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Alex Manos | 20 Jan 2025 | Gut Health

Histamine Intolerance: Everything You Need To Know

Have you ever experienced unexplained headaches, skin rashes, digestive discomfort, or a runny nose after eating certain foods? If these symptoms sound familiar, you might be dealing with a condition known as histamine intolerance. While histamine is a natural and essential part of our immune system, too much of it—or an inability to break it down properly—can wreak havoc on your body.

In this blog, we’ll take a deep dive into histamine: what it is, the vital roles it plays in the body, and how it can sometimes turn from friend to foe. We’ll explore the symptoms of histamine intolerance, uncover its potential causes, and discuss how to diagnose it. Most importantly, we’ll guide you through practical ways to manage histamine intolerance through diet, lifestyle changes, and supplements, so you can take back control of your health.

An important point that I would like to make at the start is that, usually, evaluation for histamine intolerance is not included in differential diagnoses of patients with unexplained, functional gut complaints and therefore a lot of people are potentially suffering with histamine intolerance without knowing it (source).

What Is Histamine?

Histamine is a natural chemical found in the body that plays an important role in various bodily functions. It is a type of molecule known as a biogenic amine and is produced by cells, particularly mast cells and basophils (both are types of immune cell), as part of the immune system’s response to injury, allergens, or infections.

What Does Histamine Do?

Histamine helps protect the body by triggering inflammation, which brings immune cells to the site of a problem, but it is also responsible for common allergy symptoms such as itching, sneezing, and swelling. Beyond its role in allergies, histamine acts as a chemical messenger in the brain, influencing alertness, appetite, and sleep. It also helps regulate stomach acid production, aiding in digestion. While histamine is essential for health, an overactive histamine response can lead to uncomfortable conditions such as hay fever or hives.

The reason for histamine’s wide ranging effects is because it depends on which histamine receptors it binds to. Researchers have identified four types of histamine receptors.

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What Is Histamine Intolerance?

Histamine intolerance is a condition characterised by the accumulation of histamine to a point that exceeds the body’s capacity to eliminate it.

In healthy individuals, the enzyme diamine oxidase in the gut (more often known as DAO), helps eliminate histamine taken from food. When the activity of DAO is inhibited, the body’s ability to manage histamine is significantly affected. This leads to the accumulation of histamine, causing symptoms that, among others, mimic allergic reactions (source).

Researchers have discussed several reasons for this condition, including genetic factors, medications, alcohol, and dietary deficiencies, and imbalances in the gut microbiome and gut lining (source).

What Causes Histamine Intolerance?

An Imbalance In The Gut Microbiome

Recent research (source, source) also suggests that an imbalance in gut bacteria may contribute to histamine intolerance, although only limited studies have explored this link. Some gut bacteria naturally produce histamine, and if these bacteria become too abundant, they could increase histamine levels in the body.

A study (source) investigating gut microbiome differences between people with histamine intolerance symptoms and healthy individuals found clear differences in bacterial composition. Those with histamine intolerance had lower levels of beneficial bacteria such as Prevotellaceae, Ruminococcus, and Faecalibacterium prausnitzii, which support gut health. At the same time, they had a higher presence of histamine-producing bacteria, including Staphylococcus, Proteus, Clostridium perfringens, and Enterococcus faecalis.

This imbalance, known as gut dysbiosis, may lead to excess histamine in the gut, which then enters the bloodstream and triggers symptoms—even in individuals who do not have a DAO deficiency. These findings suggest that gut health plays a key role in histamine intolerance and highlight the potential for microbiome-based treatments in the future.

Our Ultimate Gut Health Test tests for histamine producing bacteria, and, bacteria associated with good gut health such as Ruminococcus and Faecalibacterium prausnitzii.

Alcohol

Alcohol has been found to increase the release of histamine, affecting the rate of its degradation (source).

Medications

About 20% of the European population consumes medications that could decrease DAO activity, increasing the risk of histamine intolerance. Examples of drugs that have been found to affect DAO’s activity include verapamil, clavulanic acid, and isoniazid, among others (source).

Nutrient Deficiencies

Deficiencies is nutrients including copper, zinc, vitamin C, and vitamin B6 may contribute to histamine intolerance. This is because they are needed for optimal production of the histamine degrading enzyme DAO.

