The pseudoallergy

Your head is buzzing and your nose is running - after just one glass of red wine, one salami sandwich or a piece of chocolate? One normally assumes an allergy. What if you don’t have an allergy and if there is just too much histamine in your body? If histamine is not decomposed completely, headaches, gastrointestinal disorders, itching and palpitations occur. This is called histamine intolerance.

Even though histamine has been known for more than 100 years, the disease is still controversial. The first studies were published 30 years ago when scientists realized that all types of allergy tests showed negative results in people affected. It soon was confirmed that the symptoms could be reduced by a low-histamine diet. Approximately three to four percent of the population suffer from the symptoms of histamine intolerance. The main risk group are women (80 %), most of them in the age class from 35 to 45 years. Unlike allergies, it is not so easy to determine a histamine intolerance. Mostly it is diagnosed only after ruling out any allergies. This can be a very long process. Scientists are examining whether the histamine-degrading enzymes can give a hint at the intolerance.

One thing is clear: When you suffer from histamine intolerance, histamine must be eliminated from your diet in the first place. Once you have changed your diet, you can start to reintroduce small amounts of foods containing histamine and don’t have to fear possible negative effects. We explain to you how a histamine intolerance can occur, how to recognize it and how to still enjoy restaurant visits. Moreover: Can histamine intolerance cause headaches and can a diet low in histamine help to improve impure skin?

What is histamine?

Histamine is a so-called messenger substance which passes on informations between cells and spreads them. It is formed from amino acids which are produced by the body as well as obtained via food. Histamine is mainly known for its negative effects on the body though it also has a vital mediating role. Symptoms only occur if the body cannot completely break down histamine[1].
Histamine belongs to the group of biogenic amines which occur naturally and which is often produced during degradation and decomposition processes[2].

The role of histamine in the human body

The most important functions of histamine in the body are: it passes on impulses from nerve to nerve, dilates blood vessels, contracts muscles and regulates the day-night rhythm. However, these functions can also have negative effects such as cardiac arrhythmia, blood pressure fluctuations and disruptions of the nerve tracts[1].

What is histamine intolerance?

Histamine intolerance means that there is an imbalance between histamine and two histamine-degrading enzymes. Normally, the body releases histamine during an allergic response - which causes the symptoms typical for an allergy. Normally, then the enzymes diamine oxidase (DAO) and histamine N-methyltransferase decompose histamine. In case of an intolerance, this last step is disturbed so that some histamine is left. If foods rich in histamine are consumed, this leads to symptoms and this is called histamine intolerance[1].

Did you know that the term “histamine intolerance” was created analogue to the term “lactose intolerance” as this intolerance is also caused by enzyme deficiency[3]?

The role of diamine oxidase (DAO)

In connection with histamine intolerance, the term “diamine oxidase”, DAO for short, is frequently mentioned. It is the enzyme which mainly breaks down the histamine absorbed from food. If there is not enough DAO to break down histamine properly, a histamine intolerance is assumed. Especially for diagnostic purposes, the enzyme activity is relevant.

Histamine intolerance = food allergy?

The histamine intolerance is no allergy - however, these terms are often confused. Even in practice, they are hard to distinguish especially as symptoms occur after eating and are similar to those of an allergy. It is therefore important to clearly differentiate it from an allergy[4]. This is why histamine intolerance is also referred to as a pseudoallergy. If you tell your doctor about your symptoms, he normally first tests you for food allergies. This test is negative in case of an existing histamine intolerance. Then, at the latest, you or the doctor should suspect a histamine intolerance[2].

The therapy is based on two different components. In case of an allergy, the allergenic food must be avoided completely. The histamine intolerance comprises a wide range of foods which does not necessarily mean that you need to avoid them 100 percent[5]. The chapter “Histamine intolerance - Therapy” contains detailed instructions.

But what if you suffer from both an allergy and histamine intolerance?

This is not rare according to an investigation by the Allergy Center in Vienna: 30 percent of the 500 study participants which consulted a doctor for their respiratory symptoms, stated to suffer also from food intolerances. Almost half of these 30 percent had a histamine intolerance[6].

Considering the symptoms of allergies and intolerances, it is clear how unpleasant and stressful this is for all people concerned. In case of an allergy, histamine is released which causes the allergy symptoms. Due to the histamine intolerance, this histamine cannot be broken down - which causes severe complaints[6].

