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Histamine intolerance does not exist in the strict sense of the word. It does not exist in the same way that there is no intolerance to other hormones produced by the body itself (e.g., steroid or peptide hormones). By contrast, there is intolerance to substances introduced from outside the body, such as fructose and lactose. Histamine is continuously produced and broken down in the body, and histamine from external sources normally does not cause problems; in fact, it often provides benefits.

Although we believe that histamine intolerance does not technically exist, we will use this term to describe this complex phenomenon.

What is histamine?

Understanding the role of histamine in our bodies helps explain the processes behind histamine intolerance. Histamine is a tissue hormone produced from the amino acid histidine with the help of the enzyme histidine decarboxylase and vitamin B6. This process occurs in many plant and animal organisms. Histamine is widespread, highly versatile, and essential in the living world. There is no form of life or cell function it does not influence—even from the very beginning of life. For example, in the absence of histamine, the egg cell cannot implant in the uterus, and in some animal species, ovulation is also triggered by histamine. In humans, histamine additionally functions as a neurotransmitter in both the central and peripheral nervous systems.

In the body, histamine acts on cells mainly through four types of receptors. [1]

H1 receptors:

• Contract smooth muscle tissue of the intestines, bronchi, and uterus
• Constrict small veins and dilate arteries
• Nerve cells: Pain, itching sensation
• Central nervous system: increase alertness
• Ovaries: stimulate estrogen release
• Uterus: support egg implantation

H2 receptors:

• Stimulate gastric juice secretion
• Increase heart rate and cardiac output
• Increase muscle tension
• Strengthen immune defense

H3 receptors:

• Similar to H1 receptors: increase alertness and concentration
• Inhibit release of serotonin, GABA, and acetylcholine in the peripheral nervous system
• Regulate hunger and thirst in the central nervous system

H4 receptors:

• Enhance cellular immune defense
• Increase inflammatory readiness of skin cells

Breakdown of histamine

Histamine is broken down by the enzymes diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT).

DAO contains copper, with cofactors including 6-hydroxydopa, pyridoxal phosphate (vitamin B6), and vitamin C. DAO is produced in intestinal epithelial cells, in the kidneys, and in the placenta during pregnancy. DAO measured in the blood reflects the enzyme produced by the kidneys.

Most histamine, particularly in the central nervous system, is broken down by HNMT. This process also requires several micronutrients, including magnesium, zinc, folic acid, and vitamin B12.

What is histamine intolerance?

The condition commonly called histamine intolerance (also referred to as histaminosis) is complex, affecting multiple organ systems and presenting with a wide variety of symptoms that differ significantly between individuals. Despite this variability, the symptoms follow characteristic patterns. They may be triggered by certain foods, medications, chemicals, and the symptoms often intensify following psychological stress.

Histamine intolerance is not a formal diagnosis but rather a descriptive concept used to summarize symptoms. Affected individuals often react to foods that either contain histamine, block histamine breakdown pathways, or cause bloating (e.g., FODMAP fibers).

In many cases, symptoms attributed to histamine intolerance are caused by excessive mast cell activity. Inflammation of the intestinal wall and micronutrient deficiencies are also common contributors. Symptoms may result from deficiencies in the two enzymatic pathways that break down histamine—either due to low DAO levels or inadequate micronutrients required for DAO production (vitamin C, vitamin B6, copper, manganese)—as well as deficiencies in nutrients necessary for HNMT function (vitamin B12, folic acid, magnesium, zinc). Genetic factors can also reduce enzyme activity, predisposing some people to symptoms. However, with adequate nutrient supply, these symptoms often do not appear, as the body typically maintains multiple pathways for critical functions—here, two enzyme systems for histamine breakdown.

Excluding symptom-triggering foods from the diet usually provides only short-term relief. A real, lasting solution requires a complex, personalized approach. This involves regenerating the digestive system, supporting biochemical pathways necessary for histamine breakdown, regulating hormonal influences that trigger excessive activity of histamine-producing immune cells, and, when needed, identifying and treating underlying chronic infections.

Image 1: Foods and beverages containing histamine

What are the symptoms of histamine intolerance?

Individual sensitivity varies greatly. Some patients cannot tolerate any histamine in food, while others only react to foods with very high histamine content [2]. Some people react only to certain histamine-containing foods but not to others, or only to foods that cause bloating with symptoms resembling histamine intolerance. Even within this group, different foods may provoke symptoms. In the most severe cases, patients cannot tolerate even the smallest amount of histamine—or anything that causes even slight bloating. The most sensitive patients may even react to a glass of water. In such cases, histamine is released from mast cells behind the intestinal epithelial cells due to the physical pressure of the water (mast cell activation/MCAS).

