Histamine Intolerance and Gut Health

Histamine intolerance, sometimes also called histaminosis or dietary histamine sensitivity, is the imbalance between the amount of histamine in the body and its breakdown. Research into histamine intolerance is still underway, with multiple proposed underlying mechanisms, ongoing diagnostic challenges, and the added layer of complexity with the gut microbiome. Read on to learn more about histamine intolerance and gut health, where the gut microbiome fits in, and what current research actually shows about probiotics, diet, and lifestyle considerations.

What Is Histamine Intolerance?

Histamine intolerance is thought to occur when the body is exposed to more histamine than it can effectively eliminate. One of the key enzymes involved in this breakdown is diamine oxidase (DAO), and reduced activity of this enzyme is thought to be a leading mechanism underlying histamine intolerance¹.

Histamine intolerance is unlike food allergies as it does not involve the same IgE-mediated immune response¹. But because the symptoms can look very similar to an allergic reaction, and there is no single reliable diagnostic test for it, the condition remains difficult to define and diagnose. Common symptoms can vary and may affect several parts of the body¹:

• Intestinal: Bloating, diarrhoea, constipation, discomfort.
• Skin: Flushing, pruritus, urticaria, swelling, dermatitis
• Nervous system: Headache or migraine-like symptoms
• Cardiovascular system: Tachycardia, collapse, hypotension
• Respiratory system: Dyspnea, rhinorrhea, congestion, sneezing, rhinitis

The underlying cause of histamine intolerance is still under debate, and is likely to be due to multiple interacting mechanisms. Proposed contributors include genetic factors, DAO-inhibiting medications, alcohol consumption, gastrointestinal disease, or deficiencies in nutrients involved in enzyme function, such as vitamin C and copper¹.

How Is Histamine Intolerance Diagnosed?

Diagnosis of histamine intolerance remains challenging as there is currently no single validated test and the symptoms overlap with various other conditions. Serum DAO testing is limited by day-to-day and intra-day variation, while skin prick testing cannot distinguish histamine intolerance from true allergy¹. Histamine challenge testing is technically difficult and may trigger symptoms in healthy individuals, and faecal histamine levels can be influenced by gut microbiota¹.

In one placebo-controlled study investigating histamine challenge in patients with suspected histamine intolerance, over 60% of patients reacted to placebo, and histamine intolerance was ultimately excluded in around 85% of cases, highlighting the challenges with diagnostic testing².

In practice, diagnosis largely relies on excluding other causes, careful symptom assessment, and, when appropriate, a monitored dietary elimination and reintroduction approach¹. Histamine intolerance remains a debated clinical entity, so the symptoms alone should not be considered diagnostic.

The Gut Microbiome and Histamine

The relationship between gut bacteria and histamine is complex. Some bacteria in the gut can convert dietary histidine into histamine, while others can help to break histamine down³. So the link between gut health and histamine intolerance may depend on microbial balance rather than a single organism.

Excess microbial histamine may also amplify mucosal inflammation and could lead to increased intestinal permeability, also known as leaky gut, which could further impair intestinal barrier function and may reduce DAO activity, although this mechanism requires further investigation³.

Histamine is also stored and released by immune cells such as mast cells and basophils. The release of histamine can be triggered by allergens, certain medicines, and physical stressors⁴. Some foods and additives are described as histamine liberators because they may encourage mast cells to release stored histamine, even when the foods themselves are not particularly high in histamine⁵.

What Does the Research Show?

A key theory is that patients with histamine intolerance may have gut dysbiosis, which may add a potential mechanism for the pathogenesis of histamine intolerance. Two key clinical studies highlight how gut dysbiosis may occur in histamine-intolerant patients:

• In a 2018 study, researchers found that people with histamine intolerance had lower microbial diversity, higher levels of Proteobacteria, lower Bifidobacteriaceae, and elevated stool zonulin (a marker for leaky gut), suggesting dysbiosis and impaired gut barrier function⁶.
• In a 2022 study, those with histamine intolerance had higher levels of several histamine-producing bacteria, including Staphylococcus, Proteus, Clostridium perfringens, and Enterococcus faecalis, alongside lower levels of Faecalibacterium, a health-associated genus with anti-inflammatory properties³.

These studies suggest that the gut microbiome may play a role in histamine intolerance through its effects on histamine metabolism, inflammation, and gut barrier function. However, the evidence remains limited and does not yet establish whether dysbiosis is a cause or consequence of the condition.

Dietary and Lifestyle Considerations

Because of the close relationship between gut health and histamine, dietary modification, including a low-histamine diet, is one of the key management strategies for histamine intolerance. This may include limiting the consumption of the following foods, however research is still underway in this area⁵:

• High histamine foods: Tomato, spinach, fermented vegetables, eggplant, avocado, fermented meat, cured meat, smoked meat, dried meat, blue fish, canned fish, preserved fish, alcohol-containing drinks, fermented soy products, yoghurt, vinegar, cured cheese, semi-cured cheese, and smoked cheese.
• Histamine liberator foods: Lemons, limes, pineapple, kiwi, papaya, egg white, cow’s milk, seafood, coffee, tea, alcohol-containing drinks, chocolate, cocoa, liquorice, peanuts, and walnuts.
• DAO inhibitor foods: Bananas, citrus fruits, strawberries, pineapple, coffee, tea, alcohol-containing drinks, energy drinks, and chocolate.

There are key clinical studies that highlight the benefits of a low-histamine diet for histamine intolerance. In a small pilot study, women with histamine intolerance tracked their microbiota changes over 9 months with a low-histamine dietary treatment. They found reductions in histamine-secreting Proteus, Raoultella, and Proteus mirabilis, and an increase in Roseburia species, a bacterial group associated with gut health⁷. But there were no significant changes in overall microbial diversity⁷.

