Histamine intolerance
[2] The scientific proof that supports the idea that eating food containing histamine can cause health problems is currently limited and not consistent.
[1] Histamine intolerance affects a variable portion of the population, with estimates on about 1%, though exact prevalence is unclear due to diagnostic challenges.
[1] Societally, histamine intolerance has led to increased awareness and dietary adjustments, but it remains a controversial and under-recognized condition in the medical community.
[8][9] 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.
),[3][5][6] gastrointestinal (gut discomfort, stomach pain, irritable bowel, abdominal distension, postprandial fullness, diarrhea or constipation, etc.
), and nervous systems (headaches, migraine, sleep disturbances, cognitive impairment, mood disorders, dizziness or lightheadedness, muscle or eyelid twitching and other neurological symptoms).
[3][5][6] Histamine, a biogenic amine found in various food products, is frequently implicated as a potential instigator of a range of health issues.
[1][3][11][12] 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.
[5][6][13] Still, the exact prevalence of histamine intolerance is unknown due to limited data and a lack of validated diagnostic methods.
[1] A small number of studies have attempted to elucidate this relationship through the rigorous methodology of double-blind, placebo-controlled oral food challenges involving histamine.
[1] Despite the lack of robust, consistent evidence, the consumption of histamine continues to be suspected as the etiological agent (factor that causes the onset) behind a variety of nonspecific health complaints.
For example, H1 receptors are involved in allergic reactions, inflammation, and sensory perception: they can cause smooth muscle contraction (leading to manifestations such as bronchoconstriction or intestinal cramping), increased vascular permeability (resulting in edema), and stimulation of sensory nerve endings (causing itching and pain).
[28] Despite the belief shared by several researchers[24] that consuming histamine can lead to nonspecific health issues, the scientific proof to back this claim is both scarce and inconsistent, the underlying mechanisms are not understood and while several factors have been proposed for explaining the underlying mechanisms of these adverse reactions to histamine intake, no single hypothesis has gained solid scientific confirmation.
[1] Some authors[6][22][24] suggest complex approach, that includes assessments to rule out other potential causes of similar symptoms, such as allergies, mastocytosis, gastrointestinal diseases, and medication-induced inhibition of diamine oxidase (DAO) enzyme activity.
Examples of such testa are measuring plasma DAO activity levels and conducting intradermal skin allergy tests with histamine.
[6][22][24] While several factors have been proposed for diagnosing adverse reactions to histamine intake, there are still no reliable lab tests to either confirm or refute the diagnosis.
[1] The existence and clinical significance of these so-called "histamine liberators" in foods is a topic of ongoing debate in the scientific community.
Despite anecdotal reports and some theoretical discussions, there is currently no robust scientific evidence to support the notion that certain foods can act as histamine liberators.
[10] Genuine food allergies typically occur in early childhood and resolve by the time a child enters primary school.
It is also recommended by these scholars to avoid DAO-blocking medications and substances that may increase histamine levels, such as alcohol and certain food additives.
[6][22][24] Several medications, including acetylcysteine, metamizole, verapamil, metronidazole, and metoclopramide, have been reported to inhibit the activity of DAO or HNMT enzymes.
[1] Additional options in managing histamine intolerance include antihistamines, mast cell stabilizers, and supplementation with exogenous DAO, in the form of capsules or tablets.
[1] Consequently, the primary endpoint of the study was not achieved, and the basis for the authors' conclusion that DAO supplementation intake resulted in a "statistically significant reduction in symptoms" remains unclear.
[1] The exact prevalence of histamine intolerance is unknown due to limited data and a lack of validated diagnostic methods.
Still, these figures are likely incorrect and cannot be relied upon because this prevalence estimate is not supported by robust scientific evidence or validated diagnostic methods.
[8] There is limited evidence from double-blind placebo-controlled provocations studies on adverse reactions to histamine-containing foods or other agents associated with histamine intolerance.
Therefore, solid data focused on understanding pathophysiology, clinical presentation, and improved diagnostic tools is needed before reliable estimates can be made regarding epidemiological aspects of histamine intolerance.
Individuals with genetic variants in the AOC1 gene encoding the diamine oxidase (DAO) enzyme are observed to experience migraines when consuming a diet high in histamine.
The exploration of the functional interplay between exogenous histamine and CGRP could provide valuable insights into the mechanisms underlying diet-induced migraines, and this area of research continues to be actively investigated.
