Histamine intolerance is a presumed set of adverse reactions (such as flush, 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. [1] 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, [1] still, histamine intolerance is not recognized as an explicit condition with that name in the International Classification of Diseases (ICD) Edition 11, [2] or any previous edition. The scientific proof that supports the idea that eating food containing histamine can cause health problems is currently limited and not consistent. [1] [3] [4] Some studies have attempted to elucidate 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. [1]
Histamine intolerance affects a variable portion of the population, with estimates on about 1%, though exact prevalence is unclear due to diagnostic challenges. [5] Current research focuses on better understanding the condition's etiology, improving diagnostic methods, and developing effective treatments,, but no such treatment have been found so far. Research is primarily focused on dietary adjustments and lifestyle modifications which are currently the most promising options. [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. [1]
The manifestations of histamine intolerance are usually systemic, affecting the entire body; still, these symptoms are often sporadic and non-specific. [6] [5] [7]
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. [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.), [6] [5] [3] 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). [6] [5] These symptoms are not specific to histamine intolerance and may overlap with other conditions or disorders. [6] [5] [3]
Histamine, a biogenic amine found in various food products, is frequently implicated as a potential instigator of a range of health issues. [1] These issues are often collectively referred to under the umbrella term "histamine intolerance", [1] formulated drawing parallels to "lactose intolerance", a condition resulting from lactase enzyme deficiency. [10] [11] [3] [1] 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. [1]
Some scholars [12] [6] [5] 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) [13] and histamine N-methyltransferase (HNMT). [12] [6] [5] Still, the exact prevalence of histamine intolerance is unknown due to limited data and a lack of validated diagnostic methods. [6] [5] [3]
Despite this common attribution of various symptoms as adverse reactions to ingested histamine, the scientific substantiation for a direct link between the ingestion of histamine and the manifestation of clear reproducible symptoms remains inconsistent. [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. However, the results yielded from these investigations have been notably mixed and heterogeneous, further complicating the interpretation of the data and comparison of results of these studies. [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. [1] [14] [5]
The scientific support for such a clinical picture—the combination of symptoms, signs, and other medical information, associated with histamine ingestion—remains limited and presents contradictory findings: [1] for example, histamine present in dietary sources such as Emmental cheese is tolerated better compared to histamine derived from spoiled fish, [1] [14] particularly those belonging to the Scombridae family, which includes species like tuna and mackerel. [1] The adverse physiological responses associated with the consumption of such spoiled fish are typically a result of histamine toxicity rather than intolerance to histamine per se. [5] [15] [1] This response caused by spoiled fish suggests that the intake of abnormally high concentrations of histamine would elicit a reaction in any individual, irrespective of their sensitivity to histamine. [1] It is not clear whether the symptoms observed in cases of fish poisoning can be attributed solely to the histamine content of the spoiled fish, or if other factors may also be involved. [1] [14] [16]
Histamine can bind to four types of receptors (H1–H4) and trigger various physiological responses. [15] [1] The physiological responses that histamine can trigger depend on which type of receptor it binds to. 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). [17] [18] Histamine levels in the blood and inside the cells are normally regulated by two enzymes: histamine N-methyltransferase (HNMT) and diamine oxidase (DAO). [15]
In some cases, circulating histamine levels can rise and cause adverse effects. According to some authors, [5] [15] such cases can be caused by two main reasons: histamine intoxication and histamine intolerance. [5] [15]
Histamine intoxication is a condition that occurs when healthy individuals consume foods that contain high amounts of histamine, such as spoiled fish. In histamine intoxication, the ingested histamine can overwhelm the capacity of the histamine-degrading enzymes and lead to symptoms such as flushing (redness of the face), headache, nausea, diarrhea, hypotension (low blood pressure), and arrhythmia. The diagnosis of histamine intoxication is based on the clinical presentation and the history of food intake. The treatment consists of antihistamines, fluids, and supportive measures. [15] [19] [16]
