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Diamine oxidase is an enzyme that helps break down excess histamine in your body. More research is needed to establish effectiveness and dosage, though current studies report no adverse effects.

Diamine oxidase (DAO) is an enzyme and nutritional supplement frequently used to treat symptoms of histamine intolerance.

Supplementing with DAO may have some benefits, but research is limited.

This article reviews DAO supplements, including their benefits, dosage, and safety.

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What Is DAO?

Diamine oxidase (DAO) is a digestive enzyme produced in your kidneys, thymus, and the intestinal lining of your digestive tract.

Its primary function is to break down excess histamine in your body (1).

Histamine is a naturally occurring compound that helps regulate specific functions of your digestive, nervous, and immune systems.

If you’ve ever experienced an allergic reaction, you’re probably familiar with common symptoms associated with elevated histamine levels, such as nasal congestion, itchy skin, headaches, and sneezing.

You may also ingest histamine through your diet. It naturally occurs in certain foods — especially those that are aged, cured, or fermented like cheese, wine, pickles, and smoked meats (1).

DAO keeps histamine levels in a healthy range to avoid uncomfortable histamine-induced symptoms.

Diamine oxidase (DAO) is an enzyme that helps break down excess histamine in your body, thus easing uncomfortable symptoms, such as nasal congestion, itchy skin, headaches, and sneezing.

DAO Deficiency and Histamine Intolerance

Histamine intolerance is a medical condition that occurs as a result of elevated histamine levels.

One of the suspected causes of histamine intolerance is DAO deficiency (2).

When your DAO levels are too low, it’s difficult for your body to efficiently metabolize and excrete excess histamine. As a result, histamine levels rise, leading to various physical symptoms.

Symptoms of histamine intolerance often resemble those of an allergic reaction. They can range from mild to severe and include (2):

• nasal congestion
• headaches
• itchy skin, rashes, and hives
• sneezing
• asthma and difficulty breathing
• irregular heartbeat (arrhythmia)
• diarrhea, stomach aches, and digestive distress
• nausea and vomiting
• low blood pressure (hypotension)

Various factors may contribute to diminished DAO activity or overproduction of histamine, including genetic mutations, alcohol use, certain medications, intestinal bacterial overgrowth, and eating large amounts of histamine-containing foods (2).

Histamine intolerance can be difficult to diagnose, as its symptoms are ambiguous and resemble those of other medical conditions (1, 2).

Therefore, if you think you’re experiencing histamine intolerance, consult a qualified healthcare provider to thoroughly investigate the causes of your symptoms before attempting to diagnose or treat yourself.

Histamine intolerance can develop as a result of DAO deficiency and lead to various uncomfortable symptoms that often mimic an allergic reaction.

Potential Benefits of DAO Supplements

DAO deficiency and histamine intolerance can be treated in different ways, including by supplementing with DAO.

Early research suggests that DAO supplements may alleviate certain symptoms of histamine intolerance, including headaches, skin rashes, and digestive distress.

Digestive Symptoms

In a 2-week study in 14 people with histamine intolerance and symptoms that included abdominal pain, bloating, or diarrhea, 93% of participants reported a resolution of at least one digestive symptom after taking 4.2 mg of DAO twice daily (3).

Migraine Attacks and Headaches

A 1-month study in 100 people with previously diagnosed DAO deficiency observed that participants who supplemented daily with DAO experienced a 23% reduction in the duration of migraine attacks, compared to the placebo group (4).

Skin Rash

A 30-day study in 20 people with chronic spontaneous urticaria (skin rash) and DAO deficiency noted that participants who received the supplement twice daily experienced significant relief in symptoms and required less antihistamine medication (5).

Although these studies suggest that supplementing with DAO may eliminate or improve symptoms of deficiency, there’s no guarantee that it’s effective for everyone.

Ultimately, more research is needed to draw definitive conclusions.

Early research suggests that DAO supplements may improve certain symptoms associated with DAO deficiency and histamine intolerance, including migraine attacks, skin rashes, and digestive issues. Still, more studies are needed.

Not a Cure

Scientific understanding of histamine intolerance and DAO deficiency is still in a relatively early stage.

Various factors can affect the production of both DAO and histamine in different parts of your body. Addressing the root cause of these issues is not as simple as replacing DAO with a supplement (1, 2).