To those suffering from pollen allergies: The senior professor of the Allergy Center in Vienna recommends “to keep a histamine-free diet during the allergy season in order to reduce histamine levels and to reduce symptoms”[6].

Histamine intolerance – Symptoms

What are symptoms of histamine intolerance?

The symptoms of histamine intolerance are manifold and resemble those of an allergic reaction which makes it hard to diagnose. It is clear that the symptoms only occur when you eat foods with a high histamine-content. They might occur immediately after consumption or up to two hours later. They may last for half a day or longer[1, 2].

Good to know: People suffering from intolerances often - but not always - react with the same symptoms. This means that only part of the symptoms listed below may occur[1,2].

Below, we list the most frequent symptoms. As histamine affects the part of the body where it is secreted, we listed the symptoms sorted by body regions[1].

Body region

Symptoms

skin

redness, itching, swelling

gastrointestinal tract

cramps, bleeding, diarrhea

lung and respiratory tract

cough, asthma, spasms, running nose, swallowing problems

cardiovascular system

blood pressure fluctuations, palpitations, arrhythmia, unconsciousness

nervous system

headaches (e.g. migraine), dizziness

Please note that the severity of the reaction depends from your personal histamine-tolerance. The lower the activity of your DAO-enzyme, the earlier symptoms are felt - even for small quantities. Among experts, this is called the individual tolerance threshold[4].

Why symptoms occur in irregular intervals

Physical exertion, stress, cold, heat, infections, drugs or alcohol can change the effects of the symptoms. Often, they are the reason why symptoms don’t always occur after eating the same foods. Those who don’t know this often limit their choice of foods even more. Women should take into account that symptoms often worsen premenstrual.

Histamine intolerance – Causes

Histamine intolerance has been known for nearly 30 years and still there is need of information in many areas - also in cause study. From a scientific point of view, the definitive proof is still missing that an enzyme deficiency is causing histamine intolerance. Due to this uncertainty many critics consider the intolerance as pure fiction[7].

Good to know: We all can only tolerate a certain amount of histamine! According to studies, healthy people tolerate up to 100 mg histamine. This level can be reached in case of spoiled fish. If we exceed this level, this is called an intoxication. In case of a histamine intolerance you are reacting below the poisoning dosage and smaller quantities are already causing symptoms[8, 9].

Causes of histamine intolerance

The main cause of histamine intolerance is the previously described imbalance between histamine levels and the missing capacity to break it down. There are two explanatory approaches[10]:

  1. increased histamine levels e.g. by overproduction (due to allergies, bacteria or bleeding in the gastrointestinal tract) or the absorption of histamine, histidine or other biogenic amines (e.g. in the form of food or alcohol)
  2. too little or inactive form of the enzyme DAO

The end result of both explanations is identical: the histamine levels in the body are too high. This is called an acquired intolerance. Very seldom, this disorder is inherited[2].

What causes the enzyme deficiency?

  • chronic strain to the intestine
  • vitamin and zinc deficiency
  • medicines and alcohol

Chronic strain to the intestine

Persons with irritable bowel syndrome, gastritis, Crohn’s disease or gastrointestinal ulcer are particularly affected. The inflammatory changes to the bowel mucosa are responsible for it. As the enzymes are produced in this mucosa, too little enzyme DAO might be produced for breaking down histamine[2].

Vitamin and zinc deficiency

Vitamin deficiency, especially vitamin B6 and C, is closely related to an increased histamine level. Both vitamins are vital for the optimal functioning of the DAO enzyme. Zinc is another important nutrient. In case of zinc deficiency, vitamin B6 cannot be activated. Therefore, the analysis of the vitamin and zinc levels should be part of the therapy[2].

Medicines and alcohol

Medicines and alcohol can be other reasons for an acquired histamine intolerance as they inhibit the enzyme activity. Medicines with active ingredients part of the following list negatively influence histamine degradation. These are e.g.[2]:

  • acetylcystein (ACC), ambroxol (in Mucosolvan®), aminophylline (for asthma), amitriptylin (for depressions)
  • chloroquine (for malaria), isoniazid (antibiotic)
  • metamizole (for colics), metoclopramide (for vomiting), propafenone (for arrhythmia), verapamil (for coronary heart diseases)

Good to know: If you take one of these medicines regularly and complaints occur especially after eating, please consult with your doctor. Possibly it is sufficient to exchange the medicine(s) to avoid symptoms!

Briefly, the excess histamine causes the symptoms of the patient. Enzyme deficiency might be its reason.

