Histamine is often overlooked as a cause of chronic health problems yet the fix for this issue can be quite straightforward. In this article, I cover the details of histamine and how to follow a low histamine diet. Histamine intolerance (HIT) affects approximately 1% of the population. Approximately 80% of those affected are middle-aged.1 Histamine intolerance occurs when an individual has more histamine in their system than they can breakdown. Excess systemic concentrations of histamine can result from overproduction, overconsumption, and/or having a reduced ability to clear out histamine from the body. For those with HIT, eating a diet that results in increased histamine can contribute to chronic inflammation due to the ongoing exposure to histamine. This excess histamine often accumulates as a result of decreased diamine oxidase (DAO) activity.2, 3 The resulting excess histamine contributes to the physical symptoms associated with HIT. Following a low-histamine diet along with supplemental DAO is often recommended to decrease the symptoms associated with HIT. Eating a low-histamine diet involves more than simply eliminating foods that are high in histamine. This article will help to explain the challenges with following a low histamine diet and will highlight the many ways excess histamine can occur in food and in the body. Histamine Synthesis and Degradation Excess histamine concentrations may be exogenously released from food or endogenously produced. Histamine is synthesized by a variety of cells in the body including mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells. Endogenous histamine is released in response to a variety of immune and inflammatory related stimuli as well as certain foods, alcohol, or drugs which can activate release.1 Endogenous histamine supplies are also controlled by genes that code for the enzymes that synthesize and degrade histamine. Genetic polymorphisms in histamine receptors and DAO can decrease the rate of DAO activity, reducing the rate of clearance and increasing systemic histamine concentrations.3 Exogenous sources of histamine mainly comes from ingested foods. Several factors in food processing and storage can increase the histamine content of certain foods as well. Histamine is normally metabolized by amine oxidases in healthy individuals. These amine oxidases include monoamine oxidase (MAO), DAO, and histamine N-methyltransferase (HNMT), with DAO being the primary enzymes for metabolism of histamine.5 It is thought that low gastrointestinal levels of DAO contributes to an individual being unable to break down histamine in the intestines, resulting in the increased sensitivity to histamine found in common foods. As excess levels accumulate, intolerance symptoms develop.1, 2, 6, 7 Symptoms Associated with Histamine Intolerance There is great heterogeneity in the presentation of symptoms in those with HIT, making it difficult to define a clear clinical picture. Histamine intolerance is generally suspected when symptoms appear after the ingestion of histamine containing food.3 Symptoms may develop immediately or can be delayed as much as three hours following ingestion.5 Histamine receptors are found ubiquitously throughout the body, making different organ systems susceptible to adverse reactions due to excess histamine concentrations. This results in a wide variety of symptoms that may be exhibited by an individual, contributing to the difficulty in diagnosis. These symptoms include gastrointestinal issues such as abdominal pain, bloating, diarrhea, and constipation. Extraintestinal complaints may affect neurological, respiratory, dermatological, and/or hemodynamic systems.2 Histamine has vasoactive properties that may result in flushing, headaches, and/or hypertension.5 Other common symptoms related to HIT include brain fog, fatigue, dizziness, itching, and difficulty swallowing, low blood pressure, nasal congestion, sneezing, and menstrual cramps.2, 3 Low-Histamine Diet and DAO Supplementation Following a low-histamine diet along with DAO enzyme supplementation is currently the recommended strategy to prevent the symptoms associated with HIT. Sanchez-Perez et al. (2021) reported a >70% efficacy rate among the clinical studies examined in their review of low-histamine diets. They also found that only 32% of the excluded foods in a low histamine diet contained histamine.  Foods containing other biogenic amines (BAs), like putrescine, were thought to be responsible for the increased symptoms related to HIT. They state that it is possible that certain foods, while containing no or low levels of histamine, may act as histamine liberators resulting in excess accumulation of histamine.2 There is also great heterogeneity in the foods recommended for a low-histamine diet. Fermented food products and beverages were consistently recognized as a primary food group to be avoided. Decreasing the amount of histamine in the diet has been shown to decrease symptoms related to HIT. Following a low histamine diet can be confusing as there is a lack of consensus as to which foods should be included versus excluded. It can also be difficult for individuals to monitor the intake of histamine from the diet as there are no labeling requirements on foods for histamine.2 The daily intake of histamine, on average, is 1000mg/kg. Healthy individuals should be able to metabolize this amount without any problems.5 The recommended range for those undertaking a low-histamine diet is between 5-50 mg/kg.  Some experts suggests that even lower levels are necessary and recommend an intake of foods with histamine levels below 1 mg/kg.2 Supplementation with DAO may also prove beneficial in reducing symptoms. Manzotti et al. (2016) demonstrated that individuals with DAO activity