Histamine intolerance

Histamine and histamine intolerance are topics of growing interest, especially because they are often misdiagnosed as IBS. The aim of this article is to shed light on histamine intolerance, its common symptoms, diagnostic approaches, and therapeutic strategies.

This is Part 1 of the Histamine series. Read Part 2: The link between histamine intolerance and the gut microbiome, and Part 3: Histamine and Irritable Bowel Syndrome (IBS) to gain a deeper understanding of histamine and histamine intolerance.

What Is Histamine?

Histamine is a signaling molecule that communicates with cells throughout the body, including the brain, digestive system, and immune system. It is naturally produced and stored in the body—primarily by white blood cells such as mast cells and basophils—and it is also found in certain foods, such as fermented products, alcohol, and aged cheese.

In appropriate amounts, histamine has beneficial effects in the body, such as stimulating gastric acid production, regulating appetite, supporting homeostasis (e.g., body temperature), hormone function, cell growth, and sleep cycles. In addition, histamine is released as part of the immune response. When the body perceives a threat (such as pollen, food, or dust), histamine is released and acts through its four receptors (located in the brain, nose, chest, and gut), triggering protective reactions throughout the body.

Healthy histamine levels are maintained by two enzymes: diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). However, when there is an imbalance between histamine levels and the body’s ability to break it down, excess histamine can disrupt normal physiological function. High histamine levels overstimulate histamine receptors, producing allergy-like symptoms known as histamine intolerance.

Histamine Intolerance (HIT)

The symptoms of histamine intolerance can vary but usually occur after consuming foods that contain histamine in amounts that would not normally cause symptoms in healthy individuals.

Common symptoms of HIT include:

• Gastrointestinal symptoms: nausea, vomiting, constipation, abdominal pain, bloating

• Headaches and migraines

• Nasal symptoms: congestion, runny or itchy nose, sneezing

• Skin reactions: itching, rashes, flushing

• Low blood pressure

• Menstrual cramps

How Do Histamine Levels Become Too High?

Excess histamine in the body is usually caused by reduced levels or impaired activity of DAO, leading to inefficient breakdown of histamine. Genetic factors, conditions such as IBS and IBD, alcohol consumption, and certain medications can all reduce DAO levels or activity.

Histamine levels in foods can vary greatly—even within the same product—making them difficult to measure. Foods that typically contain higher histamine levels include:

• Fermented foods such as sauerkraut, kimchi, and yogurt
• Alcohol and fermented beverages
• Processed meats (e.g., sausages, salami, smoked and cured meats
• Aged cheeses
• Citrus fruits
• Spinach, avocado, eggplant
• Fish and shellfish
• Vinegar

Diagnosis

Histamine intolerance and its symptoms vary widely between individuals and even within the same person. At present, HIT is difficult to diagnose clinically because standardized diagnostic tests are still lacking.

In the absence of validated testing methods, the following diagnostic approach is recommended:

1. Rule out other causes that could explain the symptoms, such as food allergies, medications affecting DAO activity, gastrointestinal diseases (e.g., IBS, IBD), or systemic mastocytosis (excess mast cells).

2. Confirm HIT: If two or more symptoms improve on a low-histamine diet, HIT is considered likely.

3. Keep a food and symptom diary for 24 hours, followed by a 4–8-week low-histamine diet.

4. Additional tests may be useful in some cases, including DAO activity testing, oral or skin-prick histamine tests, genetic testing, and measurement of histamine metabolites (methylhistamine) in urine or stool.

Histamine Intolerance vs. Food Allergy

Food allergy, food intolerance, and histamine intolerance often produce similar symptoms and are therefore easy to confuse. Food allergies involve the immune system, where even small amounts of a food can trigger symptoms. Food intolerances primarily affect the digestive system and usually cause milder reactions.

Histamine intolerance, on the other hand, is not simply sensitivity to histamine-containing foods—it occurs when the body cannot adequately break down the histamine it contains.

Therapeutic Treatment of HIT

The gold standard treatment for histamine intolerance is a low-histamine diet, in which high-histamine foods are eliminated for a period of time. These foods are then gradually reintroduced one by one to identify individual triggers.

In addition to dietary changes, it is important to assess medications that may affect histamine levels or DAO activity and adjust them if necessary.

In some cases, DAO supplements may be recommended to help support the breakdown of dietary histamine.

There is still no universal consensus on specific dietary guidelines for HIT. However, it is generally recommended to avoid hard and semi-hard cheeses, fatty fish, shellfish, fermented meats, pickled vegetables, fermented soy products, alcohol, chicken, eggs, chocolate, and mushrooms. Meat and fish should only be eaten fresh. In addition, vegetables and fruits such as spinach, tomatoes, citrus fruits, strawberries, eggplant, avocado, papaya, bananas, kiwi, pineapple, and plums should be avoided, as they can stimulate histamine release in the body.

Key Takeaways

• Histamine intolerance (HIT) is a clinical condition of increasing interest. It results from the consumption of histamine-rich foods, primarily due to a deficiency of the DAO enzyme in the gut and insufficient histamine breakdown.
• Diagnosing HIT remains challenging due to the lack of standardized diagnostic tests.
• Although new scientific insights have clarified much about HIT, further research is needed to optimize individualized treatment strategies.