Histamine Intolerance

You might have come across the term “Histamine” at least four to five times in your life, but while others already have an idea what it is, many of us are still wondering what it is.

Histamine is an organic biochemical compound found in the body; a biogenic amine. The body makes histamine from nitrogen; that is, it is a ‘nitrogenous derivative’ secreted by basophils and mast cell found in the body’s connective tissues.

This mysterious compound is actively involved in the body’s immune response, regulating physiological functions in the gastrointestinal system and acting as a neurotransmitter for the spinal cord, brain, and uterus.

In inflammatory response, Histamine plays a typical role as a mediator of itching. In the war against foreign pathogens, histamine increases the capillaries’ permeability (blood vessels) to allow white blood cells (leukocytes) and some proteins to engage pathogens in the infected tissues.

Biochemically, histamine has a basic structure of an imidazole ring attached to an ethylamine chain. Under physiological activities, an amino group of the side-chain is protonated.

What is Histamine intolerance?

Histamine intolerance can also refer to Histamine allergy. It is not the sensitivity to excess histamine or histamine degradation, as you may deduct, but an indication your body has developed too much histamine.

When your body indicates too much histamine, it presents like a food allergy response. Too high histamine levels cause histamine reaction which is commonly as a result of either excess production or the body’s inability to properly breakdown histamine, which can affect daily normal immune system functions in the body.

Histamine allergy or Histamine intolerance is usually rare; it affects about 1% of the population. Most individuals frequently mistake it for other food allergies, gastrointestinal disorders, or other allergic reaction.

Apart from excess histamine in the digestive system, other factors that can instigate histamine intolerance reaction include:

  • A reduction in the effectiveness or abundance of a primary enzyme that breaks down ingested histamine, the enzyme diamine oxidase (DAO), is responsible for this action.
  • A reduction in the enzyme’s effectiveness or abundance that breaks down histamine within cells, the enzyme is that breaks down cellular histamine are called histamine-N-methyltransferase (HNMT).


Our body naturally produces histamine, these are known as intracellular histamine or accumulated histamine, and there is also extracellular histamine.

These extracellular histamines are histamines in food, drinks, and drugs (particularly fermented food produce).

The body, alongside histamine, produces an enzyme diamine oxidase (DAO). DAO has a principal function of breaking down extracellular histamine (histamine food).

For instance, an individual develops a deficiency in DAO production. The person becomes unable to break down histamine, which causes extracellular histamine or ingested histamine to pile up in the system, which causes high histamine level, and develops into histamine intolerance.

Several factors could hinder the production of DAO, such as:

  • Food that blocks DAO enzymes or triggers histamine release.
  • High Histamine food that causes improper functioning of DAO
  • Leaky gut syndrome or inflammatory bowel disease (gastrointestinal diseases)
  • Medications that block DAO function, hinder DAO production, or result in DAO deficiency such as analgesic drugs that increase allergen-specific histamine release in people with allergy.
  • Genetic polymorphism in the DAO gene causes an impaired ability to breakdown histamine.

Production of diamine oxidase is mostly in the intestines; due to this fact, some intestinal disorders such as leaky gut syndrome may cause histamine intolerance.

In this gastrointestinal condition, the gut is inflamed or damaged, and one of the complications of this condition is the building up of extracellular histamine. 

Generally, you may notice that women experience allergic reactions more compared to men. So also, histamine intolerance seems to be prevalent in women compared to men. This prevalence may be related to the hormonal imbalance of the female sex hormones.

Medically, female patients experience more severe histamine intolerance symptoms just before or during their menstrual flow. Estrogen (a female sex hormone) activates histamine release from immune cells of the body.

During a female’s period, there is a spike in estrogen production. If an equal amount of progesterone (another female sex hormone that counteracts estrogen) is not secreted, more histamine would be released, and these unbalanced secretions may result in worsened symptoms.

The fact that histamine intolerance is by bacteria overgrowth is quite rare, but some patients have observed it. Bacterial overgrowth may be another protonate to the development of histamine intolerance.

When a meal is not properly digested, it may cause an increase in bacteria growth, and these excess bacteria cause histamine overproduction.

The body reacts to the increased histamine levels caused by bacteria overgrowth, as normal DAO enzyme production cannot keep up with the spike in levels.

Food Causes of Histamine Intolerance

Extracellular histamines are histamine compounds found in food and drinks. High histamine food can cause an increase in the overall histamine level of the body, and this spike can trigger a histamine intolerance reaction.

The following food groups have been labeled as dietary histamine or histamine containing food:

Meat and fish

  • Fish products, particularly canned fish
  • Offal
  • Ham
  • Pork
  • Smoked meat
  • Salami
  • Seafood


  • Hard cheeses- a higher degree of ripeness, higher histamine content


  • Red wine
  • Beer (especially top-fermented and cloud/coloured)
  • Some category of French Champagne

Fruit and Vegetables

  • Avocado
  • Bananas
  • Beans
  • Citrus fruits
  • Figs
  • Tomatoes
  • Papayas
  • Cheese molds and salami molds
  • Eggplant or Garden egg
  • Strawberries

Roots and Legumes

  • Garlic
  • Bamboo sprouts
  • Horseradish
  • Mushrooms
  • Plums
  • Raisins
  • Spinach
  • Sauerkraut


  • Tobacco- active or passive exposure is suspected of favoring histamine intolerance, but this is just a hypothesis.
  • Nuts
  • Chocolate (the other biogenic amines from cocoa is what contains histamine, and not the chocolate itself)
  • Vinegar products such as mustard and pickles
  • Soy and sol products

Food that may interfere with DAO and HNMT levels include:

  • Energy drinks
  • Alcohol
  • Black, mate, and green tea
  • Raw egg whites
  • Yogurt (depending on the bacteria type)

What type of Medication causes Histamine Intolerance?