Gastrointestinal symptoms:

• Stomach cramps, IBS
• Nausea, vomiting
• Bloating
• Reflux, feeling of acidity
• Diarrhea (less often constipation)
• Mucus production
• Crohn’s disease sufferers often experience similar problems

Dermatological problems:

• Hives, eczema [3], neurodermatitis
• Local edema (e.g., around the mouth)

Image 2: Eczema can be a symptom of histamine intolerance

Cardiovascular symptoms:

• Rapid heartbeat, extrasystoles
• Low blood pressure, occasionally high or fluctuating blood pressure
• Dizziness, fainting
• Edema

Psychological and psychiatric symptoms:

• Flushing, anxiety, panic attacks
• Unusual feelings: emptiness, depersonalization, derealization

Allergic and immunological symptoms:

• Sore throat, coughing, frequent throat clearing
• Stuffy or runny nose, nasal polyps, chronic sinusitis
• Bronchial asthma (exogenous, triggered by pollen, animal hair, mold; or endogenous, without a known cause but linked to consumption of wine, cheese, or tuna)
• Certain cases of drug allergy
• Histamine in the bloodstream can also cause anaphylactic shock, for example after shaking

Gynecological symptoms:

• Menstrual pain, cramps

Other:

• Headaches, migraines
• Swelling under the eyes

Figure 1: Symptoms of histamine intolerance can affect the whole body

What are the underlying causes?

The development of histamine intolerance symptoms may involve the following problems, which can partially reinforce each other:

• Weak stomach function, low stomach acid, and digestive enzyme deficiencies:
• As a result of reduced protein digestion efficiency, undigested proteins in the intestine are broken down by pathogenic bacteria, some of which directly produce histamine.
• The entire digestive system, including the stomach and pancreas, is innervated by the parasympathetic nervous system, i.e., the vagus nerve. Weak stomach function and digestive enzyme deficiency may be caused by chronic stress, which weakens the innervation of the digestive system. The vagus nerve can also be damaged by Borrelia bacteria, the causative agents of Lyme disease, which is why Lyme disease often presents with digestive symptoms, enzyme deficiencies, and histamine intolerance.
• Severe symptoms often appear after antibiotic use. The destruction of beneficial bacteria and disruption of gut flora allow histamine-producing bacteria to multiply. Repeated or high-dose antibiotics may also damage mitochondria, leading to tissue energy deficiency, reduced steroid hormone production, mast cell activation, and histamine intolerance.
• Poor diet and micronutrient deficiencies: histamine breakdown pathways require a high demand for micronutrients and vitamins.
• Immunological factors: chronic infections such as Lyme disease are often linked to overactive histamine-producing mast cells. Dental foci may also contribute.
• Endocrine influences: high estrogen levels and low progesterone or cortisol increase the activity of histamine-releasing mast cells.
• Vitamin B12, folate, and magnesium deficiencies impair histamine breakdown. Vitamin B12 deficiency is often caused by low stomach acid (reflux) or a vegan diet.
• Vitamin D deficiency also promotes histamine release from mast cells.
• Mitochondrial dysfunction: chronic infections, nutrient and vitamin deficiencies, heavy metal exposure, and certain drugs or toxins may impair mitochondrial function, reducing energy and increasing histamine-related symptoms.
• Stress effects: CRH (corticotropin-releasing hormone, produced in the hypothalamus as the first step of stress response) has receptors on mast cells. Stress can therefore trigger histamine release—sometimes even through negative thoughts or memories related to eating certain foods. In such cases, it may be unclear whether the food itself or a nocebo effect (opposite of placebo) caused the reaction.

Figure 2: Problems underlying histamine intolerance

Which foods cause symptoms?

Histamine is heat-stable and is not destroyed by baking or cooking. Foods high in histamine include:

• Cheeses, fermented dairy products (especially raw milk and long-aged cheeses)
• Red wine, sparkling wine, white wine, beer (alcohol also blocks DAO activity, worsening symptoms)
• Dried, aged, smoked, canned fish and fish sauces; tuna (rich in histidine, which rapidly produces histamine during slow cooling due to its large body size); e.g., mackerel, sardines, herring, salmon
• Seafood stored or transported for long periods (not fresh)
• Dried, smoked, and processed meats (e.g., salami, ham, sausage, bacon)
• Sauerkraut, pickled cucumbers, and other fermented vegetables
• Wine vinegar, balsamic vinegar
• Emmental, Camembert, Roquefort, Gouda, Cheddar, moldy and smoked cheeses
• Mustard, ketchup, soy sauce
• Chocolate, cocoa (tyramine, phenylethylamine), coffee, black tea
• Yeast-containing bread and pastries
• Nuts, peanuts, sunflower seeds

