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Histamine and histamine intolerance

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EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on Scientific Opinion on risk based control of biogenic amine formation in fermented foods

Biogenic amines (BAs) are defined as low molecular weight organic bases with biological activity. They are formed and degraded as part of the normal metabolism of microorganisms, plants and animals, in which they have important physiological functions. In humans, BAs are involved in brain activity, the regulation of body temperature and stomach pH, gastric acid secretion, the immune response, and cell growth and differentiation etc. However, the consumption of foods with high concentrations of BAs can induce adverse reactions such as nausea, headaches, rashes and changes in blood pressure. The accumulation of BAs in the food matrix is mainly due to the presence of bacteria able to decarboxylate certain amino acids. The most common and powerful BAs found in food are histamine, tyramine and putrescine. Their contents vary, sometimes reaching over 2 g per kg. Histamine is the only BA for which maximum levels in food have been set, although general interest exists in reducing the presence of all BAs in all food products. This review discusses the toxic effects of BAs when ingested with food.

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Toxicological Effects of Dietary Biogenic Amines

It has been recognized for some time that biogenic amines occur in a wide range of foods, among them meat and meat products. Meat is an important component of the diet in developed countries. The presence of these amines in food is of interest for two reasons: firstly, for toxicological reasons, in the sense that high levels of dietary biogenic amines can be toxic for certain consumers, and secondly, for their role as possible quality indicators. Based on these two premises, the present article offers a new analysis on aspects of toxicology and on the use of biogenic amines as a quality control method, as well as on their presence in meat and meat products. The article focuses particularly on factors affecting the production of biogenic amines, with reference to various parameters relating to microorganisms, meat raw materials, and processing conditions. A better understanding of the factors determining their formation (i.e., microorganisms, raw materials used, and technological processes applied) and their effects could lead to ways of controlling their production, limiting their presence in the end product, and hence, rendering them less toxic.

Biogenic amines in meat and meat products

Biogenic amines (BA) are organic, basic, nitrogenous compounds with biological activity, mainly formed by the decarboxylation of amino acids. BA are present in a wide range of foods, including dairy products, and can accumulate in high concentrations. In some cheeses more than 1000 mg of BA have been detected per kilogram of cheese. The consumption of food containing large amounts of these amines can have toxicological consequences. Although there is no specific legislation regarding the BA content in dairy products, it is generally assumed that they should not be allowed to accumulate. Greater knowledge of the factors involved in the synthesis and accumulation of BA should lead to a reduction in their incidence in foods. This article focuses on the factors that affect BA production, in particular environmental conditions, the microorganisms that produce them, the genetic organization and regulation of the biosynthetic pathways involved, and the available methods for detecting the presence of BA or BA-producing microorganisms in dairy products.

Biogenic Amines in Dairy Products

In a randomized controlled trial, 30 pigs were orally treated with histamine (60 mg). In addition, half of the animals underwent a specific blockade of the enzyme diamine oxidase (DAO), which is the main histamine catabolising enzyme in the intestinal tract. Only these DAO-blocked animals exhibited severe clinical symptoms (e.g. hypotension, flush, vomiting) and, in parallel, showed tremendous elevations of plasma histamine levels of up to 160 ng/ml. 3 out of 15 animals in this group died within the experimental period. In contrast, the control animals neither exhibited plasma histamine levels above 5 ng/ml nor had any clinical reactions. These results contradict the current opinion that oral histamine intake in food is not clinically relevant, especially since many commonly used drugs are DAO-inhibitors and approximately 20% of our population take these drugs. Apart from drugs, some other factors (alcohol, spoilt food etc.) can also function via a blockade of DAO as an additional risk. DAO-blockade is therefore a real epidemiological problem. Evidence is presented here for the new disease concept: Food-Induced Histaminosis.

Food-induced histaminosis as an epidemiological problem: plasma histamine elevation and haemodynamic alterations after oral histamine administration and blockade of diamine oxidase (DAO).

Blutungen im oberen Magen-Darmtrakt neigen erfahrungsgemas uber den reinen Blutverlust hinaus zu kardiovascularen Komplikationen. Verantwortlich dafur ist wahrscheinlich die Resorption toxischer Bestandteile des ingestierten Blutes, vor allem Histamin. So kann der bakterielle Abbau des Histidins, welches reichlich im Hamoglobin vorkommt, bei langerer Verweildauer zu erheblicher Histaminanreicherung im Darm fuhren, die nur bei zusatzlicher enzymatischer Abbauhemmung eine Resorption ermoglicht. Eine solche Hemmung der Diaminoxydase (DAO) durch eine Reihe von Medikamenten der Intensivtherapie kann krankheitsverscharfend wirken, wie in einer Studie am Schwein anhand eines neuen, komplexen hamorrhagischen Schockmodells gezeigt wurde (1). Um sicherzustellen, das es tatsachlich Histamin ist, welches resorbiert wird und den Krankheitsverlauf beeinflust, wurde in Nachahmung der klinischen Situation eine randomisierte, kontrollierte Studie am Schwein durchgefuhrt mit folgenden Fragestellungen: 

1.

Gelangt unter medikamentoser DAO-Blockade ingestiertes reines Histamin aus dem Darmtrakt in die systemische Zirkulation?




2.

Fuhrt dieser Anstieg des Plasmahistaminspiegels zu klinischen Reaktionen, die lebensgefahrlich sind?

Obere gastrointestinale (GI) Blutung: Erhöhtes Risiko kardiovasculärer Komplikationen durch Aminresorption infolge medikamentöser Diaminoxydase (DAO)-Blockade

Die Therapie des chronisch-rezidivierenden Ulcus duodeni hat in den letzten 10 Jahren einen tiefgreiffenden Wandel erlebt: Die Zahl der elektiven Operationen ist zugunsten der medikamentosen Langzeittherapie mit H2-Receptorantagonisten drastisch zuriuckgegangen. 5-Jahresnachuntersuchungen nach SPV ermittelten Rezidiv-raten von 10 – 20%, nach medikamentoser Langzeittherapie dagegen von 40 – 50%. Der SPV verbleibt damit immer noch die fuhrende Rolle in der Ulcustherapie — vorausgesetzt, die Rezidivrate bleibt deutlich unter der einer medikamentosen Therapie (1). Zur Qualitatskontrolle der SPV sind eine FUlle von Testmethoden entwickelt worden.

Der endoskopische Kongorottest zur intraoperativen Qualitätssicherung der selektiven proximalen Vagotomie (SPV) in der Auseinandersetzung mit der medikamentösen Ulcustherapie

P. K. Wagner

Papers

Food-induced histaminosis as an epidemiological problem: plasma histamine elevation and haemodynamic alterations after oral histamine administration and blockade of diamine oxidase (DAO).

Obere gastrointestinale (GI) Blutung: Erhöhtes Risiko kardiovasculärer Komplikationen durch Aminresorption infolge medikamentöser Diaminoxydase (DAO)-Blockade

Der endoskopische Kongorottest zur intraoperativen Qualitätssicherung der selektiven proximalen Vagotomie (SPV) in der Auseinandersetzung mit der medikamentösen Ulcustherapie