Histamine intolerance – Therapy

The most effective therapy for histamine intolerance is the avoidance of histamine. That sounds easier than it is. Foods don’t contain a note whether they contain histamine - this note can already be found for lactose and more and more often for gluten. You should know which foods are high in histamine. However, this is not enough as there are more foods which inhibit enzyme activity.

Four-pillar therapy of histamine intolerance

Please consider that it is not possible to avoid histamine 100 percent as it is contained in many different foods. However, you should not regularly consume foods and luxury foods that either increase histamine production, contain histamine or inhibit the histamine-degrading enzymes. We show you the relevant foods and how to take the strain off your intestine.

How to treat histamine intolerance

If there are good reasons to suspect a histamine intolerance, you should change your diet in several steps as this has proven its worth in practice. The dietary change takes place in three steps. Here a detailed description:

1st stage: abstinence stage

For 14 days, you should completely eliminate foods high in histamine from your diet. Even though alcohol only contains small amounts of histamine, it puts additional strain on the intestine. In liquid form (as in alcohol), histamine is absorbed much quicker. In case of swift improvement of symptoms one can assume a histamine intolerance.

2nd stage: test stage and 3rd stage: permanent diet

After the strict abstinence of 14 days you can step by step reintroduce small amounts of histamine into your diet. The aim is to determine your individual tolerance threshold.

Tip for you: Keep a “symptom diary”, in which you list the foods containing histamine and eventual symptoms. By doing so, you can find out which foods you tolerate and in which amounts.

This test stage takes six to eight weeks in order to also check individual influences such as stress, medicines and menstruation in combination with histamine. At the beginning, just test one food per day. If there are no symptoms, the quantity of this food can be increased or another food can be added. It is important to test and note all results. However, the effort pays off. You don’t have to avoid histamine life-long. When you know which foods you tolerate and how your body reacts, you gain a new quality of life and take in sufficient nutrients. Doctors and therapists call this stage the 3rd stage, the permanent diet[11].

What can I eat when I am histamine intolerant?

The food list contains foods high in histamine which you should best avoid in case of a histamine intolerance - especially during the abstinence stage[11].

Food group

Poorly tolerated

Tolerated alternatives

Fish

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

freshly caught (!) native fish or frozen fish

Cheese

mature cheeses such as  Parmesan, Emmental cheese, mountain cheese, blue cheese, ripe camembert, raw milk cheese

Gervais cheese, cottage cheese, curd cheese, mozzarella, butter cheese, young Gouda cheese

Meat / Sausage

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

all cooked and boiled sausages such as veal sausage, ham sausage, cooked ham

Vegetables

sauerkraut, spinach, tomatoes, tomato products such as ketchup, tomato puree, tomato sauce; avocado, aubergine, pickled vegetables

all other vegetables in raw or steamed form

Fruit

ripe bananas, kiwis, strawberries, ananas, citrus fruits

all other types of fruits and juices

Sweets

chocolate, cocoa

cake and cookies without chocolate/nuts

Snacks / others

peanuts, hazelnuts, walnuts; snacks containing glutamate, balsamic vinegar

popcorn, millet balls, salty snacks, Grissini, crackers, all other vinegars

Alcohol

red wine (it contains the highest histamine levels), dessert wine, French champagne, prosecco, top-fermented beers (wheat beer), cask matured spirits (whisky, cognac), liqueurs

white wine (Grüner Veltliner, Junker); pay attention to the sulfite content, red wine histamine-free resp. low in histamine, sparkling wine or champagne histamine-free resp. low in histamine (e.g. Schlumberger, Goldeck, Hochriegel, Blanc Foussy, Veuve Oudinot), alcohol-free beer (most), Pilsner, clear spirits, vodka, gin


Please consider that even the tolerated alternatives increase histamine secretion. Choose the alcohol-free alternative - especially during the abstinence stage.

Good to know: Histamine cannot be destroyed by heat, cold or other kitchen technologies such as freezing, cooking, baking or microwave heat[2]!

