Are You Allergic to Histamine?

Runny Nose - Sneezing - Asthma?

Histamine Intolerance (HIT) is caused by the inability of the body to breakdown histamine efficiently. Inefficient levels, or reduced activity of the enzyme diamine oxidase (DAO) enables histamine to increase in the body.

This causes the symptoms of histamine intolerance; Runny Nose, Sneezing, Asthma, Diarrhoea, Abdominal Cramps, Dysmenorrhoea, Fatigue, Flushing of Face, Chest, Headaches, Hypotension, Itchiness, Urticaria.

Until recently, the conventional method for diagnosing HIT was to adopt a low-histamine diet for several weeks and then observe if symptoms improved. However, following a low histamine diet can be very restrictive, especially as it requires individuals to avoid healthy foods. 

Being able to test for histamine intolerance can provide assurance to patients that they are restricting their diet for good reason, while enabling them to find a beneficial treatment approach, such as desensitisation or immune therapy.

Testing should not be done while a patient is following a low histamine diet, taking anti-histamine medication (which should be stopped for 1 week pre test) , fasting, or pregnant as DAO levels increase during pregnancy




Histamine, found within granules of basophils and mast cells (>90% of body stores) is a biogenic amine and an organic nitrogen compound that occurs to various degrees in many foods such as cherries to about 0.17-13.46 ng/g, bananas and grapes, rice and cereals, herbs, olive oil, wine, beer, etc.. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity(a). the hormone, as a neurotransmitter is involved in regulating physiological function in the gut and immune response to foreign pathogens.

1. Histamine regulation in glucose and lipid metabolism via histamine receptors

In the study to to evaluate histamine regulation of glucose and lipid metabolism and development of nonalcoholic steatohepatitis (NASH) with a hyperlipidemic diet, showed that severe NASH with hypoadiponectinemia as well as hepatic triglyceride and free cholesterol accumulation and increased blood hepatic enzymes were observed in H2R(-/-) mice. H1R(-/-) mice showed an obese phenotype with visceral adiposity, hyperleptinemia, and less severe hepatic steatosis and inflammation with increased hepatic triglyceride. These data suggest that H1R and H2R signalling may regulate glucose(1).

2. Histamine intolerance

According to the study of University of Bonn, Bonn, diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhoea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines(2).

3. The role of histamine in allergic inflammation

Antihistamines are inflammatory responses resulting from the liberation of histamine have long been thought to be mediated by the histamine H1 receptor, and H1-receptor antagonists, researchers at the Johnson & Johnson Pharmaceutical Research & Development, L.L.C. San Diego, suggested that histamine indeed has roles in inflammation and immune function modulation in such diseases. In particular, the discovery of a fourth histamine receptor (H4) and its expression on numerous immune and inflammatory cells has prompted a re-evaluation of the actions of histamine, suggesting a new potential for H4-receptor antagonists and a possible synergy between H1 and H4- receptor antagonists in targeting various inflammatory conditions(3).

6. Histamine and sleep-wake regulation

The histamine H(3) receptors are autoreceptors damping histamine synthesis, the firing frequency of histamine neurons, and the release of histamine from axonal varicosities. It is noteworthy that this action also extends to heteroreceptors on the axons of most other neurotransmitter systems, allowing a powerful control over multiple homeostatic functions. The particular properties and locations of histamine H(3) receptors provide quite favorable attributes to make this a most promising target for pharmacological interventions of sleep and waking disorders associated with narcolepsy, Parkinson's disease, and other neuropsychiatric indications, according to the study of Integrative Physiology of Brain Arousal Systems, Claude Bernard University(6).

8. Histamine and men sexual arousal

In the study to evaluate the course of histamine plasma levels through different stages of sexual arousal in the systemic and cavernous blood of healthy male subjects of 34 healthy men, researchers at the Department of Urology & Urological Oncology, Hannover Medical School, showed that histamine slightly decreased in the cavernous blood when the penis became tumescent. During rigidity, histamine decreased further but remained unaltered in the phase of detumescence and after ejaculation. In the systemic circulation, no alterations were observed with the initiation or termination of penile erection, whereas a significant drop was registered following ejaculation. Results are not in favour of the hypothesis of an excitatory role of histamine in the control of penile erection. Nevertheless, the amine might mediate biological events during the post-ejaculatory period(8).

11. Histamine and eating behavior

Interest in the histaminergic system as a potential target for the treatment of feeding disorders is driven by the unsatisfactory history of the pharmacotherapy of obesity, researchers at the found that the appetitive phase requires a high and yet optimal arousal state, and the histaminergic system is crucial for sustaining a high degree of arousal during motivated behavior. Histamine H(1) receptors in the brain are crucial for the regulation of the diurnal rhythm of food intake and the regulation of obesity; however, from a therapeutic standpoint, no brain-penetrating H(1) receptor agonists have been identified that would have antiobesity effects. Despite conflicting preclinical data, insights are emerging into the potential role of histamine H(3) receptors as a target of antiobesity therapeutics(11)

27. The role of histamine in immune and inflammatory disorders

In the study the efficacy of a number of H4 receptor ligands has been evaluated in in vivo and in vitro animal models of disease and in human biological samples, showed that the available data strongly point to the H4 receptor as a novel target for the pharmacological modulation of histamine-transferred immune signals and offer an optimistic perspective for the therapeutic exploitation of this promising new drug target in inflammatory disorders(27).

28. The role of histamine in allergic inflammation

In the study to the effect of histamine in allergic inflammatory conditions, showed that histamine indeed has roles in inflammation and immune function modulation in such diseases. In particular, the discovery of a fourth histamine receptor (H4) and its expression on numerous immune and inflammatory cells has prompted a re-evaluation of the actions of histamine, suggesting a new potential for H4-receptor antagonists and a possible synergy between H1 and H4-receptor antagonists in targeting various inflammatory conditions(28).