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Evidence based

Evidence Based

This article is based on scientific evidence, written by experts and fact checked by experts.

Our team of licensed nutritionists and dietitians strive to be objective, unbiased, honest and to present both sides of the argument.

This article contains scientific references. The numbers in the parentheses (1, 2, 3) are clickable links to peer-reviewed scientific papers.

Everything You Need To Know About Histamine Intolerance

Written by on November 21, 2020

Heidi Turner

Written by on November 21, 2020 — Reviewed by Heidi Turner

Causes of Histamine Intolerance and How to Overcome It

You probably know that histamine symptoms like hay fever, hives, and itching can be caused by seasonal or environmental allergies to things like pollen or animal dander. But you might not know that digestive and allergic symptoms can also be caused by histamine intolerance — a food intolerance triggered by histamine-rich food and drinks.

Histamine intolerance affects approximately 1% of Americans [1]. Women are more likely to develop histamine intolerance than men [2, 3], and a surprising 30-55% of people with digestive symptoms or conditions like IBS, IBD, and Crohn’s disease have it [4].

Let’s discuss what histamine intolerance is, what causes and triggers it, how it’s connected to gut health, and how to overcome it.

What Is Histamine, and What Does It Do?

Everything you need to know about Histamine Intolerance: Woman scratching her neck

Histamine is a naturally occurring organic chemical that is produced in your body. High amounts of histamine are also present in certain foods, such as red wine, fermented foods, and aged meats and cheeses.

When your body is exposed to an allergen, like pollen or dust, histamine is released from MAST cells, which are immune cells that travel the body looking for allergens. This release of histamine directs your body to mobilize a white blood cell immune response to neutralize the threat.

When the immune system releases histamine in your tissues, you may experience allergy symptoms, such as itchy eyes, skin rashes, inflammation, or in extreme cases, life-threatening anaphylaxis.

Histamine is also a brain neurotransmitter and it’s also part of the complex series of biochemical reactions that release stomach acid [5], so a certain amount of histamine helps your body function normally.

Histamine intolerance is primarily an issue with excess histamine in the digestive tract, which can develop from gut imbalances.

Histamine Intolerance Symptoms

The common symptoms of histamine intolerance are broad, affecting not just the digestive tract, but also the skin, brain, joints, and heart. You might be familiar with the itchy eyes, runny nose, nasal congestion, skin flushing, hives, or sneezing that come with seasonal allergies, [6] and these symptoms can also happen with histamine intolerance. High levels of histamine can also trigger digestive symptoms like bloating [7], and diarrhea [8], heart rate changes or palpitations [9], low blood pressure [10], and headaches [11].

Symptoms of Histamine Intolerance

Histamine Intolerance and Your Gut

​Histamine intolerance results from an excess of histamine in the digestive system where sensitivity to high histamine foods causes both digestive and non-digestive symptoms. This sensitivity often results from poor gut health.

Histamine in the non-digestive tissues is cleared by the enzyme HNMT, but histamine in the digestive system — from bacteria, food, drinks, or an immune response to food allergens — is broken down by the DAO (diamine oxidase) enzyme [12]. If your levels of DAO enzyme are low, a build-up of histamine levels in your digestive system can cause histamine symptoms.

There are several possible underlying causes for an increase of histamine in the digestive tract or a decrease of DAO enzyme levels.

Dysbiosis & SIBO

The digestive tract is full of histamine receptors, and the expression of these histamine receptors is often altered in people with gastrointestinal diseases [13].

One study suggested that inflammation and intestinal permeability (leaky gut) caused by bacterial imbalance were likely involved in histamine intolerance [14]. Another study showed that 30%-55% of people with digestive symptoms also have histamine intolerance [15]. Bacteria produce histamine, so an overgrowth of bacteria contributes to histamine load.

SIBO (small intestinal bacterial overgrowth) is a specific type of dysbiosis that damages the lining of the small intestine and may trigger the loss of tolerance to dietary histamine [16]. SIBO symptoms overlap significantly with histamine intolerance symptoms [17], indicating that at least some portion of histamine intolerance cases are related to SIBO.

Low Levels of DAO Enzyme

The DAO enzyme is responsible for breaking down histamine in the digestive tract. Low DAO activity can lead to excess histamine and histamine intolerance symptoms. Low DAO levels have been associated with two Inflammatory Bowel Disease conditions — Crohn’s disease and ulcerative colitis [18, 19] — and histamine intolerance is associated with leaky gut [20].