Menstrual Cycle

The menstrual cycle has also been found to contribute to histamine intolerance (source).

This is because of the interplay between histamine and hormones like estrogen and progesterone. Estrogen is known to increase the release of histamine from mast cells and also reduce the activity of diamine oxidase (DAO), an enzyme responsible for breaking down histamine. Conversely, progesterone has a stabilising effect on mast cells, reducing histamine release and enhancing DAO activity. During the menstrual cycle, estrogen levels rise and peak just before ovulation, which can lead to increased histamine levels in individuals sensitive to it. This can exacerbate symptoms such as headaches, skin issues, or digestive discomfort often associated with histamine intolerance. For some people, histamine intolerance symptoms worsen during the luteal phase (after ovulation) if there is an imbalance between estrogen and progesterone, such as low progesterone levels (source).

This hormonal fluctuation highlights the close relationship between reproductive hormones and histamine, and managing these interactions through dietary changes or medical interventions may help reduce symptoms.

Health Conditions

Several inflammatory bowel diseases are known to result in impaired DAO activity, the degree of which can be correlated with the severity of damage to the gut lining. In fact, DAO activity has been proposed as a marker of integrity of the gut lining (source).

What Are The Symptoms Of Histamine Intolerance?

The symptoms of histamine intolerance include intestinal and extra-intestinal symptoms. These symptoms could be diverse and non-specific. This is because histamine intolerance is associated with excess histamine that enters the systemic circulation through the intestines, interacting with histamine receptors that are present in multiple locations across the body, which makes a typical clinical outline of symptoms challenging to achieve.

The presence of diverse, unexpected, and random symptoms, particularly after food consumption, suggests a strong possibility of histamine intolerance.

  • Intestinal Symptoms: Bloating, constipation, diarrhoea, discomfort.
  • Non-intestinal Symptoms: Sinus congestion, sneezing, rhinitis, tachycardia, headache, migraine, urticaria, swelling, pruritis, dermatitis, menstrual cramps.

Researchers found that the most frequent symptoms included gastrointestinal manifestations, with bloating being present in 92% of subjects. Other common symptoms included constipation, abdominal pain, diarrhoea, and postprandial fullness, with proportions of 55%, 68%, 71%, and 73%, respectively (source).

When the subjects were asked to rate the severity on a scale from 1 to 5 (higher, more severe symptoms), they indicated bloating as the most severe symptom with a score of 4. Regarding skin manifestations, pruritis was the most common symptom and was reported by 48% of the subjects; similar results with respiratory system manifestations of rhinorrhea, nasal congestion, and sneezing were obtained.

Concerning the cardiovascular system, dizziness (66%), headache (65%), and palpitations (47%) were the most reported symptoms (source).

Histamine And Leaky Gut

Patients with histamine intolerance showed elevated levels of stool zonulin, a marker of leaky gut (source).

Diagnosing Histamine Intolerance

There are several methods discussed in the research:

  • Serum diamine oxidase (DAO): Intra-subject variability due to factors like time of the day limits its robustness. Thus, it should be used with other diagnostic methods to confirm the diagnosis.
  • Skin prick test: This test cannot differentiate between histamine intolerance and other allergic conditions. Therefore, it should solely be used to confirm the diagnosis.
  • Histamine challenge test: It helps determine an individual’s histamine tolerance limit. However, the value of this test is limited by challenges related to accurately quantifying histamine levels in food and beverages, the need for technical supervision from a specialist, and the emergence of reports highlighting that this test triggers symptoms in healthy individuals.
  • Feacal (stool) histamine levels: Accuracy is obscured due to interference from the gut microbiota, which itself produces histamine.
  • Genetic testing: This approach is gaining momentum and adds value when combined with other methods. Listen to Emma Beswick discuss genetics and histamine intolerance with Alex Manos on the Healthpath podcast below.

A questionnaire has also been discussed in the research (source) which asks you to rank symptoms in severity from 1-5.

Treating Histamine Intolerance

A low-histamine diet is the gold standard (source). The first approach is stopping medications that interact with DAO. Other techniques involve DAO supplementation to help degrade ingested histamine (source).