Figure 3: Many favorite foods (chocolate, cheese, coffee, wine) can trigger histamine symptoms

Foods that trigger histamine release:

• Certain vegetables: tomatoes, spinach, eggplant, avocado, peas, lentils, beans
• Certain fruits: strawberries, raspberries, bananas, papayas, kiwis, pineapples, mangoes, grapefruit, tangerines, pears
• Acetaldehyde (a breakdown product of alcohol) can trigger mast cell histamine release. Individuals with genetically reduced acetaldehyde dehydrogenase activity (e.g., many Asians and women in general) are prone to redness.
• Pollen-related food allergies can also provoke symptoms: apples, nuts, carrots, soy, kiwis, figs (birch pollen allergy), celery, wormwood allergy, chamomile, sunflowers and sunflower honey, anise, dill, fennel, coriander, cumin and  parsley (mugwort allergy)

A comprehensive summary of the histamine problem is available in German: R. Jarisch, Histaminintoleranz und Seekrankheit. [4]

How does nutrition affect histamine intolerance?

The list of foods completely free of histamine is very short—essentially pure water, refined fats, sugar, and salt. Yet, even water can trigger symptoms in highly sensitive individuals.

Eliminating problem foods from the diet provides only short-term relief. Permanently avoiding histamine-rich foods does not eliminate symptoms if the underlying causes of histamine intolerance remain unresolved. Many histamine-rich foods are also nutrient-dense, so avoiding them can worsen micronutrient deficiencies and gradually deteriorate health. Long-term management requires not only regenerating the digestive system but also consuming high-quality, nutrient-rich foods that support the body’s biochemical processes, including histamine breakdown.

Foods may trigger symptoms through various mechanisms:

• Allergies
• Intolerances (IgG or IgE antibodies)
• Foods that cause bloating (FODMAP fibers)
• Direct histamine content
• In some cases, by blocking enzymes or interfering with biochemical processes (e.g., alcohol inhibits DAO)
• In cases of chronic infection, even bacteria-killing agents can provoke histamine reactions (Jarisch–Herxheimer reaction)

Micronutrient deficiencies resulting from a poor-quality diet are further aggravated by the fact that, in such conditions, the digestive system typically functions weakly (e.g., in cases of low stomach acid, which may also be related to stress). Low levels of stomach acid and digestive enzymes also promote the growth of pathogenic, histamine-producing gut bacteria. Micronutrient deficiency initially develops silently, while the body’s resistance gradually declines.

Histamine intolerance, which worsens as a result of micronutrient deficiency, creates a vicious cycle. As micronutrient deficiencies increase and the body’s biochemical functions gradually deteriorate, sensitivity to a growing number of foods develops. Consequently, the diet becomes increasingly restricted, micronutrient deficiencies worsen, and the body becomes progressively more sensitive to histamine-containing foods.

Due to gastrointestinal and immunological problems, people with histamine intolerance typically do not tolerate a range of foods, even when histamine is not the main trigger. As a result, many eventually reach the point where they can eat only rice and potatoes.

How can histamine intolerance be treated?

When addressing histamine intolerance, it is helpful to distinguish between short-term and long-term approaches. In the short term, avoiding foods that contain or release histamine can significantly help reduce symptoms. There are many detailed lists and tables that classify foods according to their histamine content (see foods that cause symptoms).

In the longer term, a comprehensive strategy is needed — one that includes micronutrient supplementation and the gradual reintroduction of foods that contain or release histamine. Foods that trigger individual sensitivity should be reintroduced slowly, alongside the body’s regeneration, always taking current individual tolerance into account.

Foods containing histamine have many beneficial effects, and some of them are particularly rich in micronutrients. Dietary histamine also helps increase stomach acid production, which improves protein digestion, supports the elimination of pathogenic bacteria that themselves produce histamine, and aids in the absorption of vitamin B12.

The problem of histamine intolerance and its biological background often overlap with mast cell activation syndrome (MCAS), so their management strategies are similar. For specific protocols and helpful active ingredients, see the MCAS article.

Histamine intolerance can be managed to a symptom-free state, and stable bodily function can be maintained even under significant physical or psychological stress. Targeted dietary, lifestyle, and supplement protocols — developed partly on the basis of laboratory results — together with the regeneration of the digestive system, help restore the body’s vitamin and micronutrient balance. Regulating digestive function and intestinal flora requires patience, but in most cases a stable, drug-free condition can be achieved.

Other connections

The different forms of histamine-related metabolic disturbances cannot always be clearly distinguished from one another. For this reason, in some cases we use terms such as histamine intolerance, mast cell activation disease (MCAD), mast cell activation syndrome (MCAS), or mastocytosis. In practice, cases of “pure” histamine intolerance are rare, with most patients presenting mixed symptoms.

