Histamine and histamine intolerance

Am J Clin Nutr. 2007 May;85(5):1185-96. doi: 10.1093/ajcn/85.5.1185.


Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. 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. 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 diarrhea, 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. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amine Oxidase (Copper-Containing) / deficiency*
  • Amine Oxidase (Copper-Containing) / metabolism
  • Food Hypersensitivity* / diet therapy
  • Food Hypersensitivity* / drug therapy
  • Food Hypersensitivity* / etiology
  • Histamine / administration & dosage
  • Histamine / adverse effects
  • Histamine / immunology
  • Histamine / metabolism*
  • Histamine Agents / administration & dosage
  • Histamine Agents / adverse effects
  • Histamine Agents / immunology
  • Histamine Agents / metabolism*
  • Histamine H1 Antagonists / therapeutic use
  • Histamine N-Methyltransferase / deficiency
  • Histamine N-Methyltransferase / metabolism
  • Humans
  • Hypersensitivity, Delayed
  • Hypersensitivity, Immediate


  • Histamine Agents
  • Histamine H1 Antagonists
  • Histamine
  • Amine Oxidase (Copper-Containing)
  • Histamine N-Methyltransferase