Is 90% of Histamine Produced in the Gut? And Why Does DAO Still Matter?

The key point is that DAO protects the body from exogenous histamine – both histamine from food and histamine produced by the gut microbiota.¹ This is precisely the principle described in the scientific review by Comas-Basté et al.: DAO plays a major role in protecting the body from exogenous histamine originating from food as well as histamine produced by the gut microbiota.¹

When discussing histamine, we sometimes encounter the claim that only 10% of histamine comes from food, while as much as 90% is produced in the gut. This is then sometimes used to argue that taking the DAO enzyme cannot be particularly effective because it supposedly addresses only a small part of the total histamine load.

However, from the perspective of histamine physiology, this conclusion is too simplistic.

First of all, there is no universally accepted, scientifically established ratio stating that 10% of histamine comes from food and 90% is produced in the gut. Current scientific reviews describe several sources of histamine but do not establish such a universal ratio.¹˒⁵ In addition, histamine is found in different biological compartments that cannot simply be added together.

Histamine Does Not Have Just One Source

One source is histamine consumed through food. After ingestion, it enters the digestive tract, where the enzyme diamine oxidase (DAO), located in the intestinal mucosa, plays an important role in its degradation. DAO is the main enzyme involved in the metabolism of ingested histamine, and an insufficient capacity to degrade it is one of the mechanisms associated with histamine intolerance.¹˒²

A second source is histamine produced by the gut microbiota. Some microorganisms possess the enzyme histidine decarboxylase and can convert the amino acid histidine into histamine. Differences in microbiota composition and a higher abundance of certain histamine-producing bacteria have been reported in people with symptoms of histamine intolerance.³

A third source is histamine released by the body's own cells, particularly mast cells and other immune cells. This occurs, for example, during allergic and inflammatory reactions. This histamine primarily acts locally within tissues and cannot simply be equated with histamine present in the intestinal contents.⁴

10% Versus 90% Is Not the Right Question

The problem with the claim that “10% of histamine comes from food and 90% is produced in the gut” is that it mixes different sources of histamine and different biological compartments.

What matters is not simply how much histamine is produced in the body. It is important to consider:

• where the histamine comes from,

• where it is located,

• whether it is present in the intestinal lumen or in tissues,

• how quickly it is degraded,

• the activity of DAO and other metabolic enzymes,

• and whether the amount of histamine exceeds the body's current capacity to metabolize it.

Histamine consumed through food is initially present in the digestive tract. This is precisely where DAO forms part of the body's natural protective barrier against exogenous histamine.¹˒²

Even more importantly, DAO does not distinguish between a histamine molecule that entered the intestinal lumen from food and one produced by a gut bacterium. From the enzyme's perspective, it is the same histamine molecule. Scientific literature therefore describes intestinal DAO as an important protective mechanism against exogenous histamine from both food and histamine produced by the gut microbiota.¹

The fact that some histamine is produced directly in the gut is therefore not an argument against DAO. On the contrary, the gut is precisely where DAO performs one of its main physiological functions.

What About Histamine Produced by Bacteria?

Bacterial histamine production is a genuine biological mechanism and should not be overlooked.

Changes in the composition of the gut microbiota can increase the abundance of microorganisms capable of producing histamine. In patients with symptoms of histamine intolerance, dysbiosis associated with a higher abundance of certain histamine-producing bacteria has indeed been reported.³

From the perspective of the intestinal epithelium and the DAO enzyme, however, it is not crucial whether a histamine molecule comes from food or from a bacterium.

What matters is the amount of histamine present and the ability of intestinal DAO to continuously metabolize it.¹

If histamine production or intake exceeds its degradation, the amount of histamine available for local effects and subsequent absorption may increase.¹ Histamine released by mast cells and other cells may also contribute to impaired intestinal barrier function under certain pathological conditions.⁴

It is therefore more accurate to say:

In some people, bacterial histamine production may represent a significant part of the overall intestinal histamine load. However, this does not mean that dietary histamine is negligible – nor does it mean that DAO loses its relevance.

DAO and Histamine in the Gut Are Not Opposing Concepts

DAO is not a universal “histamine remover” for the entire body.

Its role lies primarily in the metabolism of exogenous histamine present in the gastrointestinal tract.¹ Oral DAO should therefore not be understood as a means of removing histamine released, for example, by mast cells in the skin or other tissues.

