Histamine intolerance is a presumed set of adverse reactions (such as flushing, itching, rhinitis, etc.) to ingested histamine in food. The mainstream theory accepts that there may exist adverse reactions to ingested histamine, but does not recognize histamine intolerance as a separate medical condition that can be diagnosed. There is a common suspicion that ingested histamine in persons with deficiencies in the enzymes that metabolize histamine may be responsible for various non-specific health complaints, which some individuals categorize as histamine intolerance; still, histamine intolerance is not included as an explicit condition in the International Classification of Diseases (ICD) Edition 11. The scientific proof that supports the idea that eating food containing histamine can cause health problems is currently limited and not consistent. Some studies have attempted to establish a direct, causal link between histamine ingestion and clinical symptoms associated with histamine intolerance, but the results have been mixed, complicating the interpretation of the data. Histamine intolerance affects a variable portion of the population, with estimates on about 1%, though exact prevalence is unclear due to diagnostic challenges. Current research focuses on better understanding the condition's etiology (causes), improving diagnostic methods, and developing effective treatments, but no such treatment has been found so far. Research is primarily focused on dietary adjustments and lifestyle modifications which are currently the most promising options. Societally, histamine intolerance has led to increased awareness and dietary adjustments, but it remains a controversial and under-recognized condition in the medical community.
Signs and symptoms The manifestations of histamine intolerance are usually systemic, affecting the entire body; still, these symptoms are often sporadic and non-specific. The onset of symptoms is usually shortly (within a few hours) after specific food or drink consumption, and subsequent remission usually happens in 4-8 weeks of dieting, that is excluding food that causes the onset of symptoms. Symptoms attributed to histamine intolerance are wide-ranging and may affect various physiological systems, including the skin (flushing or redness of the face, hives, itchiness, rash, etc.), gastrointestinal (gut discomfort, stomach pain, irritable bowel, abdominal distension, postprandial fullness, diarrhea or constipation, etc.), cardiovascular (reduced or raised blood pressure or abnormal heart rhythm, etc.), respiratory (asthma, runny nose, sinusitis, etc.), and nervous systems (headaches, migraine, sleep disturbances, cognitive impairment, mood disorders, dizziness or lightheadedness, muscle or eyelid twitching and other neurological symptoms). These symptoms are not specific to histamine intolerance and may overlap with other conditions or disorders.
Causes Histamine, a biogenic amine found in various food products, is frequently implicated as a potential instigator of a range of health issues. These issues are often collectively referred to under the umbrella term "histamine intolerance", formulated drawing parallels to "lactose intolerance", a condition resulting from lactase enzyme deficiency. Nevertheless, there are no prospective, controlled studies that would have conclusively established an enzyme or a lack thereof as the root cause of adverse reactions following histamine ingestion. Some scholars suspect that histamine intolerance is a condition characterized by an imbalance between histamine intake through the diet and the body's ability to metabolize ingested histamine so that this imbalance leads to increased blood histamine concentration, which can cause adverse effects. Histamine intolerance is considered by these scholars a non-immunological disorder that results from reduced activity or levels of the enzymes that metabolize histamine: diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). Still, the exact prevalence of histamine intolerance is unknown due to limited data and a lack of validated diagnostic methods.
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![Histamine intolerance: Biological inactivation (breakdown) of histamine by the histamine N-methyltransferase (HNMT) enzyme into Nτ-methylhistamine, a chemical reaction denoted by straight arrow[24][25]—if this process if affected, histamine intolerance may develop, as believed by some scholars[26]](https://upload.wikimedia.org/wikipedia/commons/thumb/0/06/HNMT-methylation-of-histamine.svg/330px-HNMT-methylation-of-histamine.svg.png?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)

