Digestive Disorders > Intolerances > Histamine Intolerance

Histamine intolerance: The ultimate guide

Dr. med. Andre Sommer

Dr. med. Andre Sommer

A reaction to histamine is called histamine intolerance. Histamine intolerance affects about one percent of the population. Women are affected by histamine intolerance about twice as often as men.

Typical symptoms of histamine intolerance such as flatulence, diarrhea, urge to stool, nausea and cramp-like pain appear about 30 minutes after eating. However, the time period can vary greatly from person to person. The uncertainty about the exact cause of the symptoms in particular severely limits the quality of life of those affected. Histamine is an important messenger for numerous processes in our body.

Doctors are still arguing about the existence of histamine intolerance, since the symptoms reported by those affected can often not be proven under laboratory conditions. Subjectively, histamine intolerance is assumed to be much more common than can be objectively proven by doctors. However, studies of intestinal tissue samples from irritable bowel patients have shown that they have more histamine receptors in the digestive tract than healthy control groups without irritable bowel syndrome (IBS).

The following article provides information on which foods are low and high in histamine, what job histamine does in the body and how histamine intolerance works.

What is histamine?

Histamine is a substance that belongs to the group of biogenic amines. That means that it has a so-called amino group (-NH2) and is made in the body from amino acids.

Histamine occurs naturally in many foods. Processed foods have a higher histamine content than natural ones. That is why the amount of histamine ingested in our diet today is significantly higher than 50 or 100 years ago.

What is histamine intolerance?

The term histamine intolerance is often discussed by doctors. In general, it describes an imbalance in the absorption, production and breakdown of histamine in the body. However, it is not yet sufficiently understood whether the increased intake of histamine-containing foods or the inability of the body to break down histamine play a major role in histamine intolerance. There are doctors who argue that a change in diet is not necessary and others who see a change in diet as the most important means of treating histamine intolerance.

The symptoms and complaints that affected patients experience after intake of histamine are summarized by doctors under the term “histamine intolerance syndrome” (HIS).

How is histamine intolerance syndrome defined?

HIS is an acute or chronic response to the absorption of generally acceptable amounts of histamine that is not mediated by the immune system. Some patients show reduced activity of histamine-degrading enzymes, while a direct trigger cannot be found for others. It can be of various degrees and occurs almost exclusively in adulthood. Histamine intolerance syndrome affects women significantly more often than men.

There are two types of HIS:

  • Primary histamine intolerance syndrome
  • Secondary histamine intolerance syndrome

Primary HIS

Primary HIS is an intolerance reaction to normally tolerated amounts of ingested histamine. Doctors call the syndrome “primary” because the symptoms relate directly to the histamine as the cause. It is not caused by any other condition and is not caused by medication or the like. Primary HIS is rare.

Secondary HIS

With secondary HIS, the cause of histamine intolerance is another disease or a drug that interferes with histamine metabolism. One such triggering disease is celiac disease (an intestinal disease caused by gluten).

What are the symptoms of histamine intolerance syndrome?

If you suspect you are suffering from histamine intolerance, a consultation with your doctor can help to diagnose the disease and to initiate treatment in cooperation with nutritionists.

A histamine level of 0.3 to 1.0 nanograms per milliliter in the blood plasma is considered normal. Plasma levels above this can cause typical symptoms depending on the individual histamine tolerance limit. Even people without histamine intolerance can develop symptoms such as headaches or reddening of the skin with a massive intake of histamine-rich foods or histamine-releasing substances.

The symptoms of histamine intolerance can show up in different organ systems in the body and can be triggered by foods rich in histamine, but also by drugs that influence histamine metabolism.

Histamine intolerance symptoms on the skin

The skin may turn red in the event of an intolerance reaction (flush), or hives (urticaria) may occur. Itching is another symptom that people often report.

Histamine intolerance symptoms in the gastrointestinal tract

The gastrointestinal tract is also often affected by the HIS. Nausea, abdominal pain, and bloating are common. Stomach and intestinal cramps, vomiting and diarrhea occur just as often.

Histamine intolerance symptoms in the nervous system

A common symptom of HIS is headache, feeling hot, and dizziness. A short time after eating histamine-rich food, pain can occur, which many patients describe as migraine-like. In people with migraines, histamine-rich foods are typical readout factors (triggers) for a migraine attack. Histamine acts on the H1 receptors in the blood vessels in the head and can thus cause headaches. It is also believed that histamine H3 receptors can affect the sleep-wake cycle and alertness, confusion, and fatigue.

Histamine intolerance symptoms in the cardiovascular system

A reaction of the body to histamine can lead to a drop in blood pressure (also an increase in blood pressure), an increase in heart rate (rapid heart rate) and cardiac arrhythmias.

