The truth about histaminosis: low histamine diet is not the solution

March 20, 2022

La verdad sobre la histaminosis: la dieta baja en histamina no es la solución

What is histamine

Histamine, discovered in 1910 by Henry Dale and Patrick Laidlaw, is an amine (hydrophilic, aromatic and vasoactive) and we know it mostly for its role in infections and allergies. Histamine is produced by the body itself in response to allergic responses at the level of the immune system: in the event of an infection or allergy, white blood cells coordinate to release molecules that, when put together, increase the attack to eliminate the pathogen (parasites, bacteria...). increasing inflammation and recruiting other cells of the immune system to resolve the infection as soon as possible.

Where is it produced?

We have to know that blood and neuronal histamine exist. Blood histamine a is produced and stored mainly in mast cells and basophils (also in other cells, but in smaller quantities), located in the skin and respiratory system; That is why the most frequent allergic reactions are located on the skin and in the respiratory tract. When an infection or allergic reaction occurs, mast cells go into action, releasing large amounts of histamine, causing symptoms to eliminate the infection such as itching, dilation of the vessels, necessary to kill the microorganism.

In non-allergic food allergies or intolerances, the body recognizes some environmental agent or food protein as foreign, reacting as if it were a pathogenic agent (a parasite, a bacteria...) and we feel the same symptoms as if we had an infection.

We all have blood and neuronal histamine. At the peripheral level (blood histamine), this It has effects on the frequency and force of cardiac contraction, contraction of smooth muscle of the respiratory tract and gastrointestinal system, allergic and immune responses, and gastric acid secretion. Histamine is also produced in the brain: histamine is not able to cross the blood-brain barrier, so most brain histamine is synthesized by the brain itself and the neurons that synthesize histamine. In the Central Nervous System, histamine regulates the sleep-wake cycle, motor behavior, food and water intake, sexual behavior, learning and memory.

How we eliminate it

The DAO enzyme eliminates extracellular histamine and has not been detected in the CNS, however the HMNT enzyme catabolizes intracellular histamine and has been detected in the brain. It is specifically eliminated through hepatic methylation, therefore polymorphisms in methylation or deficiency of cofactors (vitamin B12, choline, betaine, folate...) can cause greater difficulties in eliminating excess histamine in the body.

Exogenous histamine: histamine in food

Exogenous histamine (which is not produced by the body, present in food) is usually associated with other biogenic amines that are pharmacologically active by microorganisms that have histidine decarboxylase activity during food processing or spoilage. For histamine to cause adverse reactions and symptoms, it must be reabsorbed in the intestine and transported through the bloodstream without being inactivated by the enzymes, diamine oxidases (DAO) and histamine N-methyltransferase (HMT) present in intestinal epithelial cells.

That is why when we eat spoiled foods or have a genetic deficiency of DAO or have great intestinal permeability, it is likely that we will not tolerate large amounts of histamine due to the deficiency of this enzyme: in this situation, as there is a decrease in the degradation of histamine, excess histamine is produced, causing symptoms similar to an allergic reaction. These symptoms, headache, diarrhea, hives, can be reduced by a histamine-free diet or with antihistamine drugs (Maintz and Novak, 2007). Some foods high in histamine are chocolate, oily fish, pork, fermented foods, tomatoes or spinach, among others. Also some microorganisms such as Candida spp or Clostridium spp can produce histamine on their own, so that in cases of intestinal dysbiosis we can have an excess of histamine.

However, it has been discovered that the amount of DAO measured in plasma is not an accurate test, since normal activity has been observed in tissues but low in blood; research is lacking in this regard to ensure that plasma DAO tests are reliable. 

- Techniques with monoclonal antibodies against DAO show normal DAO activity in tissues such as kidney, intestine and placenta, while these same patients present barely relevant DAO activities in plasma (Kofler H, 2009)

- Histamine levels in the blood increase equally in patients with normal DAO and in patients with deficiency of DAO activity in blood (Giera B, 2008)

We can also have excess histamine if we consume alcohol or take drugs that block the activity of DAO such as some antidepressants, antibiotics, diuretics or mucolytics, among others.

Endogenous histamine and food intolerances (non-allergic food histamine)

If you suffer from this condition you probably identify with the following situations:

  • When you are bitten by a mosquito, you shower with very hot water or do sports, you notice redness, itching and dermographism on your skin.
  • You notice that your energy drops after meals
  • You notice gas, constipation, or diarrhea
  • You notice a headache
  • You notice a lot of itching on your body
  • You have hormonal alterations
  • Restless legs and a long etétctera

Dermographism is usually one of the most common characteristics in patients with histamine (Lovell P, 20007).

You feel identified? I explain why:

HANA syndrome (non-allergic food histamine) is a mechanism of endogenous release of histamine, that is, the cells of the immune system themselves are the ones that release them against certain proteins in food. When some alteration has occurred in the digestive tract, proteins that should remain in the digestive tract cross the digestive mucosa, producing a negative and inflammatory reaction mediated by cells. of the immune system, specifically T Lymphocytes and Mast Cells, in which histamine is released. This histamine accumulates in the tissues slowly, so the symptoms are not always immediate; they can appear hours or days after ingesting the food.

