Histamine is a substance belonging to the class of biogenic amines, better defined as a mediator, produced by some cells of our body, in particular by mast cells and responsible for some important functions such as:

  • mediate the immediate allergic response
  • regulate acid secretion in the stomach
  • mediate the release of neurotransmitters in the central and peripheral nervous systems
  • action on the contraction of smooth muscles
  • vasodilation and pressure drop
  • increased permeability of vessels
  • stimulate the production and secretion of mucus

But what is histamine intolerance?

Histamine intolerance, sometimes erroneously called allergy, is a condition that occurs when there is an imbalance between the accumulation and breakdown of histamine within the body.

Symptoms of histamine intolerance

Some common reactions associated with this intolerance include:

  • headache or migraine
  • tiredness
  • urticaria
  • digestive problems
  • irregular menstrual cycle
  • itch
  • nausea
  • He retched

In severe cases of histamine intolerance, you may experience:

  • abdominal cramps
  • swelling of the tissues
  • high blood pressure
  • irregular heart rate
  • anxiety
  • difficulty regulating body temperature
  • dizziness

How is dietary histamine metabolized?

Histamine, present in every food (of animal and vegetable origin), must be metabolized in order to be eliminated without problems from the urine. Note that exogenous histamine does not play a functional role within the organism and, for this reason, it is eliminated without using any properties.

There are two main known pathways of histamine metabolism in living beings, in which histamine N-methyltransferase (HMT) and diamine oxidase (DAO) are involved.

HMT is an enzyme that degrades histamine in liver tissue, but it is also present in lower quantities in other tissues.

DAO is the most important enzyme that degrades histamine, but it is found only in certain tissues, particularly in the intestinal mucosa, kidneys, placenta, thymus and seminal vesicles.

What Causes High Histamine Levels?

In people suffering from histamine intolerance, there is a reduction in the activity of a particular enzyme, the DAO, diaminoxidase, responsible for the degradation of the same histamine when it is produced in excess. This reduction can be due to various causes:

  • a genetic predisposition
  • as a result of gastrointestinal diseases (such as inflammatory bowel disease) which inhibit its production
  • following the consumption of substances that inhibit its action.
  • drugs that block DAO functions or prevent production, such as antibiotics, antidepressants, diuretics, pain relievers, but also some NSAIDs (non-steroidal anti-inflammatory drugs) such as acetylsalicylic acid.
  • foods that contain histamine which cause DAO enzymes to work improperly

Researchers are still studying the amount of histamine present in most foods and beverages, as well as how some nutrients impair DAO activities, as the concentrations of histamine and other biogenic amines in foods are highly variable within the same family, and even between two samples of the same product.

Foods and histamine

We can distinguish two types of foods foods rich in histamine, such as:

  • alcohol and other fermented beverages
  • fermented foods and dairy products, such as yogurt and sauerkraut
  • dried fruit
  • avocado
  • eggplant
  • spinach
  • processed or smoked meats
  • shellfish and some types of fish
  • aged cheeses

Foods that trigger the release of histamine in the body, i.e. foods that do not contain histamine but are able to stimulate its release by the body. They contain some substances, such as proteins, which stimulate some cells of the immune system, mast cells, to degranulate (i.e. release the intracellular histamine contained in their granules), triggering all those inflammatory mechanisms involved in intolerance to the histamine itself. Among the istamine-liberating foods we remember:

  • alcohol
  • canned tuna
  • bananas
  • tomatoes
  • wheat germ
  • beans
  • papaya
  • chocolate
  • citrus fruits
  • nuts, especially walnuts, cashews and peanuts
  • food dyes and other additives

How is it diagnosed?

There is still no reliable procedure for diagnosing adverse reactions to ingested histamine. As most of the time it is self-diagnosed by the patient or based solely on the medical history.

Therefore, the diagnosis of adverse reactions to histamine has so far been made purely on the basis of symptoms and in the absence of reliable laboratory parameters. The therapeutic approach should be largely guided by the individual tolerance of the affected individuals.

Further research is needed to establish the relevance of measuring biomarkers, risk factors in intestinal barrier function, as well as the dose of histamine causing pharmacological effects. Until then, expert nutrition counseling can help patients avoid diets that result in an unnecessary reduction in their quality of life.

My advice?

If you have a histamine intolerance, supplementing low-histamine foods in your diet can help reduce symptoms. Unfortunately, there is no histamine-free diet. Consult your nutritionist, who may suggest you follow an elimination diet for 14-30 days. This removes all foods rich in histamine or histamine triggers and then slowly reintroduced to observe any tolerances to certain foods.


  • Kofler L, et al. (2011). Histamine 50-skin-prick test: A tool to diagnose histamine intolerance.
  • Maintz L, Novak N. "Histamine and histamine intolerance." Am J Clin Nutr. 2007
  • Mayo Clinic Staff. (2018). Allergy skin tests.
  • https://www.deficitdao.org/
  • Reese, I., Ballmer-Weber, B., Beyer, K. et al. German guideline for the management of adverse reactions to ingested histamine. Allergo J Int 26, 72–79 (2017).
See the author's articles
Dr.ssa Marina Putzolu

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