Histamine-Intolerance: Pseudo Allergy 

Is your head buzzing and your nose running after a glass of red wine, a salami sandwich or a piece of chocolate? Something that initially appears to be an allergy could be due to histamine intolerance.

Histamine has a bad reputation. The messenger substance is mainly known to cause discomfort, especially in the case of allergies. In fact, histamine does important work in the body and is essential for our immune system. The inflammations triggered by histamine help fight pathogens and toxins that enter the body. 

However, in some people, the body is unable to break down histamine quickly enough. If histamine enters the system through food, inflammation takes over, leading to headaches, gastrointestinal complaints and itching. This is called histamine intolerance.

What you can expect from this article:

Histamine intolerance: In case of a histamine intolerance too much of the messenger substance histamine is in your body. This is probably due to the fact that too little of the enzyme diamine oxidase (DAO) is present in the intestine.

Causes: At present, only theories exist on the causes of histamine intolerance. It is possible that chronic gastrointestinal diseases, alcohol and certain medications contribute to the body producing not enough of the enzyme DAO.

Symptoms: The symptoms of histamine intolerance are similar to those of an allergy. Itching, a cold, headaches and gastrointestinal problems are some of the symptoms.

Treatment: The most important measure is to avoid foods with a high histamine content, such as red wine, tomatoes, cured sausage and ripe cheese. In the short term, medications, so-called antihistamines, can also alleviate the symptoms.

What is histamine?

Histamine is a so-called messenger substance, which passes on and spreads information between the cells and is important for our immune system, among other things. Histamine is produced by an amino acid, which is produced by the body itself as well as ingested through food. Complaints only arise when the body cannot completely break down the histamine after it has used it[1].  

Histamine belongs to the group of biogenic amines that occur in nature and are frequently produced during spoilage and decomposition processes[2].

What function does histamine have in the body?

As a messenger substance, histamine takes on a whole range of tasks: It transmits stimuli from one nerve to the next, expands blood vessels and ensures that the muscles contract and relax. Histamine is also involved in the digestion of fats, the immune system, blood formation, wound healing and the regulation of the day-night rhythm.

If there is too much histamine in the body, problems may occur in precisely these areas. The consequences are heart rhythm disturbances, blood pressure fluctuations and disturbances in the neurological pathways[1].

What is a histamine intolerance? 

In the case of histamine intolerance, also known as histamine incompatibility, the interaction of histamine and two enzymes is presumably disrupted. The body is therefore unable to break down histamine effectively enough, not even the histamine found in certain foods. If you experience symptoms after eating foods with a high histamine content, this is referred to as histamine intolerance[1].

Did you know that the term "histamine intolerance" is derived from the term lactose intolerance? Enzyme deficiency is also decisive for the intolerance to lactose[3].

4 histamine-rich foods

What role does diamine oxidase play?

 

In connection with histamine intolerance, the term diamine oxidase, DAO for short, is often used. DAO is the enzyme that is primarily responsible for breaking down the histamine that you ingest through your diet. The most common theory on the development of histamine intolerance is based on the following: The activity of the DAO is disrupted, the enzyme breaks down the histamine very slowly, and the excess histamine causes discomfort.

Histamine intolerance and Food allergies?

Histamine intolerance is not an allergy. However, it is often difficult to distinguish between the two conditions precisely because the symptoms occur after food consumption in both cases and are virtually identical. This is why histamine intolerance is also called pseudo-allergy. 

This makes it all the more important to clearly distinguish intolerance from allergy[4]. In response to the typical symptoms, doctors usually initiate a test for food allergies, which results in a negative histamine intolerance. Then you and your doctor or therapist should become aware of a possible histamine intolerance[2].

Of course it can also be the case that you suffer from a food allergy as well as from histamine intolerance - however, different foods are usually responsible for the respective reactions[5].  

