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Those of us who suffer from allergies—whether to pollen, animals, or certain foods—are likely familiar with the term “antihistamine.” Found on the labels of numerous over-the-counter medications, we may rely on them to combat our runny noses, headaches, itching, and hives. However, despite the prominence in our local pharmacy, many of us underestimate the role of histamines in our health.

Histamine Function

First, what do histamines do? For one, they mediate allergic responses and help regulate the activity of immune cells, such as monocytes, neutrophils, and macrophages. They also stimulate gastric acid secretion, are involved in the sleep/wake cycle, and act as neurotransmitters, among other functions.

In small amounts, histamines are essential components of a healthy, well-functioning body. Problems don’t arise until the body receives an excess of histamines from external sources and/or is unable to process the appropriate amount of endogenously-produced histamine.

Histamine Intolerance

While the body can generally process the amount of histamines it produces, some people may have lower levels of important histamine-degrading enzymes called diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT). DAO is genetically expressed primarily in the placenta, kidneys, small intestine, and ascending colon. There are as many as fifty different genetic polymorphisms for the DAO gene, which influences histamine receptor activity and the body’s ability to process histamine. DAO synthesis may be influenced by the use of certain medications, alcohol, nutrient deficiencies such as copper and vitamin C, and even by different phases of the menstrual cycle. HNMT is found in the bronchial tissues and reduced enzymatic activity may manifest as respiratory symptoms and asthma.

Perturbations to the gut microbiome may also play a role in histamine intolerance. A study of healthy controls and individuals with either food hypersensitivity, food allergy, or histamine intolerance found that participants with histamine intolerance had significantly reduced alpha-diversity in their gut microbiome. They also had increased Proteobacteria and Roseburia, as well as decreased Bifidobacteriaceae, Butyricimonas, and Hespellia. Finally, researchers found elevated zonulin levels in these individuals, which is a marker that is often used to assess intestinal hyperpermeability. Researchers concluded that this dysbiotic state can create inflammation, which then influences DAO stored in the mucosal cells of the gut.

While histamines are produced by the body, they can also be found in food. Certain foods have high levels of histamines or other amines that trigger the release of histamine and eating too many of these foods can cause symptoms of histamine intolerance in some people.

Histamine intolerance is marked by a variety of allergy-like symptoms, including flushing, headaches, runny nose, rashes, nausea, swelling, and dizziness. There can also be gastrointestinal symptoms, such as bloating, diarrhea, and constipation. Histamine intolerance is said to affect about 1-3% of the population. Unfortunately, histamine tolerance is often difficult to diagnose, as symptoms are often attributed to a food or environmental allergy instead of an inability to process histamine in the body.

Interventions

After ruling out other potential pathologies, the current strategies for addressing histamine intolerance include testing for DAO genetic polymorphisms, measuring DAO levels, implementing a low-histamine diet, and/or administering DAO enzyme supplementation. A low-histamine diet often also excludes foods that contain histamine-triggering amines, such as putrescine and tyramine. The diet is not a cure-all but may be helpful in some cases.

A study of children with mild asthma showed that a high-histamine diet led to significantly higher mean air flow obstruction, while respiratory symptoms decreased following a low-histamine diet. On average, study participants had twice as many symptom-free days during the low-histamine diet.

In a separate study of adults with chronic urticaria, a four-week trial of the histamine-free diet led to significantly reduced levels of plasma histamine. However, DAO levels did not change, and there was not a significant decrease in the number of antihistamine pills that participants used after the implementation of the diet.

The success of the low-histamine diet may depend on a patient’s baseline DAO levels. A retrospective outpatient study found that participants with low or intermediate DAO levels had better success with the low-histamine diet and/or with DAO supplementation compared to those who had high DAO levels.

The low-histamine diet can be restrictive and is meant to be temporary with a reintroduction phase. The consensus is that high-histamine foods are avoided for 10 days to several weeks, after which a reintroduction period occurs to better understand a person’s unique trigger foods. Keeping a food and symptom journal can be helpful in pinpointing problematic foods that should be kept out of a person’s individualized diet for longer.

If you suspect you have a histamine intolerance, check with your healthcare provider as a trial of a low-histamine diet may reduce your symptoms and decrease the burden of histamines in your body. Experts analyzed the levels of histamine and other amines in various foods and discovered the following foods have the potential for high levels of histamines:

1. Cheese
2. Canned, cured, and fermented meats and fish
3. Fermented or pickled vegetables, like sauerkraut
4. Fruits and vegetables including spinach, tomatoes, strawberries, and citrus
5. Alcohol, particularly wine and beer

The freshness, preparation, and storage of food can all influence the level of histamines found in the food. As you can see from the list above, foods that are fermented tend to be much higher in histamines than their fresh form (such as meat and fish).

Closing Thoughts

• To ensure you are minimizing your histamine load, try to eat as many fresh foods as possible. Visit your local farmers’ market for local fruits and vegetables.
• Purchase or make your own fresh juices and smoothies instead of drinking the bottled, sugar-heavy alternatives that line the shelves of the grocery store.
• If you eat meat, purchase from local suppliers and refrain from eating leftovers.
• If you eat dairy, replace aged cheeses with mozzarella, goat cheese, ricotta, and other fresh cheese options.

Minimizing your intake of histamine-heavy foods is a simple way to reduce your symptoms and lower the burden of histamines in your body.

If you have environmental and/or food allergies, suspect that you may have environmental and/or food allergies, have questions about which foods can best support your health, or have questions or concerns about histamine or allergies, talk to your doctor, nutritionist, dietician, or another member of your healthcare team for personal options based on your individual circumstances.