Histamine intolerance, in contrast to histamine intoxication, is a presumed disorder that affects individuals who are supposed to have a reduced or impaired activity of the histamine-degrading enzymes, either due to genetic factors, medications, or gastrointestinal diseases. [1] [15] In healthy individuals, the consumption of small amounts of histamine typically does not have any adverse health effects. However, in supposedly affected individuals, ingesting histamine through food at levels well below those associated with scombroid poisoning (from eating spoiled fish) can lead to symptoms related to histamine intolerance. [9] [12] [1] [14] In the ICD-11, there is a condition "XM74Y6 Scombroid fish seafood poison", [2] but not "histamine intolerance". [2] In the supposed histamine intolerance, these affected individuals supposedly have a lower threshold for histamine and can develop symptoms even after consuming foods with normal or moderate amounts of histamine, [1] [14] such as tomatoes, eggplants, spinach, strawberries —plants which naturally contain histamine [20] [15] —or wine. [15] The symptoms of alleged histamine intolerance are similar to those of histamine intoxication, but they can also include chronic conditions such as urticaria (hives), asthma, rhinitis, or migraine. [15] Some scholars [15] believe that the diagnosis of histamine intolerance is challenging and requires the exclusion of other causes of histamine-related symptoms, as well as a positive response to a low-histamine diet, and the treatment of histamine, involves avoiding histamine-rich foods. [15] Still, there are currently no measurable indicators that can confirm the occurrence of adverse reactions due to the ingestion of histamine. [1]
The exact causes of histamine intolerance are not fully understood, but they can be multifactorial. One of the factors believed to cause histamine intolerance is an imbalance between uptake of histamine through the diet and a diminished capacity to metabolize ingested histamine, leading to an increased blood concentration of the amines which may potentially cause adverse effects. The primary cause of histamine intolerance is considered by several authors [6] [21] to be insufficient activity or reduced levels of the enzyme diamine oxidase (DAO), which normally metabolizes histamine in the gut; these scholars suspect the factors that may contribute to histamine include endogenous overproduction of histamine due to allergies or mastocytosis, genetic inheritance resulting in reduced DAO activity or effectiveness, pathological factors such as intestinal diseases affecting DAO production or function, pharmacological factors like medications inhibiting DAO activity, and alterations in gut microbiota leading to increased levels of bacteria secreting biogenic amines, including histamine. [6] [21] [22] It has been established that certain bacteria within the gut microbiota, notably lactobacilli, have the ability to produce substantial amounts of histamine—the recognition of histamine as a significant metabolite of these intestinal bacteria raises doubts about the reliability of diagnostic stool analysis. [1]
Some scholars [25] suspect that the pathogenesis (the process of disorder development) of histamine intolerance involves an imbalance between uptake of histamine and other amines through the diet and a diminished capacity to metabolize those amines and that this imbalance can be due to insufficient activity or levels of the enzymes diamine oxidase (DAO), and histamine N-methyltransferase (HNMT), which are responsible for breaking down histamine. [25] While deficiencies in DAO are considered by these scholars the primary cause of histamine intolerance, variations in both DAO and HNMT genes could play a role in its development. The interplay between these enzymes influences how effectively histamine is broken down and cleared from the body. [25] [8] Still, a definitive causal relationship between adverse reactions following histamine ingestion and a compromised histamine catabolism due to a deficiency in DAO or HNMT is still lacking. [1]
Several authors [5] suspect that the imbalance in histamine intolerance is between the consumption, biosynthesis and selective release of histamine from certain granulocytes (i.e., mast cells and basophils), versus the breakdown of histamine by the enzymes which metabolize it, such as DAO and HNMT. [5] These scholars suspect that in contrast to histamine intolerance, allergic reactions involving an immediate allergic response to an allergen are caused by anaphylactic degranulation, which is the abrupt and explosive release of "pre-formed mediators", including histamine and tryptase, from mast cells and basophils throughout the body. [26]
Despite the belief shared by several researchers [22] 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]
The diagnosis of histamine intolerance is challenging due to its nonspecific symptoms and lack of validated diagnostic tools. [6] [21] [22]
Histamine intolerance is not recognized as an explicit medical condition with that name in the International Classification of Diseases (ICD) Edition 11, [2] or any previous edition of the ICD.
