Summary:
Food intolerance affects about 15-20% of people and differs from food allergies as it does not involve immune mechanisms. Causes include enzyme deficiencies, chemical reactions, and non-specific gut responses such as those seen in irritable bowel syndrome. Diagnosis is challenging because symptoms overlap with other gastrointestinal disorders and diagnostic criteria vary. Histamine intolerance (HIT) is of growing interest and occurs when the body’s ability to break down dietary histamine is reduced. Diamine oxidase (DAO), an enzyme in the small intestine, is responsible for most histamine degradation. Reduced DAO activity allows histamine to enter circulation, leading to symptoms such as bloating, diarrhea, headaches, skin rashes, and nasal congestion. DAO deficiency may be genetic, or secondary to intestinal damage and microbiome imbalances that increase histamine-producing bacteria. HIT frequently coexists with other food intolerances, such as lactose or fructose malabsorption. DAO activity can also be impaired by alcohol, certain drugs, and other biogenic amines. DAO activity is also influenced by hormonal changes, with evidence suggesting variation across the menstrual cycle and possible estrogen-related effects. While most cases are seen in adults, DAO deficiency is also reported in children. Management is primarily dietary, focusing on limiting histamine-rich foods and, in some cases, foods believed to trigger histamine release. However, food histamine levels vary and evidence for excluding some foods is inconsistent, making dietary guidance difficult. DAO enzyme supplements have been investigated and may improve tolerance to histamine-containing foods, though results vary depending on the enzyme source and cofactors. Currently, there is no validated biomarker for diagnosis, which is usually based on symptoms and dietary response. Treatment relies mainly on a low-histamine diet, sometimes supported by DAO supplementation, although evidence for long-term effectiveness remains limited.
Abstract:
Self-reported food intolerances are estimated to affect between 15–20% of the population. Among them, histamine intolerance (HIT) has emerged as a focus of particular interest. It is defined as a disequilibrium between dietary histamine and the capacity of the organism to degrade intestinal histamine, leading to the appearance of intestinal and extra-intestinal symptoms. HIT is thought to be associated with low activity or blockade of diamine oxidase (DAO), the main enzyme for histamine degradation. The diagnosis is hampered by the lack of a validated biomarker and is mainly based on clinical assessment and response to a low histamine diet and reintroduction. The therapeutic approach is centered on dietary management, restricting foods that may increase circulating histamine levels. DAO supplementation has been shown to potentially contribute to histamine degradation in the intestinal lumen, but its activity varies depending on the presence of cofactors and the enzyme’s origin. Limited clinical evidence reflects the difficulty of dietary management and suggests a beneficial role of DAO supplementation on the clinical manifestations associated with HIT.
Article Publication Date: 20/09/2025
DOI: 10.3390/ijms26189198
