Diamine Oxidase Supplements Review – Benefits for Histamine Intolerance

Diamine Oxidase supplements are used to prevent histamine imbalance in the digestive tract. It is commonly taken to reduce symptoms of food intolerance linked to histamine overload.

Diamine oxidase (DAO) is an enzyme that occurs naturally in the body. It is found predominantly in the gastrointestinal tract and in small amounts within the blood.

This enzyme is also known as histaminase and is primarily involved in breaking down histamine found in foods that we eat. Foods such as shellfish, beans, nuts, fermented foods and alcohol can contain high amounts of histamine.

Histamine is a natural chemical that is involved in the body’s immune response but can have negative consequences if it builds up in large amounts.

Excessive consumption of histamine food sources can result in side effects such as itching, bloating, hives, headaches, a puffy face, changes in blood pressure or coughing.

DAO supplements are used to prevent symptoms of histamine intolerance and support the breakdown of this chemical within the intestines. These supplements are said to support relief of gas, bloating, abdominal swelling and intestinal cramping.

Diamine Oxidase

Enzyme Supplement

Digestion

Inflamm-ation

Food Intolerance

How It Works:

• Increases DAO levels in the gut
• Breaks down excess histamine from foods
• Supports digestive comfort and well-being

Dosage:

10,000 - 20,000 HDU per day

Safety:

Generally well tolerated

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Diamine Oxidase for Histamine Levels

Histamine is an important part of the body’s natural immune response but can have negative consequences if it accumulates in high amounts.

Having adequate diamine oxidase in the body is important to ensure that excess histamine is quickly degraded and removed. DAO is found in highest concentrations in the human digestive system.

Under normal circumstances, our bodies can make enough DAO to break down histamine in the gut. This prevents excessive levels from being absorbed into the bloodstream.

However, there may be some cases where the body does not naturally make enough of this enzyme and symptoms of an allergy or a histamine intolerance can appear. These symptoms can be aggravated by eating foods known to contain high amounts of this enzyme.

Taking a DAO supplement can help to reduce histamine accumulations in the small intestine before they are able to enter the bloodstream. This may be beneficial for individuals who have been diagnosed with a food intolerance or a histamine intolerance.

What is Histamine?

Histamine is an inflammatory chemical that regulates gut function, the immune response and plays a role as a neurotransmitter in the brain.

Our bodies naturally make a small amount of histamine in response to injury, selling or allergy.

Endogenous histamine is naturally secreted by immune system cells called mast cells. It causes smooth muscles to relax and small blood vessels called capillaries to dilate. [1]

When a patient has a disorder caused by elevated endogenous histamine, a doctor might treat it with allergy management programs, mast cells stabilizers, or antihistamine drugs. [2]

The histamine that is contained in dietary foods and beverages is exogenous. Diamine oxidase supplements are primarily used to break down and eliminate exogenous histamine from the body.

Histamine circulates throughout the body “looking” for allergens. When an allergen is detected, this immune system chemical causes an allergic reaction like sneezing, itching, coughing, or skin flushing.

By stimulating inflammation, increased mucus production, and other allergic symptoms, histamine prompts further action from the immune system.

WebMD states, “As part of an immune response to foreign pathogens, histamine is produced by basophils and by mast cells found in nearby connective tissues.” [3]

Histamine is an organic nitrogenous compound that is released by the immune system to protect the body. the release of this chemical as an early immune response involves the following:

1. The brain sends a chemical message to mast cells to release histamine;
2. Histamine increases capillary permeability to allergen-affected areas;
3. Blood flow to the targeted area is increased, resulting in inflammation;
4. The inflammation triggers further immune system responses;

Histamine Intolerance

Histamine intolerance is the medical term for having too much histamine in your blood. It can develop from eating too many histamine-rich foods, allergic reactions to foods or the environment, SIBO (small intestinal bacterial overgrowth), leaky gut syndrome, or having too little of the diamine oxidase enzyme available.

When histamine is released, it causes an immediate inflammatory response, making blood vessels in the area dilate. Expansion of these blood vessels or vasodilation facilitates increased blood flow and allows white blood cells to enter the affected area.

Normally, the body has sufficient diamine oxidase available to prevent excess histamine from accumulating. If there is insufficient DAO to break down the histamine, an intolerance can result.

