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ACCUMULATION OF HISTAMINE, how does it affect us? How to treat it

Source: Journal “Médicos y Medicinas”, January 2012. Every food contains nutritive substances that require a proper metabolism since they enter the oral cavity. The digestive organs carry out the digestion of food thanks to digestive enzymes, obtaining the nutrients required for the proper functioning of the organism.

Histamine is a vital biogenic amine necessary for life. It is a biogenic amine formed in food by action of the microorganism enzymes from amino acids precursors.
Histamine, that is present in every food (of animal and plant origin) in different amounts, should be metabolized in order to be eliminated by urine out problems.

The problem appears when the organism has low activity of the main enzyme responsible for the metabolization of the ingested histamine in food, the Diamine oxidase or DAO.
DAO is mainly in the intestinal mucosa and its low activity results in an accumulation of histamine. When it exists an imbalance between the ingested histamine and the capacity of metabolizing it due to DAO deficiency, histamine passes through the intestinal epithelium to the bloodstream, which results in accumulation in plasma and tissues, and appearing the adverse effects without a direct temporal relationship between the ingested food and the symptom.

The genetic origin is the most common factor of DAO deficiency, followed by pharmacological factors (drugs of common use that inhibit the enzymatic activity) and pathological ones (specially in intestinal inflammatory diseases).

Therefore, in healthy people, histamine from diet is degraded quickly by DAO enzyme in the small bowel; but people with low functional DAO activity have the risk of suffering the called histamine intolerance or food histaminosis ("blaming" the food), currently referred by health community as "DAO deficiency" ("blaming" the individual).

DAO deficiency symptoms
The appearance of the symptoms is not linked to the consumption of a certain product, but it could be associated to a widely range of foods with different content of histamine. Effects could even appear after the consumption of products with low levels of histamine, because the problem appears with the accumulation of histamine along time and not due to a punctual intake. This represents a difficulty to establish a maximum acceptable dose.
The different symptoms produced by DAO deficiency correspond to pathologies considered chronic, under-diagnosed and under-treated until now.

Migraine is the most outstanding syndrome due to its disabling nature, and this is therefore the most important for patients that highlight it from the rest in the personal interview with the physician. This result was contrasted with the study made by the Department of Nutrition and Bromatology of the University of Barcelona in 2010, revealing that the 95% of patients diagnosed with migraine have a reduced DAO activity.
Other common symptoms are gastrointestinal disorders (constipation, flatulence, swollen feeling); skin disorders such as dry, atopic skin or even psoriasis; osteopathic pain mainly back pain; soft-tissues pain and asthenia or unjustified feeling of tiredness.

Probably lots of the described symptoms are associated to the fibromyalgia diagnosis and maybe for this reason, the Moises Broggi Hospital of Barcelona has recently launched an open, comparative and placebo controlled study, to evaluate the effectiveness of the administration of exogenous DAO enzyme in patients diagnosed with fibromyalgia.
The most highlighted symptoms of DAO deficiency are shown in the box:

Adverse effects due to accumulation of histamine by DAO deficiency:
- Central Nervous System Migraine, headaches, dizziness...
- Cardiovascular system Hypotension, hypertension and arrhythmia
- Epitelial system Urticarial, edema, atopic skin, eczema, itching, psoriasis, dermatitis...
- Digestive system Irritable bowel, constipation, diarrhea, stomach ache, swelling, feeling of fullness, sickness.
- Muscular system Muscular pain, fibromyalgia
- Skeletal system Osteopathic pain, mainly spine pain.

Detecting DAO deficiency
Currently, functional DAO activity can be measured by an analytic test that many medical centers and hospital offer in Spain. This test measures the amount of histamine that can be degraded by the sample of DAO enzyme, evaluating its activity. A reduced DAO activity is detected when the level is less than 80 HDU/ml (Histamine Degrading Units).

Foods involve in the accumulation of histamine
Assuming that the origin of the histamine accumulation or histaminosis is the individual itself and that the food is only the access road of the component that helps this accumulation, it is important to control those histamine-rich foods, and know which food contains other biogenic amines such as putrescine or cadaverine. These amines compete with histamine because they are also degraded by DAO (therefore, they provoke the indirect accumulation of histamine). Alcohol as a blocker or inhibitor of DAO (in case of low DAO activity, its consumption will aggravate the symptomatology) and foods releasing endogenous histamine, should be taken into account.

Highlighted histamine-rich foods, defined such those that exceed 200mg of the amine are: cured sausages, cava, champagne (besides alcohol), all kind of cheese except fresh cheese, semi-preserve oily fish (anchovies or herring), fermented vegetable products (derived from soybeans) and balsamic vinegar, among others.

The elevated consumption of biogenic amines-rich foods such as putrescine or cadaverine, the most competitive amines with histamine, may provoke DAO saturation, hindering it of degrading properly histamine from food. The most Highlighted foods are: chocolate, orange, tomato, avocado, nuts and beer, among others.

In the group of foods releasing endogenous histamine we can mention citrus fruits, tomato sauce, seafood and chocolate, among others. The physiological mechanism remains unknown, although it has been linked to stress and various emotional situations.

Preventive solution
As it has been described above, histamine and other amines are present in all food. For this reason, it is impossible to make a diet without biogenic amines. It is recommended to make a diet as low as possible in histamine, controlled by a nutritionist and if necessary, take a supplementation of exogenous DAO to avoid any possible symptom of DAO deficiency.

Adriana Duelo
Nutritionist and expert on DAO deficiency by Ramon Llull University

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