Differences between intolerance, allergy and histamine poisoning

Histamine allergy

Food allergy is a reaction in which our body perceives a substance, usually a protein, as harmful, which we call an allergen, which is not.

Contact triggers an exaggerated immune response that can manifest in various organs of the body.

Food allergy is generally IgE-mediated and is characterized by a rapid onset that can be minutes to an hour after ingesting the allergen, according to the World Allergy Organization (WAO).

Histamine intolerance

Food intolerance is an abnormal response of the body to the intake of food or its components in normally tolerated doses.

In histamine intolerance, the cumulative amount of histamine ingested plays a key role.

Unlike allergy:

  • there is a delayed onset of symptoms
  • the symptomatic phase is prolonged
  • the IgE serology is negative

It is a pathological process in which, due to the disproportion between the intake of histamine and the body’s ability to eliminate it, there is an excessive accumulation of histamine and the development of symptoms caused by its binding to the corresponding receptors (H1, H2, H3 or H4).

Histamine intoxication

In histamine intoxication, the blood tryptase is within physiological values. Symptoms appear 20-30 min after ingestion and may be present for a few hours or a day.

The symptoms that histamine poisoning produces are usually:

  • Sensation of itching and/or burning on the tongue.
  • Redness and swelling of the face and neck.
  • Headache and dizziness.
  • Abdominal pain, nausea, vomiting and diarrhoea.

Generally, they are mild symptoms that disappear within a few hours of starting.

Who metabolizes histamine? DAO and HNMT enzymes

  • DAO (Diamine oxidase)

It is found mainly in the small intestine, the ascending colon, the placenta, and the kidneys.

In the intestine, DAO activity increases progressively from the duodenum to the ileum and is mainly located in the intestinal villi.

  • HNMT (Histamine N-methyltransferase)

It is mainly expressed in the kidneys, liver, spleen, colon, prostate, ovaries, spinal cord and respiratory tract.

Elmore BO, et al. (2002); Gludovacz E., et al. (2018); Elsenhans B., et al. (1999); Maints L. (2007).


Degradation of histamine in the intestine

Kovacova-Hanuskova. et al. (2015)

A) Healthy person

There is a normal concentration of histamine in food. Most of the histamine is inactivated by the DAO and HNMT enzymes in the intestine and only a small amount of histamine passes into the bloodstream and does not cause symptoms.

B) Histamine poisoning in a healthy person

Intake of foods with high histamine content (more than 500mg/kg). The enzymatic activity of DAO and HNMT is normal, but it is insufficient to inactivate an excessive amount of histamine, which passes into the bloodstream and causes symptoms.

Histamine can be generated in some foods, especially in certain fish that have high concentrations of histidine, which is a substance that forms part of their normal composition. When the fish dies, the histidine is converted into histamine by the action of some microorganisms.

Histamine formation in food depends on various factors such as:

  • The conditions of temperature and pH (high temperature and low pH).
  • The content of histidine, which is the precursor of histamine.
  • The presence of enzymatic substances produced by bacteria, which are capable of transforming histidine into histamine.
  • Unhygienic food handling.

Its formation is mainly related to a lack of hygiene when handling food. Freezing or refrigeration below 4ºC minimizes its formation.

However, once histamine is generated in food, it cannot be eliminated, since it is a substance that is resistant to thermal processes such as cooking, pasteurization, and/or sterilization, and is also resistant to refrigeration and freezing.

Histamine is produced above all in fish associated with a high histidine content such as tuna, mackerel, bonito, sardines or anchovies.


Histamine can also be formed in fermented and/or matured products such as cheese, wine, or beer, among others, but poisoning from these foods is less common than that produced by certain fish.

What can we do as consumers?

Take precautions to avoid histamine poisoning, especially when buying fish:

  • Maintaining the cold chain from the purchase to the arrival home. It is recommended to use isothermal bags to store the fish during the journey.
  • When you get home, refrigerate or freeze the fish immediately.
  • It should be kept in the fridge at a temperature below 4ºC until it is consumed.
  • Do not thaw fish at room temperature.
  • Maintain good hygiene in the kitchen and adopt the habit of washing hands before handling food and use clean and BPA-free utensils.

C) Person with an intolerance to histamine.

The enzymatic activity of the DAO and HNMT enzymes in the intestine is decreased or inhibited and is insufficient to inactivate histamine, it passes into the bloodstream and causes symptoms.

Under normal circumstances, DAO is secreted in the intestine and protects us from the reabsorption of histamine into the bloodstream, both from histamine present in ingested food and from histamine generated by intestinal bacteria.

Both DAO and HNMT enzymes are present in intestinal epithelium.

The main barrier to histamine absorption into the bloodstream is DAO (HNMT plays a minor role in this process).

Therefore, the supplementation of NATURDAO is useful and effective in people with intolerance to histamine while treating the intestine.

This 100% vegetable and certified product is available worldwide through its digital sales channels. You can discover more on this website or on Naturdao Amazon UK and Naturdao Amazon USA.

Anna Nadal

Physiotherapist and Postgraduate in PNIE

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