What is Histamine Intolerance


  • Histamine intolerance is thought to result from an imbalance between eating foods high in histamine and your body’s ability to break it down.
  • Different factors like genetic mutations and your gut microbiome can predispose you to develop histamine intolerance.
  • There are many tests used to diagnose histamine intolerance, many of which have not been validated or standardized. The most recommended approach to confirm histamine intolerance is to follow a 3-phase low histamine diet plan for 4 to 8 weeks, with the guidance of a healthcare provider.
  • Treatment of histamine intolerance involves a personalized long-term diet plan low in foods that contain histamine.


Ever heard of histamine intolerance (HIT)? In recent years, this health condition has gained increased attention. From pesky headaches to puzzling digestive pain or runny nose, the symptoms associated with HIT can be diverse and challenging to pinpoint.

In this blog post, we’ll delve into the basics behind HIT and factors that predispose you to it. We’ll also explore how HIT is connected to the gut microbiome and how it’s diagnosed.

What is histamine?

We tend to think of histamine as bad because we associate it with allergic reactions like runny nose and sneezes. But histamine is essential for maintaining good health, and is actually important for many different physiological processes. Among other things, histamine has a role in:

  • Mediating inflammatory and allergic responses
  • Promoting gastric acid production
  • Influencing temperature regulation, alertness, and cognitive and behavioral functions [1]

In the human body, histamine is produced by immune cells, like when your body reacts to an allergen and produces histamine at the site. It’s also produced by cells in your stomach and even neurons [2]–[4]. What’s more, certain microbes in your gut are capable of producing histamine [5], [6], and you can also get histamine from certain foods [1], [7], [8]. But more on that later. Then there are histamine receptors, which ‘react’ to histamine, present all over the body [9]. Through these, histamine acts as a chemical messenger, promoting for example, the recruitment of immune cells to sites of inflammation.

Histamine levels in your body are kept under control by two different enzymes that break histamine down. One of these is diamine oxidase, or DAO, which is mainly produced in your intestines [10]. Among other things, this is important to prevent an exacerbated immune response or too much gastric acid production due to excess histamine.

What is histamine intolerance?

Histamine intolerance (HIT) is described as a type of food intolerance that doesn’t involve an immune response. It’s different from immune-mediated food allergy, in which immune cells react to an allergen by releasing histamine and other inflammatory compounds. There is no such immune response in HIT. Instead, HIT it’s thought to result from an imbalance between eating food high in histamine and your body’s ability to break it down [1]. Scientists think this occurs when your body doesn’t produce enough DAO enzyme (also known as DAO deficiency). 

DAO deficiency may occur due to genetic factors, that is, mutations in the DAO gene that lead to limited production of the enzyme or reduced activity [11]. And certain medications such as ambroxol, metoclopramide, amitriptyline, and ibuprofen may reduce DAO activity, although evidence of this only comes from laboratory studies [12].

Having increased levels of histamine-producing bacteria in your gut is another factor that seems to predispose you to HIT [6], [13].

HIT is different from an allergic reaction in which even the smallest amount of allergen can cause severe symptoms. In HIT, the severity of symptoms depends on how much food with histamine you eat.

Since histamine receptors are present all over the body, symptoms vary a lot among people. Most common symptoms include:

  • Bloating
  • Headache
  • Gassiness
  • Diarrhea
  • Heartburn
  • Intermittent vomiting
  • Abdominal, muscular, and articular pain [6], [14]

For some people, HIT can also manifest with skin symptoms (skin rash, erythema, itchiness, hives, edema) or respiratory symptoms (runny nose, shortness of breath) [1], [6], [14].

Chronic allergic diseases (eczema, allergic rhinitis, asthma) and intestinal diseases (celiac disease, food allergy, inflammatory bowel disease) have been associated with HIT [15]–[18].

Histamine intolerance diagnosis

A practitioner will usually diagnose HIT based on symptoms, clinical history, presence of chronic diseases, and possible relationships with food. But given that symptoms vary so much among people, it may be difficult to reach a diagnosis. Besides, HIT is sometimes confused with other allergic diseases, which should be ruled out appropriately.