Medical associations in Germany and Switzerland, beginning in 2017, [27] and Austria, starting in 2021, [1] have posited that the evidence supporting a causal relationship between adverse reactions to dietary histamine and a compromised histamine catabolism resulting from a deficiency in diamine oxidase (DAO) remains insufficient. These associations advise against the use of the term "histamine intolerance" and instead advocate for the more accurate descriptor, "adverse reactions to ingested histamine", to better reflect the current understanding of the condition—this clarification in terminology underscores the lack of understanding of the precise causes and mechanisms underlying these adverse reactions observed. [1]
In 2017 German guideline for the management of adverse reactions to ingested histamine, the following categories from ICD-10 are indicated adverse reactions to ingested histamine: [27]
Figuring out adverse reactions to ingested histamine typically involves a thorough analysis of patient history, taking into account clinical manifestations associated with the ingestion of high-histamine foods as well as response to dietary changes such as low-histamine diets. [6] [5] [1]
There are no specific tests that can definitively diagnose histamine intolerance—the primary approach is through a thorough evaluation of clinical symptoms and their improvement or resolution after following a low-histamine diet; an assessment should also be made 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; additionally, genetic testing for single-nucleotide polymorphisms (SNPs) in genes related to DAO function may provide supportive evidence for the diagnosis but cannot confirm it on its own; and other complementary tests have been proposed but require further validation before being widely accepted as diagnostic tools for histamine intolerance, such as measuring plasma DAO activity levels and conducting intradermal skin allergy tests with histamine. [6] [21] [22] Despite the common belief that consuming histamine can lead to nonspecific health issues, the scientific proof to back this claim is both scarce and inconsistent. 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 such a diagnosis. [1]
The concentration of histamine in various food items can exhibit significant variability, influenced by factors such as the maturity of the food, the duration of storage, and the processing techniques employed. As a result, even within a single type of food product, there can be substantial differences in histamine levels. [3] [1] For instance, the histamine content in Emmental cheese can range from less than 0.1 mg/kg to as high as 2,000 mg/kg, while in smoked mackerel, it can vary from less than 0.1 mg/kg to up to 1,788 mg/kg. This variability makes it challenging to accurately estimate the histamine content of individual meals. Observations suggest that the tolerance to histamine can differ depending on the food matrix, and provocations with orally administered histamine have not been consistently reproducible, which raises questions about the feasibility and validity of a quantitative classification of foods based on their histamine content. [3] [1] There is a great heterogeneity in the type of foods that are advised against for histamine intolerant individuals, and a review found that exclusion of 32% of foods could be explained by the occurrence of high contents of histamine, while there was a range of excluded foods with an absence or very low levels of biogenic amines including histamine. [3] Some dietary recommendations that have been proposed are not backed by robust scientific evidence. For example, certain foods that do not contain significant amounts of histamine (e.g., yeast) are sometimes prohibited, while others are avoided due to their potential role as "histamine liberators"—pharmacologically active substances purported to induce histamine release from human mast cells or basophils, still, there is currently no reliable evidence supporting the existence of such "histamine liberators" in foods, nor their clinical significance in adverse reactions to food or food ingredients. [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. [1] Whereas the concept of "histamine liberators" is frequently mentioned in discussions about histamine intolerance and dietary management, it is important to note that the scientific evidence supporting their existence and clinical relevance is currently limited and inconsistent. [1] [3]
While some scholars [22] believe that DAO activity determination offers additional diagnostic utility for histamine intolerance, supplementing clinical evaluation and assessment, they caution that sole reliance on DAO activity measurements may not sufficiently establish the supposed diagnosis due to the limited correlation between the result serum DAO activity measurement and the supposed condition. [31] These scholars believe that reduction of symptoms typical for histamine intolerance—such as symptoms of irritable bowel syndrome (IBS) [12] [13] —after adherence to a histamine-reduced diet supports the diagnosis of histamine intolerance. [12] They also suppose that to diagnose histamine intolerance, an analysis of meticulous and systematic medical history is needed that focuses on symptoms specifically related to histamine and their association with food intake. [12] Using a questionnaire that encompasses symptoms associated with the four histamine receptors can be an effective tool for this purpose. [12] This questionnaire should include categories such as gastrointestinal, cardiovascular, respiratory, and skin symptoms. [12]
As of 2025, [update] despite extensive research, there are no definitive, objective measures or indicators that can conclusively validate the occurrence of adverse reactions due to the consumption of histamine that will allow to classify histamine intolerance as an identifiable medical condition. [1]
Currently, a low-histamine diet is recommended by some scholars [6] [21] [22] as the primary approach for managing symptoms of histamine intolerance. 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] [21] [22] Several medications, including acetylcysteine, metamizole, verapamil, metronidazole, and metoclopramide, have been reported to negatively affect enzymes that break down histamine, particularly DAO, still, the data from these studies is inconsistent according to later literature reviews, therefore, the significance of specific drugs in relation to DAO's ability to break down histamine was not confirmed by reliable studies. [1] Additional options in histamine intolerance include antihistamines, mast cell stabilizers, and supplementation with exogenous diamine oxidase (DAO supplementation in the form of capsules or tablets), however, there is no solid research to validate the effectiveness of these additional treatment options in histamine intolerance. [6] [21] [22]