Also, in a retrospective study of 101 patients, all participants had higher serum DAO values due to a histamine-reduced diet, and 50 of the 63 patients who completed the questionnaire had symptom improvement or no continuing symptoms⁸.

In addition to dietary intervention, other interventions may include DAO supplementation. In a clinical study of 82 patients with histamine intolerance, a capsule containing a DAO supplement, vitamin C, and catalase improved symptoms, including gastrointestinal, skin, nervous and respiratory, and circulatory symptoms⁹. In an additional study in patients with episodic migraines, DAO supplementation reduced the duration of migraine attacks¹⁰.

Probiotics and Histamine Intolerance

The use of probiotics for histamine intolerance is an emerging area of research. However, currently, there is no human clinical trial data specifically on the use of probiotics for histamine intolerance. A clinical trial (NCT07397962) was registered and completed in 2025 to test a probiotic-based treatment containing a combination of several Bifidobacterium and Lactobacillus species in histamine-intolerant patients. However, data are currently not yet published or finalised in public registries¹¹.

While there is currently a lack of clinical studies for probiotics and histamine intolerance specifically, there is some evidence for probiotics for urticaria, a common symptom of histamine intolerance. In a systematic review and meta-analysis of nine trials examining oral probiotics for chronic urticaria, single-strain probiotics showed a significantly better therapeutic effect than placebo, and single-strain probiotics combined with antihistamines outperformed antihistamines alone¹².

Clinical Takeaways

Histamine intolerance is poorly understood and difficult to diagnose, with no standardised test and several possible underlying mechanisms. Because symptoms are non-specific, food allergy and other gastrointestinal or allergic conditions should also be considered.

Current evidence suggests there may be a histamine intolerance and gut microbiome relationship through interactions between the gut microbiome, intestinal barrier function, and immune signalling. Early studies suggest that some patients with suspected histamine intolerance have altered microbial profiles, but it is not yet clear whether these changes are a cause or consequence of the condition.

Probiotics may become a useful area of research, but current evidence for histamine intolerance is lacking. For now, gut health may have a role in symptom management, although more high-quality studies are needed.

References

1. Jochum C. Histamine Intolerance: Symptoms, Diagnosis, and Beyond. Nutrients. 2024 Apr 19;16(8):1219. doi:10.3390/nu16081219
2. Bent RK, Kugler C, Faihs V, Darsow U, Biedermann T, Brockow K. Placebo-Controlled Histamine Challenge Disproves Suspicion of Histamine Intolerance. The Journal of Allergy and Clinical Immunology: In Practice. 2023 Dec;11(12):3724-3731.e11. doi:10.1016/j.jaip.2023.08.030
3. Sánchez-Pérez S, Comas-Basté O, Duelo A, Veciana-Nogués MT, Berlanga M, Latorre-Moratalla ML, et al. Intestinal Dysbiosis in Patients with Histamine Intolerance. Nutrients. 2022 Apr 23;14(9):1774. doi:10.3390/nu14091774
4. Borriello F, Iannone R, Marone G. Histamine Release from Mast Cells and Basophils. In: Hattori Y, Seifert R, editors. Histamine and Histamine Receptors in Health and Disease. Cham: Springer International Publishing; 2017. p. 121–39. doi:10.1007/164_2017_18
5. Jackson K, Busse W, Gálvez-Martín P, Terradillos A, Martínez-Puig D. Evidence for Dietary Management of Histamine Intolerance. Int J Mol Sci. 2025 Sep 20;26(18):9198. doi:10.3390/ijms26189198 PubMed PMID: 41009760; PubMed Central PMCID: PMC12470264.
6. Schink M, Konturek PC, Tietz E, Dieterich W, Pinzer TC, Wirtz S, et al. Microbial patterns in patients with histamine intolerance. J Physiol Pharmacol. 2018 Aug;69(4). doi:10.26402/jpp.2018.4.09 PubMed PMID: 30552302.
7. Sánchez-Pérez S, Comas-Basté O, Duelo A, Veciana-Nogués MT, Berlanga M, Vidal-Carou MC, et al. The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study. Front Nutr. 2022 Oct 21;9:1018463. doi:10.3389/fnut.2022.1018463
8. Lackner S, Malcher V, Enko D, Mangge H, Holasek SJ, Schnedl WJ. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance. Eur J Clin Nutr. 2019 Jan;73(1):102–4. doi:10.1038/s41430-018-0260-5
9. O’Connor ME, Terradillos-Guillén A, Gálvez-Martín P, Martínez-Puig D. Observational study to assess the efficacy and safety of diaminooxidase (DAO) supplementation in patients with histamine intolerance (HIT). Clinical Nutrition ESPEN. 2023 Dec;58:741. doi:10.1016/j.clnesp.2023.09.892
10. Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, Lorente-Gascón M, Duelo A, Soler-Singla L, et al. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial. Clinical Nutrition. 2019 Feb;38(1):152–8. doi:10.1016/j.clnu.2018.01.013
11. ClinicalTrials.gov. Treatment of Histamine Intolerance Using Probiotic Intervention (ID: NCT07397962) [Internet]. Available from: https://clinicaltrials.gov/study/NCT07397962
12. Fu H, Yu H, Bai Y, Yue L, Wang H, Li L. Effect and safety of probiotics for treating urticaria: A systematic review and meta-analysis. J of Cosmetic Dermatology. 2023 Oct;22(10):2663–70. doi:10.1111/jocd.15782