DAO supplements work to break down histamine that enters your body externally, such as from food or beverages.

Taking this supplement will not affect the levels of histamine produced internally, as this type of histamine is broken down by a different enzyme called N-methyltransferase (2).

Though DAO supplements may ease symptoms by reducing external histamine exposure, research indicating that they can cure histamine intolerance or DAO deficiency is lacking.

If you’ve been diagnosed with histamine intolerance or suspect you may have it, consult a qualified healthcare practitioner to develop a personalized plan according to your unique needs and health goals.

To date, no scientific research indicates that DAO supplements can cure DAO deficiency or histamine intolerance.

Nutritional Therapies for DAO Deficiency

Histamine intolerance and DAO deficiency are complex conditions with multiple factors that influence the severity of associated symptoms.

Currently, one of the main ways to treat these conditions is through diet.

Because certain foods are known to contain varying levels of histamine, specific dietary modifications may improve symptoms of histamine intolerance by reducing exposure to histamine food sources and the intake of foods that may block DAO function.

Enhancing DAO Function

Nutritional therapy designed to improve histamine tolerance and DAO function seeks to ensure adequate intake of nutrients that are involved in breaking down histamine, including copper and vitamins B6 and C (2).

Some research also suggests that an adequate intake of healthy fats and other nutrients — like phosphorus, zinc, magnesium, iron, and vitamin B12 — may play a role in enhancing DAO activity (6).

Eating mainly low-histamine foods may reduce exposure to histamine and lower its accumulation in your body. Low-histamine foods include:

• fresh meat and fish
• eggs
• most fresh vegetables — except spinach, tomatoes, avocado, and eggplant
• most fresh fruit — except citrus and some berries
• oils like coconut and olive oil
• grains, including rice, quinoa, corn, teff, and millet

Foods to Avoid

Reducing or eliminating foods high in histamine or those that trigger histamine production is another strategy for managing symptoms of histamine intolerance and low DAO production.

Some foods that contain high levels of histamine and may trigger histamine release include (2):

• alcoholic beverages, such as beer, wine, and liquor
• fermented foods, such as sauerkraut, pickles, yogurt, and kimchi
• shellfish
• dairy
• aged foods, such as cheeses and smoked and cured meats
• wheat
• nuts, such as peanuts and cashews
• certain fruits, including citrus fruits, bananas, papaya, and strawberries
• certain vegetables, including tomatoes, spinach, eggplant, and avocado
• certain food additives, colorings, and preservatives

Because food choices permitted on a low-histamine diet can be limited, you may be at risk of nutritional deficiencies and reduced quality of life (1, 2).

Therefore, a strict low-histamine diet should only be used temporarily to assess sensitivities to specific foods.

Some people with histamine intolerance can tolerate small amounts of high-histamine foods.

An elimination diet can help identify which foods trigger the most symptoms and should be avoided indefinitely and those you can safely continue to eat in small quantities.

Ideally, this process is completed under the guidance of a qualified healthcare provider to prevent complications.

Nutritional therapies to support DAO function and reduce histamine exposure include elimination diet protocols and adequate intake of specific nutrients known to enhance DAO function.

Safety Precautions and Dosage Recommendations

No adverse health effects have been reported in studies on DAO supplements.

However, research is still scarce, so a clear consensus regarding dosing for this particular supplement has yet to be established.

Most available studies used doses of 4.2 mg of DAO at a time up to 2–3 times daily just before meals (3, 4, 5).

Thus, similar dosages are likely safe for most people — but that doesn’t mean it’s 100% risk-free.

Some countries like the United States don’t regulate nutritional supplements. Therefore, it’s a good idea to ensure your chosen product has been tested for purity and quality by a third party, such as the U.S. Pharmacopeia Convention (USP).

Always consult your healthcare provider before introducing a new supplement into your diet.

Doses of 4.2 mg of DAO 2–3 times daily before meals have been researched with no reports of adverse reactions. However, a clear consensus for DAO dosing has not been established.

The Bottom Line

DAO supplements cannot cure histamine intolerance or DAO deficiency but may ease symptoms by breaking down external sources of histamine like those from food and beverages.

More research is needed to establish their effectiveness, safety, and dosage, though current studies report no adverse effects.

Be sure to consult talk to a qualified healthcare provider before adding any new supplement or medication to your wellness routine.