Histamine intolerance, sometimes called histaminosis, is an over-accumulation of dietary

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

in the human body. Histamine intolerance is sometimes informally called an

allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

; however, the intolerance is technically caused by the gradual accumulation of

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

histamine due to an imbalance. Roughly 1% of the population has histamine intolerance; of those, 80% are middle-aged.

General

The imbalance in histamine intolerance is between the

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors ** Organic synthesis, the chemical synthesis of organ ...

and selective release of histamine from certain

granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

s (i.e.,

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

s and

basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...

s), versus the breakdown of histamine by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s which metabolize it, such as

diamine oxidase Diamine oxidase (DAO), also known "amine oxidase, copper-containing, 1" (AOC1), formerly called histaminase, is an enzyme () involved in the metabolism, oxidation, and inactivation of histamine and other polyamines such as putrescine or spermid ...

(DAO) and

histamine N-methyltransferase Histamine ''N''-methyltransferase (HNMT, HMT) is an enzyme involved in the metabolism of histamine. It is one of two enzymes involved in the metabolism of histamine in mammals, the other being diamine oxidase (DAO). HNMT catalyzes the methylation o ...

(HNMT). In contrast, allergic reactions involving an immediate allergic response to an

allergen An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical terms ...

are caused by anaphylactic degranulation, which is the abrupt and explosive release of " pre-formed mediators", including histamine, from

s and

s throughout the body.
Figure 1: Mediator release from mast cells
br
Figure 2: Model of genesis of mast cell secretory granules
br
Figure 3: Lipid body biogenesis
br
Table 2: Stimuli-selective mediator release from mast cells
/ref>

Symptoms

Possible symptoms after ingestion of histamine-rich food include: * Skin rash, hives, eczema, itching * Headache, flushing, migraine, dizziness * Narrowed or runny nose, difficulty breathing, bronchial asthma, sore throat * Bloating, diarrhea, constipation, nausea / vomiting, abdominal pain, stomach sticking, heartburn * High blood pressure (

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

s, low blood pressure (

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

) * Menstrual disorders (

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...

cystitis A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

urethritis Urethritis is the inflammation of the urethra. The most common symptoms include painful or difficult urination and urethral discharge. It is a commonly treatable condition usually caused by infection with bacteria. This bacterial infection is oft ...

and mucosal irritation of female genitalia * Water retention (

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

), bone marrow edema (BME), joint pain * Fatigue, seasickness, tiredness, sleep disorders * Confusion, nervousness, depressive moods

Metabolism

In the human body, histamine is

metabolize Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

ly by the

(DAO), and

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

ly by

(HNMT) and

aldehyde oxidase Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydroxylation of some heterocycles. I ...

s (AOX1). In histamine intolerance, the activity of DAO is limited, and histamine taken up by the diet and formed in the body is only partially metabolized. The consumption of histamine-containing food (e.g., red wine or hard cheese) leads to a pseudoallergic reaction. It is unclear how histamine passes through the

intestinal wall The gastrointestinal wall of the gastrointestinal tract is made up of four layers of specialised tissue. From the inner cavity of the gut (the lumen) outwards, these are: # Mucosa # Submucosa # Muscular layer # Serosa or adventitia The mucosa ...

during absorption and enters the blood without coming into contact with the aldehyde oxidases expressed in intestinal cells and histamine N-methyltransferases.

Potentially harmful foods

The following food categories have been quoted in literature as histamine rich:

Meat and fish

* Fish products, especially canned fish * Ham *

Offal Offal (), also called variety meats, pluck or organ meats, is the organs of a butchered animal. The word does not refer to a particular list of edible organs, which varies by culture and region, but usually excludes muscle. Offal may also refe ...

* Pork * Salami * Smoked meat * Other seafood

Dairy

* Matured ("hard") cheeses - the higher degree of ripeness, the higher histamine content

Alcohol

* Beer (especially top-fermented and cloudy/colored) * Some French Champagne (made partially with red grapes) * Red Wine

Tobacco

Active or passive exposure to tobacco smoke is suspected of favouring histamine intolerance, but has not been adequately studied.

Fruits, vegetables, legumes and roots

* Avocado * Bamboo sprouts * Beans * Citrus fruits * Eggplant * Horseradish * Mushrooms * Papayas * Plums * Raisins * Sauerkraut * Spinach * Strawberries * Tomatoes * Other molds (e.g. noble-mold from cheeses and salamis)

Other

* Chocolate (chocolate itself does not contain histamine, but it does contain cocoa, which blocks the function of the histamine-clearing enzyme DAO) * Nuts * Products with vinegar, such as pickles or mustard * Soy and soy products (e.g., tofu) (This list is drawn from the German Wikipedia article on histamine intolerance. It has been further expanded usin
Verträglichkeit von histaminhaltigen Lebensmitteln
(PDF; 28 kB)).