HANA mechanism (Prepared by Maria Puntí, 2022)

It is characterized by being a silent reaction, that is, those affected do not lose their health immediately, but instead enter into a progressive deterioration of their health that worsens their quality of life. 

When histamine accumulates, the symptoms are very similar to allergies:

  • Skin: rashes, atopy and urticaria, localized inflammation, erythema on face, neck and trunk, dry skin, tingling
  • Digestive: nausea, vomiting, diarrhea, epigastric pain, colic. 
  • Circulatory: hypotension or hypertension, edema, tachycardia, palpitation and conjunctival injection. 
  • Neurological: vertigo, headache, tingling, cramps, sensation of perioral heat, loss of vision, insomnia, memory problems, fatigue
  • Respiratory: bronchoconstriction, respiratory distress, congestion, dyspnea, chronic rhinitis
  • Digestive: reflux, heartburn or hypochlorhydria, nausea and vomiting, gas, colic, constipation, diarrhea, abdominal pain
  • Osteoarticular pain, fluid retention and pressure pain 
  • Mucous membranes: excessive salivation, dry eyes, vaginal dryness, salivation
  • Hormonal: long cycles, infertility, dysmenorrhea, recurrent abortions

Symptoms of histamine intolerance (Maintz and Novak, 2007)

Histamine shares some symptoms with allergies , such as rhinitis, itching, redness, inflammation, etc. Therefore, it is quite common for people with excess histamine to have been referred to an allergist, however, this mechanism is not mediated by IgE and has nothing to do with allergies, that is, we can develop HANA to wheat but not be celiac. , so wheat in this patient should be temporarily withdrawn even if he does not have a wheat allergy, since he has HANA to wheat. 

These people who have usually been incorrectly diagnosed are fibromyalgia, chronic rhinitis, central sensitivity syndrome or irritable bowel syndrome. Furthermore, we usually observe in consultation that patients with histaminosis usually relapse into processes such as bacterial overgrowth, fungal overgrowth or parasitosis, so it is essential to make an appropriate plan for them.

The solution is not a low histamine diet, but rather detecting which foods your body is producing histamine against.

With the third generation histamine release test and adequate treatment with histamine specialists, we can reverse this situation. The test we perform is done via blood extraction and we can evaluate against which proteins your body is releasing histamine (chicken, turkey, rice, potatoes, soy, certain fruits and vegetables...) by exposing the blood to possible food allergens. Finally, a diet is carried out according to the results while we repair the digestive tract and intestinal dysbiosis. 

Do you want to take the test and have your dietary plan to eliminate these symptoms once and for all? Hire the initial pack ( Online or In-person in Madrid or Valencia ) or write us an email to


Elorza, FL.; Rubio N.; Lizaso M. Standardization of the histamine release test. Allergology and Immunopathology, 1982; 10 (3), 221-228.

Mowat Allan McI. Anatomical basis of tolerance and immunity to intestinal
antigens. Nature Reviews Immunology, 2003; 3 (4),331-341.

Nakane, H., et al. Histamine: Its novel role as an endogenous regulator of Con A dependent T cell proliferation. Inflammation Research, 2004; 53 (7), 324-328.

Passani, M., Panula, P., & Lin, J. (2014). Histamine in the brain. Frontiers In Systems Neuroscience , 8 . doi:10.3389/fnsys.2014.00064

Kofler H, Aberer W, Deibl M, Hawranek TH, Klein G, Reider N, Fellner N. Diamine oxidase (DAO) serum activity: not a useful marker for diagnosis of histamine intolerance. Allergologie. 2009; 32: 105–109.

Giera B, Straube S, Konturek P, Hahn EG, Raithel M. Plasma histamine levels and symptoms in double blind placebo controlled histamine provocation. Inflamm Res. 2008; 57(Suppl 1): S73– S74.

Rosell-Camps A, Zibetti S, Pérez-Esteban G, Vila-Vidal M, Ferrés-Ramis L, García-Teresa- García E. Histamine intolerance as a cause of chronic digestive complaints in pediatric patients. Rev Esp Enferm Dig. 2013; 105: 201–206.

Ramos-Jiménez J, et al. Histamine and intercellular communication: 99 years of history. Rev Biomed 2009; 20:100-126

Manzotti G, Breda D, Di Gioacchino M, Burastero SE. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol. 2016; 29: 105-111.

Schwelberger HG. Histamine intolerance: overestimated or underestimated? Inflamm Res. 2009 Apr;58 Suppl 1:51-2. doi:10.1007/s00011-009-2004-4. PMID: 19271146.

Petersen, J., et al. Analysis of genetic polymorphisms of enzymes involved in histamine metabolism. Inflammation Research, 2003; 52, 69-70.
RILEY JF. HISTAMINE AND SIR HENRY DALE. Br Med J. 1965;1(5448):1488-1490. doi:10.1136/bmj.1.5448.1488

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