Further tips how to achieve freedom of symptoms by adequate diet

There are several things to consider for nutrition in case of histamine intolerance. Apart from the histamine present in the body and the foods high in histamine there are foods releasing histamine. The enzyme is another obstacle as its activity cannot be controlled by the diet[12]:

Foods which increase histamine release in your body, are[12]:

  • strawberries, citrus fruits, ananas, kiwis
  • seafood
  • milk

The last food group associated with histamine are foods that impair the enzyme DAO. These are the following foods [12]:

  • chocolate
  • fruits: citrus fruits, ananas, papaya, raspberries, pears, bananas
  • tomatoes
  • legumes
  • wheat germs
  • cashew nuts, walnuts

Good to know: The histamine content of foods may vary considerably (wine / cheese: 0,4–250 mg histamine per 100 g) and depends on freshness, maturity and type of food13]!

Intestine and histamine intolerance: a healthy intestine as adjuvant treatment

Heal yourself from inside out. A healthy intestine can produce more histamine-degrading enzyme DAO. If the intestinal mucosa is inflamed or if intestinal epithelial cells are damaged, not enough enzyme can be produced. A bacterial miscolonisation of the intestine can cause further problems. The renovation of the intestinal flora can produce relief and raises the DAO enzyme production. This renovation should take place at least once a year. It pays off as the acquired histamine intolerance can be reduced or even cured.

Treating histamine intolerance with tablets

Histamine-intolerance cannot be cured by tablets - however, symptoms can partly be alleviated considerably. Unfortunately, mostly only for a short period of time. You should, nevertheless, avoid wine, cheese, chocolate etc. The most used drugs are antihistamines and DAOsin.

8 tips for histamine intolerant people

How to know when to take antihistamines

Especially in case of diarrhea the use of antihistamines can be useful. If you suffer from headaches, they are not very helpful. In principle, antihistamines are prescribed by your doctor to treat single symptoms. A permanent use is not advisable[12].

Tipp for eating out

The consumption of foods containing histamine cannot always be avoided, especially when visits to a restaurant or celebrations are planned. In this case, animal diamine oxidase (in capsule form) can help to break down histamine in your bowel. The only product available is DAOsin which is taken with a meal. Studies have not yet been able to proof its effectiveness whereas users report less symptoms. In case of repeated use, a decreasing effect is reported. Therefore, DAOsin should only be used if absolutely necessary[11].

According to Jarisch, the head of the Allergy Center in Vienna and expert in the field of food intolerances, there is no medicine available at present which can increase enzyme activity[11].

Information for allergy sufferers

Allergy sufferers should avoid anti-inflammatory drugs as they increase histamine secretion. These are: meclofenamic acid, mefenamic acid, diclofenac, indomethacin, flurbiprofen, naproxen, ketoprofen, acetylsalicylic acid (ASS). Instead, prefer the anti-inflammatory alternatives that reduce the histamine secretion: Fenbufen, levamisole and ibuprofen.

Briefly, if a histamine intolerance is suspected, alcohol, foods high in histamine and foods that can unspecifically release histamine in the body should be avoided as well as the above-mentioned medicines.

Histamine intolerance – Test

Fact or fiction? This question is currently subject of much discussion among experts when histamine intolerance is involved. In the clinic and in medical practices it is reality - but elusive in diagnostics. Particularly because the reasons of histamine intolerance are still not well known, there is no well-defined procedure for measuring the intolerance. The following two options are used in practice:

  1. The provocation test: This is a medical clinical trial whereby the patients are orally exposed to a certain amount of histamine, normally in tablet form. The doctor closely monitors the body reaction[3].
  2. Diagnostic parameters: In practice and in many scientific studies, the measuring of the DAO-enzyme is increasingly used.
    The measuring of methylhistamine in urine is currently heavily criticized as the values are very imprecise and can be raised by protein rich foods. If the patient already follows a diet low in histamine, the histamine levels also cannot be measured[3].

Which test tells me whether I am histamine intolerant?

In contrast to an allergy, it is not so easy to confirm histamine intolerance. In case of an allergy, the antibodies show a clear reaction. So far, the histamine intolerance can only be determined indirectly: The symptoms plus the omission of foods high in histamine produce a first diagnosis. The measuring of DAO-levels can confirm the suspicion.

Scientific findings

One study mentioned the measuring of the enzyme DAO in blood (serum) as the suitable diagnostic parameter and another large-scale study proved its benefits. It has been shown that the study participants had a significantly lower blood concentration of the enzyme compared to healthy study participants[14, 15].

During the last 3 years, the nutrition expert Dr. med Pfisterer has measured the activity of diamine oxidase in more than 350 of his patients. 160 patients showed a severe subfunction and further 80 patients showed a slight subfunction of the enzyme. These numbers emphasize the clinical relevance and existence of histamine intolerance[2].