Histamine intolerance symptoms of the respiratory tract

Runny nose, sneezing and a stuffy nose are also symptoms of histamine intolerance syndrome. Strong reactions can also lead to shortness of breath, asthma attacks and an allergic shock.

Gynecological symptoms of histamine intolerance

Some women have reported painful menstrual periods with abdominal cramps. Researchers believe that histamine can affect estrogen levels and thus affect the menstrual cycle.

How does the doctor diagnose histamine intolerance syndrome?

The symptoms described by patients give a first indication of the presence of histamine intolerance syndrome. Since there is no way to reliably diagnose this syndrome based on blood values or other laboratory values, the doctor may use a so-called provocation test. To do this, the doctor will first rule out that other diseases trigger the symptoms or that the reaction to histamine is so severe that testing would be dangerous for the patient.

For provocation testing, 50–150 milligrams of histamine are administered to the patient orally, usually in the form of a tablet. Another day, a placebo is given. The patient does not know when the histamine or placebo are given. Two to four hours after administration of the preparation, the doctor will monitor the response to the histamine preparation compared to the response to the placebo. In order to objectify the evaluation as far as possible, the doctor fills out a symptom score. Depending on how many points are reached, the test is repeated or the diagnosis of histamine intolerance syndrome is made.

Are there laboratory tests to diagnose histamine intolerance?

No, there are still no suitable laboratory tests to diagnose histamine intolerance.

Tests offered to measure the level of diamine oxidase in the blood or the determination of histamine in the blood plasma or urine are not very meaningful and are not recommended. The same applies to the so-called “histamine 50 prick test”.

How is histamine intolerance syndrome treated?

The most important step in the therapy of HIS is a reduction in histamine intake. It can be achieved through a low-histamine diet. Doctors recommend that you also keep a symptom diary or food diary. With its help, a record can be kept documenting when the symptoms appear after what foods and whether changing the diet reduces the occurrence of the symptoms.

The goal of the low-histamine diet should not be to create a simple list of prohibited foods. Rather, it should be found out how much histamine is tolerated in which foods (individual tolerance limit). In addition, focus should be placed on the composition of the food and on the intervals between meals. It has been shown that simply removing histamine-rich foods from your diet is not enough. Rather, a reduced starch and sugar and at the same time high vegetable, protein and fat diet has a better effect on the symptoms. The histamine content of food alone is not very informative about the tolerance.

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Can you treat histamine intolerance with medication?

If a consistent change in diet is not possible, medication can be taken that bind to and block the histamine receptors H1 and H2. These drugs, known as antihistamines, include, for example, cetirizine and cimetidine.

Drugs that promote the activity of diamino oxidase (DAO) have also shown good effectiveness in the treatment of HIS in studies. Studies show how important DAO is for people in which DAO is restricted in its function. If DAO is no longer active and large amounts of histamine are ingested, life-threatening body reactions such as a drop in blood pressure, shortness of breath and shock can occur.

What are the causes of histamine intolerance syndrome?

In most cases, the intolerance develops over the course of life. The exact mechanisms have not yet been clarified. However, we now know that there is a certain genetic component in histamine intolerance, which is also found in the following diseases:

  • Crohn's disease
  • Ulcerative colitis
  • Celiac disease
  • Adenomatous colon polyps

It is also believed that the permeability of the intestinal barrier plays a role in histamine intolerance.

What diseases are associated with histamine intolerance syndrome?

The following diseases and intolerances should not be confused with histamine intolerance syndrome:

  • Lactose intolerance
  • Salicylate intolerance
  • Fructose intolerance
  • Irritable bowel syndrome
  • Food allergies (e.g. nuts)

These can occur independently but also in combination with histamine intolerance.

Which drugs can lead to an increased release or a reduced breakdown of histamine?

Different drugs can worsen or even cause histamine intolerance. For this reason, if you suspect histamine intolerance syndrome, the medication you take should be checked with a doctor

Substance class Active ingredient
X-ray contrast media
Muscle relaxants Pancuronium, alcuronium, D-Tubocurarin
Anesthetic Thiopental
Painkiller Morphine, pethidine, NSAID, ASA, metamizole
Drug to combat high blood pressure Dobutamine
Local anesthetic Prilocain
Antihypertensives Verapamil, alprenolol, dihydralazine
Remedies for irregular heartbeat Propafenone, quinidine
Diuretics Amilorid, furosemid
Drugs influencing motility Metoclopramid
Antibiotics Amoxicillin, cefuroxime, cefotiam, isoniazid, pentamidine, clavulanic acid, choroquin, paromomycin
Expectorant Acetylcysteine, ambroxol
Drug for expanding the respiratory tract e.g. in asthma Aminophylline
Antihistamines (H2-receptor antagonists) Cimetidine
Chemotherapy drug Cyclophosphamide
Antidepressants Amitriptyline

Which foods are high in histamine?

