Histamine: Formation, Breakdown and When an Intolerance Is Possible

A headache after a glass of red wine, a runny nose after aged cheese, stomach pain after sauerkraut: many people suspect histamine behind it. Histamine is a messenger the body makes itself and which is also found in many foods. This article explains in general terms how histamine is made and broken down, what is discussed in histamine intolerance and why it is difficult to clarify.

What histamine does in the body

Histamine acts through four receptors. Via H1 it widens blood vessels, causes itching and keeps us awake; via H2 it increases stomach acid and speeds up the heartbeat; H3 influences messengers in the brain; H4 sits on immune cells. It is stored mainly in mast cells, which release it during an allergic reaction, for example.

The cascade: formation and breakdown

Histamine is made from the amino acid histidine; the enzyme needs vitamin B6 for this. It is broken down in two ways: outside the cells, mainly in the gut, by diamine oxidase (DAO), and inside the cells by histamine N-methyltransferase (HNMT), which uses SAMe from methylation metabolism.

Vitamin B6

formation of histamine from histidine

Copper

building block of diamine oxidase (DAO)

SAMe

methyl group for breakdown by HNMT

Alcohol

can inhibit DAO and often brings histamine itself

The path of dietary histamine

In histamine intolerance it is assumed that DAO in the gut does not break down enough histamine. More of it then reaches the blood and can act on different organs.

Symptoms that can occur

None

These symptoms are unspecific and can have many other causes, such as an allergy, coeliac disease, inflammatory bowel disease or fructose or lactose intolerance (bloating despite a healthy diet).

Foods: where a lot of histamine is found

Histamine forms when bacteria break down protein. That is why the content rises with ripening, storage and fermentation, and it varies strongly even within the same food. The list is a guide, not a diet plan (leaflet, TUM University Hospital rechts der Isar).

None

Some foods are also said to release histamine in the body, such as citrus fruits, strawberries, nuts or chocolate. The evidence for this is thin.

Medications that can affect histamine

Some medicines release histamine from mast cells, others can inhibit its breakdown by DAO (Maintz and Novak, Am J Clin Nutr 2007). Examples named include:

• Releasing histamine: X-ray contrast media, morphine and some other opioids, some muscle relaxants used in anaesthesia.
• Inhibiting DAO: for example the antibiotic metronidazole; leaflets also name groups such as certain sleeping and pain medications, anti-rheumatic drugs, cough suppressants and psychotropic drugs (TUM leaflet).

Important: never stop prescribed medication on your own. Talk to your doctor or pharmacist, and mention a suspected histamine intolerance before an examination with contrast media or before anaesthesia.

Microbiome and probiotics

Gut bacteria also produce histamine if they have the enzyme histidine decarboxylase. This is a property of individual strains, not of whole species. A genome study found numerous possible histamine producers among gut bacteria, 37 of which had already been confirmed in the laboratory (BMC Genomics 2021).

• Named in lists as histamine producers: certain strains of Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus reuteri and Streptococcus thermophilus.
• Named in lists as neutral or degrading: certain strains of Lactobacillus plantarum, Lactobacillus rhamnosus GG, Bifidobacterium longum and Bifidobacterium infantis.

These classifications are based mainly on laboratory experiments and manufacturer information, not on studies in humans. Whether a probiotic helps or harms with symptoms cannot be reliably derived from them. A stool analysis can show which bacteria live in your own gut (laboratory diagnostics).

Gut, strain and the whole system

In holistic medicine we rarely see histamine intolerance as an isolated problem. From the practice’s experience it often appears together with an irritated gut, altered gut flora, nutrient gaps or persistent strain. This is a view drawn from our work with people, not a proven model. It explains why we look at the gut and life circumstances as well as the diet (Gut & digestion).

What studies and the guideline say

The guideline. The German-speaking allergy societies state that there is so far no established method to determine an intolerance to dietary histamine (S1 guideline, AWMF 061-030). They advise against permanent strict avoidance of histamine-rich foods, because its benefit is not proven. A broad clarification of other causes is important to them.

Reviews. One review describes DAO deficiency as the main suspected cause and considers more research necessary to determine the intolerance reliably (Comas-Basté et al., Biomolecules 2020). A second review describes a time-limited low-histamine diet as the usual approach; a clear improvement is regarded there as an indication (Hrubisko et al., Nutrients 2021). Experts therefore do not agree.

IgE and IgG: two different reactions

IgE is the immune system’s immediate reaction. Symptoms usually appear within minutes to about two hours, and the link to a food is often obvious. IgE diagnostics are recognised.

IgG is associated with delayed reactions that can appear only after hours. The link to food is then hard to see. At Natura Heilpraxis we use the IgG test as supplementary guidance: it can help plan a time-limited elimination trial followed by reintroduction. In our experience, many patients find this helpful.

Important: professional societies do not recognise the IgG test as proof of an intolerance (EAACI 2008, AAAAI 2010). Raised IgG values can also simply show that a food is eaten regularly. A result alone is therefore no reason to avoid foods permanently.

Our goal: relieve the load and treat the causes

The aim is not to avoid foods permanently. We leave out conspicuous foods for a while to relieve the body of histamine. At the same time we treat the gut and digestion, the body’s readiness to react and the cofactors of histamine breakdown. The goal is for the body to react less strongly and for the foods to return to the diet step by step. For us, that is the actual therapy.

Clarification and lab values

• Symptom diary: what was eaten and drunk, and what occurred when? This is often more informative than a single value.
• Rule out other causes: allergies, coeliac disease, inflammatory bowel disease, fructose and lactose intolerance.
• DAO in the blood: is offered, but according to the guideline it is suitable neither as a screening test nor on its own to confirm or exclude. A low value is unspecific.
• Time-limited dietary change: only with support and with a plan for how to widen the diet again.

The reference range comes from the laboratory. We do not set our own limits; we show the laboratory’s range and discuss what it can mean in your case.

How we proceed at Natura Heilpraxis

We begin with a conversation about symptoms, diet and life circumstances and decide together which examinations fit the question. Permanent strict avoidance is not the goal; if we change the diet, then for a limited time and with a way back. More about the gut on the page Gut & digestion, about laboratory services under Laboratory Diagnostics. Our discussion does not replace medical diagnostics.

Sources

• Reese I. et al.: Procedure for suspected intolerance to orally ingested histamine. S1 guideline DGAKI, GPA, ÄDA, SGAI, ÖGAI. Allergologie 2021;44(10):761–772. AWMF
• Comas-Basté O. et al.: Histamine Intolerance: The Current State of the Art. Biomolecules 2020;10(8):1181. PubMed
• Hrubisko M. et al.: Histamine Intolerance – The More We Know the Less We Know. Nutrients 2021. PubMed
• Maintz L., Novak N.: Histamine and histamine intolerance. Am J Clin Nutr 2007;85(5):1185–1196. PubMed
• Stapel S. O. et al.: Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report. Allergy 2008;63:793–796. Summary
• AAAAI: statement on the EAACI report on IgG4 testing, 2010. PDF
• Leaflet histamine intolerance: food and drink. TUM University Hospital rechts der Isar, 2023. PDF
• Putative histamine-secreting gut bacteria (genome analysis). BMC Genomics 2021. PMC