DAO and, to a lesser extent, HNMT primarily breaks down ingested and intracellular histamine.

However, these enzymes also prevent histamine from being absorbed from the guts into the bloodstream. Many prescriptions drugs may interfere with the production and functions of DAO and HNMT.

Medications such as:

  • Antibiotics
  • Antipsychotics
  • Diuretics
  • Antidepressants
  • Analgesics
  • NSAIDs (anti-inflammatory drugs)
  • Muscle relaxants
  • Medications for tuberculosis, malaria, GI disorders, heart conditions, and airway complications.

NB: Not all these medications actively cause histamine intolerance. Some may be as a result of long-period usage.

What are the Symptoms of Histamine Intolerance?

How do you know you have Histamine intolerance? Some of you may ask. Well, Histamine intolerance reaction is usually likened to familiar allergic responses and allergy symptoms. Most allergic reactions are commonly associated with histamine.

While symptoms may vary with each reaction, some commonly seen reactions with histamine intolerance sufferers include:

But in more severe cases caused by high histamine levels, a person may experience:

  • Migraines
  • Tissue swelling
  • Skin redness
  • itching
  • Abdominal cramping
  • Anxiety
  • Dizziness
  • Irregular body temperature (fever)
  • Increased blood pressure and heart rate

How is Histamine Intolerance Diagnosed?

When allergic reactions become troublesome and continuous, a diagnosis from a doctor may be necessary.

Before arriving at a conclusive diagnosis, your primary health care officer or doctor will examine a case history to eliminate other possible allergies presenting similar symptoms. Your doctor secondly may suggest that you adhere to an elimination diet for 14 to 30 days.

This elimination dieting system requires you to stop any food high in histamine content completely, or that can serve as a histamine trigger and gradually reintroduce these meals to watch for new reactions.

Blood tests will also be conducted to analyze DAO (diamine oxidase) level and also test for mast cell activation.

Another diagnostic pattern examined and proposed by a 2011 study is the prick test. This 2011 study examined the prick tests’ effectiveness against histamine intolerance; the skin of 156 individuals was pricked, and applied 1% of histamine solution was applied.

For suspected histamine intolerance cases, a small red, itchy bump appeared on the skin’s pricked area. The test came out positive for 79% of these individuals.

The bumps did not resolve until about 50mins.

Differential Diagnosis

Other disorders or conditions that can present symptoms as histamine intolerance include:

  • Toxic reactions
  • Lambliasis
  • Reaction to sulfites
  • Psychosomatic reactions
  • Neuroendocrine tumors
  • Other food allergies

How do you Treat Histamine Intolerance?

The Right Food

People who may suffer from histamine intolerance or food intolerance; individuals looking to prevent or reverse the condition will often need to take-on a low-histamine diet or histamine free diet.

Typically, this means reducing the intake of histamine rich food and not getting rid of them completely. If you suffer from histamine intolerance or know someone who does, they should rather focus on increasing their low-histamine diets.

These food and drinks include:

  • Cooked egg yolk
  • Fresh skinned chicken
  • Fresh vegetables except for tomatoes and eggplant
  • Fresh, pasteurized milk
  • Fresh or flash-frozen meat and fish
  • Whole grain noodles, bread, crackers, and pasta
  • Butter
  • Cream cheese
  • Coconut and rice milk
  • Most cooking oil
  • Leafy greens except for spinach

For the proper production and functioning of DAO and HNMT, several vitamins and minerals are necessary.

It will be more beneficial to include more food and drinks with these necessary nutrients.

Nutrients include:

  • Vitamin B6
  • Vitamin C (helps lower blood histamine levels)
  • Magnesium
  • Manganese (enhances DAO activity)
  • Copper (helps raises DAO blood levels and helps DAO breakdown histamine)
  • Zinc (possess anti-allergic and anti-inflammatory properties)
  • Calcium (to help reduce hives and skin flushing)
  • Vitamin B1, vitamin B6, and vitamin B12
  • Folic acid

Due to low-histamine diet restriction or availability, some nutrients may seem difficult to get; in such cases, a supplement may be employed by patients to substitute such nutrients.

Medical Treatment

Apart from low-histamine diets and nutrient supplements, there is not yet a set treatment for histamine intolerance. However, depending on the symptoms experienced, some people benefit from a few different medical treatments.

These medical treatments may include:

  • Taking DAO enzyme supplements
  • Taking antihistamine medications
  • Avoiding medications associated with histamine intolerance such as NSAIDs and analgesics.
  • Taking corticosteroids.
  • Switching prescription medications.


Infrequent cases, engaging in dietary changes and administration of DAO levels supplements or antihistamine medications may help manage histamine intolerance for a few weeks. There is no permanent or one-in-all treatment for histamine intolerance. But to keep symptoms at bay, it is advisable to avoid histamine rich foods for few months especially in cases of seasonal allergies. Individuals recovering from histamine intolerance will be generally required to limit the use of medications known to be histamine triggers or histamine liberators for some time.