Histamine intoleranceT78.1

• Prevalence: 1% of the German population (acquired form > congenital form)
• Mostly affects women aged 40-45 years.

Congenital or acquired (e.g. in the context of an inflammation of the intestinal mucosa, symptoms then often only passager), reduced activity or functional inhibition of the enzyme diamine oxidase (DAO), which is responsible for histamine degradation and occurs in the enterocytes of the small intestine, in the liver, kidneys and leukocytes. DAO, which is continuously secreted into the intestinal lumen, degrades histamine intraluminally, the rest is degraded in the enterocytes. Cofactors are 6-hydroxydopa and vitamin B6 (pyridoxal phosphate).

The biological importance of an effective and rapid histamine degradation can be measured by the fact that during pregnancy, from the 3rd month of pregnancy onwards, DAO increases 50 to 1000 times in order to protect the fetus!

Normally, "histamine dioxydase" leads to a rapid breakdown of histamine. A reduced DAO activity is detectable in persons with histamine intolerance. This defect can be congenital. A temporary histamine intolerance can occur as a result of an inflammation of the intestinal mucosa (Jäger L et al. 2001). This reduction in DAO activity leads to a disproportion between histamine supply and histamine degradation as well as an increase in histamine concentration in the serum with corresponding clinical symptoms.

The histamine content is increased by:

• consumption of beverages and food containing especially histamine (see table)
• intake of histamine liberators (e.g. strawberries or citrus fruits provoke increased (non-immunological) release of histamine from mast cells and basophilic leucocytes)
• Intestinal bleeding (passagere activity reduction of DAO)
• Intestinal bacterial infections (possible reduction of DAO activity)
• Increased histamine sensitivity (e.g. in atopic patients)
• Drugs (see table), alcohol (alcohol and histamine compete for the same degrading enzyme, aldehyde dehydrogenase.
• Simultaneous supply of other biogenic amines, which are degraded by DAO.

• Leading symptoms are gastrointestinal disorders such as diarrhea, diffuse stomach pain, colic, flatulence. A frequent leading symptom is an "intolerance to red wine".
• Further: vasomotor headache, dysmenorrhoea, rarely involvement of the cardiovascular system.
• Skin and mucous membrane symptoms: itching, urticaria, bronchial asthma, angioedema, rhinitis, worsening of an existing atopic eczema.

• The following questions must be clarified:
• Frequent headaches, migraines?
• Incompatibility of (southern) red wine, red wine vinegar, and other alcoholic beverages (e.g. wheat beer, champagne)
• intolerance of hard cheese, perennial sausages, tomatoes or tomato - ketchup as well as chocolate
• stomach and intestinal disorders, especially diarrhoea over a longer period of time
• Hypotension
• Tachycardia, cardiac arrhythmia
• Dysmenorrhoea
• In vitro method (total IgE, specific IgE-AK against food/inhalation allergens; DAO concentration in serum)
• Skin testing ( prick test, prick-to-prick test with food)
• oral provocation test (double-blind, placebo-controlled oral food provocation).

Histamine-free diet: yeast-free bread, pastries, potatoes, rice, pasta, milk and dairy products (except hard cheese), fresh meat, fresh or frozen fish, eggs, most vegetables (except tomatoes, spinach, sauerkraut, avocado) and herbs.

Avoiding histamine-rich foods such as red wine, all long-aged cheeses (e.g., hard cheeses, Emmental), cured meats, yeast-raised baked goods, canned fish meats.

Discontinue or change DAO-blockers, see under remarks

Antihistamines, in severe cases combination of H1- and H2-receptor antagonists. Comment: Regarding the use of anthistamines, the S1 guideline (Reese et al. 2012) states: "It is conceivable as a pragmatic procedure to treat patients with a suspected histamine intolerance over a defined period of time with H1/H2 receptor antagonists in order to check whether the symptoms change"!

Cromoglicic acid.

Preparations that promote the breakdown of histamine can help: DAOSIN® , a food supplement containing the enzyme DiAminOxidase (DAO), which supports the breakdown of ingested histamine from food in the intestine.

Note: This table does not say anything about the actual compatibility of a product. Large amounts of histamine are better tolerated in cheese than in fish. This is due to the slower release of histamine. Therefore this table is only a rough orientation.

• Acetylcysteine
• Ambroxol
• Aminophylline
• Amitriptyline
• Chloroquine
• Clavulanic acid
• Isoniazid
• Metamizole
• Metoclopramide
• Propaphenone
• Verapamil.

1. Bodmer S et al (1999) Biogenic amines in foods: histamine and food processing. Inflamm Res 48: 296-300
2. Jäger L et al (2001) Food allergies and intolerances. Urban & Fischer Publishing House Munich, Jena S 59
3. Jarisch R et al (2012) Histamine intolerance. Act Dermatol 38: 159-166
4. MacGlashan D Jr (2003) Histamine: A mediator of inflammation. J Allergy Clin Immunol 112: S53-59
5. Ortolani C et al (2006) Food allergies and food intolerances. Best Pract Res Clin Gastroenterol 20: 467-483
6. Reese I et al. (2012) Procedure in case of suspected intolerance to orally ingested histamine. Allergo J 21: 22-28
7. Vassilopoulou E et al (2007) Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome. Int Arch Allergy Immunol. 143: 92-102