerance. These include alcohol, certain medications (like antacids and non-steroidal anti-inflammatory drugs and ironically, antihistamines), and foods rich in histamine or histamine-releasing substances. Common high histamine culprits include aged cheeses, processed meats, fermented foods (such as sauerkraut and soy sauce), and alcohol. The levels of histamine in foods are variable and influenced by storage conditions, refrigeration, processing techniques and preservatives. This variability is what can make histamine intolerance challenging to identify, as everyone’s individual capability (or threshold) for managing histamine is different.

To best manage histamine intolerance, we need to strike a balance between avoiding or reducing DAO inhibitors and simultaneously supporting optimal function with cofactor nutrients and robust gut health.

The Gut's Critical Role in DAO & Histamine Levels

Your gut plays a pivotal role in managing histamine because it's the primary location where it is broken down by DAO. When your gut is healthy and functioning optimally, DAO can more efficiently process histamine coming from your food, preventing it from entering your bloodstream in excessive amounts.

However, if you experience imbalances in gut health, such as gut dysbiosis (an imbalance in gut bacteria), leaky gut syndrome (increased intestinal permeability), or conditions like irritable bowel syndrome (IBS), your DAO activity may be disrupted and this can contribute to histamine intolerance. These imbalances can lead to more histamine being absorbed into the bloodstream, resulting in unpleasant and unwanted symptoms.

Maintaining a healthy gut through a balanced diet rich in fibre, probiotics, and prebiotics can provide support for better DAO function and help manage histamine intolerance.

The Gut-Brain Effects of Excess Histamine

Excess histamine in the body can affect not only the gut but also the brain. This is due to the gut-brain connection, our bidirectional communication system linked by the vagus nerve that travels between the gut and the brain. When histamine levels rise excessively, it can lead to neuroinflammation and contribute to symptoms like anxiety, mood swings, and cognitive issues.

Furthermore, histamine can impact the gut's nervous system (the enteric nervous system and vagus nerve), leading to digestive disturbances and exacerbating symptoms such as nausea, abdominal pain, and diarrhoea. For some people, discovering they have histamine intolerance may be a missing link in managing these gut-based symptoms.

The bottom line is that maintaining a healthy, well-supported gut is essential in preventing histamine buildup and addressing the gut-brain effects of excess histamine. This close gut-brain relationship highlights the importance of addressing histamine intolerance comprehensively. Not only by managing dietary choices and supporting optimal DAO activity, but with a focus on supporting and nourishing a healthy gut environment and a robust microbiome. What’s clear is that the health of our digestive system plays a significant role in the development of and ongoing management of histamine intolerance.  


Maintz L, et al. Histamine and histamine intolerance. Am J Clin Nut. 2007 May;85(5):1185-1196. 

Music E, et al. Serum diamine oxidase activity as a diagnostic test for histamine intolerance. Wien Klin Wochenschr 2013;125(9-10):239-243.

Manzotti G, et al. Serum diamine oxidase activity in patients with histamine intolerance. International Journal of Immunopathology and Pharmacology. 2016;29(1):105-111. 

Sánchez-Pérez S, et al. Intestinal Dysbiosis in Patients with Histamine Intolerance. Nutrients. 2022 Apr 23;14(9):1774.

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