What is histamine intolerance, what are the causes, symptoms and treatment?

What is histamine intolerance, what are the causes, symptoms and treatment?
Photo source: Getty images

Histamine intolerance is hypersensitivity to histamine. It's not an allergy. Histamine is produced naturally in our body, but we also take it through food consumption. Some contain more of it, and it causes a variety of difficulties for people suffering from it.


Histamine intolerance is a disease characterized by hypersensitivity to histamine, that is intolerance. It is also referred to as a disorder of histamine metabolism.

It is not an allergy.

So what histamine intolerance actually is?

The definition says that, in particular, it is a situation where there is a disparity between the supply and the mechanism of histamine degradation. An imbalance can arise from several factors.

How does the imbalance in the above equation result in histamine supply and degradation:

  1. increased histamine content in the diet
  2. increased supply of histamine-releasing substances, so-called histamine liberators
  3. supply of substances that block the enzyme which  breaks down histamine
    • N-methyltransferase, which breaks down endogenous histamine
    • diamine oxidase  degrades exogenous histamine (DAO)
  4. by flushing the body's own histamine to an increased extent
  5. decreased function of the enzyme  that affects the breakdown of histamine

And what is histamine?

Histamine is a biologically active amine. It is found in both plant and animal cells, mainly through degradation as a product of cell metabolism. It is formed during the decomposition of the amino acid histidine or the transamination of aldehydes and ketones.

It was discovered by the British physician, biochemist, physiologist Sir Henry Dale in 1910.

Examples of other biogenic amines are serotonin, adrenaline, noradrenaline, dopamine, or tyramine. These substances are also known as mediators and are used to transmit signals in cells, between cells, and also between organs.

Like other mediators, histamine plays a number of important roles in the body and is essential for life. The body makes it itself, hence it is called endogenous histamine. Exogenous histamine is that which enters the body from outside through food intake.

The level of histamine in food is not constant. It increases during microbial and biochemical processes. This will not prevent food exposure to low temperatures, such as in the refrigerator. Therefore, its values ​​are lower in fresh food and food storage contributes to its increased values. 

As described, it is found in both plant and animal cells. It is typically more abundant in fish, cheese, salami, fermented, fermented, or canned foods. It is present in the body mainly in granulocytes and mast cells, where it is bound and released by various stimulations.

Its role in the body is irreplaceable, it is essential for life. People associate it mainly with an allergic reaction when it is released together with other substances after stimulation of IgE antibodies. The action of allergen and IgE antibodies thus causes an allergic reaction.

However, histamine intolerance is not an allergy

There is a fundamental difference between an allergic reaction and intolerance to a substance.

An allergic reaction is an exaggerated response of an organism to a substance that does not normally elicit an immune response. Allergy is mediated by IgE antibodies that the body has developed for the allergen.

These are, for example, mites, dust, pollen, mold, food ingredients, or animal fur. Typically, this reaction is detected by skin tests.

Food component intolerance, as well as histamine intolerance, does not involve an IgE antibody response. Although the reaction is characterized by hypersensitivity, it lacks an allergic basis.

Allergy is characterized by a set of difficulties, such as:

  • skin changes
  • swelling of the mucous membranes
  • swelling of the skin
  • sowing of rashes, hives
  • itching
  • rhinitis and increased mucus secretion or cough
  • possibly difficulty breathing
  • only one symptom may occur or they may be combined with each other 

A feared form of allergy is an anaphylactic reaction.

Interesting information about the anaphylactic reaction in a separate article at the Medical Center.

Where is histamine needed and what is its function?

Histamine is not only present in an allergic reaction. It has various roles throughout the body. It serves as a mediator, also mediates information in cells, between cells and organs.

Its effect on smooth muscles is well known. During an allergic reaction, it acts on the smooth muscle in the wall of the blood vessels, which expands its effect. This causes blood pressure drop or reddening of the skin. Widening of the vessel wall also results in easier fluid leakage from the vessels.

Leaking fluid from the blood vessels causes swelling but also the well-known hives on the skin. Hives are also known under the professional name urticaria. The skin also looks like hives when swallowed, hence the name hives. Dilation of blood vessels in the head causes migraine headaches, abdominal cramps in the digestive system. Histamine irritates nerve endings.

