Causes, symptoms and treatment options

Histamine intolerance is an often underestimated disease that can cause symptoms for years without the exact cause being known. This can significantly limit the everyday life of those affected. Histamine intolerance can lead to a variety of symptoms. These range from headaches and gastrointestinal complaints to serious allergic reactions. This article defines histamine intolerance precisely and explains the causes, symptoms and possible treatment measures.

What is histamine intolerance?

Histamine is an organic compound that occurs in the human body, but also in plants and animals. Histamine can therefore also be absorbed through food. Histamine belongs to the group of biogenic amines. It is a naturally occurring metabolic product that is created when proteins are broken down or converted.
Histamine intolerance occurs as a result of an imbalance between histamine and enzymes that break down histamine (1). Histamine intolerance affects 1 to 3% of the population. Women suffer from histamine intolerance more often than men (2). The intolerance can affect each person differently. Symptoms can range from a runny nose to asthma and cardiovascular problems. Similar symptoms often occur in other diseases, which is why it is challenging to diagnose histamine intolerance. As a result, those affected often suffer from symptoms for a long time and do not know the exact cause. Unrecognized histamine intolerance can therefore also have a negative impact on the psyche.
People who suffer from histamine intolerance should be informed about the symptoms and effects of this disease. In this way, unpleasant and sometimes life-threatening symptoms can be alleviated or completely avoided. For this reason, this article is aimed at people who suffer from histamine intolerance or are interested in this topic.

What are the causes of histamine intolerance?

As already described in the introduction, histamine is not only absorbed through food, but is also found in tissue. The highest concentration of histamine is found in the lungs, skin, gastrointestinal tract and brain. Histamine has various effects on the human body, which are triggered by stimulation of histamine receptors H1 to H4 (1).

The following describes how histamine affects the body:

• _H1 :
  • Dilation/constriction of blood vessels, hypotension (low blood pressure), tachycardia (increased heart rate)
  • Narrowing of the nasal passages, asthma
  • Itching, redness of the skin, eczema
• _H2 :
  • Flatulence, diarrhea, constipation
  • nausea
  • Secretion of hydrochloric acid
• _H3 :
  • Reduced release of neurotransmitters such as acetylcholine and serotonin
  • Regulation of the sleep-wake rhythm
  • Headache, migraine
• _H4 :
  • Inflammations
  • Hypersensitivity reactions (2)

Histamine is an important compound in the body. In addition to being involved in the sleep-wake cycle and the production of stomach acid, histamine contributes to a healthy intestinal flora. It is necessary for the survival of intestinal bacteria and helps to remove harmful substances from the body. Histamine also plays a role as a messenger for the immune system (3).

Fig. 1: Physiological effects of histamine receptors (1).

In order for histamine to reach the corresponding receptors, it must first be released from the cells. This happens in various ways. First, specific antigens can bind to receptors, which trigger the release of histamine. In addition, injuries, extreme temperatures, and also certain medications and alcohol can damage body cells, which releases histamine.

Normally, the histamine concentration in the body is regulated to avoid undesirable effects. Two enzymes are responsible for breaking down histamine: diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). HNMT is a histamine-specific enzyme. However, DAO plays a greater role in histamine breakdown. DAO can also break down other biogenic amines such as serotonin and tryptamine through oxidation. In order for histamine breakdown to work, the body must have sufficient amounts of vitamin B, vitamin C and copper. Histamine is absorbed through food and, in a healthy person, broken down directly in the intestine.

However, an imbalance between histamine intake and degradation can lead to an accumulation of histamine in the body. This promotes the development of symptoms that occur in various organ systems (2).

This imbalance can arise due to various factors. There are people who have a genetic deficiency in DAO, a so-called "primary" histamine intolerance. "Secondary" histamine intolerance is characterized by the simultaneous presence of an intestinal disease that promotes histamine intolerance. In addition, some substances can inhibit the activity of degrading enzymes, causing histamine to accumulate in the body and cause discomfort (1).

Symptoms of histamine intolerance

When histamine exerts its effect via the receptors, various symptoms can occur throughout the body. The severity of these symptoms varies depending on the person affected. Even an amount of 100 mg of histamine can trigger mild reactions in sensitive people.

In principle, anyone can react to histamine in unnaturally large amounts, regardless of intolerance. In addition to the amount, the type of histamine consumed also plays a role. For example, histamine in cheese is much better tolerated than histamine in (spoiled) fish.

Common symptoms of histamine intolerance are:

• Headaches, migraines
• nausea
• Vomit
• Flush (hot flush with skin redness)
• itching
• Skin rashes
• Gastrointestinal complaints such as abdominal pain, diarrhea, cramps

In addition, other serious, chronic histamine intolerance symptoms can develop. These affect the respiratory and cardiovascular systems: high blood pressure, narrowing of the airways and asthma. In severe cases, anaphylaxis, a life-threatening allergic reaction of the body, can occur (4).