Two investigations, financially backed by the manufacturer of the oral DAO supplementation, have posited that DAO supplementation could alleviate patient symptoms. [1] The first study sought to "objectify and quantify histamine-associated symptoms and to analyze whether oral administration of the histamine-degrading enzyme DAO caused a reduction of symptoms". [1] In this study, neither major nor minor symptoms could be replicated in 39 individuals who initially responded to an open challenge with 75 mg histamine in peppermint tea, using a double-blind, placebo-controlled challenge. [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. The second study was purely observational, lacking a control group: it compared symptomatology with and without DAO use in 28 individuals. [1] The chosen design was not suitable to demonstrate causal effects and carried a high risk of attributing placebo effects. [1] The effectiveness of DAO supplementation has not been scientifically validated and is not recommended by the medical associations in Germany, Austria and Switzerland. [1]
The exact prevalence of histamine intolerance is unknown due to limited data and a lack of validated diagnostic methods. The diagnosis typically involves a thorough patient history, taking into account clinical manifestations associated with the ingestion of high-histamine foods as well as response to dietary changes such as low-histamine diets. There is some prediction that the incidence of histamine intolerance in the general population is estimated to be about 1%, with 80% of them being middle-aged. 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. Because histamine intolerance symptoms can mimic those seen in other conditions such as food allergies or intolerance to sulfites and biogenic amines such as tyramine, there is often confusion in differentiating the causal agent responsible for adverse reactions. [5] Other biogenic amines, such as histidine, can cause symptoms that are similar to that of histamine intolerance, or aggravate the symptoms of histamine intolerance. [12] This further complicates accurate diagnosis and estimation of disease burden. [5] Diamine oxidase (DAO) can metabolize not only histamine, but also some other biogenic amines such as putrescine and cadaverine, but not tyramine. [9] Histamine N-methyltransferase (HNMT) has a strong preference for histamine, therefore, it cannot metabolize other biogenic amines. [9] 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. [5]
During episodes of migraines, there is a marked increase in the plasma concentrations of calcitonin gene-related peptide (CGRP) and histamine. These two substances are known for their strong vasodilatory properties and have been observed to mutually stimulate each other's release within the trigeminovascular system, which could potentially contribute to the onset of migraines, so that individuals with genetic variants in the AOC1 gene encoding the diamine oxidase (DAO) enzyme, which lead to a deficiency in histamine degradation, often experience migraines when consuming a diet high in histamine, which suggests that ingested histamine could potentially aggravate migraines, highlighting the importance of ongoing research into the potential adverse reactions to dietary 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. [32]
The term "histamine intolerance" gained visibility through personal experiences shared by public figures. For example, in a 2023 publication in Miami Herald, former Olympic gymnast McKayla Maroney publicly shared her struggle with what she called "histamine intolerance". [33]
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases.
Lactose intolerance is caused by a lessened ability or a complete inability to digest lactose, a sugar found in dairy products. Humans vary in the amount of lactose they can tolerate before symptoms develop. Symptoms may include abdominal pain, bloating, diarrhea, flatulence, and nausea. These symptoms typically start thirty minutes to two hours after eating or drinking something containing lactose, with the severity typically depending on the amount consumed. Lactose intolerance does not cause damage to the gastrointestinal tract.
A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Friedrich von Recklinghausen and later rediscovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumors.
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. They are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, and heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from the blood into their resident tissues, but they are now known to be different types of cells.
Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 1910, histamine has been considered a local hormone (autocoid) because it's produced without involvement of the classic endocrine glands; however, in recent years, histamine has been recognized as a central neurotransmitter. Histamine is involved in the inflammatory response and has a central role as a mediator of itching. As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues. It consists of an imidazole ring attached to an ethylamine chain; under physiological conditions, the amino group of the side-chain is protonated.
Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.
Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).
Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism caused by a deficiency of the enzyme aldolase B. Individuals affected with HFI are asymptomatic until they ingest fructose, sucrose, or sorbitol. If fructose is ingested, the enzymatic block at aldolase B causes an accumulation of fructose-1-phosphate which, over time, results in the death of liver cells. This accumulation has downstream effects on gluconeogenesis and regeneration of adenosine triphosphate (ATP). Symptoms of HFI include vomiting, convulsions, irritability, poor feeding as a baby, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and potentially kidney failure. There are reported deaths in infants and children as a result of the metabolic consequences of HFI. Death in HFI is always associated with problems in diagnosis.
Food intolerance is a detrimental reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but generally refers to reactions other than food allergy. Food hypersensitivity is used to refer broadly to both food intolerances and food allergies.
Salicylate sensitivity is any adverse effect that occurs when a usual amount of salicylate is ingested. People with salicylate intolerance are unable to consume a normal amount of salicylate without adverse effects.
Sucrose intolerance or genetic sucrase-isomaltase deficiency (GSID) is the condition in which sucrase-isomaltase, an enzyme needed for proper metabolism of sucrose (sugar) and starch, is not produced or the enzyme produced is either partially functional or non-functional in the small intestine. All GSID patients lack fully functional sucrase, while the isomaltase activity can vary from minimal functionality to almost normal activity. The presence of residual isomaltase activity may explain why some GSID patients are better able to tolerate starch in their diet than others with GSID.