The most recommended approach to properly diagnose HIT is to follow a low histamine diet plan for 4 to 8 weeks [19]. This plan considers 3 different phases:

Phase 1: elimination of all foods containing histamine. Foods most often recommended to be avoided include:

  • Canned or fermented fish products like sardines in oil and canned tuna
  • Fatty fish like salmon, mackerel, and herring
  • Hard and semi-hard mature cheese like Parmesan, Cheddar, and Camembert
  • Cured, air-dried sausages, hams, and smoked meats
  • Certain vegetables like tomato, sauerkraut, and spinach
  • Citruses like lemon, orange, and grapefruit
  • Strawberries
  • Wine and beer

Phase 2: Some of the excluded foods are slowly reintroduced to evaluate if symptoms reappear.

Phase 3: Trial of a long-term diet.

It’s important to follow this low histamine diet plan with the guidance of a healthcare provider.

Additional tests that are sometimes used to support HIT diagnosis include:

  • Determination of DAO concentration in blood serum. This is the most used approach to diagnose HIT, but it’s also controversial because serum levels don’t entirely correspond to intestinal levels, which is where DAO is most active [20]–[22].
  • Histamine 50 skin prick test (SPT). This is similar to a standard SPT to diagnose allergy, except that the size of the histamine wheal is assessed after 50 minutes. The problem with this test is that it may be difficult to differentiate between HIT and other allergic disorders and that it may give a positive result to people without HIT [23].
  • Intestinal biopsy. Highly sensitive and specific, but invasive and of high cost, so not often used [24].
  • Oral histamine challenge test. It involves taking a solution containing histamine and observing clinical symptoms. It’s not recommended because it can also trigger a positive response in people without HIT [25], [26].
  • Genetic test. A non-invasive test that looks for mutations in histamine-degrading enzymes, using a sample of blood or from the oral mucosa. This is not used in routine diagnosis [11].
  • Determination of histamine levels in blood serum. This is of high cost, low availability, and not good to differentiate people with and without HIT [27].

Histamine intolerance treatment

If your provider confirms HIT, treatment will be a long-term diet that limits the amounts of foods that contain histamine. This diet should be personalized for you, as a diet that completely eliminates all foods with histamine is not feasible.

You may also be prescribed a supplement of DAO enzyme. Take into account that there are only a few studies evaluating the effectiveness of these supplements. Some are of low quality, some were supported by the supplement manufacturer, and results regarding effectiveness of the supplements are mixed [25], [28]–[30]. More studies are needed to clearly demonstrate if DAO supplements are a good treatment choice for HIT.

Histamine intolerance and the gut microbiome

Some gut bacteria (e.g. Klebsiella aerogenes, Clostridium perfringens, and Citrobacter youngae) are capable of producing histamine [5], and thus may contribute to your overall levels of histamine. In certain people, having too much of these bacteria could increase sensitivity to ingested histamine, because total levels of histamine circulating in your body will be higher.

Compared to healthy people, those with asthma or inflammatory bowel disease seem to have higher levels of histamine-producing species in the gut [5], [31].

If you have taken a Tiny Health Gut Test, you’ll see a section that reports the levels of histamine-producing species.

It’s important to interpret this section correctly:

  • If you have high levels of histamine-producing species but don’t experience any symptoms when eating foods that contain histamine, it’s likely you don’t have HIT. It’s still a good idea to focus on improving your gut microbiome in any areas that need support. This will likely decrease the levels of these unfriendly species.
  • If you have low or absent levels of histamine-producing species but experience symptoms or have been diagnosed with HIT, you should take into account that the gut microbiome is only one part of the picture. Genetics and food choices are important factors that may contribute to HIT.
  • If you have high levels of histamine-producing species and you’re experiencing symptoms when eating foods with histamine, it’s possible you have HIT. We recommend trying a low histamine diet with the guidance of a healthcare provider to get a proper diagnosis.


[1] M. Hrubisko, R. Danis, M. Huorka, and M. Wawruch, “Histamine Intolerance-The More We Know the Less We Know. A Review,” Nutrients, vol. 13, no. 7, p. 2228, Jun. 2021, doi: 10.3390/nu13072228.

[2] K. N. Dileepan et al., “Mast cell-mediated immune regulation in health and disease,” Front. Med., vol. 10, p. 1213320, 2023, doi: 10.3389/fmed.2023.1213320.