After being taken up from the gut, histamine is transported throughout the circulatory system and can build up in the intestines, skin, heart, blood vessels, lungs, and the brain. This makes histamine intolerance difficult for doctors to diagnose in many cases.

The most common symptom of an intolerance is a migraine or a non-migraine headache.

Dr. Amy Myers reports that some other typical histamine intolerance symptoms include: [4]

• Vestibular disorders like vertigo (sense of whirling);
• Dysmenorrhea (irregular menstrual cycle);
• Difficulty regulating body temperature;
• Hypertension (high blood pressure);
• Difficulty falling or staying asleep;
• Irregular or accelerated heart rate;
• Nasal congestion or sneezing;

Some other symptoms of intolerance include anxiety, nausea, stomach cramps, vomiting, flushing, swelling, redness, itching, hives, and fatigue.

Dr Janice Joneja states that a histamine intolerance may also develop due to: [1]

• Mast cell activation disorders;
• Chronic inflammation;
• Infection;
• Trauma;
• Allergy;

The current medical protocol for treating histamine intolerance is to exclude high-histamine foods. A low-histamine diet may or may not be used along with a diamine oxidase supplement to lower levels of this inflammatory chemical.

How Diamine Oxidase Works

According to Montana State University, “Humans have three functioning genes that code for copper-containing amine oxidases. The product of the AOC1 gene is a so-called diamine oxidase (hDAO), named for its substrate preference for diamines, particularly histamine.” [5]

Diamine oxidase works together with another enzyme to break down histamine before it can accumulate and cause adverse effects. That other enzyme is called HNMT (histamine N-methyltransferase).

DAO works primarily to keep histamine in check in the digestive system while HNMT works mainly to degrade histamine in the CNS. After histamine is broken down, the byproducts are transported to the kidneys and then excreted in urine.

If diamine oxidase or histamine N-methyltransferase are not available in adequate amounts, then histamine intolerance symptoms may develop.

Diamine Oxidase in the Digestive Tract

Diamine oxidase is found in digestive system components called the jejunum and ileum. Along with the duodenum, the jejunum and ileum make up the small intestine.

DAO encounters foods we consume as they make their ways through the digestive system. When this enzyme encounters histamine molecules contained in the foods we eat, it breaks them down before they enter the bloodstream.

In healthy people, about 99% of exogenous histamine sources (foods and beverages) get broken down in the lumen of the digestive tract. That means that normally only about 1% of exogenous histamine makes it into the circulatory system.

However, if there is insufficient diamine oxidase available or if histamine metabolism is impaired in some other way, levels of this chemical may rise sharply.

How Diamine Oxidase Supplements Work

Unlike other dietary supplements, diamine oxidase supplements are not designed to be absorbed by the body. Instead, they are designed to increase DAO levels in the digestive tract to help break down exogenous histamine.

Dr. Joneja says that it is very important to note that taking a diamine oxidase supplement will not raise your body’s levels of this enzyme. DAO has a short half-life and is recommended to be taken as an oral supplement very shortly before eating meals.

Restricting the foods you consume in your diet is the best way to keep your histamine levels in check. Dr. Joneja says that most people should have no real need to take a DAO supplement with the right food choices.

However, she also says that following a histamine-restricted diet plan and taking a quality DAO supplement can help to reduce exogenous histamine levels to almost zero in most people.

It is also important to note that reducing intake of high-histamine foods or taking a diamine oxidase supplement will not reduce the amount of histamine your body produces. These interventions do not affect endogenous production of this inflammatory molecule.

While some of the exogenous histamine we consume in our diets may get absorbed by the body, the majority of it does not get absorbed into the blood.

Diamine Oxidase Research

According to PubMed, DAO has been studied in research trials since 1945. [6]

Researchers have investigated the effects of DAO supplementation for migraine headaches, early-onset pre-eclampsia, and CSU (chronic spontaneous urticaria).

There is limited research available on the use of this product as a dietary supplement. While much is known about its endogenous roles in the body, only a smaller number of studies have looked at the effects of taking it in pill form.

Migraine Headache

A migraine or a non-migraine headache are the most common symptoms of histamine intolerance. Migraines can cause intense pain that lasts for hours, nausea, vomiting, and heightened sensitivity to light.

A one-month randomized, double-blind, placebo-controlled trial with 100 patients assessed the efficacy of diamine oxidase as a preventive migraine treatment. [7]

All patients in the study had a diamine oxidase deficiency, meaning their serum levels of the enzyme were less than 80 HDU/ml. They were divided into two randomized groups. One group received a DAO supplement and the other a placebo agent.

