Histamine intolerance: Gaining relief from a poorly understood disorder

Histamine intolerance(HIT) is a dietary intolerance that presents with symptoms similar to allergy. During allergic reactions, mast cells release inflammatory mediators, including histamine, that cause the classic symptoms of allergy.

However, foods also contain histamine. As a result, when people with HIT ingest high amounts of histamine, they experience symptoms of allergy. But, it gets worse.

Histamine has many roles in the human body. For example, histamine stimulates acid production in the stomach. Furthermore, it plays an important role in the nervous system, and lowers blood pressure.

In HIT, histamine builds up in the gut, crosses into the blood, and can impact systems throughout the body. Consequently, common symptoms of HIT include:

Histamine intolerance symptoms

Factors leading to histamine intolerance

Unfortunately, HIT isn’t a simple condition. The major problem is a build up of histamine, which can occur due to many factors. First, it can accumulate due to excess production AND consumption.

But, we have a couple of enzymes that break it down. The primary one of concern found in the gut and blood is diamine oxidase(DAO). A deficiency in DAO functions as a marker of histamine intolerance. Several factors negatively impact DAO including genetics, alcohol, medications, other food components, the intestinal environment, and microbial factors.

Another enzyme that breaks down histamine is histamine N-methyltransferase(HMNT). However, this enzyme is found in the cell and thus breaks down histamine produced in the cell. It, therefore, does not break down histamine in the diet to a large extent.

Finally, the microbiome may play a very important role as well. Many bacteria produce histamine, which is why it’s common in fermented foods. Additionally, some members of the microbiome degrade histamine.

Moreover, the microbiome plays a critical role in regulating the intestinal environment. Many of these environmental factors have direct and indirect roles in regulating histamine release and DAO activity. This includes pH, pO2, inflammation, and the presence of other biogenic amines that compete with histamine for DAO.

A recent paper found low prevalence of keystone species in the gut of people with HIT. Keystone species help stabilize the gut, promoting an environment that supports DAO activity and reduces histamine. We covered keystone species in a blog you can check out here.

In addition to a drop in keystone species, people with HIT also had higher levels of histamine producing bacteria.

Addressing histamine intolerance

Currently, reducing histamine in the diet is the most popular approach to addressing histamine intolerance. Unfortunately, most lay-folk view a low histamine diet as a permanent diet. This is similar to the low FODMAP diet in people with IBS.

Like the low FODMAP diet, a diet low in histamine can be problematic long term. This is why, like the low FODMAP diet, a low histamine diet should progress from a period of elimination to a period of reintroduction where patients try different foods. In the end, the goal is ultimately a personalized diet that fits the patient.

During the elimination phase, it’s important to consume food as fresh as possible. As food sits, histamine is produced as a natural product of aging, even in the fridge. For a list of high histamine foods to avoid, check out section 3 of this review article.

Supporting DAO levels is also important. Low levels of histamine stimulate production of DAO, but high levels suppress it. Additionally, several other factors impact DAO and HNMT negatively, so addressing those factors is critically important.

Some pharmaceutical medicines temporarily inhibit DAO or HMNT. Coming off these meds returns enzyme activity back to normal. Go to https://www.mdpi.com/2218-273X/12/3/454/htm for a full list of these meds.

Other important things to consider for addressing histamine intolerance

Some people, specifically those with funky genes that produce DAO or HMNT, will have an upper limit on the amount of histamine they can consume. Others may simply need to limit histamine for a period while addressing environmental factors to re-establish harmony in the gut.

Probably the most important factor to address is gut health. Inflammation leads to higher histamine release and inhibits DAO activity. Creating a pristine intestinal environment is essential during the dietary elimination of histamine to prepare the gut for reintroduction.

Doing this requires a good deal of work including:

  • Establishing strong circadian rhythms
  • Addressing metabolic dysfunction(NAFLD, type 2 diabetes)
  • High polyphenol/fiber intake
  • Limiting alcohol

Doing all these things is essential to re-establishing harmony in the gut. In other words, none of them optional if your goal is normalcy.

Another important factor is being pragmatic about reintroduction. Don’t jut randomly choose high histamine foods for reintroduction. Try foods such as fermented foods that actually help stabilize the gut and lower inflammation.

This makes reintroduction more effective. And don’t forget to use tools such as DAO supplements to make that process easier and more effective.

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Histamine, IBS, & the gut

Gastrointestinal symptoms are quite common for people with histamine intolerance. Histamine plays an important role in gut health and regulates things like gut motility, acid and ion secretion, and regulates inflammatory processes.

In fact, gut symptoms are the most common symptoms of HIT. Specifically, gas/bloating, nausea, diarrhea, constipation, and abdominal pain.

Further evidence supports the idea that histamine plays an important role in IBS. People with IBS have an increased number of mast cells in localized regions of the gut that cause pain. The theory is that people with IBS become sensitized to a food when it accompanies a GI infection.

This expands mast cells in that area. As a result, it causes a localized reaction that releases histamine as well as other inflammatory when that food is consumed. In this instance, it’s not dietary histamine that is the problem, but another food that causes histamine release.

However, this histamine still competes with dietary histamine for DAO. Therefore, in complex cases that include HIT and IBS, it’s important to also identify foods that trigger histamine release and remove them during both the elimination and reintroduction phases.

These foods should be the last foods for reintroduction.


Dealing with histamine intolerance is not like other health issues such as bacterial or viral infections. You don’t just take a drug for a couple weeks and then feel fine.

Like IBS, HIT takes quite a while to address. It also requires substantial changes to a person’s lifestyle, which we are not generally good at.

To make this process “easier” and “faster”, it’s important to be vigilant and understand the cause of the problem. Removing histamine from your diet is a critical first step, but it’s only a first step. To maintain sanity, reintroduction is crucial to get back to a “normal”-ish diet.

It’s also important to be pragmatic about reintroduction. Use tools such as DAO to help with the process, and start with small amounts of fermented foods to help re-establish a healthy gut environment.

Building a stable and resilient gut is your best hope to reverse HIT if it’s an environmental issue. Even in people with genetic polymorphisms in DAO and HMNT, it’s essential to optimizing digestion and preventing major gut issues from taking root.

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