What is histamine intolerance and what are its causes


Digestive problems such as dyspepsia or diarrhea can indicate intolerance to histamine, caused by an excess of this substance in the body. We explain how to identify and prevent this disorder.

Histamine is a fundamental substance for life found in multiple organs and tissues of the body naturally. It is necessary for the proper functioning of the body, and for this, it must be manufactured and released at the correct times and in the right amount. Likewise, it must be degraded if it is excessive or when its action is no longer needed. The histamine present in ingested food must also be degraded so that it does not pass in excessive amounts into the body after its ingestion.

Histamine intolerance is when food is usually well-tolerated in healthy person symptoms caused by the histamine content that does not decompose properly. It is estimated to affect 1% of people, especially middle age. However, the figure is probably much higher in reality.

Among its consequences is mainly digestive disorders (cramps, diarrhea, swelling ), but respiratory, neurological symptoms, or skin reactions may also appear. And among its causes, as the main one, a deficit in the intestine of an enzyme known as DAO is identified, although it is usually associated with digestive problems such as undiagnosed celiac disease, SIBO, or alterations in the microbiota such as dysbiosis.

The histamine release can occur, for example, in response to an allergen. Other non-immune stimuli also cause the release and manufacture of histamines, such as certain substances produced by the immune system’s cells, lack of oxygen, extreme temperatures, trauma, alcohol, some foods, and certain medications. The activation of mast cells, the cells most associated with histamine, is related to allergic and autoimmune diseases.

What is histamine, and what functions does it perform in the body

Histamine is a biogenic amine: this means that it is a low molecular weight nitrogen molecule that is produced by living organisms. It was synthesized in a laboratory in 1907, and in 1910 it was discovered to exist naturally in the fungus known as ergot.

Later, in 1927, it was possible to isolate human and animal tissues. It was called ‘histamine’ because it is an ‘amine’ (a molecule with nitrogen) found in tissues (‘ history in Greek). Although this molecule has been known for so many years, its role in human and animal physiology is continually being investigated, and discoveries are constantly being made.

Histamine is manufactured in stomach enterochromaffin cells, histaminergic neurons, mast cells, and basophils in humans. Other cells can also make histamines, such as platelets, monocytes and macrophages, dendritic cells (a type of modified macrophage present in multiple tissues and organs), neutrophils, and lymphocytes.

Histamine has multiple functions in the body because there are different types of receptors in different organs:

  • It produces contraction of smooth muscle such as that of the bronchi and the intestine.
  • It dilates the blood vessels and increases their permeability. It causes tachycardia and influences blood pressure. It can reduce blood flow to the intestine.
  • It increases mucous secretion in general and stimulates gastric secretion.
  • It irritates the nerve fibers that conduct painful stimuli. Also, it acts as a neurotransmitter and participates in the modulation of the circadian rhythm.
  • It has an immunomodulatory effect due to multiple mechanisms of action.
  • It also participates in the regulation of hematopoiesis (manufacture of blood cells).

Causes of histamine intolerance

The inactivation of histamine is carried out mainly with DAO or diamine oxidase, so a deficiency of this enzyme in the intestine is the main cause of histamine intolerance. For proper operation, the DAO requires sufficient presence of vitamin B6, copper, and vitamin C. This enzyme is in multiple tissues, but especially in the small intestine, the ascending colon, the placenta (in pregnant women), and the kidneys. DAO is released from the vesicles, which are stored outside the cells to carry out its function.

The deficit DAO rarely has a genetic cause but is usually a secondary situation intestinal disorders as inflammatory bowel disease, dysbiosis, the SIBO, parasitic diseases, celiac disease, or taking drugs that inhibit the action of the DAO. Also, the deficiency, often subclinical, of vitamin C or B6, or copper, can cause the malfunction of DAO. Even stress – be it physical or psychological – can influence histamine concentration in the blood by multiple mechanisms and not only at the intestinal level.

There is another enzyme called HNMT or histamine-N-methyltransferase, which works only inside cells. Although it is also present in the intestine, the most important barrier to histamine passage that comes from food is DAO. Under normal conditions, DAO is continuously synthesized and secreted into the intestine lumen to break down the histamine present in food.

There are multiple situations in which dietary histamine can be a problem, even in a healthy person. If a food contains too much histamine, there may not be enough DAO to break it down. This situation is called ‘ histamine poisoning ‘ and has also been called scombroidosis, fish pseudo-allergy, or histamine overdose.

Some fish have many histidines (an amino acid ), and bacteria in their normal flora transform it into histamine. In the European Union, an acceptable upper limit of histamine content in fishery products has been established to avoid this situation.