[3] C. Prinz, R. Zanner, and M. Gratzl, “Physiology of gastric enterochromaffin-like cells,” Annu. Rev. Physiol., vol. 65, pp. 371–382, 2003, doi: 10.1146/annurev.physiol.65.092101.142205.

[4] T. Yoshikawa, T. Nakamura, and K. Yanai, “Histaminergic neurons in the tuberomammillary nucleus as a control centre for wakefulness,” Br. J. Pharmacol., vol. 178, no. 4, pp. 750–769, Feb. 2021, doi: 10.1111/bph.15220.

[5] Z. Mou, Y. Yang, A. B. Hall, and X. Jiang, “The taxonomic distribution of histamine-secreting bacteria in the human gut microbiome,” BMC Genomics, vol. 22, no. 1, p. 695, Sep. 2021, doi: 10.1186/s12864-021-08004-3.

[6] S. Sánchez-Pérez et al., “Intestinal Dysbiosis in Patients with Histamine Intolerance,” Nutrients, vol. 14, no. 9, p. 1774, Apr. 2022, doi: 10.3390/nu14091774.

[7] S. Sánchez-Pérez, O. Comas-Basté, J. Rabell-González, M. T. Veciana-Nogués, M. L. Latorre-Moratalla, and M. C. Vidal-Carou, “Biogenic Amines in Plant-Origin Foods: Are They Frequently Underestimated in Low-Histamine Diets?,” Foods Basel Switz., vol. 7, no. 12, p. 205, Dec. 2018, doi: 10.3390/foods7120205.

[8] I. San Mauro Martin, S. Brachero, and E. Garicano Vilar, “Histamine intolerance and dietary management: A complete review,” Allergol. Immunopathol. (Madr.), vol. 44, no. 5, pp. 475–483, 2016, doi: 10.1016/j.aller.2016.04.015.

[9] M. E. Parsons and C. R. Ganellin, “Histamine and its receptors,” Br. J. Pharmacol., vol. 147 Suppl 1, no. Suppl 1, pp. S127-135, Jan. 2006, doi: 10.1038/sj.bjp.0706440.

[10] Y. Ji et al., “Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release,” Am. J. Physiol. Gastrointest. Liver Physiol., vol. 304, no. 8, pp. G732-740, Apr. 2013, doi: 10.1152/ajpgi.00399.2012.

[11] L. Maintz et al., “Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities,” Allergy, vol. 66, no. 7, pp. 893–902, Jul. 2011, doi: 10.1111/j.1398-9995.2011.02548.x.

[12] L. Maintz and N. Novak, “Histamine and histamine intolerance,” Am. J. Clin. Nutr., vol. 85, no. 5, pp. 1185–1196, May 2007, doi: 10.1093/ajcn/85.5.1185.

[13] M. Schink et al., “Microbial patterns in patients with histamine intolerance,” J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc., vol. 69, no. 4, Aug. 2018, doi: 10.26402/jpp.2018.4.09.

[14] A. Rosell-Camps, S. Zibetti, G. Pérez-Esteban, M. Vila-Vidal, L. Ferrés-Ramis, and E. García-Teresa-García, “Histamine intolerance as a cause of chronic digestive complaints in pediatric patients,” Rev. Esp. Enferm. Dig., vol. 105, no. 4, pp. 201–206, Apr. 2013, doi: 10.4321/s1130-01082013000400004.

[15] R. Meza-Velázquez et al., “Association between two polymorphisms of histamine-metabolising enzymes and the severity of allergic rhinitis in a group of Mexican children,” Allergol. Immunopathol. (Madr.), vol. 44, no. 5, pp. 433–438, 2016, doi: 10.1016/j.aller.2016.01.002.

[16] A. Szczepankiewicz, A. Bręborowicz, P. Sobkowiak, and A. Popiel, “Polymorphisms of two histamine-metabolizing enzymes genes and childhood allergic asthma: a case control study,” Clin. Mol. Allergy CMA, vol. 8, p. 14, Nov. 2010, doi: 10.1186/1476-7961-8-14.

