Histamine is a compound mainly produced in our body and in the gastrointestinal mucosa. It has a variety of functions, such as its immune function in allergic inflammation and hypersensitivity, induction of smooth muscle cells, blood vessel dilation, neurotransmission, etc. Recent research has found that histamine plays a role in the development and progression of diseases such as inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and colorectal cancer by increasing gut permeability, leading to inflammation and immune activation that contribute to these diseases. In the human body, immune cells such as mast cells and basophils are the primary sources of histamine. However, approximately 5% of the total histamine in our body is derived externally from the food we eat and microbial fermentation products. In some individuals, histamine is not readily metabolized or broken down in the intestine, leading to its concomitant rise in the body — a condition known as histamine intolerance.

Histamine intolerance (HIT) is a debated condition that some experts attribute to the body's reduced ability to break down histamine, leading to symptoms that mimic allergic reactions and gastrointestinal disturbances. Histamine is a naturally occurring compound involved in immune responses, digestion, and neurological functions, but it is also found in various foods. While HIT is often discussed in medical circles, it is not officially recognized as a distinct medical condition by organizations such as the American Academy of Allergy, Asthma, and Immunology (AAAAI). Recent research, including a 2023 study, has suggested that many individuals who suspect they have HIT may actually have other underlying conditions that produce similar symptoms. As a result, it is crucial to consult a healthcare provider for an accurate diagnosis and appropriate management of symptoms.

Despite its allergy-like manifestations, histamine intolerance is not classified as a true food allergy. Allergies involve an immune system response to specific proteins, whereas HIT is thought to result from an enzymatic deficiency—particularly of diamine oxidase (DAO), an enzyme responsible for histamine breakdown. Because of this, some experts refer to HIT as a “pseudoallergy,” meaning it can resemble an allergic reaction but does not involve the same immune mechanisms.

Histamine intolerance should not be confused with histamine intoxication, also known as histamine poisoning. Histamine intoxication is a well-documented form of foodborne illness that occurs when individuals consume foods with dangerously high levels of histamine, often due to improper storage and bacterial contamination, particularly in certain fish species. Unlike HIT, which is an individualized response, histamine poisoning typically affects multiple people who have eaten the same contaminated food. The controversy surrounding histamine intolerance remains, as experts continue to debate whether low levels of dietary histamine can truly cause symptoms or if conditions such as irritable bowel syndrome (IBS) or other digestive disorders are responsible for the reported reactions.

Common symptoms of histamine intolerance include shortness of breath, nasal congestion, digestive issues, headaches, etc. Typically, histamine intolerance is due to low levels of the enzyme diamine oxidase (DAO), which is known to break down digested histamine. Interestingly, recent research has shown that gut bacteria also play a key role in modulating histamine levels in the body. For example, a specific gut bacterium, Klebsiella aerogenes, derived from IBS patients, was reported to produce high amounts of histamine, leading to inflammation and pain in the gut of mice colonized with the gut microbiota from IBS patients. This study found that the bacterium Klebsiella aerogenes, found in 25% of IBS patients, converts dietary histidine, an essential amino acid found in animal and plant protein, into histamine, which mediates pain. The bacterial histamine then activates the gut immune system, thereby attracting immune mast cells into the intestinal tract. The activation of mast cells further produces more histamine and triggers pain and inflammation. This probably explains why IBS patients show high amounts of mast cells and inflammatory biomarkers in their colon.

Bacterial histamine may be a therapeutic target for treating chronic abdominal pain in patients with IBS. However, working with a healthcare provider to develop an individualized treatment plan that addresses the underlying causes of chronic pain is essential. The gut microbiota appears to play a crucial role in the modulation of histamine levels, further emphasizing the need to maintain a healthy gut.

Histamine levels in foods can be highly variable and challenging to measure, as they depend on factors such as aging, fermentation, storage conditions, and additives. Even within the same food category—such as a block of cheddar cheese—histamine content can fluctuate significantly.

In general, fermented, aged, or processed foods tend to have the highest histamine levels, whereas fresh, minimally processed foods typically contain lower amounts. Additionally, some foods, despite not being rich in histamine themselves, are believed to trigger the body's histamine release. These are known as histamine liberators, though scientific evidence supporting this concept remains inconclusive.

For individuals managing histamine intolerance, reducing or eliminating high-histamine foods from their diet may help alleviate symptoms. The following foods are known to contain elevated histamine levels and are often restricted on a low-histamine diet:

• Dairy and Fermented Products: Aged cheeses (e.g., cheddar, parmesan, gouda), yogurt, sour cream, buttermilk, kefir.
• Fermented and Pickled Foods: Sauerkraut, kimchi, pickles, pickled vegetables, kombucha.
• Cured and Fermented Meats: Salami, pepperoni, sausages, fermented ham.
• Alcoholic Beverages: Wine, beer, champagne, aged spirits (e.g., whiskey, rum).
• Soy-Based Fermented Products: Soy sauce, miso, tempeh, natto.
• Certain Vegetables: Tomatoes, eggplant, spinach.
• Fish and Seafood: Canned fish (e.g., tuna, sardines, mackerel), salted or smoked fish, and frozen fish (if improperly stored, as histamine accumulates in spoiled fish).
• Other High-Histamine Foods and Condiments: Vinegar (e.g., balsamic vinegar, apple cider vinegar), ketchup, sourdough bread (due to fermentation).

Since histamine intolerance affects individuals differently, some may tolerate small amounts of these foods, while others experience symptoms even with minimal exposure. Keeping a detailed food diary and consulting a healthcare professional or registered dietitian can help identify specific triggers and guide dietary modifications.