In the table is shown the cross-body activity of histamine

Organ system Effects
Central nervous system
  • dizziness
  • headache
  • nausea to vomiting (a central form of vomiting)
  • affects vigilance and circadian rhythm
  • thermoregulation
  • memory
  • it also stimulates peripheral nerves
  • also nerve endings
Cardiovascular system
  • speeds up the heart
  • causes arrhythmias
  • dilates blood vessels
  • lowers blood pressure
Digestive system
  • increases gastric acid production
  • causes bloating
  • diarrhea
  • stomach ache
Blood and bone marrow
  • acts on hematopoiesis
  • mast cell secretion
Skin and mucous membranes
  • itching
  • swelling
  • redness
  • hives
Respiratory system
  • bronchoconstriction
  • shortness of breath
  • increased mucus production
  • secretion from the nose and full nose, also for swelling of the mucosa
  • a cough
and female reproductive system
  • increases estrogen production
  • painful menstruation


The cause of histamine intolerance is a disorder of histamine metabolism.

There is a mismatch between the supply and degradation of histamine in the body. Its increased amount in the body is often manifested by various difficulties. Histamine enters the body to a greater extent through food.

The source of histamine is the food itself (plants, animals), but also microorganisms.

These are bacteria that act on food during storage. Examples are products with high protein content, such as fish, meat, cheese. Subsequently, there are foods that indirectly increase histamine levels, such as egg whites, pork, strawberries, citrus, or tomatoes.

It is said to be rare in children if it usually affects boys.

The level of histamine is also increased by pathological intestinal microflora, bleeding in the digestive tract, and also substances that release histamine, so-called liberators. Decreased activity of enzymes, ie their blockade is caused by various substances, some drugs, diseases of the digestive tract, especially chronic inflammation of the intestine. Although rare, a genetic defect in enzyme production can also be the cause, and a mismatch in the mechanism sometimes occurs in a healthy person.  

Histamine intolerance arises due to a disproportion in the level of:

  1. excessive histamine intake in food
  2. increased supply of histamine-releasing substances, so-called  histamine liberators
  3. supply of substances that  block the enzyme that  breaks down histamine
    • N-methyltransferase, which breaks down endogenous histamine
    • diamine oxidase  degrades exogenous histamine
  4. by flushing the  body's own histamine to an increased extent
  5. reduced function of the enzyme  acting on the breakdown of histamine

The enzyme that is responsible for the breakdown of exogenous histamine, or diamine oxidase (DAO), is present in different amounts in each person and its functionality is different. The best effectiveness of this enzyme is in childhood. It is said to decrease with age.

Histamine intolerance affects approximately 3% of the population.
80% of them are middle-aged.
It affects women more often.

The enzyme DAO is found and acts in the digestive tract, it is also found in the kidneys or placenta. This form affects the exogenous type that we eat. The enzyme N-methyltransferase is responsible for the endogenous type and elimination of histamine, which the body produces itself. It works inside the cell, so it doesn't even get into the blood.

Histamine values ​​and histamine intolerance

The highest secretion of DAO occurs in the small intestine and the descending part of the large intestine. This part of the digestive tract is a major barrier to histamine's access to the blood. The normal level is 0.3 - 1.0 ng / ml. Difficulties occur if this value is exceeded.


Symptoms of histamine intolerance stem from the broad scope of histamine. They are diverse and occur in different intensities and combinations. They may not all occur at once. Although the disease has a condition similar to allergies, it is not an allergy.

Histamine intolerance is not an allergy, although some symptoms are misleading.

