Histamine intolerance occurs when histamine accumulation exceeds the capacity for its degradation, mainly by diamine oxidase (DAO). Histamine is present in many foods, and healthy individuals can rapidly detoxify it. However, those with low DAO activity risk histamine toxicity. Impaired histamine degradation due to reduced DAO activity can cause various symptoms resembling an allergic reaction, such as diarrhea, headache, asthma, hypotension, urticaria, and flushing. These symptoms can be triggered by histamine-rich food, alcohol, or drugs that release histamine or block DAO.

Histamine intolerance (HIT) is a condition where excessive histamine accumulation in the body leads to various symptoms. In healthy individuals, histamine intoxication can occur after consuming histamine-rich foods. However, in HIT, even normal levels of dietary histamine can cause symptoms due to decreased activity of histamine-degrading enzymes. Diagnosing HIT is challenging as its multifaceted, nonspecific symptoms are often attributed to other conditions like allergies, mastocytosis, or psychological disorders. Accurate HIT diagnosis and treatment with a histamine-free diet and diamine oxidase supplementation can improve patients' quality of life.

In a study involving four Austrian centers, patients suspected of histamine intolerance underwent open oral provocation with 75 mg of liquid histamine. Those who developed symptoms were then tested in a randomized, double-blind, crossover provocation using histamine-containing and histamine-free tea, along with diamine oxidase (DAO) capsules or placebo. The main and secondary symptoms were not consistently reproducible, suggesting that histamine-intolerant individuals may react with different organs on different occasions. However, the total symptom scores showed statistically significant differences between the treatment groups, with DAO intake resulting in a significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).

A randomized, double-blind, placebo-controlled cross-over study in 10 healthy females (age range 22-36 years, mean 29.1 +/- 5.4) who were challenged on two consecutive days with placebo (peppermint tea) or 75 mg of pure histamine (equaling 124 mg histamine dihydrochloride, dissolved in peppermint tea).We conclude that 75 mg of pure liquid oral histamine--a dose found in normal meals--can provoke immediate as well as delayed symptoms in 50% of healthy females without a history of food intolerance.

Diagnosing HIT is challenging due to the inconsistency and variety of symptoms, which may result from various pathophysiological mechanisms. A multidisciplinary approach is required for diagnosis, including the systematic elimination of disorders with similar manifestations. The gold standard treatment for HIT is a low-histamine diet, with a positive response confirming the diagnosis. DAO supplementation and consciously administered antihistamines may be considered as subsidiary treatments.

Histamine intolerance arises from an impaired ability to metabolize dietary histamine due to diamine oxidase (DAO) enzyme deficiency, potentially caused by genetics, inflammatory bowel diseases, or DAO-inhibiting drugs. Diagnosis is challenging without validated tests, but following a low-histamine diet and observing symptom improvement is commonly used. The main treatment is a low-histamine diet, but foods excluded vary across proposed diets. Oral DAO enzyme supplementation from plant or animal sources shows promise as a complementary treatment to enhance histamine degradation.

A histamine-free diet was trialed in 45 patients with suspected histamine intolerance causing food/wine intolerance (n=17) or chronic headaches (n=28). After 4 weeks on the histamine-free diet eliminating foods like fish, cheese, and alcohol, 33/45 patients showed significant improvement in symptoms, with 8 achieving complete remission. Symptoms could be reproduced by reintroducing histamine-rich foods. In the food/wine intolerance group, symptoms decreased significantly, suggesting the diet is an effective treatment. Chronic headache patients also saw reduced frequency, duration and intensity. The results support the hypothesis of diamine oxidase deficiency underlying histamine intolerance in these patients.

This open-label pilot study evaluated oral diamine oxidase (DAO) enzyme supplementation in 28 patients with suspected histamine intolerance (HIT). Patients took DAO capsules before meals for 4 weeks, followed by a period without supplementation. A questionnaire assessed 22 HIT-related symptoms across 4 categories, along with symptom severity scores. All symptoms improved significantly during the 4-week DAO supplementation period. Without DAO, symptom sum scores increased again during follow-up. Symptom intensity scores were reduced across all symptoms with DAO supplementation. The study demonstrated significant reductions in both the presence and intensity of HIT-related symptoms when patients received oral DAO enzyme supplements.