Genetics also play an important role in levels of DAO enzyme. Some people have variations in the genes that affect DAO enzyme function. If those gene variants are turned on, that person may be less efficient at breaking down dietary histamine due to a shortage of DAO enzyme [21].

Hormone Fluctuations

Some women notice that their histamine intolerance symptoms are worse during certain parts of their menstrual cycle. This may be one reason why histamine intolerance is more common for women than men [22, 23]. Several studies suggest that estrogen fluctuations may decrease the amount of DAO enzyme available to help break down histamine [24, 25, 26].

Over-Consuming Histamine Foods or DAO-Blockers

If you eat lots of high-histamine foods, or foods the block DAO, such as alcohol [27], or black or green tea, your levels of histamine may exceed your ability to break down histamine. When levels of histamine build-up, either due to eating high-histamine foods or reduced DAO action in the gut, histamine symptoms occur.

In your unique situation, there is likely not one particular cause, but a perfect storm of causes and triggers that tips the balance toward histamine intolerance.

One way this can happen is when people shift to a healthier diet but include high amounts of high histamine foods, like spinach, avocados, sauerkraut, and kombucha. These are all perfectly healthy foods. But if you already have a brewing histamine problem close to the tipping point, suddenly increasing them could lead to histamine symptoms.

How To Test for Histamine Intolerance

There’s no clear-cut test for histamine intolerance. Avoid getting pulled into the thinking that you need expensive testing to sort this problem out. That said, there are several options that provide at least partial answers.

The most accurate test would be a positive response to a low-histamine diet. If your symptoms resolve on a low-histamine diet and return with the reintroduction of high-histamine foods, this highly suggests your symptoms are caused by histamine intolerance.

Testing serum DAO levels may also help diagnose histamine intolerance. Research suggests serum DAO levels correlate with histamine intolerance symptoms [28, 29, 30]. In one study, DAO levels below 10 U/ml were shown to increase the risk of histamine intolerance, especially in people who also showed digestive symptoms and responded to a low histamine diet [31].

Testing serum DAO levels chart

Similar to a histamine elimination diet, doing a trial with a DAO supplement may give you good information. If your symptoms subside when using DAO, that’s a sign that histamine intolerance is the cause of your symptoms.

Allergy tests, like the skin prick tests offered by allergists, check for IgE-mediated allergies to things like dust, pollen, or certain foods. Positive results on skin prick tests do not indicate intolerance to histamine foods. People with histamine symptoms but negative results on a skin prick test may still find relief from a low-histamine diet.

Everything you need to know about Histamine Intolerance: different products on wooden table

Treating Histamine Intolerance: Diet, Probiotics, & Supplements

A low histamine diet, coupled with a DAO enzyme and gut health support is the best option available to help you reduce your histamine burden and resolve histamine intolerance symptoms.

Eating a basic, anti-inflammatory diet to avoid common food sensitivities and additives is one of the first steps to take to repair your gut health. The paleo diet is a good, basic option.

Low-Histamine Diet

If you continue to have histamine symptoms on a basic healing diet, adapt that diet to the low-histamine diet. A low-histamine diet has been shown to reduce or eliminate histamine intolerance symptoms [32], and to increase levels of DAO enzyme [33]. Eliminate high histamine foods for 2-3 weeks and assess your symptoms. If they haven’t changed, chances are histamine isn’t the cause.

If you do experience relief on the low-histamine diet, you can slowly reintroduce histamine foods to try and discover your unique tolerance threshold.

High-Histamine Foods

Everything You Need To Know About Histamine intolerance: Pouring red wine from a bottle into a glass

Histamine in food is produced by bacteria and yeast as they break the amino acid histidine down into histamine. This means that fermented foods, or foods made with yeast, like alcohol or vinegar, are higher in histamine than other foods. Histamine liberators, like citrus fruits or energy drinks, may also need to be avoided.

In addition to high-histamine foods, a key thing to avoid during a low-histamine diet is leftovers. Histamine levels in protein-rich leftovers, like meat dishes, or raw meat and fish, increase the longer they are stored in the refrigerator. Store leftovers in the freezer, and cook or freeze raw meat quickly to avoid high histamine levels.

