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Histamine intolerance

Dietary management of histamine intolerance has been an area of focus in central Europe for decades, but remains relatively unknown elsewhere.


A few recent studies have ignited interest because of important reported benefits of a low-histamine diet.

What is histamine intolerance?

Histamine intolerance (HIT), also known as enteral histaminosis, is a condition that is characterised by the development of a diverse set of problematic symptoms after the ingestion of histamine containing foods. Importantly, current thinking is that HIT is not solely due to dietary histamine exposure, but exposure coupled with insufficient or impaired histamine detoxification

What causes histamine intolerance?

Elevations in histamine due to an imbalance between detoxification and dietary exposure can cause histamine receptor mediated complications with allergic type symptoms such as flushing, headaches or urticaria, and gastrointestinal symptoms including diarrhoea and abdominal pain. Dietary histamine is found at particularly high concentration in aged foods (eg cheeses, alcoholic beverages, cured meats, fermented or spoiled foods) where it is produced by bacterial or yeast fermentation of the amino acid histidine to histamine. Other foods, such as citrus for example, may have the capacity to enhance histamine release even though they contain low levels of histamine themselves.

Detoxification of dietary histamine normally occurs in intestinal epithelial cells via the enzyme diamine oxidase (DAO) as well as histamine-N-methyl-transferase (HNMT) in the liver. If DAO fails to inactivate histamine, it can be absorbed through the gut epithelium and enter the bloodstream and systemic circulation where it can cause the typical symptoms of Histamine intolerance.

There have been associations between genetic variants that affect DAO and/or HNMT activity and inflammatory bowel disease, asthma, allergic rhinitis and migraine headache, suggesting increased susceptibility to histamine intolerance in some individuals

How is histamine intolerance diagnosed?

The diagnosis of HIT typically requires the presence of two or more symptoms, improvement with a low histamine diet and/or antihistamines, and the exclusion of food allergies. Testing remains controversial as blood and urine histamine is often normal,and the usefulness of determining DAO levels or DAO and HNMT genotype is unclear.

HIT appears to be transient, and may depend more on modifiable physiological and environmental factors than genetic susceptibility. Damage to the gastrointestinal mucosa, as in inflammatory bowel disease or coeliac disease, may reduce histamine detoxification capacity and should be considered. Limiting exposure to histamine provoking foods as well as alcohol, which competitively inhibits intestinal DOA, are common clinical practices. After dietary histamine removal and symptom improvement many patients may be able to tolerate histamine-containing foods again and return to a normal diet. In addition to dietary therapy, nutritional supplementation with nutritional co-factors for DOA has been suggested, in particular zinc, copper, vitamin C and vitamin B6. Of these nutrients, both vitamin C and B6 have some evidence to suggest they would support histamine detoxification.

Gut bacteria and histamine intolerance

Finally, although it has been relatively unexplored, it is plausible to suggest that differences in gut bacteria could result in increase histamine production through fermentation of histidine to histamine,or have direct affects on intestinal DOA activity. Lending support to this idea the GG strain of Lactobacillus rhamnosus (LGG) was found to reduce allergy-related immune activation by down regulation of the expression of histamine receptor genes.

In summary, it appears more attention should be given to the possibility of HIT as a clinical diagnosis, namely because nutritional therapy appears to be a safe and effective treatment for symptoms that may be otherwise misdiagnosed and treated with little hope for resolution.

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