Food Intolerance: The Role of Histamine

Abstract

Histamine is a natural amine derived from L-histidine. Although it seems that our knowledge about this molecule is wide and diverse, the importance of histamine in many regulatory processes is still enigmatic. The interplay between different types of histamine receptors and the compound may cause ample effects, including histamine intoxication and so-called histamine intolerance or non-allergic food intolerance, leading to disturbances in immune regulation, manifestation of gastroenterological symptoms, and neurological diseases. Most cases of clinical manifestations of histamine intolerance are non-specific due to tissue-specific distribution of different histamine receptors and the lack of reproducible and reliable diagnostic markers. The diagnosis of histamine intolerance is fraught with difficulties, in addition to challenges related to the selection of a proper treatment strategy, the regular course of recovery, and reduced amelioration of chronic symptoms due to inappropriate treatment prescription. Here, we reviewed a history of histamine uptake starting from the current knowledge about its degradation and the prevalence of histamine precursors in daily food, and continuing with the receptor interactions after entering and the impacts on the immune, central nervous, and gastrointestinal systems. The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.

Keywords: food intolerance; health; histamine; irritable bowel syndrome; metabolite.

Figure 1

Biogenic amine histamine metabolism. In the human body, histamine is metabolized in two ways: (1) extracellular oxidative deamination of the primary amino group by the enzyme diamine oxidase (DAO) and (2) intracellular methylation of the imidazole ring by the enzyme histamine N-methyltransferase. Inhibition of enzymes is carried out by reaction products of the type of negative feedback and xenobiotics (drugs). Oxidative deamination of histamine DAO leads to the formation of imidazole acetaldehyde, then via aldehyddehydrogenase, imidazole-4-acetic acid is formed. The latter product, after the attachment of the ribose molecule, forms another form for excretion. The product of histamine methylation, catalyzed by histamine-N-methyltransferase, is tele-methylhistamine, which is subsequently converted by monoamine oxidase to tele-methylimidazole acetaldehyde. The latter is then converted to tele-methylimidazoleacetic acid with the participation of aldehyde dehydrogenase.

Figure 2

The biological effects of histamine receptors. Histamine of exogenous or endogenous origin is involved in the regulation of a wide range of metabolic transformations by binding to four types of receptors, designated as H1–H4 subtypes. Receptors of the H1 subtype are localized in the GI tract and endoteium and are involved in allergic inflammation and vasodilation, while receptors of the H2 subtype are highly expressed in various cells and tissues, such as B cells, T cells, dendritic cells, and gastric parietal cells. H2 receptors are involved in gastric acid secretion, relaxation of smooth muscle cells, and immune cell differentiation. The H3 receptors are expressed in neurons and play an important role in neurotransmission (neuronal function cognition, regulation of neuronal histamine turnover). The histamine H4R is expressed in a variety of immune cells and is involved in immunomodulation, including immune cell chemotaxis, immune response, and inflammation. The last two subtypes are characterized by high affinity for histamine.