Briefly, the measuring of the activity of the enzyme diamine oxidase in serum can provide evidence of histamine intolerance.

What to pay attention to when testing for histamine intolerance?

If you suffer from gastrointestinal complaints, your doctor should first rule out diseases such as gastritis or Crohn’s disease. As histamine intolerance occurs seldom alone, other intolerances such as lactose, fructose or sorbitol intolerance should be checked. If one of these intolerances is present, it has to be considered for your diet as well[2].

Where can I test for histamine intolerance?

In general, the test can be carried out by all practitioners who offer this laboratory service or who specialized in intolerances. The practitioner will first perform an anamnesis and diagnosis of exclusion and sometimes ask you to keep a symptom diary. Another alternative is the self-test for use at home.

By means of the cerascreen® Histamine Intolerance Test you can easily check whether you are histamine intolerant. The test measures the DAO levels in your blood. In addition to the exact DAO-value you also receive a comprehensive result report with valuable health tipps on the topic histamine.

Histamine and migraine

Anyone can be affected. Histamine can cause headaches in healthy people as well as migraine patients[4]. Migraine is characterized by recurrent severe headaches. The mechanism of migraine onset has not yet been finally clarified. Scientists assume an inflammatory reaction which releases messenger substances including histamine. Histamine causes vascular dilatation which in turn causes migraine pain[16].

Scientific findings

Studies show that numerous migraine patients have low DAO levels in their blood. These low DAO levels was found both during migraine attacks and in seizure-free periods. Moreover, patients report more severe and more frequent migraine attacks when consuming foods containing histamine. These include wine, beer, tuna, mackerel, cured or smoked meat, cheese and sauerkraut. Those foods rank among the factors causing migraine. If patients started a low-histamine diet, symptoms could be alleviated or even avoided completely[17].

Alleviation of symptoms in pregnant women

Scientists found a strong decline in symptoms in pregnant women - their DAO blood levels are strongly increased. This excess is due to the fact that the female body protects the embryo from histamine deposits. Thus, pregnant women are mostly completely free of any symptoms but not cured. After delivery, the intolerance re-emerges[4].

Histamine intolerance and female sex hormones

Histamine is closely related to hormones. It can increase the production of the female sex hormones estradiol and progesterone[18]. Due to the raised production, the hormone prostaglandin is reduced. This may result in worsening symptoms e.g. during menstruation which express themselves as headaches or abdominal cramps. If you are histamine intolerant, the duration and intensity of symptoms may increase. During menstruation, the female DAO levels are highest so they can break down the secreted histamine[19, 20].

Hint: Histamine also is a messenger substance which causes labor in pregnant women. An impaired DAO activity can therefore cause an apparent infertility. In this case, please consult a physician.

Histamine and skin problems

Patients with histamine intolerance often suffer from atopic dermatitis - a mostly chronic inflammatory disease. It is often referred to as neurodermatitis. The symptoms can spread over the whole body, but are mostly limited to hands, hollows of the knees and crooks of the arms. The spots are itchy and skin rashes (eczemas) appear[21].

Relationship between histamine, skin and atopic dermatitis

Studies reveal that neurodermatitis patients often show low DAO levels in their blood and thus have too much histamine. In patients who are on low-histamine diet, the skin improves and the itchy spots decrease. In nutrition therapy, for some years already the correlation between an appropriate diet and neurodermatitis is emphasized. This diet excludes foods high in histamine[21].

Summary

  • Histamine is a messenger substance with vital functions for the body - but it can also cause many symptoms.
  • The term “histamine intolerance” describes the intolerance of high-histamine foods. In people concerned, there is an imbalance between histamine and the histamine-degrading enzyme DAO.
  • Typical symptoms are: headaches, running nose, arrhythmia and skin rashes.
  • So far, the causes of histamine intolerance have not finally been clarified - an enzyme deficiency and enzyme subfunction is assumed.
  • A chronic strain to the intestine, vitamin and zinc deficiency as well as drugs and alcohol can affect enzyme production and quality.
  • At present, there is no medicine which can cure the intolerance.
  • Histamine is contained in various foods - its content varies widely and can change during the maturing process. A complete avoidance is impossible.
  • The therapy comprises a low-histamine diet, based on the three stages of dietary change.
  • Diagnosis takes place according to several criteria - one of which is the measuring of diamine oxidase (DAO) in blood.

 

Reference list

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