However, when histamine is present in the lumen of the digestive tract – whether it originates from food or is produced by gut microorganisms – it is present in precisely the environment where DAO can enzymatically degrade histamine.¹˒⁵

If dysbiosis or an allergic or inflammatory condition is also present, DAO supplementation alone will, of course, not eliminate its underlying cause. This does not mean that DAO is irrelevant. It simply means that different mechanisms contributing to an increased histamine load may require different approaches.

Clinical studies suggest that oral DAO supplementation may help reduce symptoms in some patients with symptoms of histamine intolerance. In a small open-label study involving 28 patients, symptom scores decreased significantly during DAO supplementation and increased again after supplementation was discontinued.⁶ However, the current evidence remains limited and cannot be generalized to everyone experiencing symptoms attributed to histamine intolerance.⁵˒⁶

Intestinal degradation of histamine by the DAO enzyme in three different situations: in a healthy individual, with histamine intoxication, and with histamine intolerance. Adapted from Comas-Basté et al., 2020.¹

This Is Precisely Why the Argument Cannot Be Based on a 10:90 Ratio

The statement:

“Only 10% of histamine comes from food and 90% is produced in the gut, so DAO is not relevant.”

confuses several different biological processes.

A more appropriate question is:

How much histamine is present in the gut at a given moment, and is the body able to degrade it quickly enough with the help of DAO?

From this perspective, it is useful to distinguish between two main groups:

1. Histamine present in the intestinal lumen

– histamine consumed through food– histamine produced by the gut microbiota

2. Histamine released in the body's tissues

– particularly histamine released by mast cells and other cells during immune, allergic, and inflammatory reactions.

The first group represents histamine against which intestinal DAO has a direct physiological role.¹ The second group represents a different biological compartment and requires a different approach.

Put simply, from the perspective of DAO, it does not matter whether a histamine molecule comes from cheese, fermented food, or is produced by a bacterium in the gut.

What matters is the total amount of histamine in the intestinal lumen and DAO's ability to continuously degrade it.¹

DAO and supporting a healthy gut microbiota are therefore not competing approaches. They may address two different aspects of the same problem.

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Scientific References

1. Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla ML, Vidal-Carou MDC.Histamine Intolerance: The Current State of the Art.Biomolecules. 2020;10(8):1181.DOI: 10.3390/biom10081181. PMID: 32824107; PMCID: PMC7463562.PubMed | Full text – PMC | Full text – publisher

Key source supporting the statement that DAO protects the body against exogenous histamine originating from both food and histamine produced by the gut microbiota.

2. Maintz L, Novak N.Histamine and histamine intolerance.American Journal of Clinical Nutrition. 2007;85(5):1185–1196.DOI: 10.1093/ajcn/85.5.1185. PMID: 17490952.PubMed

DAO is described here as the main enzyme involved in the metabolism of ingested histamine.

3. Sánchez-Pérez S, Comas-Basté O, Duelo A, et al.Intestinal Dysbiosis in Patients with Histamine Intolerance.Nutrients. 2022;14(9):1774.DOI: 10.3390/nu14091774. PMID: 35565742; PMCID: PMC9102523.PubMed | Full text – PMC

The study describes changes in the gut microbiota in people with symptoms of histamine intolerance and a higher abundance of certain histamine-producing bacteria.

4. Barbara G, Zecchi L, Barbaro R, et al.Mucosal permeability and immune activation as potential therapeutic targets of probiotics in irritable bowel syndrome.J Clin Gastroenterol. 2012;46 Suppl–S55.DOI: 10.1097/MCG.0b013e318264e918. PMID: 22955358.PubMed

The paper describes the role of mast cells and their mediators, including histamine, in the regulation of intestinal permeability and neural responses.

5. Jackson K, Busse W, Gálvez-Martín P, Terradillos A, Martínez-Puig D.Evidence for Dietary Management of Histamine Intolerance.International Journal of Molecular Sciences. 2025;26(18):9198.PubMed | Full text – PMC | Full text – publisher

This recent review confirms the key role of intestinal DAO in the metabolism of exogenous histamine and summarizes the current evidence regarding oral DAO supplementation.

6. Schnedl WJ, Schenk M, Lackner S, et al.Diamine oxidase supplementation improves symptoms in patients with histamine intolerance.Food Science and Biotechnology. 2019;28(6):1779–1784.DOI: 10.1007/s10068-019-00627-3. PMID: 31807350; PMCID: PMC6859183.PubMed | Full text – PMC

This small open-label clinical study reported a reduction in symptoms associated with histamine intolerance during oral DAO supplementation; the findings are supportive but not conclusive.