Histamine intolerance - Causes

To date, from a scientific point of view, there is no definitive proof that the cause of histamine intolerance can be attributed to a problem with the enzyme DAO. Some critics even suspect that the clinical picture of histamine intolerance does not exist or is psychosomatic[6].

Good to know: We can all only tolerate a certain amount of histamine! In healthy people, this is a maximum of 100 milligrams of histamine per day. This much can be found in spoiled fish, for example. If we cross this threshold, we are already speaking of poisoning. If you have a histamine intolerance, you will react to a much smaller dose that might not trigger poisoning[7, 8].

What are the causes of histamine intolerance?

A histamine intolerance means that the body cannot keep up with the breakdown of histamine. There are two possible explanations for this[9]:

  1. Affected individuals have too much histamine, for example due to overproduction (due to allergies, bacteria or bleeding in the gastrointestinal tract) or absorption of histamine, histidine or other biogenic amines (in the form of food or alcohol)
  2. There is too little or only the inactive form of the enzyme diaminoxidase (DAO) in the body of the affected individual.

The result is the samT in both cases: there is too much histamine in the body[2].

What causes an enyzme deficiency?

But why do some people lack the enzyme DAO? There are different explanations and possible causes for this, especially:

  • Chronic intestinal strain
  • Vitamin and zinc deficiency
  • Medication and alcohol

Chronic intestinal strain 

Chronic diseases of the gastrointestinal tract can presumably contribute to the development of histamine intolerance. People with irritable bowel syndrome, gastritis, Crohn's disease or gastrointestinal ulcers are often affected. In these cases, changes in the intestinal mucosa can lead to the enzyme DAO no longer being produced in sufficient quantities[10].

Medication and Alcohol

Other possible causes of acquired histamine intolerance are medications and alcohol. Both can inhibit the activity of the enzyme DAO. For example, the following active substances can influence the function of DAO and consequently, the histamine level[2]:

Active ingredient

Contained in what?

Acetylcysteine (ACC)

pain medications

Ambroxol

cough syrup

Aminophylline

asthma 

Amitriptyline

depression

Chloroquine

malaria

Isoniazide

antibiotics

Metamizole

colic

Metoclopramide

nausea

Propafenone

cardiac arrhythmias

Verapamile

coronary heart diseases

If you are taking any of these medications regularly and experience symptoms of histamine intolerance, consult your doctor. Changing your medication may be enough to alleviate symptoms.

Vitamin and zinc deficiency

The two vitamins B6 and C work closely together with the enzyme DAO to break down histamine in the body. If the two vitamins are deficient, the histamine level increases accordingly. Some researchers have considered this as a possible explanation for histamine intolerance in people who did not have reduced DAO levels. However, other experts doubt that vitamin B6 and C can really contribute to the intolerance[10].

Good to know: In a roundabout way, the mineral zinc can also potentially help with histamine intolerance. Zinc is needed to activate vitamin B6, which in turn supports the enzyme DAO in breaking down histamine.

In short: People with histamine intolerance have too much of the messenger substance histamine in their bodies, especially after they consume histamine-rich foods. The reason for this may be an enzyme deficiency caused by gastrointestinal diseases or medication.

Histamin intolerance - Symptoms

Woman with headache - symptom of histamine intolerance

How does a histamine intolerance manifest itself?

The symptoms of histamine intolerance are initially reminiscent of an allergic reaction. This often makes it difficult to identify the intolerance. Complaints occur after consuming foods with a high histamine content, usually immediately or up to two hours later. These symptoms can last up to 12 hours or longer.

Since histamine can attach itself to certain cells in the entire body and trigger inflammatory reactions, histamine intolerance is often felt in many parts of the body. Typical symptoms are[1, 2]:

Body part

Symptoms

Skin

Redness, itching, swelling 

Intestinal tract

Cramps, bleeding, diarrhea

Lungs and respiratory tract

Cough, asthma, cramps, runny nose, difficulty swallowing

Cardiovascular system

Changes in blood pressure, palpitations, heart rhythm abnormalities, unconsciousness

Nervous system

Headache, migraine, dizziness

The symptoms do not manifest in the same way for everyone. In some people they may appear earlier, in others the reaction is stronger, and most develop only part of the possible symptoms. In addition, each person has a different individual tolerance level. This means, for example, that one person will react immediately after sipping red wine, while the other will only notice after drinking an entire glass[4].

