Histamine intolerance

Histamine intolerance, sometimes called histaminosis[1], is an over-accumulation of histamine in the human body.[2] Histamine intolerance is sometimes informally called an allergy;[2] however, the intolerance is technically caused by the gradual accumulation of extracellular histamine due to an imbalance.

Histamine intolerance
Other names	Histaminosis
Specialty	Immunology

Roughly 1% of the population has histamine intolerance;[2] of those, 80% are middle-aged.[2]

General

The imbalance in histamine intolerance is between the synthesis and selective release of histamine from certain granulocytes (i.e., mast cells and basophils), versus the breakdown of histamine by the enzymes which metabolize it, such as diamine oxidase (DAO) and histamine N-methyltransferase (HNMT).[2]

In contrast, allergic reactions involving an immediate allergic response to an allergen are caused by anaphylactic degranulation, which is the abrupt and explosive release of "pre-formed mediators", including histamine, from mast cells and basophils throughout the body.[3]

Symptoms

Possible symptoms after ingestion of histamine-rich food include[4]:

• Skin rash, hives, eczema, itching
• Headache, flushing, migraine, dizziness
• Narrowed or runny nose, difficulty breathing, bronchial asthma, sore throat
• Bloating (flatulence), diarrhea, constipation, nausea / vomiting, abdominal pain, stomach sticking, heartburn
• High blood pressure (hypertension), tachycardia, cardiac arrhythmias, low blood pressure (hypotension)
• Menstrual disorders (dysmenorrhea), cystitis, urethritis and mucosal irritation of female genitalia
• Water retention (edema), bone marrow edema (BME), joint pain
• Fatigue, seasickness, tiredness, sleep disorders
• Confusion, nervousness, depressive moods

Metabolism

In the human body, histamine is metabolized extracellularly by the enzyme diamine oxidase (DAO), and intracellularly by histamine N-methyltransferase (HNMT)[5] and aldehyde oxidases (AOX1)[6][7]. 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 during absorption and enters the blood without coming into contact with the aldehyde oxidases expressed in intestinal cells and histamine N-methyltransferases. Active or passive exposure to tobacco smoke is suspected of favouring histamine intolerance, but has not been adequately studied.[8]

Potentially harmful foods

The following food categories have been quoted in literature[9] as histamine rich:

Meat and fish

• Fish products, especially canned fish
• Ham
• Offal
• 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

Fruits, vegetables, legumes and roots

• Avocado
• Bamboo sprouts
• Bananas
• Beans
• Citrus fruits
• Eggplant
• Figs
• Garlic
• 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 the other biogenic amines from the cocoa do)
• Nuts [10]
• 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.[11] It has been further expanded using 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).[12]
• 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: List from page 125 in:^[8]

Active ingredient	Drugs containing the active ingredient
Mefenamic acid	Parkemed
Diclofenac	Dedolor, Deflamat, Diclo B, Diclobene, Diclomelan, Diclostad, Diclovit, Dolo-Neurobion, Neurofenac, Tratul, Voltaren
Indometacin	Flexidin, Indobene, Indocid, Indohexal, Indomelan, Idometacin, Indoptol, Luiflex, Ralicid
Acetyl salicylic acid	Aspirin

Anti-inflammatory/analgesic drugs that inhibit the allergen-specific histamine release in people with allergies are not reaction inducing.

List from page 126 in:^[8]

Active ingredient	Drugs containing the active ingredient
Fenbufen	Lederfen
Levamisole	Ergamisol
Ibuprofen	Avallone, Brufen, Dismenol new, Dolgit, Ibudol, Ibumetin, Ibupron, Ibuprofen Genericon, Kratalgin, Nurofen, Tabcin, Ubumetin, Urem

• 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 ^[8]

Diagnosis

For a diagnosis, the case history is essential. However, since many complaints such as headaches, migraines, bronchial asthma, hypotension, arrhythmia and dysmenorrhea (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 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, fructose malabsorption, lactose intolerance, and celiac disease should be excluded.