Diagnosis of histamine intolerance

Diagnosing histamine intolerance can be challenging. The symptoms mentioned above also occur in other medical conditions that must be differentiated from histamine intolerance. These medical conditions include skin conditions such as hives, chronic inflammatory bowel disease, carbohydrate metabolism disorders, celiac disease, mastocytosis and allergies. For this reason, it is advisable to speak to specialists in this field so that a correct diagnosis can be made.

In order to make a definitive diagnosis, it is helpful to keep a symptom and food diary. This way, connections between the consumption of histamine-rich foods and the resulting symptoms can be established (4). During a medical history, other factors that promote the occurrence of allergies should also be clarified. These include alcohol, stressful situations, infections or medication (2). When it comes to medication, particular attention should be paid to expectorants such as ambroxol, acetylcysteine ​​and almost all painkillers. X-ray contrast media and muscle relaxants also have a histamine-releasing effect (1).

The most common methods for diagnosing histamine intolerance are:

• Elimination test: This test eliminates histamine from food for 1 to 2 weeks. If histamine intolerance is present, there should be a significant improvement in symptoms during this period. A diet and symptoms log should also be kept during this period. This method is a safe way to test for histamine intolerance yourself.
• Provocation test: In contrast to the first test, in a provocation test the occurrence of symptoms is “provoked” with histamine-rich food. However, if an anaphylactic reaction is suspected, the test should be carried out under inpatient observation (2).
• Histamine 50 prick test : Measurement of the slowed breakdown of histamine by applying histamine to the skin. If a wheal (itchy swelling of the skin) appears and remains unchanged after 50 minutes, this indicates a disorder in the breakdown of histamine.

DAO test : Measurement of DAO enzyme activity in the blood. However, this method does not provide a meaningful diagnosis. Basically, only a very low concentration of DAO can be found in the blood. However, if histamine levels are elevated, this can increase considerably. This can lead to false-negative results (1, 4)

Nutrition for histamine intolerance

Histamine is found in only a few fresh foods. Histamine is formed with other biogenic amines such as tyramine or cadaverine when foods ripen or spoil.

Histamine is only formed in food under certain conditions. The decisive factors are:

• The presence of certain bacteria
• Storage temperature
• The pH value
• The presence of fermentable carbohydrates such as glucose
• Lack of hygiene during food processing.

Histamine is not only found in spoiled food. It is also found in foods that have been fermented to preserve them or to develop flavors. The following table shows selected foods with their histamine content to give a better picture:

Groceries	Histamine (mg/100 g)
Pork liver	22.5
Mettwurst	8.2
Anchovies, canned	125
trout	33.3
Herring in tomato sauce	50-300
Whole milk	0.06-0.31
Emmental	0.01-250
Gouda	1,3-85
sauerkraut	0.6-20
Tomatoes	1.1-2.2
red wine	2.2
Red wine vinegar	400

Tab. 1: Histamine content in selected foods (1)

However, there are other points to consider when it comes to food if you have a histamine intolerance. Some fruits, such as pineapples, kiwis and ripe bananas, do not have a high histamine content. However, they can cause discomfort because they contribute to the release of histamine in the body. Any processing of fruit and vegetables can produce high levels of histamine. To get a better picture, the table below lists potentially harmful foods and suitable alternatives.

Poorly tolerated	Tolerable alternative
Canned fish: tuna, sardines, anchovies, mackerel, smoked salmon	Fresh and frozen fish
Parmesan, old Gouda, Emmental, Tilsiter, mature Camembert	Butter cheese, young Gouda
Cured, dried, smoked meat and sausage products, raw ham, salami, mettwurst, smoked pork	Fresh sausage slices such as ham sausage, beer ham, turkey breast, cooked ham
Sauerkraut, spinach, tomato, eggplant, avocado	All other vegetables
Pineapple, ripe bananas, oranges, lemons, strawberries, kiwi	All other fruits
Chocolate, hazelnuts, walnuts, peanuts, products containing glutamate	Fruit gums, cookies, cakes, lollipops
Red wine, sparkling wine, champagne	Possibly in small quantities: clear spirits, dry white wine, bottom-fermented beers such as Pils
Soy sauce, vinegar, spice mixtures with glutamate, yeast extract	Herbs, spices, salt, mustard, eggs

Tab. 2: Harmful foods and suitable alternatives for histamine intolerance (1)

Histamine intolerance insider tips for everyday life:

• Carry out a "smell test" on fish. The typical fishy smell is a sign of biogenic amines such as histamine and trimethylamine being formed during spoilage. This fishy smell may no longer be noticeable after preparation, e.g. by heating. However, histamine remains after processing.
• Avoid processed products.
• Minimize alcohol consumption.
• Avoid DAO-blocking foods: green, black, and mate tea, cocoa, energy drinks, and foods high in biogenic amines.
• Eat fresh food (1).