Histamine and Migraines

Histamine can cause headaches in people with and without migraines.[4]. How exactly a migraine develops has not yet been conclusively determined, but is probably related to messenger substances that trigger inflammatory reactions. Histamine could also play a role by dilating blood vessels, which then triggers migraine pain[11]. This theory is supported by the fact that studies have often identified low DAO concentrations in the blood of people suffering from migraines. In addition, many people with migraines have observed a link between eating histamine-containing foods and their migraine attacks[12].

Histamin intolerance and female sex hormones

Scientists have observed that pregnant women are less likely to suffer from histamine intolerance. Migraines and headaches in particular are less common or do not occur at all during pregnancy. This could be due to the fact that hormone fluctuations during pregnancy ensure that there is significantly more DAO in the body. After the birth, however, the values return to normal and histamine intolerance usually returns at full intensity[4].

During menstruation, the symptoms of histamine intolerance may also be more severe. On the other hand, women with histamine intolerance often suffer from more pronounced menstrual symptoms, especially painful cramps in the abdomen. This is probably due to the interaction between histamine and the female sex hormones. If there is a lot of histamine in the body, estrogen production is promoted and progesterone production is inhibited. This leads to an increased release of pain messengers and the menstrual symptoms are more severe.[13, 15-17].

Histamine and atopic dermatitis

Histamine intolerance is considered a possible trigger of a atopic dermatitis flare-ups. The skin disease causes itching and dry skin rashes and the messenger substance histamine plays an important role. Studies have shown that atopic dermatitis patients often lack enough of the enzyme DAO and have too much histamine in their blood. A diet low in histamine can presumably improve skin appearance and lead to less frequent outbreaks. In nutrition therapy, people with atopic dermatitis are therefore often advised to avoid foods rich in histamine[17].

Histamine intolerance - Treatment

If you are suffering from histamine intolerance, the most effective therapy is to avoid foods that are very rich in histamine. However, easier said than done. Histamine is present in many foods and manufacturers do not need to include information if histamine is present on the packaging

Furthermore, it is almost impossible to completely circumvent histamine, as it is present almost everywhere, at least in small amounts. But many sufferers are relieved by avoiding certain foods that contain a lot of histamine or that promote the production of the messenger substance.

6 Tips for Histamine Intolerance

How is histamine intolerance treated? 

You have a well-founded suspicion of histamine intolerance? You can gradually change your diet. This happens in several phases:

Phase 1: Waiting period

Initially, remove histamine-rich foods from your diet for 14 days. If you notice a rapid improvement, this is a clear indication of an intolerance to histamine.

Phase 2: Test phase

After the 14-day strict waiting period, you may now gradually reintroduce small amounts of histamine into your diet. It is best to test only one food per day. The goal is to check your tolerance, the so-called tolerance threshold. It is best to keep a symptom diary in which you list what you ate when and which symptoms occurred at which times. In this way, you can find out which foods you tolerate and in what quantity.

This test phase should last about six to eight weeks. During this time, you will also be able to observe what other factors influence your symptoms. These can include stress, medication and menstruation.

Phase 3: Long-term nutrition

You have reached the third phase when you have an overall view of which foods you can tolerate and in what quantities. As a rule, you will then have established a balanced and tasty diet. Since it may be appropriate in some cases to adhere to this diet for an indefinite period of time, doctors and therapists speak of the phase of permanent nutrition.[18].

Which foods should I avoid in case of histamine intolerance?

