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 ].
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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 ]. 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 ].
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.
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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 can high blood sugar cause palpitations can also be helpful.
In varga gyógygomba inzulinrezisztencia 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.
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 ]. 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 can high blood sugar cause palpitations.
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 ]. 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 ]. The same authors, however, pointed out that 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 DAO.
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 ].
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Conversely, an increase in DAO production of up to fold has been reported during pregnancy, accompanied by a 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 histamine is administered intravenously and yet are triggered when the same amounts of histamine are consumed cognac kezelés cukorbetegség foods containing other amines [ 4 ].
Alcohol and its metabolite acetaldehyde can also have a potentiating effect. Competition for the ALDH enzyme, which is involved in the metabolism of both alcohol and histamine, results in an accumulation of histamine [ 112 ]. A total of outbreaks were reported in — by different EU member states according to the EFSA reports on food-borne outbreaks [ 57 ]. In of the outbreaks, the food responsible was determined with strong evidence, involving can high blood sugar cause palpitations than cases of which were hospitalised Figure 3.
No deaths due to histamine intoxication were reported during this period. According to these data, there is no clear declining trend in the incidence of histamine intoxication in recent years, in contrast with other types of food poisoning Figure 3.
Assessment of the incidence of histamine intoxication in EU countries during the — [ 57 ]. On the other hand, according to information extracted from the Rapid Alert System for Food and Feed RASFFthere was a clear rise in notification of histamine intoxication cases linked to tuna consumption during —, with a particularly sharp increase in [ 57 ].
In MaySpain and France reported a high incidence of histamine intoxication after the consumption of yellowfin tuna from Spain. Additional cases may have arisen in other countries that imported this food product. More than people in Spain and more than 40 in France were affected after consuming tuna that was allegedly treated with a vegetable extract to alter the colour and enhance display freshness [ 58 ].
The modification of colour may mask spoilage responsible for the production of histamine and other biogenic amines. The overall exposure to dietary histamine is difficult to estimate due to its multiple potential sources and variable concentration.
Figure 4which shows the distribution of histamine contents in different foods retailed in Spain, reflects this characteristic high variability, both diabetes kezelés elhelyezése different food categories and within the same category.
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Figure 4. Fresh fish and fishery products usually do not contain histamine or only low levels [ 59 ].
Histamine and Other Biogenic Amines in Food. From Scombroid Poisoning to Histamine Intolerance
As shown in Figure 4in most of the Spanish retail fish samples reported by Bover-Cid et al. Notably, when freshness is lost, in addition to high amounts of histamine, other amines related to the decarboxylase activity of spoilage bacteria, such as cadaverine and putrescine, also frequently accumulate.
In fresh, cooked or cured meat, as in fish, no histamine occurrence is expected as can high blood sugar cause palpitations as freshness and a proper hygienic status of the products or manufacturing processes are ensured [ 1360 ]. In contrast, fermented foods are susceptible to accumulating large amounts of histamine [ 13561 ].
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In fermented beverages e. The occurrence of putrescine and cadaverine is also quite common but at lower and more variable concentrations than tyramine. Among foods of plant origin, only some vegetables usually show significant levels of histamine, such as spinach, tomato and eggplant [ 13 ].
In these products low levels of histamine may have a physiological origin, but undesirable microbial enzymatic activity during storage can lead to the accumulation of high levels [ 1362 ]. Lavizzari et al. Histamine formation in this type kezelése görcsök éjjel diabetesben vegetables was attributed to the activity of some Gram-negative bacteria, mainly belonging to Enterobacteriaceae and Pseudomonadaceae groups, as their growth is favoured by the relatively high pH of spinach.
Asparagus, pumpkin, chard and avocado rarely contain histamine and at very low levels [ 13 ]. Other types of frequently consumed foods, such as cereals, milk, yoghurt and eggs, do not show significant contents of histamine or any other biogenic amine [ 3 ]. In addition to can high blood sugar cause palpitations content, another fundamental issue when assessing exposure to histamine is the actual consumption of food by the population.
Food consumption data need to be as representative as possible, with sources such as the most recent national dietary surveys. Likewise, in an assessment of the dietary histamine exposure of Austrian consumers, it was concluded that tuna fish and some fermented products cheese and sauerkraut were the top contributors to the total histamine intake [ 24 ]. According to this study, a typical meal with fish as a main dish could contribute from 2. Recently, Latorre-Moratalla et al.
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The larger serving size of fish products, together with the extremely high histamine contents arising from hygienic defects in their conservation or manufacturing can high blood sugar cause palpitations, could explain why these foods contribute more to histamine exposure than others, such as cheese or dry-fermented sausages, which a priori have higher average histamine contents.
This could also explain why fish and fishery products are the predominant cause of histamine intoxication. However, a qualitative approach, taking into account the limited data available, suggests that the risk of suffering histamine intoxication is relatively low, since exposure exceeds the safety limit on very few occasions.
However, it is stressed that this upper limit may be exceeded by the consumption of more than one food item with high histamine content during the same meal.
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Likewise, Latorre-Moratalla et al. It should be noted that all available studies have been carried out on specific food groups and to date none have dealt with the full range of histamine-containing foods. The risk for the histamine-intolerant population is higher, because even small amounts of histamine may trigger adverse effects [ 163 ].
No studies have been carried out to evaluate this risk. Advertisement 3. Risk management From the perspective of risk management, decision-makers or the food industry should consider different actions to reduce consumer exposure to dietary histamine. For example, regulatory measures or strategies to prevent, reduce or eliminate the presence of histamine and other amines in foods could be implemented.
From a legal perspective, tolerable limits of histamine have been fixed by different countries only for fish and fishery products. As histamine and other biogenic amines are a food safety concern, the food industry needs to consider improving control strategies. Available knowledge about biogenic amine formation in certain foods has made it possible to design measures to prevent or at least reduce their accumulation during manufacture and storage.
A key strategy is to guarantee and improve the hygienic quality of raw materials and manufacturing processes.
Since contaminant microorganisms are responsible for biogenic amine formation in many products, food quality and safety management based on hazard analysis and critical control points HACCP are essential [ 47 ]. Predictive models of biogenic amine formation in perishable products as a function of time and temperature could be used to avoid hazardous storage conditions [ 1167 ].
This approach has already been implemented to reduce histamine accumulation in seafood, which is particularly associated with histamine formation by Morganella psychrotolerans and M. Other factors that inhibit or reduce aminogenic activity, such as the packaging atmosphere and the addition of salt and other preservatives, should be taken into account for lightly preserved fish, meat and vegetables [ 611 ]. In the case of fermented foods or beverages, the hygienic quality of raw materials may be enhanced by decreasing the microbial load through pasteurisation, a common practice in the cheese-making industry [ 5 ].