A diet that is completely free of histamine is not effective in treating histamine intolerance. If histamine is avoided permanently, this can lead to an increase in DAO levels, which in turn can cause problems. Before starting the diet change, it is advisable to have the levels of vitamin C, vitamin B ₆ and copper in the blood determined (1).

The change in diet should take place in three phases. First, histamine and other biogenic amines should be avoided for 10 to 14 days. Since histamine intolerance can cause weight problems, a diet with a balanced ratio of carbohydrates, protein and fats should be aimed for. The amount of starchy and sugary foods should be minimized. This type of diet should improve the intestinal flora and permeability of the intestinal wall and slow down the gastrointestinal passage. This gives the degrading enzymes better conditions to break down histamine and other biogenic amines.

In the second phase, a targeted introduction of histamine-rich foods should be introduced for up to 6 weeks. This serves to cure the histamine intolerance, while observing the individual tolerance threshold. In the last phase, the balanced diet should be maintained and histamine should be consumed within the scope of individual tolerance (5).

Lifestyle adjustments and stress management with histamine intolerance

In order to keep the histamine levels in the body in balance, holistic health should be taken into account. In the industrialized world and the lifestyle adapted to it, people are often affected by stress, lack of exercise and sleep disorders. These also have an impact on the way histamine works in the body, can activate it and thus cause problems.

When experiencing stress, the brain and central nervous system are activated, involving several neurotransmitters. The body reacts to stress with various symptoms, such as sweating, rapid heartbeat, inner restlessness and tension, diarrhea, headaches or insomnia. Long-term stress can even result in cardiovascular, psychological and neurodegenerative diseases (6).

In the context of sporting activity, the research on histamine is still controversial. Training causes tiny tears in the muscle fibers, which releases histamine. This causes increased release of histamine during training and acts on the muscle tissue by activating histamine receptors. This can have positive effects such as better blood circulation and improved glucose availability. On the other hand, the release of histamine could also cause inflammatory reactions, pain, dizziness and weakness (7, 8).

Here, too, as with nutrition, it is important to find an individual tolerance threshold. Moderate physical activity has numerous health-promoting effects. It can reduce the risk of many diseases and act as a supportive measure in treatment. Diseases that are positively influenced include cardiovascular diseases, diabetes mellitus, obesity, diseases of the musculoskeletal system such as osteoarthritis, and mental illnesses. The World Health Organization (WHO) recommends that adults do at least 150 minutes of aerobic or endurance-oriented activity at moderate intensity per week. Alternatively, 75 minutes at high intensity can also be done. It is also recommended to do muscle-strengthening activity 2 to 3 times a week (6).

Lack of sleep or sleep disorders also lead to an increased risk of cardiovascular disease and depression. The histamine receptor H ₃ plays a role here, as it is involved in regulating the "wakefulness state". Antihistamines are therefore sometimes used to treat lack of sleep, as they inhibit the effect of H ₃ (6, 9).

Measures that contribute to holistic health are:

• Regular physical activity
• Integrate walking and cycling into everyday life
• Balanced diet
• Regular relaxation through meditation, yoga, autogenic training, breathing exercises and Tai Chi
• Promote “positivity”
• Avoid naps and stress before bedtime (6)

Drug treatment and nutritional supplements for histamine intolerance

The primary treatment for histamine intolerance is dietary changes. In addition, certain medications in the form of tablets and nutritional supplements can be used to relieve symptoms:

• H ₁ -antihistamines : suitable for prophylactic or acute use, effective for dermatological complaints, asthma, runny nose and watery eyes, but not for gastrointestinal complaints
• H ₂ -antihistamines: suitable for gastric complaints
• DAO substitution : dietary food, has a prophylactic effect

DAO supplementation is an enzyme replacement therapy. If this dietary supplement is taken before eating foods containing histamine, it is said to prevent symptoms. This supplement is obtained from the kidney parenchyma of pigs (1). Different enzyme activities have been detected in different DAO supplements. In general, further studies should be carried out on this topic to check the exact effectiveness. There is also new research examining DAO from sprouts (2). However, like all other drugs, these can cause side effects. Therefore, their intake should be discussed with the doctor and the necessity critically questioned.

Conclusion

Histamine intolerance represents a complex challenge in the lives of those affected. The symptoms of histamine intolerance are very diverse and can have different effects on the body. Symptoms can occur in the gastrointestinal tract, the cardiovascular system, but also in the brain and central nervous system. Those affected can suffer from nausea, diarrhea and headaches, but also from cardiovascular diseases and respiratory diseases. An effective measure for treating these symptoms is to change the diet to foods that are low in histamine. This includes avoiding processed and fermented foods such as sauerkraut, as well as preserved and smoked fish and meat products. In addition, some antihistamine medications and nutritional supplements can support treatment. Although coping with this disease is challenging, those affected can develop a better understanding of their needs and improve their quality of life through self-help and support.

Sources

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