DAO Supplementation

Exogenous DAO supplementation is one proposed approach to control histamine intolerance. In this regard, several studies have shown positive results in terms of symptom improvement, antihistamine medication use, and serum DAO increase. In one study, the impact of oral DAO supplementation on 39 patients who displayed histamine intolerance symptoms was investigated. The results revealed that when compared to the placebo, DAO supplementation resulted in a statistically significant improvement in histamine intolerance symptoms (source).

In fact in a retrospective study (source) symptom severity was associated with the degree of DAO deficiency, and, patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation).

DAO value could arguably be considered as a predictor of clinical response to treatment.

Recommended Product: DAOZym

Optimise Nutrient Status

Research suggests supplementing with minerals and vitamins like copper and zinc, vitamin C, and vitamin B6 in the case of known deficiency, malnutrition, or restrictive diet. This is because such elements are cofactors for the DAO enzyme and should be used in conjunction with other approaches (source).

Gut Health

Because imbalances in the gut microbiome can contribute to histamine intolerance then, when appropriate, improving gut health is necessary. Things to consider include SIBO, SIFO, or an overgrowth/infection in the large intestine.

Consider our Ultimate Gut Health Test to explore and/or SIBO testing.

The Low Histamine Diet

In foods, the manufacturing process, the cleanliness of materials, the microbial composition, and the fermentation influence the amount of histamine contained (source).

The low-dose histamine diet mainly revolves around avoiding foods that contain excessive amounts of histamine. These foods include seafood, dried meat, fermented products like kefir and sauerkraut, aged cheese, avocado, alcohol, cocoa, chickpeas, nuts, milk, legumes, and fruits like bananas.

Examples of foods low in histamine (when used in normal quantities) include carrot, rice, fresh meat and poultry, coconut oil, courgette among others (there are various websites providing extensive lists of what is allowed and not allowed).

When using this approach, it is important to appreciate that these food groups should be reintroduced at later stages . In this context, research shows that patients who respond to this approach should continue it for a month until symptoms are no longer present. Then, food is gradually reintroduced. When a low-dose histamine diet approach was used, gastrointestinal, cutaneous, and other manifestations were reported to improve, in addition to enhancing DAO levels when subjects were compliant with the diet.

Approaches like dietary restriction, while they may work for some patients, cannot tackle the problem for all patients, as they do not address the root causes of the disease. This is where working with an experienced Functional Medicine practitioner, or, registered Nutritional Therapist can be helpful.

Supplements For Histamine Intolerance

Ideally working with a Functional Medicine Practitioner or registered Nutritional Therapist would be the starting point as the most effective supplements will be personalised based on your needs. This would be informed via an analysis of your current diet and potentially functional lab testing. Options to consider include:

  • DAO – this is the enzyme that helps degrade histamine in the gut.
  • Quercetin and Vitamin C. A good quercetin and vitamin C combo is Quecertin Ascorbate from Designs For Health.
  • Co-factors for DAO production include copper and zinc, and vitamin B6.
  • Lactobacillus Rhamnosus GG. I have had great success personally and clinically with this specific strain of probiotic, but there are others out there that can be considered.

It’s important to note that these supplements are primarily managing symptoms, rather than getting to the root cause of your histamine intolerance. So these are not long term solutions, but excellent options to provide some symptom relief while you investigate, determine, and address the underlying imbalances.

Root Causes Of Histamine Intolerance

It’s important to try and get to the bottom of your intolerance (it is possible!). The low histamine diet is not to be followed long term as it was cause nutrient deficiencies which may lead to further health complications later on. Some of the underlying contributory factors to histamine intolerance include:

  • Gut issues such as SIBO and imbalances in the large intestine (source, source).
  • Mould and mycotoxins (source).
  • Chronic stress (source, source).
  • Allergies. While this technically is a separate ‘diagnosis’ I think some struggling with symptoms we label as histamine intolerance do have some low level allergies that they are not aware of.

This is where working with an experienced practitioner is so important. They will be able to educate you around the different tests that are available, and work with you to understand which test(s) might be most helpful based on your health history, lifestyle, and diet.

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