Therapy

The basis of treatment is a reduction of the dietary histamine through a histamine-poor diet. An extreme variant is the "potato rice diet" that has been successfully used by dermatologists for decades in the treatment of hives, i.e. only potatoes, rice, salt, sugar and water. Certain foods (e.g. citrus fruits) and certain medicines (e.g. morphine) 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).[13]

If eating histamine-containing foods is unavoidable, antihistamines and cromolyn sodium may be effective. The intake of diaminoxidase (DAO) in capsule form with meals may reduce the symptoms of histamine intolerance.[14]

In cases of high blood glutamate, such as can occur in some cases of eczema and histamine intolerance, Reinhart Jarisch recommends vitamin B6 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.[15]

Literature

• Abbot, Lieners, Mayer, Missbichler, Pfisterer, Schmutz: Nahrungsmittelunverträglichkeit (Histaminintoleranz). HSC, Mauerbach 2006, ISBN 3-9502287-0-5.
• Reinhart Jarisch: Histamin-Intoleranz, Histamin und Seekrankheit. Thieme 2004, ISBN 3-13-105382-8.
• Nadja Schäfers: Histaminarm kochen – vegetarisch. pala-Verlag, Darmstadt 2009, ISBN 978-3-89566-263-8.
• Anja Völkel: Gesunde Küche: bewusst genießen – schmackhaft & lecker. AVA-Verlag, 2013, ISBN 978-3-944321-13-4.
• I. Reese: Streitthema Histaminintoleranz. (CME zertifizierte Fortbildung) In: Der Hautarzt. 65, 2014, S. 559–566, doi:10.1007/s00105-014-2815-2.

See also

• Mast cell
• Basophil
• Food intolerance
• Red wine headache

References

1. "HIT > Histaminosis". Histamin Intoleranz.
2. Maintz, L.; Novak, N. (2007). "Histamine and histamine intolerance". American Journal of Clinical Nutrition. 85 (5): 1185–96. doi:10.1093/ajcn/85.5.1185. PMID 17490952.
3. Moon TC, Befus AD, Kulka M (2014). "Mast cell mediators: their differential release and the secretory pathways involved". Front Immunol. 5: 569. doi:10.3389/fimmu.2014.00569. PMC 4231949. PMID 25452755. This release of pre-formed mediators enables not only rapid anaphylactic reactions and allergic responses but also initiates recruitment of leukocytes to sites of pathogen invasion, activation of innate immune processes, and inflammatory responses (1). ... Two types of degranulation have been described for MC: piecemeal degranulation (PMD) and anaphylactic degranulation (AND) (Figures 1 and 2). Both PMD and AND occur in vivo, ex vivo, and in vitro in MC in human (78–82), mouse (83), and rat (84). PMD is selective release of portions of the granule contents, without granule-to-granule and/or granule-to-plasma membrane fusions. ... In contrast to PMD, AND is the explosive release of granule contents or entire granules to the outside of cells after granule-to-granule and/or granule-to-plasma membrane fusions (Figures 1 and 2).
   Figure 1: Mediator release from mast cells
   Figure 2: Model of genesis of mast cell secretory granules
   Figure 3: Lipid body biogenesis
   Table 2: Stimuli-selective mediator release from mast cells
4. Healthline https://www.healthline.com/health/histamine-intolerance#symptoms. Retrieved Histamine Intolerance: Causes, Symptoms, and Diagnosis. Check date values in: |accessdate= (help); Missing or empty |title= (help)
5. "Tissue Expression of HNMT - Summary - Protein Atlas". Tissue Expression of HNMT - Summary - Protein Atlas. Retrieved 3 June 2019.
6. Maintz, Laura; Bieber, Thomas; Novak, Natalija (25 December 2006). "Die verschiedenen Gesichter der Histaminintoleranz: Konsequenzen für die Praxis". Deutsches Ärzteblatt. 103 (51–52): A-3477 / B-3027 / C-2903. Retrieved 3 June 2019.
7. "Tissue Expression of AOX1 - Summary - The Human Protein Atlas". Retrieved 3 June 2019.
8. Wilhelm, T. "Tabakrauch ist bedeutende Histaminquelle". Deutsches Ärzteblatt. Köln 104.2007: A 1768.
9. "Histamine Food List" (PDF). Healing Nore: Health Coaching.
10. Schaefers, Nadja (2009). Histaminarm kochen - vegetarisch. pala-Verlag.
11. "Histamin Intoleranz". Wikipedia DE.
12. "Histamine intolerance: Causes, symptoms, and test". Medical News Today.
13. Vogelreuter, Axel (2015). Nahrungsmittelunverträglichkeiten. Stuttgart: S. Hirzelverlag. ISBN 978-3-7776-2349-8.
14. "Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: A randomised, double-blind, placebo-controlled cross-over study". Wiener Klinische Wochenschrift. 2011: 1–2. Retrieved 3 June 2019.
15. Greiling, Helmut; Gressner, A.M. (1987). Lehrbuch der klinischen Chemie und Pathobiochemie. Schattauer Verlagsgesellschaft. ISBN 3-7945-0949-8.

External links

Classification	D ICD-10: T78.1