The table shows the distribution of symptoms according to the body system

Organ system Symptoms Description
Digestive tract
  • diarrhea
  • abdominal pain, abdominal cramps
  • bloating
  • return of acidic content
  • reflux of gastric contents into the esophagus
difficulties occur mainly after eating a risky diet
after a few minutes to an hour The cause of pain is the expansion of smooth muscle in the walls of blood vessels and intestines Contributions are caused by conditions such as:
irritable bowel syndrome
Crohn's disease
ulcerative colitis
  • urticaria
  • rash
  • angioedema, ie swelling
  • itchy skin
  • reddening of the skin 
urticaria is also a consequence of the dilation of small skin vessels,
and thus the passage of fluid outside the blood vessels
as well as greater swelling,
there is also a connection with diseases such as:
atopic eczema
or hypersensitivity to the sun
Joints and muscles
  • knuckle pain
  • pain muscles
  • muscle weakness
  • decreased muscle tone
as a consequence of inflammation, ie arthritis,
and thus an association with rheumatoid arthritis 
  • fatigue
  • memory failure
  • central type of vomiting
  • headache
  • dizziness
  • affects alertness
  • sleep and daily rhythm
  • insomnia
  • excitement
histamine affects nervous excitability
but also other neurotransmitters
headache has a migraine character
also for dilation of blood vessels in the brain
worsens its head movement
  • nervousness
  • depression
  • anxiety
  • schizophrenia
connection with action on the CNS
Cardiovascular system
  • low blood pressure
  • cardiac arrhythmia
  • accelerated heart rate
  • collapse to impaired consciousness
also as a consequence of vasodilation, it
affects hematopoiesis
such as mast cell secretion
or white blood cells
Respiratory system
  • coughing
  • swelling of the mucosa. lips, tongue, vocal cords
  • hoarse voice
  • increased congestion
  • secretion of water discharge from the nose
  • bronchoconstriction
  • shortness of breath
  • wheezing when breathing, as in asthma
Female genital system 
  • increases estrogen production
  • painful menstruation
  • high-risk pregnancy
  • abortion
 difficulties tend to be chronic


The diagnosis of histamine intolerance is based mainly on the anamnesis and the clinical picture. Other diseases, such as inflammation of the intestine, Crohn's disease, Helicobacter pylori, must be ruled out. Allergy exclusion and a skin test are also reported.

The DAO enzyme level can be determined during diagnosis. However, this method does not have 100% success and may show false results. The value of histamine alone is difficult to determine because it has a very short disintegration time.

Differential diagnosis also includes blood tests for basic parameters, blood count, biochemistry, sugar, liver tests. IgE level, inflammatory parameters, CRP, eosinophil count are determined. In addition, other examinations are supplemented according to the difficulties encountered. Such as neurological, dermal, cardiological. Endoscopy, X-ray, USG, or CT for abdominal pain.

Caution: it is important to think about milk or gluten intolerance .

The main method for making a diagnosis is, in particular, the thorough collection of information about the clinical picture, ie the difficulties affecting the person concerned. An elimination diet and a subsequent load test with foods that have a higher concentration of histamine are helpful.

The doctor finds out various information and the main questions include:

  • is there a link between food consumption and difficulties?
  • what is the time period from consumption to symptoms
  • identification of problematic foods even with their approximate histamine value
  • there are other diseases or allergies
  • what is the clinical finding and examination from head to toe
    • for example, the condition of the skin, its color, rash
    • breathing, cough, wheezing
    • heart rate, acceleration, irregularity, blood pressure
    • examination of the abdomen by touch, tapping


The course of histamine intolerance depends on several factors, of course, also on the dose of histamine that enters the body. The symptoms are acute, starting a few minutes from eating a risky diet to an hour.

Difficulties such as diarrhea, abdominal cramps, bloating are the first wave of digestive problems along with skin manifestations.

Histamine intolerance and abdominal pain shortly after a meal
Abdominal pain shortly after consuming risky foods. Photo source: Getty images

The skin shows redness, rashes, and the familiar urticaria, ie hives. The skin itches, even irritate nerve endings. Dilation of blood vessels causes fluid to penetrate from the blood vessels, causing swelling. Dilation of the bloodstream results in low blood pressure. This can cause a collapse.

Symptoms appear in combination, but it is not necessary that they all be named.

Other symptoms, such as those listed in the table, may or may not occur. The overall symptomatology can be mild but also severe. Chronic problems also occur, for example, in the long term in terms of acting on the CNS. There is fatigue or rapid fatigue, memory disorders, concentration, nervousness. Anxiety, depression, even schizophrenia may be associated.

