What causes histamine intolerance?

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From the Guidelines

Histamine intolerance is primarily caused by an imbalance between accumulated histamine and the capacity to break it down in the body, often due to reduced activity of the enzyme diamine oxidase (DAO). This condition can be triggered by various factors, including:

  • Genetic predisposition
  • Gastrointestinal disorders like inflammatory bowel disease or leaky gut syndrome
  • Certain medications, such as antibiotics, antidepressants, and some pain relievers
  • Alcohol consumption
  • Consuming histamine-rich foods, which can include foods with high levels of vasoactive amines, as mentioned in the study by Bailey and Stover 1
  • Nutritional deficiencies in copper, vitamin B6, vitamin C, and zinc, which can impair DAO function
  • Bacterial overgrowth in the small intestine, which may increase histamine production Some medical conditions, like mastocytosis, where mast cells accumulate abnormally and release histamine, can also lead to histamine intolerance symptoms. According to the study by Bailey and Stover 1, nonimmune, host-independent food intolerances involve chemicals with pharmacological activity in food, including vasoactive amines like histamine, which can affect sensitized individuals. Managing histamine intolerance typically involves dietary changes to reduce histamine intake, addressing underlying gut health issues, and sometimes supplementing with DAO enzymes before meals containing histamine.

From the Research

Causes of Histamine Intolerance

  • Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation 2
  • A deficiency of the gastrointestinal enzyme diamine oxidase (DAO) is assumed to be a primary cause of histamine intolerance, leading to impaired degradation of ingested histamine 3
  • Low DAO activity can be caused by various factors, including certain medications and gastrointestinal disorders 3

Role of DAO in Histamine Intolerance

  • DAO is the main enzyme responsible for the metabolism of ingested histamine 2, 3
  • Reduced DAO activity can lead to an accumulation of histamine in the body, causing various symptoms 2, 4
  • Supplementation with oral DAO capsules has been shown to improve symptoms in patients with histamine intolerance 4, 5

Symptoms and Diagnosis of Histamine Intolerance

  • Histamine intolerance can cause a range of symptoms, including gastrointestinal and non-gastrointestinal complaints 2, 3, 6
  • Diagnosis of histamine intolerance is challenging and often relies on a thorough medical history and a standardized questionnaire 3
  • A low-histamine diet and DAO supplementation are commonly used to diagnose and treat histamine intolerance 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Histamine and histamine intolerance.

The American journal of clinical nutrition, 2007

Research

Serum diamine oxidase activity in patients with histamine intolerance.

International journal of immunopathology and pharmacology, 2016

Research

[Histamine intolerance].

Vnitrni lekarstvi, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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