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Histamine in food

Origin of biogenic amines

Biogenic amines, including histamine, are formed in food from amino acid precursors, by the action of decarboxylase-type enzymes in microorganisms.

This process does not happen to natural or physiological amines, which are formed during the metabolic processes of plants and animals.

The possibility of alternative ways of biosynthesis, the combined participation of different types of microorganisms and their possible interactions make it more complicated to determine exactly the genesis of these amines in food.

Therefore, in order for histamine to form in food, several specific requirements are needed:

  • Growth of microorganisms with decarboxylase-type activity.
  • Availability of amino acid precursors and cofactors.
  • Favorable environmental conditions for the synthesis and activity of decarboxylases (pH, Aw, Tª …)

Metabolism of food histamine

Food is complex structures formed by nutrients that are degraded from the moment it enters the oral cavity. The digestive organs carry out enzymatic digestion of food that reaches the intestinal tract with the help of several secretions (salivary, gastric, pancreatic, intestinal, and biliary) obtaining the nutrients necessary for the proper functioning of the body.

Histamine, which is present in every food (of animal and vegetable origin), must be metabolized to be eliminated through the urine without problems. Exogenous histamine does not have a demonstrated functional role within the body and, for this reason, it is eliminated without any property being used.

There are two main ways of metabolizing histamine in living beings, where histamine N-methyltransferase (HMT) and diaminoxidase (DAO) are involved:

Degradation by histamin-N-methyltransferase (HMT or HNMT)

HMT inactivates histamine by methylating the imidazole ring to form N-methylhistamine, which becomes N-methylimidazole acetaldehyde by the action of monoamine oxidase (MAO), and finally the enzyme aldehyde-dehydrogenase (ALDH) converts it into N-methylimidazole acetic acid.

HMT is an enzyme that degrades histamine from liver tissue, but is present in a smaller amount in other tissues.

Many studies establish a minor involvement of HMT in the metabolism of histamine from the intestinal mucosa, since its activity is almost insignificant compared to the activity of DAO.

It is a cytosolic protein, and therefore can convert histamine only in the intracellular space of cells. This demonstrates that it has a lower histamine degradation capacity than the diaminoxidase pathway, which has an important role in the inactivation and removal of extracellular histamine; and this confirms, therefore, that pathologies related to a high concentration of histamine in the blood are associated with DEFICIENCY of DAO and not of HMT.

Degradation by diaminoxidase (DAO)

In this way histamine undergoes an oxidative disamination by DAO. The resulting products are imidazole acetic acid and its riboside. Both metabolites of the histamine pathway, imidazole acetic acid and N-methylimidazole acetic acid (on the HMT pathway) have low activity and are eliminated through the urine.

DAO is the most important enzyme that degrades histamine, but is localized only in some tissues, especially in the intestinal mucosa, kidneys, placenta, thymus and seminal vesicles.

DAO also has a reduced participation, and in liver tissue.

It is located mainly in the intestinal epithelium, where histamine (and endogenous histamine) is absorbed, which the DAO degrades by controlling the passage into the portal blood.

DAO localized in the liver controls the passage of histamine to the systemic circulation and when it is present in the kidneys, it degrades the reabsorbed histamine in the proximal tube.

Diaminoxidase is also involved in other processes, such as regulating cell division or differentiating in rapidly proliferating tissues (bone marrow and intestinal mucosa) and can act as a neurotropic connection.

In pregnant women, DAO activity is more intense, and can also be 500 to 1000 times higher than in unpregnant women. The placenta produces additional amounts of DAO as a measure of protection of the fetus, ensuring the correct degradation of histamine.

Foods rich in histamine

There are differences in the criteria that help to evaluate histamine-rich foods.

Some authors suggest eliminating from the diet foods with concentrations higher than 20 mg / kg, while other authors are more demanding and appreciate foods with low histamine as those with amounts below 1 mg / kg. However, it is clear that the symptomatic dose is much lower in histaminosis than in toxicity, respectively, 15-20 mg and 150 mg, since the tolerable dose in both cases is 100 mg / kg.

In Europe there are several initiatives (ALBA, Allergen dataBAnk; TNO Nutrition & Food Research) which aims to provide an exhaustive database on the histamine content of food, produced as a result of the decarboxylation of its aminic precursor, histidine. The disadvantage of this data lies in the very wide variation from one food to another.

Concentrations of histamine and other biogenic amines in food are highly variable within the same family and even between two samples of the same product.

Table with foods rich in histamine (histamine content in mg / kg): eggplant 26, avocado 23, red wine 13, white wine 21, sparkling wine 6,3, bottle of beer 2, sausages (bacon, sausages, mallorca sausages) 350, cooked meat (ham) 5, champagne 67, fermented white cabbage 10-200, spinach 20-30, wheat flour and rice 5, goat cheese 87,1, ripened cheese 162,1, emmental cheese 10 -500, fresh cheese 5, grated cheese 556,4, roquefort cheese 2,000, yogurt 13, legumes (lentils, chickpeas and beans) 10, raw milk 389.9, mushrooms 1.8, sausages (pressed ham) 10, fresh meat (beef, pork) 4, beans 2, pasteurized milk 162, olives 2, semi-preserved blue fish 1,500, fresh fish 19.75, fresh blue fish (tuna, sardines) 10, frozen fish 894, fresh and frozen blue fish 2, fermented vegetable products (derived from soybeans) 2,300, fruit juice 1.5, tomatoes (fresh, sauce) 0.5-8, vinegar 500, apple cider vinegar 20, balsamic vinegar 4,000, chocolate 0.5.

Foods rich in other amines

In addition to histamine-rich foods, in patients with low DAO activity, high intake of foods rich in other amines, such as putrescein, cadaverine, b-phenylethylamine, triptamine, serotonin, tyramine and aggmatin can trigger DAO saturation, affecting the adequate degradation of ingested histamine.

The most competitive amines against histamine to be degraded by DAO are putrescin and caderine, since their degradation is faster than histamine and captures the enzyme faster. The amount of amines can be different in each type of food, as in the case of histamine. Depending on the concentration of biogenic amines, foods with the same amount of histamine may or may not trigger symptoms. However, in order for the symptoms not to appear, specific amounts for amines are established, indicating the maximum tolerable level, but only refer to toxicity, since the values that report the intake of amine-rich foods to DAO saturation have not yet been established.

Endogenous foods that release histamine

This group consists of those foods that, without having a high concentration of histamine or amines, release endogenous histamine, that is, histamine localized in mast cells.

Several foods with this feature have been described: milk, cereals and egg white (especially milk protein). Some food additives such as glutamate, benzoate, several dyes (yellow E-102 and E-110, E-124, amaranth E-123), sulfites and nitrites can release endogenous histamine.

The intake of foods or drugs that release endogenous histamine causes the same symptoms as the intake of foods rich in histamine.


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