The first histamine intoxication was reported in sailors some centuries ago, but it was not until that publications began to describe the relationship between histamine and intoxication symptoms [ 92223 ].
In the s, the WHO recommended using the term histamine poisoning or intoxication, as the condition could be caused by the consumption of other fish species, as well as other foods [ 2 ].
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The symptomatology associated with histamine intoxication is closely related to the different physiological actions of histamine in the organism. The main symptoms are neurological, gastrointestinal, dermatological and respiratory, notably rash, erythema, sweating, nausea, vomiting, diarrhoea, a sensation of burning in the mouth, swelling of tongue and face, headache, respiratory distress, palpitations and hypotension [ 41521 ].
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Symptoms are generally mild, appearing 30 minutes after ingestion and disappearing within 24 hours [ 41024 ]. On rare occasions, they can be more severe and require medical attention [ 34 ]. The severity or type of reaction depends on the amount of histamine in the plasma.
The similarity between the described symptomatology and that of allergic reactions can lead to an incorrect diagnosis. Intoxication may be distinguished from a food allergy by taking into account the absence of an allergy history and its occurrence in an outbreak involving more than one patient over a short period of time after the consumption of foods with a high histamine load [ 9 ].
For a differential diagnosis, the concentration of serum tryptase measured within 1—2 hours of the onset of symptoms can also be helpful.
In food allergy, the activity of serum tryptase increases, whereas in histamine intoxication it should remain within normal physiological values [ 1525 ].
Moreover, intoxication may be confirmed by elevated histamine levels in the suspected implicated food [ 1 ]. This disorder is not so widely known as histamine intoxication, since the first reference regarding histaminosis or histamine intolerance dates fromand most of the studies have appeared during the last 15 years [ 28 ].
DAO enzyme deficiency may have a genetic aetiology.
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A significant relationship has been found between lower DAO activity and the presence of different single-nucleotide polymorphisms SNPs in the AOC1 gene located on chromosome 7 7q The secretion of DAO may also be inhibited by certain pathologies, especially inflammatory bowel diseases, and also by the action of drugs acetylcysteine, clavulanic acid, metoclopramide, verapamil, etc.
Individuals with histamine intolerance due to DAO deficiency may suffer symptoms similar to those of intoxication, but they appear after a lower histamine intake. The diagnosis is based on the presentation of at least two clinical symptoms, which go into remission when a low-histamine diet is adopted always after ruling out positive results for food allergy [ 1942 ].
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Individuals with histamine intolerance can also be identified by determining serum DAO activity, although evidence for the usefulness of this analysis is still scarce and inconclusive [ 2734364344 ]. Dose-response data from food histamine are scant [ 24 ]. According to some studies in healthy volunteers, histamine was found to trigger intoxication symptoms at levels of 75— mg when administered with food fish or non-alcoholic drinks [ 1 ].
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When histamine was administered with alcoholic beverages, levels of 0. Wantke et al. On the other hand, when mg of histamine was introduced directly into the duodenum not transported by foodsymptoms appeared in patients diagnosed with chronic urticaria but not in healthy volunteers [ 1 ]. The majority of histamine poisoning outbreaks described in the literature occurred after the consumption of high amounts of histamine, mainly in fish [ 1 ]. Due to the lack of consensus to establish a threshold toxic dose for histamine intoxication, some authors have proposed some safe levels [ 34 ].
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The same authors, however, pointed out diabetes journal 2021 the accuracy of their calculation was limited by an incomplete understanding of histamine intoxication. Later, Rauscher-Gabernig et al. A safe level of histamine intake for intolerant individuals is not proposed in any of the studies on this disorder.
The only recommendation available is from EFSA, which carried out a risk assessment of biogenic amine formation in fermented products and concluded that only foods with histamine levels below detectable limits can be considered safe for intolerant patients [ 1 ]. An impaired enzymatic activity may have a genetic explanation or be caused by intestinal pathologies or the action of drugs with an inhibitory effect [ 151920 ].
In this context, the most studied enzyme is 2 fokozat a cukorbetegség kezelése. The enhanced sensitivity of women to histamine in certain physiological states, such as in the premenstrual period, is attributed to a reduced DAO activity [ 55 ]. Conversely, an increase in DAO production of up to fold has been reported during pregnancy, accompanied by turn drable kezelés remission of certain symptoms related to histamine intolerance [ 56 ].
Therefore, from the metabolic point of view, there is inter- as well as intra-individual variation in sensitivity.
The toxicity of histamine may be enhanced by dietary components, such as other biogenic amines or alcohol. Putrescine, cadaverine, tyramine and spermidine are biogenic amines usually found together with histamine in food and likewise are DAO substrates. Due to competition for intestinal mucin attachment sites and metabolisation, the ingestion of high quantities of these other amines may potentiate the adverse effects of histamine [ 1101554 ].
This effect has been demonstrated in amines such as putrescine, cadaverine and tyramine, among others, in both in vitro and animal studies [ 111 ]. These amines were found to exert an inhibitory effect on histamine metabolism when present at levels 4—5 times higher than that of histamine [ 11 ].
This potentiation mechanism could explain why symptoms do not appear when can low blood sugar cause heart palpitations is administered intravenously and yet are triggered when the same amounts of histamine are consumed in foods containing other amines [ 4 ]. Alcohol and its metabolite acetaldehyde can can low blood sugar cause heart palpitations have a potentiating effect.