For your reference, here is a partial list of histamine-rich foods to avoid on a low-histamine diet. For a more complete list, see our Histamine Diet mini eBook.

  • Alcoholic beverages of any kind (especially red wine)
  • Certain fruits and vegetables, including avocado, dried fruits, eggplant, spinach, and tomatoes, and ketchup
  • Fermented meat and dairy products, including aged cheeses, salami, sausages, and pepperoni
  • Fermented foods, including kombucha, water kefir, kimchi, sauerkraut, pickles, miso, natto, soy sauce, tamari, coconut aminos, liquid aminos, and vinegars
  • Fish and seafood, particularly tuna or mackerel, especially if left over, smoked, salted, or canned, or not gutted and frozen immediately after harvest [34]
  • Tea (black, green, white, or yerba mate tea)
  • Yeast products

Low-Histamine Foods

There are plenty of delicious foods to eat on a low-histamine diet. Build healthy, simple, and tasty menus centered around:

  • Fresh meat and lower histamine fish
  • Gluten-free grains like rice, quinoa, or millet
  • Fresh vegetables like lettuce, cucumbers, zucchini, kale, onions, green beans, peppers, or sweet potatoes
  • Fresh fruits like apples, blueberries, kiwis, or pears
  • Healthy fats like olive oil, butter, ghee, coconut oil, or coconut milk
  • Herbal teas

See How to Use a Low Histamine Diet for Histamine Intolerance for more detailed information.

Probiotics for Histamine Intolerance

The low-histamine diet, DAO enzymes, and antihistamine medications can help reduce histamine intolerance symptoms, but one study showed that once DAO supplementation was stopped, the symptoms returned [35]. Probiotics are one strategy for resolving the underlying dysbiosis that may be increasing inflammation, damaging the small intestinal lining, and reducing DAO levels.

There is some controversy about whether or not probiotics improve histamine intolerance. We don’t have direct research that shows probiotics improve histamine intolerance, but we do have evidence that probiotics benefit immune- and histamine-mediated conditions.

Research suggests that probiotics actually lower histamine levels in the digestive tract [36].

Research clearly shows that probiotics reduce gut inflammation and help resolve infections that increase histamine intolerance, such as SIBO [37, 38, 39], as well as bacterial and parasitic infections [40, 41, 42, 43]. Probiotics have also been shown to benefit histamine-mediated conditions, such as seasonal allergies [44, 45], non-allergic rhinitis [46], and eczema and asthma [47, 48, 49]. Though the specific mechanism has not been demonstrated in studies, these data suggest that probiotics can help mediate histamine symptoms.

Some suggest the need to take special, “low-histamine” probiotics. This isn’t necessary because probiotics appear to be net-antihistamine. Including a quality probiotic from each of the three main categories — Lactobacillus and Bifidobacteria blends, Saccharomyces boulardii, and soil-based probiotics — is an effective strategy to improve histamine intolerance. For more on how to use probiotics, see our Probiotics Starter Guide.

Other Supplements To Help Histamine Intolerance

Vitamin B6 is an important cofactor for the efficient function of the DAO enzyme. Several studies demonstrated that vitamin B6 supplementation helps reduce symptoms of histamine intolerance, suggesting that B6 deficiency may reduce levels of DAO enzyme [50, 51, 52].

Quercetin is a plant flavonoid that has demonstrated an antihistamine and anti-inflammatory effect and may help reduce histamine intolerance symptoms [53, 54, 55].

Vitamin C has been shown to reduce serum histamine levels [56], and is known to have antihistamine properties [57]. Supplemental vitamin C may help you manage your symptoms of histamine intolerance while you work on the underlying causes.

The Bottom Line

Digestive, allergic, and neurological symptoms may be caused by histamine intolerance, which is a loss of your body’s ability to properly break down dietary histamine. Testing your response to a low-histamine diet or a DAO supplement can help you determine if histamine intolerance is the cause of these symptoms. Probiotics can improve the gut dysbiosis and inflammation that is likely causing your histamine intolerance.

Dr. Michael Ruscio is a DC, Naturopathic Practitioner, researcher, and clinician. He serves as an Adjunct Professor at the University of Bridgeport and has published numerous papers in scientific journals as well as the book Healthy Gut, Healthy You. He also founded the Ruscio Institute of Functional Health, where he helps patients with a wide range of GI conditions and serves as the Head of Research.
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