Sausage, cheese, red wine contain a lot of histamine

Histamine is found mainly in foods that are fermented or in which fermentation processes play a role, for example in foods that have matured for a long time. For example, freshly caught fish contains very little histamine, while heavily processed and preserved fish contains a lot of histamine. In general, the list of histamine-containing foods is long[18]:

Food group

Histamine content

Suitable alternatives

Fish

Canned fish (tuna, anchovies, mackerel), marinated and smoked fish

Freshly caught (!) domestic fish or frozen fish

Cheese

Aged varieties such as parmesan cheese, Swiss cheese, Mountain cheese, Blue cheese, ripe camembert, Cheese with raw milk

Gervais, cottage cheese, cheese curds, mozzarella, butter cheese, young gouda

Meat/Sausage

Cured, smoked and air-dried sausages and meat products such as salami, raw ham and bacon

Sausages for cooking and boiling such as veal sausage, ham sausage, cooked ham

Vegetables

Sauerkraut, spinach, tomatoes, tomato products such as ketchup, tomato paste, tomato sauce; avocado, eggplant, pickled vegetables

All other types of raw or steamed products

Fruits

Ripe bananas, kiwi, strawberries, pineapple, citrus fruits

All other types, including juices

Sweets

Chocolate, cocoa 

Cakes and cookies without chocolate/nuts

Snacks/Others

Peanuts, hazelnuts, walnuts; glutamate-containing snacks, balsamic vinegar

Popcorn, millet balls, salty pastries, Grissini, crackers, all other types of vinegar

Alcohol

Red wines, dessert wines, French champagne, Prosecco, top-fermented beers (wheat beer), cask aging spirits (whisky, cognac), liqueurs

White wine, red wines low in histamine, sparkling wine or champagne low in histamine, non-alcoholic beer (mostly), Pilsner, clear schnapps, vodka, gin

Alcoholic beverages tend to promote the release of histamine. It may therefore be worth avoiding alcohol, especially in the waiting phase.

Good to know: Unfortunately, you can't remove histamine from food when cooking, whether you freeze it, bake it, fry it or put it in the microwave. Heat and cold do not destroy histamine[2].

Additional nutritional tips 

There are not only foods that themselves contain a lot of histamine - but also foods that ensure that the body releases more histamine. These include[19]:

  • Strawberries, citrus fruits, pineapple, kiwi 
  • Seafood
  • Milk

Other foods can interfere with the histamine-degrading enzyme DAO[19]:

  • Chocolate
  • Fruit: citrus fruits, pineapple, papaya, raspberries, pears, bananas
  • Tomatoes and legumes
  • Wheat germ
  • Cashews, walnuts

That's good to know: The histamine content in food can vary greatly depending on how fresh and ripe the food is and which variety it is[20].

Colon therapy and histamine intolerance

A healthy colon can contribute to an improved production of the histamine-degrading enzyme DAO. If your intestinal mucosa is inflamed or there is damage to the cells of the intestinal epithelium, the enzyme can no longer be produced sufficiently. A bad colonization of bacteria in the intestine can be another problem. A colon therapy can remedy this situation and encourage the development of DAO enzymes again. A reconstruction of the natural colonization with microorganisms at least once a year is the basic building block for this. It is worth it, because an acquired histamine intolerance can be reduced or even cured.

Does medication improve histamine intolerance?

Histamine intolerance cannot be cured by medication. However, medication can help you to relieve the symptoms in the short term. And even with medication you should continue to avoid red wine, mature cheese and such. The most common medications are antihistamines and the product DAOsin.

When is the use of antihistamines recommended?

Antihistamines prevent cells of the immune system from releasing histamine. They are also the active ingredient of anti-allergy medications. Whether they relieve histamine intolerance depends on the symptoms that are bothering you. If the intolerance causes diarrhea, antihistamines can often help. They are less effective for headaches. As a rule, doctors prescribe antihistamines in any case to treat certain symptoms. They should not be taken continuously[19].