Drug interactions

* Some medicines or so-called histamine-liberators (e.g., certain food additives) may delay the breakdown of histamine, or release histamine in the body. * Alcohol consumption increases the permeability of the cell membrane and thus lowers the histamine tolerance limit, which is why particularly strong reactions can occur when mixing alcohol and histamine-rich foods (e.g., red wine and cheese). * Incompatibility of anti-inflammatory and analgesic medications in persons with histamine intolerance: *: Anti-inflammatory / analgesic drugs that increase allergen-specific histamine release in allergy sufferers are reaction inducing:^{/sup>

: Anti-inflammatory/analgesic drugs that inhibit the allergen-specific histamine release in people with allergies are not reaction including:^{/sup>

* Contrast agents – X-ray contrast allergy:
*: R. Jarisch: Contrast reaction is misleadingly referred to as allergy and, because contrast media contain iodine, is almost always mistaken for iodine allergy. "Contrast agents release histamine. The reason why, in most cases, nothing happens when administering contrast media is that most patients have no histamine intolerance. But if a patient reacts, anaphylactic shock is inevitable. "For safety reasons, an antihistamine should always be given to people with histamine intolerance prior to examination with an X-ray contrast medium. In addition, adherence to a histamine-free diet 24 hours before x-ray studies with contrast agents is recommended for minimizing histamine exposure. p. 127/128 in ^{/sup>

Diagnosis

For a diagnosis, the case history is essential. However, since many complaints such as headaches, migraines, bronchial asthma

Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coug ...
, hypotension

Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
, arrhythmia

Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
and dysmenorrhea

Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...
(painful periods) may be caused by something other than histamine intolerance, it is not surprising that half of suspected diagnoses are not confirmed.

The diagnosis is usually made by intentionally provoking a reaction. However, since histamine can potentially cause life-threatening conditions, the following procedure is preferred: take blood samples before and after a 14-day diet, and measure changes in histamine and diamine oxidase

Diamine oxidase (DAO), also known "amine oxidase, copper-containing, 1" (AOC1), formerly called histaminase, is an enzyme () involved in the metabolism, oxidation, and inactivation of histamine and other polyamines such as putrescine or spermid ...
(DAO) levels. Rather than increase histamine during the test diet, eliminate it. This procedure does not endanger the patient. Quite the contrary: in the presence of histamine intolerance, the symptoms have improved or disappeared completely. At the same time, the histamine blood level halves and the DAO increases significantly. If there is no histamine intolerance, the blood levels do not change and neither do the symptoms. Simultaneously, food allergy, cross-reactions with pollen

Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametophyt ...
, fructose malabsorption

Fructose, or fruit sugar, is a ketonic simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed ...
, lactose intolerance

Lactose intolerance is a common condition caused by a decreased ability to digest lactose, a sugar found in dairy products. Those affected vary in the amount of lactose they can tolerate before symptoms develop. Symptoms may include abdominal pa ...
, and celiac disease

Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...
should be excluded.

Therapy

The basis of treatment is a reduction of the dietary histamine through a histamine-poor diet. Certain foods (e.g., citrus fruits) and certain medicines (e.g., morphine

Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
) which do not contain histamine per se are also to be avoided, because they are known to release histamine stored in the body (histamine liberation).

If eating histamine-containing foods is unavoidable, antihistamines and cromolyn sodium

Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. ...
may be effective. The intake of diaminoxidase (DAO) in capsule form with meals may reduce the symptoms of histamine intolerance.

In cases of high blood glutamate, such as can occur in some cases of eczema

Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thick ...
and histamine intolerance, Reinhart Jarisch recommends vitamin B6

Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphat ...
treatment. This promotes the body's own synthesis of DAO and thus fights the effects of histamine intolerance. The reference ranges (normal values) for blood glutamic acid are 20–107 in infants, 18–65 in children and 28-92 μmol / ml in adults.

See also

* Mast cell

A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...

* Basophil

Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...

* Food intolerance

Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Fo ...

* Red wine headache

References

Literature

* Abbot, Lieners, Mayer, Missbichler, Pfisterer, Schmutz: ''Nahrungsmittelunverträglichkeit (Histaminintoleranz)''. HSC, Mauerbach 2006, .
* Reinhart Jarisch: ''Histamin-Intoleranz, Histamin und Seekrankheit.'' Thieme 2004, .
* Nadja Schäfers: ''Histaminarm kochen – vegetarisch.'' pala-Verlag, Darmstadt 2009, .
* Anja Völkel: ''Gesunde Küche: bewusst genießen – schmackhaft & lecker.'' AVA-Verlag, 2013, .
* I. Reese: ''Streitthema Histaminintoleranz.'' (CME zertifizierte Fortbildung) In: ''Der Hautarzt.'' 65, 2014, S. 559–566, doi:10.1007/s00105-014-2815-2.

External links

{{Medical resources
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, ICD10 = {{ICD10, T78.1
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Allergology
Intolerance

Intolerance may refer to:

* Hypersensitivity

Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usual ...

Histamine
Sensitivities}}}