General Information
Histamine intolerance is the result of disequilibrium between the histamine accumulated in the body and its breakdown capacity. This disease is not mediated by IgE antibodies; therefore, skin tests and specificIgEdosages may present negative results.
Histamine is a biogenic amine found in varying amounts in many foods. Histamine nutrients are normally rapidly detoxified by aminooxidases; People with decreased activity in these enzymes are at risk of developing histamine intolerance. The main enzyme involved in the metabolism of ingested histamine is daimine oxidase (DAO).This is a protein stored in vesicular structures attached to the plasma membrane of epithelial cells and released into the circulation in the presence of sufficient stimuli.
Due to a low DOA activity. As a result, the decrease in histamine degradation capacity causes a series of clinical symptoms similar to an allergic reaction: diarrhea, headache, urticaria, pruritus, skin flushing, rhinoconjunctival symptoms, bronchospasm hypotension, cardiac arrhythmias. Histamine intolerance becomes clinically manifest when the body is loaded with more histamine than it can catalyze (consumption of histamine-rich foods, alcohol, or histamine-releasing or DAO-suppressing drugs). Allergic diseases such as hay fever or fungal sensitivities are an additional source of histamine. Women between the ages of 30 and 55 are most commonly affected.
Histamine is formed through amino acid decarboxylation due to bacterial activity in foods. Therefore, it can be found in large amounts in fermented foods (e.g. cheese, saurkraut or vine) and protein-rich foods (e.g. fish, meat, sausages). It is also found in high levels in spoiled foods.
Histamine levels increase with the storage time of foods, so they should be processed quickly, not stored for a long time, and not reheated! Due to its sensitivity to heat, histamine may not be destroyed by freezing, boiling, frying or baking.
In most cases, it is due to gastrointestinal diseases that reduce the production of DAO or due to inhibition of enzymes by the consumption of alcohol and different drugs DAOdeficiency is acquired. However, recent studies have shown that intestinal epithelial cells revealed wide individual variability in DAO expression and various polymorphisms in the DAO gene associated with gastrointestinal disorders. It has demonstrated the existence of a genetic predisposition in the subgroup of patients with histamine intolerance.
Patients diagnosed with DAOdeficiency may benefit from an appropriate diet that excludes foods with high histamine content. Since alcohol increases intestinal permeability and therefore histamine level, alcoholic beverages should be avoided during meals. Analgesics also cause increased intestinal permeability.
Foods rich in histamine
Wine and other alcoholic beverages
Histamine is also formed during the alcoholic fermentation process. Acidifying bacteria such as Pediococcus cerevisiae have been found to produce histamine. Histamine content is a criterion for wine quality. Red wines often have high histamine content. Histamine concentrations up to 3000 µg/l are often detected in wines that cause headaches.
Average histamine content:
- Red wine: 60-3800 µg/l
- Champagne: ~ 670 µg/l
- Sparkling wine: 15-80 µg/l
- Dessert wine: 80-400 µg/l
- Red wine: 3-120 µg/l
- Beer: 20-300 µg/l
Fish
The fish categories in which poisoning symptoms usually occur after consumption belong to the family Scombridae (mackerel). For this reason, poisoning situations are defined as “scombroid poisoning” in English literature. Fish in this family (especially tuna and mackerel) have a lot of red meat with a high histamine content. High levels of histamine have also been measured in other fish species, including herring, sardines and anchovies. Histamine production is affected by the degree to which the fish is stored until processing. If large amounts of histamine have been detected in canned tuna or smoked mackerel, studies have shown that the fish was not transported properly frozen or was stored improperly. Surprisingly, more histamine was detected in the marinade than in the fish meat.
- Tuna fish. i: up to 8000 mg/kg
- Smoked mackerel: up to 788 mg/kg
- (Canned) mackerel: 15 mg/kg' up to
- Sardines: up to 1,500 mg/kg
- Anchovies: up to 180 mg/kg
- Herring: up to 12 mg/kg (especially marinade)
Milk/cheese
Although unprocessed and drinking milk contains minimal amounts of histamine, some Cheese types have high levels. It is generally accepted that histamine levels increase with ripening and storage. The bacteria accused are various lactobacilli and streptococci.
- Emmental cheese: 10-500 mg/kg
- English blue cheese (moldy cheese): approximately 160 mg/kg
- Italian moldy cheese: up to 160 mg/kg
- Camber: 10-300 mg/kg
- Parmesan: 10-580 mg/kg
Meat/sausage
The biogenic amine content in meat products is quite dense. While some types of sausages contain quite high amounts of histamine, fresh products rarely reach critical levels. However, other biogenic amines are also found in meat. The study showed that cadaverine and putresciine diamines – both substrates on DAO are an indicator of meat freshness
- Salamari: up to 280 mg/kg
- Cervelas sausage: 100 mg/ up to kg
- Westphalian ham: 40-270 mg/kg
Other Foods
Red wine vinegar Contains up to 4000 µg/l histamine. In chocolate, depending on the type, the content varies between 5-100 mg/kg.
Drugs that release histamine or inhibit DAO
- muscle relaxants:
- narcotics:
- analgesics and anti-inflammatories:
- anti-hypertensive:
- antiarrhythmics
- diuretics:
- antiemetics
- antibiotics:
- mucolytics
- broncholytics:
- H2 receptor antagonists:
- chemotherapy drugs:
- antidepressants:
Recommendations for DAO activity determination
Other gastrointestinal disorders Testing after exclusion of systemic mastocytosis (negative result for tryptase) and food allergies (negative skin tests and specific IgE), clinical diagnosis of histamine intolerance Indicated in suspected patients (presence of ≥2 typical symptoms with positive response to a non-high histamine diet).
Patient preparation- on an empty stomach.
Collected sample– venous blood.
Collecting receiver– vacutainer with/without separation gel without anticoagulant.
Sample quantity– minimum 0.5 ml serum.
Reasons for sample rejection– heavily hemolyzed, icteric, lipemic or bacterially contaminated sample1.
Required handling after collection- serum is separated by centrifuge and transported frozen.
Sample stability– serum is stable for 1 week at 4-8ºC.
>Method – REA (radioextraction): C-labeled putrescine, a high affinity substrate for DAO, is added to the patient's serum sample, DAO effect below, putrescine is converted to delta-pyrroline; The amount of pyrroline obtained correlates with the DAO activity in the patient's serum.
Reference values -14-33 IU/mL.
Interpretation of the results
Low DAO activity values indicate a low capacity for histamine degradation.
High DAO activity values suggest enzyme induction in an active allergic process.
DAO activity values at the lower normal limit exclude the presence of a genetic deficiency; However, if the body is loaded with histamine, for example through fluoride allergies or histamine-rich foods, clinical symptoms occur (latent deficiency).
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