Histamine Intolerance: Signs, Symptoms, Solutions

Histamine participates in immune reactions and other metabolic functions but can become toxic if not broken down effectively.

Histamine is a biogenic amine that participates in several metabolic functions:

• Inflammation
• Neurotransmitter functions
• Smooth muscle contraction
• Stimulation of cytokine production
• Stimulation of gastric acid secretion
• Vasodilation

Histamine must be enzymatically degraded by histamine-N-methyltransferase (HNMT) found in a wide range of tissues throughout the body, or diamine oxidase (DAO), found primarily in the small intestine, ascending colon, placenta, and kidney. Histamine can also be metabolized by aldehyde dehydrogenase (ALDH), an enzyme that also breaks down alcohol and its metabolite acetaldehyde. Therefore, alcohol intake may trigger histamine excess in some individuals.

Histamine is produced and stored in basophils and mast cells. It is also present in various amounts in several foods and has significant toxicity potential and food safety implications.

Histamine intolerance results from an inability to break down ingested histamine. It is also known as enteral histaminosis or sensitivity to dietary histamine. This condition may be caused by a deficiency of intestinal DAO, the enzyme that breaks down ingested histamine.

Histamine intoxication is considered a type of food poisoning caused by very high concentrations of food histamine, e.g., more than 500 mg/kg, that overwhelm degradation mechanisms, even in those without DAO insufficiency. Histamine intoxication is most often associated with the consumption of spoiled fish, especially those in the Scombridae and Scomberesocidae families, e.g., tuna, herring, and mackerel). However, it may be caused by other fish species and possibly from consuming cheese.

Excess histamine can cause

• Nausea
• Vomiting
• Diarrhea
• Edema
• Headache
• Hypotension
• Local inflammation
• Palpitations
• Pruritus
• Rash
• Skin redness
• Tingling
• Urticaria

Gastrointestinal symptoms are the most frequent and severe symptoms of HIT and include postprandial fullness, diarrhea, abdominal pain, and constipation. The second most frequent symptoms are nervous system impairments, including dizziness, headache, and palpitations, followed by respiratory and dermatological symptoms. Symptoms often involve at least three organ systems and average 11 symptoms per patient.

Primary symptoms of histamine intolerance and possibly corresponding histamine receptors

Summary of the described approaches to the diagnosis of histamine intolerance

Foods that potentially contain high levels of histamine

• Microbiologically altered, such as fish and meat
• Derived products that may have been preserved or processed in unsuitably hygienic conditions
• Fermented products, in which the bacteria responsible for the fermentation process
  
  

Histamine content in different food categories

n – number of foods   ND: Not detected

Foods Excluded by Low-Histamine Diets

>60% of low-histamine diets exclude:

• Cured and semi-cured cheese
• Grated cheese
• Oily fish
• Canned and semi-preserved oily fish derivatives
• Dry-fermented meat products
• Spinach
• Tomatoes
• Fermented cabbage
• Citrus
• Strawberries
• Wine
• Beer

20–60% of low-histamine diets exclude:

• Shellfish
• Eggs
• Fermented soy derivatives
• Eggplant
• Avocado
• Banana Kiwi
• Pineapple
• Plum
• Nuts
• Chocolate

<20% of low-histamine diets exclude:

• Milk
• Lentils
• Chickpeas
• Soybeans
• Mushrooms

Histamine-producing bacteria

Several Gram-positive and Gram-negative bacteria responsible for microbial spoilage or fermentative processes in food are able to produce histamine

Enterobacteriaceae species (mainly in fish)

• Hafnai aluei
• Morganella morganii
• Klebsiella pneumonia

Lactobacillaceae species (mainly in cheese, fermented meat, fermented beverages, and vegetable derivatives

• Lactobacillus hilgardii
• Lactobacillus buchnerii
• Lactobacillus curvatus
• Oenococcus oeni

Optimal Takeaways

• Histamine intolerance and excess histamine can cause unpleasant gastrointestinal, skin, nervous system, circulatory, and respiratory symptoms.
• DAO insufficiency should be considered.
• Factors that reduce DAO should be investigated, including genetic factors, intestinal inflammation, and certain medications, including chloroquine, clavulanic acid, verapamil, and histamine receptor antagonists.
• A low-histamine diet and supplemental DAO can help control histamine intolerance.
• Fermented foods may be exceptionally high in histamine, including raw milk cheese, cured cheese, oily fish, canned fish, sausage, and other fermented foods.
• Alcohol may interfere with histamine breakdown and trigger symptoms.
• Polymorphisms in the genes encoding the enzymes L-histidine decarboxylase, DAO, HNMT, and the different histamine receptors may contribute to histamine intolerance.

Reference

Comas-Basté, Oriol et al. “Histamine Intolerance: The Current State of the Art.” Biomolecules vol. 10,8 1181. 14 Aug. 2020, doi:10.3390/biom10081181 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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