[17] W. J. Schnedl, H. Mangge, M. Schenk, and D. Enko, “Non-responsive celiac disease may coincide with additional food intolerance/malabsorption, including histamine intolerance,” Med. Hypotheses, vol. 146, p. 110404, Jan. 2021, doi: 10.1016/j.mehy.2020.110404.

[18] Y. Honzawa, H. Nakase, M. Matsuura, and T. Chiba, “Clinical significance of serum diamine oxidase activity in inflammatory bowel disease: Importance of evaluation of small intestinal permeability,” Inflamm. Bowel Dis., vol. 17, no. 2, pp. E23-25, Feb. 2011, doi: 10.1002/ibd.21588.

[19] I. Reese et al., “Guideline on management of suspected adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergology and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA) as well as the Swiss Society for Allergology and Immunology (SGAI) and the Austrian Society for Allergology and Immunology (ÖGAI),” Allergol. Sel., vol. 5, pp. 305–314, 2021, doi: 10.5414/ALX02269E.

[20] V. Cucca et al., “Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study,” Nutrients, vol. 14, no. 7, p. 1513, Apr. 2022, doi: 10.3390/nu14071513.

[21] J. van Odijk, A. Weisheit, M. Arvidsson, N. Miron, B. Nwaru, and L. Ekerljung, “The Use of DAO as a Marker for Histamine Intolerance: Measurements and Determinants in a Large Random Population-Based Survey,” Nutrients, vol. 15, no. 13, p. 2887, Jun. 2023, doi: 10.3390/nu15132887.

[22] K. Arih, N. Đorđević, M. Košnik, and M. Rijavec, “Evaluation of Serum Diamine Oxidase as a Diagnostic Test for Histamine Intolerance,” Nutrients, vol. 15, no. 19, p. 4246, Oct. 2023, doi: 10.3390/nu15194246.

[23] L. Kofler, H. Ulmer, and H. Kofler, “Histamine 50-skin-prick test: a tool to diagnose histamine intolerance,” ISRN Allergy, vol. 2011, p. 353045, 2011, doi: 10.5402/2011/353045.

[24] W. U. Schmidt et al., “Human intestinal diamine oxidase (DAO) activity in Crohn’s disease: a new marker for disease assessment?,” Agents Actions, vol. 30, no. 1–2, pp. 267–270, Apr. 1990, doi: 10.1007/BF01969057.

[25] P. Komericki et al., “Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study,” Wien. Klin. Wochenschr., vol. 123, no. 1–2, pp. 15–20, Jan. 2011, doi: 10.1007/s00508-010-1506-y.

[26] S. Wöhrl, W. Hemmer, M. Focke, K. Rappersberger, and R. Jarisch, “Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine,” Allergy Asthma Proc., vol. 25, no. 5, pp. 305–311, 2004.

[27] B. Giera, S. Straube, P. Konturek, E. G. Hahn, and M. Raithel, “Plasma histamine levels and symptoms in double blind placebo controlled histamine provocation,” Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al, vol. 57 Suppl 1, pp. S73-74, 2008, doi: 10.1007/s00011-007-0636-9.

[28] J. Izquierdo-Casas et al., “Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial,” Clin. Nutr. Edinb. Scotl., vol. 38, no. 1, pp. 152–158, Feb. 2019, doi: 10.1016/j.clnu.2018.01.013.

[29] M.-R. Yacoub et al., “Diamine Oxidase Supplementation in Chronic Spontaneous Urticaria: A Randomized, Double-Blind Placebo-Controlled Study,” Int. Arch. Allergy Immunol., vol. 176, no. 3–4, pp. 268–271, 2018, doi: 10.1159/000488142.

[30] W. J. Schnedl, M. Schenk, S. Lackner, D. Enko, H. Mangge, and F. Forster, “Diamine oxidase supplementation improves symptoms in patients with histamine intolerance,” Food Sci. Biotechnol., vol. 28, no. 6, pp. 1779–1784, Dec. 2019, doi: 10.1007/s10068-019-00627-3.

[31] W. Barcik et al., “Histamine-secreting microbes are increased in the gut of adult asthma patients,” J. Allergy Clin. Immunol., vol. 138, no. 5, pp. 1491-1494.e7, Nov. 2016, doi: 10.1016/j.jaci.2016.05.049.