Mast Cells & Supporting Healthy Immune Function | Exogenous & Endogenous Histamine

Mast Cells & Supporting Healthy Immune Function | Exogenous & Endogenous Histamine: Overview

In this article, we discuss mast cells as primary sources of endogenous histamine, focusing on mast cell degranulation, histamine release, and seasonal allergies. Furthermore, we note differences between IgE-mediated and non-IgE-mediated mast cell activation. We briefly shift the conversation to exogenous histamine exposure as well as how exogenous dietary histamine is broken down within the gastrointestinal tract during digestion. We highlight the role of the enzyme diamine oxidase while further detailing symptoms of histamine intolerance characterized by insufficient diamine oxidase production or activity. We finish the conversation by going through mast cell support in the context of seasonal allergies, detailing an exceptional tool that can aid in supporting both immune function and the breakdown of exogenous dietary histamine during digestion.

Mast Cells

Mast cells are tissue-resident immune cells derived from CD34⁺ hematopoietic stem cells in the bone marrow. In more detail, immature progenitors— biologically intermediate cells between stem cells and fully differentiated cells— migrate into peripheral tissues, where mast cell maturation is shaped by the local microenvironment. These mature mast cells are strategically positioned at barrier interfaces such as the skin, respiratory tract, and gastrointestinal mucosa—with prominence in the intestinal lamina propria—where they function as sentinels of immune surveillance. Additionally, mast cells are densely packed with what are termed cytoplasmic secretory granules; these are membrane-bound vesicles that contain preformed mediators such as histamine, tryptase, and more.

In expanding briefly upon intestinal barrier anatomy, the intestinal wall is composed of several layers, beginning with the mucosa. The mucosa consists of three key sublayers: the epithelium, the lamina propria, and the muscularis mucosae. In more detail, the intestinal epithelium is composed of a monolayer of epithelial cells including enterocytes, the main absorptive cells. Beneath the intestinal epithelium lies the lamina propria, a connective tissue-rich compartment densely populated with immune cells including T cells, dendritic cells, macrophages, plasma cells, mast cells, and more. These tissue-resident mast cells can aid in detecting and responding to environmental insults—such as from dietary antigens, microbial components, and endogenous danger signals. Their positioning at this mucosal interface aids in supporting rapid immunological responses, which may include degranulation, cytokine and chemokine release, and the synthesis of lipid-derived inflammatory mediators.

Mast cell residence is not limited to the intestinal mucosa; as noted previously, mast cells are distributed throughout the body, strategically positioned at barrier interfaces including the skin, respiratory tract, and more. Moreover, mast cells may be activated through IgE-mediated and non-IgE-mediated mechanisms. In IgE-mediated activation—such as that which occurs with seasonal allergies, for example—mast cells are coated with a type of antibody called Immunoglobulin E (IgE), which can bind to specific receptors (The FcεRI receptor) on the surface of the mast cell. When the matching allergen, such as pollen, enters the body, it may trigger mast cells to release inflammatory chemicals, which will be detailed further below. Symptoms of seasonal allergies, such as those which may be experienced when exposed to pollen, may include sneezing, nasal congestion, runny nose, itchy or watery eyes, and more.

Mast cell degranulation refers to the process by which these cells release the contents of their cytoplasmic granules into the extracellular environment following activation. These granules contain preformed bioactive mediators such as histamine and tryptase. In more detail, histamine is a compound classified as a biogenic amine, and biogenic amines are nitrogen-containing organic molecules typically generated through the enzymatic decarboxylation of amino acids—a biochemical reaction in which a carboxyl group (–COOH) is removed by a specialized enzyme. In the case of histamine, the enzyme histidine decarboxylase (HDC) catalyzes the conversion of the amino acid L-histidine into histamine. Shifting from histamine to tryptase: tryptase is a serine protease—an enzyme that cleaves peptide bonds and is characterized by a serine residue at its active site. In more detail, an active site refers to the region on an enzyme where substrate molecules bind and undergo a chemical transformation. In the case of serine proteases like tryptase, the active site contains a serine residue that participates in the cleavage of peptide bonds within target proteins. It may be noted that these preformed bioactive mediators, particularly histamine, play central roles in symptom manifestation and inflammatory signaling processes, influencing vascular dynamics, tissue responses, communication with other immune cells, and more.

Once triggered, and separate from potential degranulation, mast cells may also initiate responses that include the transcriptional upregulation and secretion of cytokines, such as interleukin-4 (IL-4); additionally, mast cells may initiate responses that include the generation of lipid-derived mediators, such as prostaglandins and leukotrienes. Through the release of preformed granule constituents, de novo–synthesized lipid mediators, transcriptionally upregulated cytokines and chemokines, and more; mast cells can contribute to inflammation and the propagation of inflammatory responses.