The headache has a migraine character, it is impaired by movement. Over time, muscle weakness and other complications occur, for example in women with difficulties with menstruation, and therefore also with fertility, pregnancy is at risk. The risk of miscarriage is serious.

Suitable and unsuitable foods for histamine intolerance

From the above information, it appears that certain content of histamine is found in every plant or animal product. Of course, there is a difference in the total value of the substance contained.

Diet includes limiting the consumption of foods that have higher levels of histamine, but also diets that affect the production of histamine.

It is important to realize what one can eat, and what should not be eaten. 

The table shows the approximate values ​​of histamine in some foods and beverages

Product Approximate histamine content in mg per 100 g
Sardines up to 1500
Tuna up to 1300
Mackerel to 30
Salami to 28
Ham, sausages  to 16
Emmental to 60
Parmesan to 20
Gouda to 18
Cheddar to 5
Yogurt up to 0.2
Sauerkraut to 20
Spinach to 6
Tomatoes to 2
Wine vinegar (balsamic) up to 400
Apple vinegar to 2
Alcohol Value in / g / 100 g
Red wine to 380
Wine to 40
Beer to 30

The value of histamine with food is not constant. Fresh products contain the smallest amount.

Subsequently, it gradually increases.

This is due to the action of microorganisms and breakdown mechanisms in the cells themselves. Even storing food in a refrigerator at 4 ° C will not prevent it from deteriorating. Freezing and preparation immediately after thawing will help.

Histamine intolerance - suitable and unsuitable foods
Histamine intolerance - suitable and unsuitable foods. Photo source: Getty images

The table lists permitted and prohibited foods and regimens for histamine intolerance

Appropriate food Prohibited foods
plain milk fish
Emmental or Gouda cheeses
yogurt without flora  sausages, hot dogs
cottage cheese
red wine
beer - yeast
dark flour  sauerkraut
dark pastry  tomatoes
plain bread and rolls citrus
homemade cakes and desserts
without the content of prohibited ingredients 
pure cereal  eggplant
oat flakes  strawberries
rice bread  bananas (histamine is mainly in the peel)
persimmon chocolate
pea sprouts  stored meat, chicken meat
other fermented foods
sweet potatoes
fresh pastry
white flour
commercially sold cakes, desserts,
baking mixes
Brazil nuts
olive oil,
coconut oil
sour, ie acidophilic milk
probiotic yogurts
or sheep milk cheese
mulberry nuts
thyme  basil
tarragon  canned food
nettle margarine 
measure spices such as cloves, anise, or cinnamon
ginger some fruit teas, artificially flavored
turmeric additives such as colorants, stabilizers, flavorings
some drugs from the group:
contrast agents
real tea from tea tree
even though it contains histamine, but its negative effect on long-term drinking has not been proven
can be white, green, oolong (partially fermented), or fermented
allergic reaction (releases histamine)
injury, shock
Suitable mode Inappropriate mode
consumption of food with a histamine content of less than 5 mg / 100 g
and restriction of histamine in other dietary components
combination of several foods containing histamine
consumption of fresh fish food storage
The maximum storage time of 24 hours is
conditional on cold storage after consumption
food heating
probiotics smoked, salted, and preserved foods
vitamin C long cooking and roasting of meat
vitamin B 6  maximum 50 mg per day
raw fruits and vegetables
storage of meat only by freezing

How it is treated: Histamine intolerance

Treatment of histamine intolerance: medication and diet

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What we know about histamine intolerance

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Interesting resources

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  • "Histamine Intolerance". Healthline
  • "Tissue Expression of HNMT - Summary - Protein Atlas". Tissue Expression of HNMT - Summary - Protein Atlas
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  • "Tissue Expression of AOX1 - Summary - The Human Protein Atlas". 
  • "Histamine Food List" (PDF). Healing Nore: Health Coaching.
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  • "Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: A randomised, double-blind, placebo-controlled cross-over study". Wiener Klinische Wochenschrift2011: 1–2. Retrieved 3 June 2019.
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