Red wine headache ("RWH") describes a headache, often accompanied by nausea and flushing, that occurs after consuming red wine by susceptible individuals. White wine headaches have been less commonly reported.
Diamine oxidase (DAO), also known "amine oxidase, copper-containing, 1" (AOC1), formerly called histaminase, is an enzyme involved in the metabolism, oxidation, and inactivation of histamine and other polyamines such as putrescine or spermidine. The enzyme belongs to the amine oxidase (copper-containing) (AOC) family of amine oxidase enzymes.
Histamine N-methyltransferase (HNMT) is a protein encoded by the HNMT gene in humans. It belongs to the methyltransferases superfamily of enzymes and plays a role in the inactivation of histamine, a biomolecule that is involved in various physiological processes. Methyltransferases are present in every life form including archaeans, with 230 families of methyltransferases found across species.
An elimination diet, also known as exclusion diet, is a diagnostic procedure used to identify foods that an individual cannot consume without adverse effects. Adverse effects may be due to food allergy, food intolerance, other physiological mechanisms, or a combination of these. Elimination diets typically involve entirely removing a suspected food from the diet for a period of time from two weeks to two months, and waiting to determine whether symptoms resolve during that time period. In rare cases, a health professional may wish to use an elimination diet, also referred to as an oligoantigenic diet, to relieve a patient of symptoms they are experiencing.
Food protein-induced enterocolitis syndrome (FPIES) is a systemic, non-immunoglobulin E (IgE)-mediated food allergy to a specific trigger within food, most likely food protein. As opposed to the more common IgE food allergy, which presents within seconds with rash, hives, difficulty breathing or anaphylaxis, FPIES presents with a delayed reaction where vomiting is the primary symptom. In its acute form, FPIES presents with vomiting that typically begins 1 to 4 hours after the trigger of food ingestion, alongside paleness of the skin, lethargy, and potentially blood-tinged diarrhea. In the severe form of acute FPIES, continued vomiting may cause severe dehydration or hypotensive shock-like state, requiring hospitalization. In its chronic form, continued exposure to trigger foods results in chronic or episodic vomiting, poor weight gain, failure to thrive, and watery or blood-tinged diarrhea. FPIES can potentially develop at any age, from infancy to adulthood, but most commonly develops within the first few years of life and resolves in early childhood. Atypical FPIES presents with evidence of specific IgE-sensitization via positive specific serum or skin IgE testing to trigger foods. Atypical FPIES may prolong time to disease resolution or increase risk of conversion to IgE-mediated food allergy.
Alcohol intolerance is due to a genetic polymorphism of the aldehyde dehydrogenase enzyme, which is responsible for the metabolism of acetaldehyde. This polymorphism is most often reported in patients of East Asian descent. Alcohol intolerance may also be an associated side effect of certain drugs such as disulfiram, metronidazole, or nilutamide. Skin flushing and nasal congestion are the most common symptoms of intolerance after alcohol ingestion. It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome. Severe pain after drinking alcohol may indicate a more serious underlying condition.
Histamine is an organic compound that primarily functions in service of the human body's immune responses as well as for the regulation of many physiological functions. Since their discovery in 1910, histamines have been known to trigger inflammatory responses such as itching as part of an immune response to foreign pathogens; for example, mosquito bites or allergens. It is released in granular form by mast cells, a type of white blood cell in connective tissues close to the site of interaction. Upon releasing, it increases the permeability of the blood capillaries for white blood cells and other proteins to enter in order to eliminate the foreign pathogens. The highest concentrations in mammalian tissue occur in the skin, intestines and lungs, sites where most symptoms of allergic responses are felt.
This release of pre-formed mediators enables not only rapid anaphylactic reactions and allergic responses but also initiates recruitment of leukocytes to sites of pathogen invasion, activation of innate immune processes, and inflammatory responses (1). ... Two types of degranulation have been described for MC: piecemeal degranulation (PMD) and anaphylactic degranulation (AND) (Figures 1 and 2). Both PMD and AND occur in vivo, ex vivo, and in vitro in MC in human (78–82), mouse (83), and rat (84). PMD is selective release of portions of the granule contents, without granule-to-granule and/or granule-to-plasma membrane fusions. ... In contrast to PMD, AND is the explosive release of granule contents or entire granules to the outside of cells after granule-to-granule and/or granule-to-plasma membrane fusions (Figures 1 and 2).