Histamine

As introduced previously, histamine is a biogenic amine; and within the body, histamine can arise from both endogenous biosynthesis and exogenous exposure. In the context of endogenous production, histamine can be synthesized within various tissues by cells that express the enzyme histidine decarboxylase (HDC)—histidine decarboxylase catalyzes the conversion of L-histidine to histamine. Furthermore, mast cells are among the primary sources of endogenously-produced histamine within the body.

Histamine may also be obtained through exogenous exposure, such as through dietary sources. These may include aged, fermented, or possibly improperly stored foods—resulting from microbial decarboxylation of histidine by bacteria through histidine decarboxylase activity. Moreover, bacterial production of histamine may also occur within the gut lumen and can be relevant in the context of intestinal dysbiosis or histamine accumulation.

Exogenous Histamine, Diamine Oxidase, & Digestion

The intestinal barrier functions as a dynamic and selective interface separating the contents of the intestinal lumen—including dietary components, microbes, and their metabolites—from the internal systemic environment of the body. This barrier includes the intestinal mucosa, whose epithelial layer comprises absorptive enterocytes along with specialized secretory and immune-modulating cells such as goblet cells, enteroendocrine cells, Paneth cells, and more. These epithelial cells are sealed together by tight junctions which aid in limiting paracellular permeability and preserving mucosal integrity.

Within this context, diamine oxidase (DAO)—a copper-dependent enzyme expressed by cells including mature enterocytes in the small intestine—plays a central role in the degradation of luminal histamine. In more detail, DAO can catalyze the oxidative deamination, a biochemical reaction in which an amine group (–NH₂) is removed, of extracellular histamine. This converts histamine into imidazole acetaldehyde, hydrogen peroxide, and ammonia. The efficient functioning of histamine degradation pathways is needed for preventing its accumulation, with enzymatic clearance at the level of the intestinal mucosa playing a key role. Moreover, unchecked absorption of dietary histamine may contribute to downstream effects or manifestations within the body; likewise, histamine intolerance (HIT) is the name given to this non-immunologic condition characterized by an imbalance between accumulated histamine—such as that which can be derived from certain dietary sources—and the intestine's ability to degrade histamine, primarily via the enzyme diamine oxidase (DAO). Symptoms of histamine intolerance may include flushing, hypotension, headaches, gastrointestinal motility disruption, and more.

Supporting Healthy Mast Cell Function | Seasonal Allergies

& Supporting the Breakdown of Exogenous Histamine

Quercetin, widely distributed in fruits, vegetables, and other plants, is classified as a flavonoid, which is a large subclass of polyphenolic compounds. More specifically, quercetin is placed within the flavonol subclass of flavonoids and is widely recognized for its immune-supportive properties — including its potential to aid in stabilizing mast cells — a property which may support individuals prone to seasonal allergies. Likewise, limited to the gastrointestinal tract, supplemental diamine oxidase (DAO) can support the enzymatic degradation of dietary histamine, aiding individuals with histamine intolerance, a non-immunologic condition characterized by reduced endogenous DAO activity. The combined support of immune function and dietary histamine degradation reflects a complementary and synergistic approach in supporting homeostasis.

OmneDiem® Histamine Complete

OmneDiem® has an exceptional line of diamine oxidase supplements offering phenomenal support for breaking down histamine within the gut. Their Histamine Digest® Histamine Complete reflects a synergistic approach offering both dietary and seasonal support, and is characterized by supporting the breakdown of dietary histamine within the intestines and supporting healthy immune function. OmneDiem®'s Histamine Digest® Histamine Complete contains Quercetin; other complementary immune-supporting ingredients including Vitamin C, Bromelain, and Stinging Nettle Root Extract; and 2.1 milligrams of diamine oxidase showcasing an exceptional 15,000 Histamine Digesting Units (HDU). HDU reflects how much histamine a given amount of DAO can break down within a set timeframe under defined conditions, aiding in characterizing the enzyme’s activity and biological effectiveness. OmneDiem® has exemplified exceptional innovation and scientific precision in the extraction and stabilization of their DAO supplements allowing for outstanding enzyme preservation and phenomenal levels of Histamine Digesting Units (HDUs).

OmneDiem®'s natural-source DAO is also delivered in targeted-release capsules designed for small intestinal enzymatic activity, offering digestive support and aiding in reducing the histamine burden at this key site of absorption.

OmneDiem® truly sets the standard in diamine oxidase supplementation. A remarkable culmination of advanced science, superior enzyme stability, and an unwavering dedication to research-driven innovation in digestive health: OmneDiem®'s full supplement line can be experienced here.

*Always consult with a licensed medical professional for all of your medical needs.