How is Histamine Intolerance Affected By Food, Medication & Genetics?

Although histamine is very important in our body, at high levels, it can cause symptoms such as runny nose, itchy eyes and more.

What is histamine?

Histamine is a natural molecule that is found nearly everywhere in our body. It has a variety of key roles in the immune system, stomach, blood vessels, and nerve cells. Histamine is made from amino acids in our body by an enzyme called histidine decarboxylase (1). Although histamine is very important in our body, at high levels, it can cause symptoms such as runny nose, itchy eyes and more. As a result, we have two major enzymes that break it down and keep its levels in check: diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) (2). The table below summarizes the roles of these 2 enzymes.

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Histamine Breakdown Enzymes (3)
Enzyme	DAO	HNMT
% Histamine broken down	50-80%	15-30%
Location	Primarily outside of cells: breaks down histamine from foods or outside sources	Primarily inside of cells: breaks down histamine made inside the cells

What does histamine do?

Histamine can produce a wide variety of effects by binding to any one of four histamine receptors (homes) scattered all over the body. When histamine binds, each receptor produces a unique set of effects (1).

Histamine Receptors (1, 4, 5)
Receptor	Receptor Location	Effects
H1R	Brain, blood vessels, smooth muscle, and heart.	Seasonal allergy symptoms: runny nose, sore throat, congestion, itchiness Causes increased alertness, trouble sleeping Food Intake Regulation Temperature Regulation Improved memory Motion Sickness
H2R	Mainly gut, but also smooth muscle and heart.	Stomach acid secretion Anaphylaxis reaction Blood pressure drop Increased heart rate Lungs closing up
H3R	Throughout nervous system	Reduce histamine release
H4R	Immune cells	Activation of immune cells

What is histamine intolerance (HIT)?

We have discussed ways we obtain histamine from inside our body, but there are many foods that contain histamine as well. The environment surrounding us contains a lot of bacteria that are able to make histamine and release it. Much of this histamine ends up in the foods we eat, especially fermented food or food that is left out (6). Some examples include fish, cheese, fermented meat, vegetable derivatives, and fermented beverages (7). As histamine enters our gut, DAO is responsible for breaking it down. It turns out, the more DAO present in our gut, the more we are “protected” from this environmental histamine (3).

Histamine can become toxic when we get too much of it in our body. This phenomenon is known as histamine intolerance. It results from an imbalance between intake and breakdown of histamine (8). This imbalance is caused by high amounts of histamine in our food or inefficient DAO enzymes (9). In either case, histamine builds up in our body and we start to experience side effects like upset stomach, dizziness, headaches, breathing issues, and skin rashes (3).

How do genes play into histamine intolerance?

Scientists have identified variations in the DAO gene, called single nucleotide polymorphisms (SNPs), that can affect DAO. They can either change how much DAO we make or how efficient our enzyme is at breaking down histamine (9). Thus, depending on which variation of the DAO enzyme we have, we each have different chances of experiencing HIT. The table below summarizes some key SNPs in the DAO gene.

DAO Variations (3, 10, 11, 12)
SNP RSIDs	Effect	Ethnicity Affected
rs2052129	Reduced amount of DAO enzyme made, leading to higher histamine levels	Caucasians
rs45558339 and rs35070995	Reduced amount of DAO enzyme made, leading to higher histamine levels	Asians and Africans
rs10156191, rs1049742, rs2268999, rs1049793	Decreased ability to break down histamine, leading to increased histamine levels	Caucasians

I suspect I have HIT, what should I do?

Histamine intolerance is difficult to diagnose because people experience it in different ways (3). If you suspect you have histamine intolerance, you first need to make sure you don’t have food allergies or gut problems. Once those are ruled out, start paying close attention to your diet, alcohol intake, and medications. It turns out, many foods and compounds (i.e. fermented foods) can affect histamine levels and DAO enzyme activity. Limiting alcohol intake can also be beneficial. Studies have found that alcohol can reduce DAO activity and lead to increased histamine levels (3, 13). On a similar note, certain medications (see table below) may also interfere with DAO activity (14). Thus it is a good idea to review your medications with your practitioner to make sure your medications aren’t contributing to the problem.

DAO enzymes are a great option to help you break down histamine. These are supplements that contain the enzymes your body may not be producing adequate levels. you try a low histamine diet for 1-2 months under the supervision of a nutritionist or trained practitioner (7). While you try a low histamine diet, it’s a good idea to create a detailed diary of all foods you eat. Be sure to take note of your side effects and track improvement/worsening of these symptoms. You can also give genetic tests a shot. Genetic tests are a great tool to help you find more definite answers sooner. Toolbox Genomics offers a histamine panel that can identify genetic variants in DAO that may cause histamine intolerance. We want to help you, please feel free to reach out to us for more information.

Sample Low-Histamine Diet (8,15,16,17)
Breakfast	Lunch	Dinner	Supplements
Steamed tofu Steamed egg Toast Cereal Flakes	Green Pumpkin salad Cucumber Salad Black beans Egg soup Stir-fried shitake	Grilled Beef Grilled Tofu White Rice Grilled Sole Bean sprouts soup Bulgogi	Diamine Oxidase Vitamin C Quercetin

High-Histamine Foods (8, 14)
Food Item	Examples
Fish (frozen or canned)	Mackerel, herring, sardine, tuna, anchovy
Cheese	Gouda, camembert, cheddar, emmental, swiss, parmesan
Meat	Fermented sausage, salami, fermented ham, pork, chicken
Vegetables	Sauerkraut, spinach, eggplant, tomato ketchup
Vinegar	Red wine vinegar
Alcohol	White wine, red wine, fermented beer, champagne
Fermented Foods	Fermented cabbage, radish, soy bean paste, red pepper paste, mayonnaise, yogurt

Medications associated with higher histamine (14)
Medication Class	Examples
Analgesics	Morphine, NSAIDs, Aspirin
Antihypertensives	Alprenolol, dihydralazine, verapamil, clonidine
Antibiotics	Cefuroxime, Isoniazid, Clavulanic Acid, Chloroquine,
Diuretics	Amiloride
Antidepressants	Amitriptyline
H2-Receptor Antagonists	Cimetidine
Muscle relaxants	Pancuronium, alcuronium

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