The following table shows foods containing histamine, measured in milligrams per kilogram of food. The histamine content can be read here. The content of histamine increases with the maturity of the food. In addition, foods modified by microorganisms such as mature cheese, sauerkraut, wine and processed meat are richer in histamine.

Food list with histamine-rich foods
Group Food Histamine content in mg/kg
Fish Mackerel 1–20 (frozen) 1–1788 (smoked/salted)

up to 210 (canned)

Herring 1–4 (frozen) 5–121 (smoked/salted)

1–479 (canned)

Sardines 14–150 (smoked/salted)3–2000 (canned)
Tuna fish 1–402 (canned)
Cheese Gouda 10–900
Camembert 0–1000
Cheddar 0–2100
Emmentaler 5–2500
Swiss cheese 4–2500
Parmesan 10–581
Meat Salami 1–654
Ham 38–271
Raw sausage Up to 650
Vegetables Sauerkraut 0–229
Spinach 30–60
Eggplant 26
Tomato ketchup 22
Red-wine vinegar 4
Alcohol White wine Up to 10
Red wine Up to 30
Top-fermented beer Up to 14
Bottom-fermented beer Up to 17
Champagne Up to 670

Which foods promote histamine release in the body?

Some foods, such as citrus fruits, also have the potential to release the body's histamine. The following table shows histamine-releasing foods:

Plant-based histamine releasing foods Animal-based histamine releasing foods Further
Citrus fruits Fish Licorice
Papaya Crustaceans Spices
Strawberries Pork Additional ingredients
Pineapples Protein
Nuts, peanuts
Tomatoes
Spinach
Chocolate

What does a change in diet look like with histamine intolerance?

If other diseases and allergies are excluded, a three-stage change in diet to treat histamine intolerance symptoms can be carried out. This should be accompanied and documented in a symptom and food diary. A radical and long-term change in diet should always be done in consultation with a doctor or nutritionist to avoid malnutrition.

  1. Basic diet (phase 1): The first two weeks aim to alleviate the symptoms by reducing the intake of biogenic amines (e.g. histamine, tyramine, tryptamine, phenylethylamine, serotonin, putrescin) and changing the food selection and the intervals between meals.
  2. Test phase (phase 2): Trial and gradual reintroduction of foods that were previously reduced. This second phase builds on the first step by step. Other disruptive factors such as stress, menstruation and medication should also be taken into account.
  3. Individual well-being nutrition (phase 3): In the third phase, conclusions are drawn from the test phase: tolerated foods are included in the long-term daily diet, poorly tolerated foods are omitted. This results in an individual diet that is less restricted and more versatile than the basic diet in phase 1.

How does histamine metabolism work in the body?

Histamine can either be ingested with food or produced by the body itself.

In the body it is made from the amino acid histidine. Histidine is an essential amino acid, which means that the body cannot make it itself and it has to be ingested with food.

The histamine content of foods can change depending on how they are processed or how long they are stored.

Histamine is broken down by two enzymes: diamino oxidase (DAO) and histamine N-methyltransferase (HNMT). Histamine, which is still in the intestine, can also be broken down by intestinal bacteria.

The following table summarizes a comparison of low-histamine and high-histamine foods and lists the difference between foods that release histamine and those that inhibit DAO:

Low-histamine foods High-histamine foods Foods that release histamines Foods that inhibit DAO
Cream cheese Hard cheese (mature) Citrus fruits, strawberries, pineapples Alcohol
Fresh meat, fresh fish Smoked meat, smoked fish Nuts Black tea, green tea
Fresh fruits and vegetables Canned food and ready meals Chocolate, cocoa Chocolate, cocoa
Rice, corn, oats Yeast Tomatoes Energy drinks

What role does histamine play in the body?

Histamine binds to histamine receptors. This includes:

  • H1, H2, H3 and H4 receptors on the cell surface
  • Intracellular histamine receptors

After binding to these receptors, histamine mediates many processes that also play a role in allergic reactions. These include the dilation of blood vessels, the contraction of smooth muscle cells, increased permeability of blood vessels as well as an acceleration of the heartbeat (tachycardia) and changes in blood pressure. Histamine also plays an important role in the brain as a so-called “neurotransmitter”, for example in the development of nausea.

In an acute allergic reaction, mast cells that are in the skin release large amounts of histamine.

What is the course of the disease and the prognosis?

Overall, histamine intolerance is easy to treat. The most important goal is freedom from symptoms by avoiding the triggering factors. If the disease is under control and there are no deficiencies, those affected have the same life expectancy as healthy people. If there is a simultaneous intolerance to other foods (e.g. lactose, fructose, sorbitol, salicylate), the change in diet should be discussed with a nutritionist.

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Dr. med. Andre Sommer

Dr. med. Andre Sommer

I’m André, a medical doctor from Berlin. Together with a team of medical doctors, nutritionists and data scientists we empower people to understand digestive issues with our app Cara.

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