Medications for eating out:

Especially at parties and during restaurant visits it is often difficult to avoid histamine-containing food completely. Many affected individuals rely on the product DAOsin from the pharmaceutical manufacturer STADA for such cases. The dietary supplement contains DAO derived from animals. It is intended to support your intestines in breaking down histamine. Studies have not yet confirmed the effect of the product - some experts say that there is currently no medication that can increase the activity of the enzyme DAO[18].

In short: If histamine intolerance is suspected, you should avoid alcohol, histamine-rich foods and foods that may release histamine. You can take antihistamines to combat the symptoms for a short period of time.

Histamine intolerance test

Since it is not yet clear exactly what happens in the body in case of histamine intolerance, there is no standardized method for measuring intolerance. The first step is usually to determine the symptoms and specifically omit food in order to observe possible changes.

Which test can tell me if I suffer from a histamine intolerance?

There are two ways to confirm your initial suspicion:

1. Provocation test: Your physician will administer you a certain amount of histamine, usually in the form of a tablet. On a different day you will receive another tablet without histamine. The physician will observe how your body reacts in each case[3].

2. Laboratory diagnostics: In practice and in scientific studies the measurement of the DAO enzyme is increasingly used. Studies revealed that people who had observed histamine intolerance had significantly lower concentrations of the enzyme in their blood than healthy control groups.[3, 14, 15].

The measurement of methylhistamine in urine, on the other hand, is strongly criticized. According to some experts, the value is very inaccurate and can also be increased by a protein-rich diet.

What other diseases should I check for?

The symptoms indicating histamine intolerance may also be related to other health problems. Especially if you regularly have gastrointestinal discomfort, you should consult a doctor about possible inflammatory bowel diseases such as gastritis and Crohn's disease. There may also be other intolerances such as lactose, fructose and sorbitol intolerance[2].

Where can I take a histamine intolerance test?

cerascreen histamine intolerance test

If you want to perform a histamine intolerance test, you can do this at a physician´s office, for example - family doctors often offer DAO tests. Physicians will usually ask you about your symptoms and may instruct you to keep a symptom diary.



An alternative is a self-test at home. With our cerascreen® Histamine Intolerance Test, for example, you can simply test how high the DAO levels your blood are - and obtain an idea of possible intolerance. For the test , take a small amount of blood from your fingertip and send the sample to a specialist laboratory. You will receive a comprehensive result report with your DAO level along with valuable health tips.

Histamine intolerance: At a glance

What is histamine?

Histamine is a messenger substance with important functions for the immune system. It is also responsible for allergy symptoms.

What is a histamine intolerance?

People with histamine intolerance suffer from intolerance to histamine-rich foods. You may have too little of the enzyme DAO that breaks down histamine in your body.

What are the symptoms of histamine intolerance?

Typical symptoms are headaches, runny nose, heart rhythm abnormalities and skin rashes. Histamine intolerance can also make the symptoms of menstrual cramps, migraines and atopic dermatitis more severe.

What are the causes of histamine intolerance? 

Researchers have not yet fully understood the cause of histamine intolerance. Some believe that chronic gastrointestinal diseases, medication and alcohol can prevent the DAO enzyme from properly doing its job.

How can I combat histamine intolerance?

There is no medicine that cures the intolerance. All you can do is try to see if antihistamines can relieve the symptoms in the short term. The only effective therapy is to avoid histamine-rich foods as much as possible, preferably with a three-stage change in diet.

Which foods contain a lot of histamine?

Histamine is found mainly in fermented and highly matured foods - for example in canned fish, red wine, mature cheeses and cured sausage.

Sources

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  14. Bódis, J., Tinneberg, H.R., Schwarz, H., Papenfuss, F., Török, A., Hanf, V.: The effect of histamine on progesterone and estradiol secretion of human granulosa cells in serum-free culture. Gynecol. Endocrinol. 7, 235–239 (1993)
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