Mast cell activation syndrome / Histamine intolerance

Histamine, tyramine and mast cell activation

Mast cell activation syndrome / Histamine intolerance


Histamine intolerance is thought to result from an imbalance between accumulated histamine and the capacity for histamine degradation.

Elevated histamine may be caused by histamine overproduction in the body, increased intake of histamine (from food, alcohol, or bacteria), or impaired enzymatic break down of histamine (genetic or acquired dysfunction of main enzymes, DAO or HNMT). Histamine and other biogenic amines, such as tyramine, putrescine, spermine, spermidine, and cadaverine, are also compounds formed during the course of desired or undesired microbial fermentation of food or as a consequence of food spoilage. Histamine is contained in many immune cells and is released during allergic reactions. Higher levels of biogenic amines are toxic and cause symptoms. Certain foods naturally contain high levels of histamine, tyramine and/or other biogenic amines. These include: cheeses (especially ripe cheeses– “cheese-reaction”), wine, kefir, dry sausage, fermented meats, sauerkraut, mushrooms, miso and soy sauce, chocolate and yeast (see links at bottom of page).

Sensitivity to histamine varies widely between individuals. Normally biogenic amines are rapidly broken down by enzymes. Some drugs inhibit the action of the enzymes. These include: antibiotics: (amoxicillin/clavulanic acid; doxycyline, isoniazide), metoclopramide, verapamil, promethazine, older antidepressants (monoamine oxidase inhibitors), possibly herbal and nutritional supplements. Other drugs promote histamine release from immune cells, including some opioids, muscle relaxants, x-ray contrast media, as well as alcohol.

Spoiled food and the associated bacterial breakdown are a common source of biogenic amines.

So-called scombroid poisoning is a major reason for adverse reactions to fish.

Inadequately cooled (interrupted cold chain), dark meat fish are especially implicated: tuna, kahawai, mackerel, bonito, kingfish, but also Western Australian Salmon, sardines, mahi-mahi and Blue Marlin. The biogenic amines, once formed, are not destroyed by heating or re-cooling. Properly cooled, fresh fish does not induce these reactions.

Frequency in population

It is estimated 1% of adults may suffer from histamine intolerance (80% of reactions are in middle-aged women), but the condition remains contested due a paucity of confirmatory clinical studies.


Symptoms can be a burning or itching sensation in the mouth, nausea, vomiting, flushing, skin rash or hives, itching, diarrhea, headache, blood pressure changes (both high or low possible), dizziness, problems with concentration, “mental fog” and fainting. The usual onset of symptoms is within a few minutes after ingestion of the offending food. Some cases of asthma may be attributable to histamine intolerance.

The duration of symptom ranges from a few hours to 24 h.

Normally no specific treatment is required, as symptoms subside spontaneously. 

Biogenic amine reactions are not allergic reactions and can be distinguished from fish allergy by the typical previous tolerance of similar fish.


No proven diagnostic test currently exists, so the diagnosis relies heavily on classic clinical symptoms, which involve the skin and intestines and often the airways and brain (see above).

Low levels of an important histamine –degrading enzyme in the blood, diamine oxidase (DAO), can be suggestive of a histamine intolerance.

Blood and urinary histamine levels and genetic analyses are not considered helpful. Histamine provocation tests in conjunction with blood level determination have been propagated, but interpretation remains ambiguous and the risk of adverse events is elevated. A structured elimination diet with subsequent re-challenge is diagnostically useful, even if cumbersome due to the wide range of histamine-containing or –releasing foods.


Avoidance of the main histamine- or tyramine-containing or –releasing foods is the mainstay of treatment, best performed under the guidance of an experienced dietician due to the complexity of the adaptation. A wide range of food are relevant in histamine and tyramine intolerance and tolerance levels vary between individuals.

Some of the most relevant foods are:
Plants: citrus fruit, papaya, strawberries, pineapple, nuts, tomatoes, spinach and chocolate.
Animals: fish, crustaceans (seafood), pork, egg white.
Other sources: additives, licorice, herbs and spices.

 Mast cell stabilizers, such as cromoglycate or ketotifen are often helpful for long term symptom reduction and also enable a less restrictive diet. Antihistamines (a combination of H1 and H2 antagonists) are a further treatment modality, used especially for rapid symptom relief.

Vitamin B6, vitamin C in larger doses and pancreatic enzymes can also reduce symptoms due to histamine intolerance. Certain spices, such as curcuma and garlic reduce the formation of biogenic amines in food. DAO-containing preparations, e.g. Daosin®, have shown anecdotal effectiveness and are not generally recommended.


Mast cell activation syndrome; histamine intolerance


A comprehensive website for further information on histamine intolerance:

Histamine Intolerance Awareness

or (take with “a pinch of salt” as otherwise overwhelming):

Swiss Interest Group Histamine Intolerance