Mastocytosis is a specific form of mast cell activation syndrome, and the two terms are often confused. In mastocytosis, large numbers of mast cells accumulate in the skin or in certain organs. The cause of this process remains unknown. Correlations have been observed with IgE-mediated allergies, with psychological and psychiatric disorders, and with low vitamin D levels. [5]

Image 3: Mast cell: Cytoplasm (green), histamine-containing vesicles (blue), cell nucleus (brown). The photograph was taken with a transmission electron microscope, and the colors were added later

Mast cell activation

Mast cells are white blood cells that occur in large numbers near the external and internal surfaces of the body, such as in the skin, lungs, and intestinal tract. They are not only important for allergic reactions but also play a role in the formation of new white blood cells, in wound healing, in maintaining the balance of the immune system, and in protecting the blood–brain barrier. [6–7]

Because mast cells and histamine receptors are present in all tissues of the body, mast cell activation syndrome (MCAS) can in principle affect any organ system. [8]

Clinically, MCAS often manifests as a multi-organ condition in the form of generalized, allergic, or inflammatory symptoms. It has also been associated with obesity, diabetes, skin diseases, irritable bowel syndrome (IBS), depression, and numerous other disorders. [9]

Mast cells can also be destabilized by heavy metals such as aluminum and mercury. This explains their presence in certain vaccines, where they serve the purpose of stimulating an immune response. Other metals, including lead, cadmium, and bismuth, are likewise capable of activating mast cells [10]. Infections and intestinal dysbiosis are among the most important triggers of mast cell activation. Around 70% of our immune system is located in the intestines [11], which are rich in mast cells. Parasitic, bacterial, viral, and fungal infections can all activate mast cells [12], as can Candida [13–14]. Mast cells and the gut microbiota are in constant interaction, and dysbiosis itself can be sufficient to trigger MCAS. [15]

Regarding food-related symptoms, in histamine intolerance the source of histamine is the food itself, whereas in MCAS, the histamine originates from mast cells in the immune tissue surrounding the intestines and from the intestinal microbiota. Therefore, histamine-related symptoms that appear after eating freshly prepared broccoli or other bloating foods are not caused by the histamine content of the food. Although the mechanism behind bloating is similar to that in histamine intolerance — namely, a deficiency of digestive enzymes and the overgrowth of pathogenic bacteria — in MCAS the histamine comes from the mast cell–rich immune tissue around the intestines. When bloating occurs, the expanding intestines physically compress the mast cells, which acts as a mechanical trigger for histamine release. Because of this mechanism, even drinking a glass of water can sometimes provoke symptoms.

The relationship between circadian rhythm and histamine

One of the major achievements of modern life, artificial lighting, also has drawbacks: light containing a high proportion of blue wavelengths inhibits the production of melatonin. In recent years, people have spent more and more time in the evenings in front of computers or televisions, or using smartphones, thereby exposing their eyes to this type of artificial light.

Reduced melatonin production contributes not only to sleep disorders but also to metabolic disturbances and histamine-related symptoms. The literature also describes a higher incidence of inflammatory and oncological diseases in connection with melatonin deficiency, and research on this topic has also been conducted in relation to Covid-19. [16]

Melatonin is a hormone produced by the pineal gland. Unlike cortisol, melatonin is one of the hormones whose production decreases markedly with age [17]. Melatonin and cortisol act as antagonists and are regulated by the suprachiasmatic nucleus (SCN) and by exposure to sunlight. As long as blue light from the sun reaches our eyes, melatonin production is inhibited. When the sun’s light shifts to yellow and red, this inhibition is lifted, and melatonin is released into the bloodstream from the pineal gland. The melatonin inhibits steroid hormone synthesis, thereby protecting the body from the harmful effects of elevated cortisol levels. On the other hand, the low steroid levels that occur at night under melatonin’s influence allow glucocorticoid receptors to regenerate, ensuring the proper effect of steroid hormones and protecting against receptor resistance.

Melatonin is much more than just a sleep hormone: it is a powerful antioxidant, immunomodulator, histamine release inhibitor, and mast cell–stabilizing hormone [18]. Furthermore, melatonin also protects against the harmful effects of stress. [19]

Measures to restore circadian rhythm contribute significantly to recovery. It is recommended to spend as much time as possible in strong natural daylight during the day. In the evening, and especially in the hours before bedtime, exposure to blue light should be minimized. If avoiding screens or bright lights is not possible, light-filtering applications or blue-light-filtering glasses can be used. Such glasses are only effective if they visibly tint the light yellow or orange. Melatonin is also available as a dietary supplement and can be taken before bedtime.