May 28, 2025 | Black & Kletz Allergy
Histamine is a biogenic amine (i.e., an organic compound made up of carbon and nitrogen bonds) with several biological effects across different types of cells, mediated through the activation of histamine receptors. Histamine is normally present within mast cells and other similar cell types such as basophils. Mast cells are cells of the connective tissue that contain many granules rich in histamine and other chemicals. Histamine is also present in various types of food, such as cheese, fermented foods, wine, spinach, some types of fish and meats.
During an allergic reaction, the mast cells are triggered to release their “granules” which contain histamine and other active substances (e.g., leukotrienes, prostaglandins) into the bloodstream. It is these substances that are responsible for causing allergic symptoms which vary depending on the organ and the sensitivity of the allergic individual.
H1 (histamine 1) receptors are predominantly present in the skin and mucous membranes. When these receptors are activated by histamine, they result in allergic symptoms such as itching (i.e., pruritus), rashes, flushing, hives (i.e., urticaria), and/or soft tissue swellings (i.e., angioedema). Stimulation of the H1 receptors in the mucous membranes by histamine causes allergic symptoms such as sneezing spells, nasal congestion, runny nose, post-nasal drip, itchy throat, sinus congestion, headaches, itchy eyes, watery eyes, and/or redness of the eyes.
Allergies and excessive histamine release also play a role in asthma symptoms such as chest tightness, coughing, wheezing, and/or shortness of breath. In addition to stimulating H1 receptors, histamine also stimulates H2 receptors in the stomach and thus plays a role in acid production and digestion. Excessive levels of histamine can lead to the overproduction of stomach acid and as a result, in can cause heartburn and other gastroesophageal reflux disease (GERD) symptoms.
Histamine intolerance occurs when the body’s capacity to eliminate histamine is exceeded by the rate of histamine accumulation. In healthy individuals, the enzyme called intestinal diamine oxidase (DAO) helps eliminate histamine that was consumed from food. When the activity of DAO is inhibited by certain factors, the body’s ability to manage histamine is significantly affected. Genetic mutations causing the decreased expression of the DAO enzyme and some medications are 2 factors that can reduce the effectiveness of DAO. As a result of these factors (i.e., genetic mutations, medications), an accumulation of histamine may occur which cause symptoms that can mimic true allergic reactions. Some examples of drugs that have been found to affect DAO’s activity include verapamil, clavulanic acid, and isoniazid, among others. Certain mineral and vitamin deficiencies (e.g., vitamin C, copper) are also known to decrease DAO activity. Alcohol, on the other hand, has been found to increase the release of endogenous histamine, affecting the rate of its degradation.
Symptoms: The symptoms of histamine intolerance are varied and may involve different systems of the body.
- Skin: pruritus, flushing, urticaria, dermatitis, and/or swelling.
- Gastrointestinal: abdominal bloating, abdominal discomfort, gas, diarrhea and/or constipation
- Respiratory: runny nose, nasal congestion, post-nasal drip, itchy throat, sneezing, sinus congestion, chest tightness, coughing, wheezing, and/or shortness of breath
- Cardiovascular: cardiac rhythm disturbances and/or blood pressure variations
- Neurological: headaches
Diagnosis:
There are no standardized tests to confirm the diagnosis of histamine intolerance. The normal levels of DAO in the serum (i.e., blood) and the diagnostic levels for histamine intolerance have not been established. High DAO levels may exclude histamine intolerance, whereas low levels are quite common and not diagnostic of histamine intolerance.
At this time, in the absence of clear diagnostic guidelines, the diagnosis rests primarily on clinical manifestations and therapeutic trials.
Treatment:
- Restrict foods that contain high levels of histamine (e.g., seafood, fermented soybean products, aged cheese, avocado, chocolate, nuts, milk, legumes, certain fruits such as bananas). Instead, substitute histamine-rich foods with foods that are low in histamine (e.g., water, fresh juices, herbal teas, bread, rice, eggs, honey).
- Keep a food and symptom diary for 4 to 6 weeks and eliminate the suspected foods for 4 to 6 weeks and gradually reintroduce them while closely monitoring the symptoms.
- Empirical trials with antihistamine drugs, though there are no randomized trials to prove the value of this treatment in addressing histamine intolerance.
- Mast cell stabilizer medications such as cromolyn and ketotifen may be helpful in selective cases.
- The approach of supplementation with over-the-counter DAO enzyme in order to reduce excessive levels of histamine in the serum is controversial and there are no standardized guidelines available regarding the dosage.
- Supplementing with minerals and vitamins such as copper, zinc, vitamin C, and/or vitamin B6 in the case of a known deficiency, malnutrition, or restrictive diet, may be beneficial, if approved by one’s physician.
Note: The American Academy of Allergy, Asthma and Immunology does not currently recognize histamine intolerance as a condition. Before implementing any of the above “treatments,” one’s symptoms should be discussed with one’s allergist or primary care physician. The treatment recommendations listed above should only be adhered to if one’s doctor agrees with them in that specific individual’s situation.
If you suffer from symptoms of histamine intolerance or any other food or environmental allergies, please call us in order to schedule an appointment with one of our board-certified allergy doctors at Black & Kletz Allergy. You may also click Request an Appointment and we will respond within 24 hours by the next business day. All 3 of our offices have on-site parking and the Washington, DC and McLean, VA offices are Metro accessible. The McLean office has a complementary shuttle that runs between our office and the Spring Hill metro station on the silver line. The allergy doctors of Black & Kletz Allergy diagnose and treat both pediatric and adult patients. The allergy specialists at Black & Kletz Allergy have been helping the residents and visitors of the Washington, DC, Northern Virginia, Maryland metropolitan area for more than 50 years and are pleased to help you improve the quality of your life by alleviating those unwanted and annoying allergy and asthma symptoms.