After one month, the group receiving DAO experienced significant reductions in the average duration of their migraine attacks (1.4 hours). The placebo group also experienced a reduction in migraine duration; this was not a statistically significant result.

There was also a decrease in the use of anti-migraine drugs called triptans in the DAO supplement group. Both groups showed similar reductions in pain perception scores and number of migraine attacks.

Researchers from the study also reported that use of the supplement caused no adverse effects.

More research is needed to determine whether DAO supplements can help to prevent or reduce the severity of migraines generally or if this effect will only be observed in subjects who are deficient in DAO.

There is insufficient research available to rate its efficacy as an anti-migraine supplement and the FDA has not approved it as a drug for the prevention or treatment of headaches.

Early-Onset Pre-Eclampsia (eoPE)

Pre-Eclampsia is a severe disorder that develops during pregnancy and is commonly marked by hypertension, fluid retention, and excessive amounts of proteins in the urine (proteinuria). It is the leading cause of infant mortality and morbidity in the United States.

Early-Onset Pre-eclampsia is pre-eclampsia that develops before the 34th week of gestation. In pregnant women, DAO is also found in high amounts in the kidneys, thymus, and especially the placenta.

Placental cells called extravillous trophoblasts release large amounts of DAO into the bloodstream during pregnancy because histamine accumulations can be harmful to the developing fetus.

In 2018, a study was conducted by the Medical University of Vienna in Austria to determine if DAO is decreased during pre-eclampsia.

The researchers from this study reported, “DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid-gestation.” [8]

Low levels of diamine oxidase could be a predictive marker for eoPE or help to improve its symptoms, but more research is needed in this area to make firm determinations.

There is no research available to determine whether DAO is effective for pre-eclampsia or for lowering blood pressure in pregnant women. More study is needed to determine whether this supplement is safe for pregnant mothers or their developing babies as well.

If you think you may have Early-Onset Pre-eclampsia or high blood pressure and are pregnant, it is important to consult with a doctor to determine the right treatment protocol.

CSU

Urticaria is a skin condition marked primarily by recurring eruptions of red, severely-itchy hives. Chronic spontaneous urticaria is diagnosed when the symptoms are present for six consecutive weeks or more.

About 45% of CSU patients have an autoimmune disorder. Therapy for CSU is difficult for doctors to determine in many cases. The common approach to treating CSU is using non-sedating antihistamine drugs. Some patients take these drugs up to 6 times a day. [9]

Because diamine oxidase inactivates and catabolizes (breaks down) histamine, researchers have tested it for possible effects in CSU patients.

A 2018 double-blind, placebo-controlled crossover study investigated 22 patients with CSU that was incompletely-controlled by antihistamine therapy. [10]

The researchers hypothesized that oral supplementation for 30 days with a DAO supplement could reduce CSU severity.

After one month they concluded, “DAO may be involved in the pathogenic cascade of CSU and that DAO supplementation could be effective for symptom relief in patients with low DAO levels in serum.”

More study is needed to understand if and how diamine oxidase supplementation can help to improve CSU symptomatology. It has not been approved by the FDA as a drug for the prevention or treatment of this condition.

Diamine Oxidase Supplements

There are a number of over-the-counter diamine oxidase supplements available. Some popular brand names for sale online include:

• Nutricology’s Dao Histamine Digester Supplement
• Allergy Research Group’s DAO Histaminase
• Seeking Health’s Histame
• Swanson’s HistamAid 88
• Sciotec’s DAOSin

DAO supplements contain varying amounts of the diamine oxidase enzyme. Some products include other constituents like quercetin, vitamin C, calcium, emulsifiers, stabilizers, rutin, or preservatives.

Dr. Janice Joneja states, “Taking DAO supplements will not cure histamine intolerance: the supplement will reduce the amount of histamine entering the body and thus decrease the total level of histamine within the body (endogenous plus exogenous histamine) by removing the exogenous source.” [1]

In some cases, this reduction in total body histamine might be sufficient to provide some degree of relief to symptoms.

The only long-term way to reverse histamine intolerance is to determine the cause of the elevated histamine levels and then remedy it. In most cases, this will involve identification of foods to eliminate from the diet.

Dr. Joneja says that if the underlying cause of histamine intolerance turns out to be a diamine oxidase deficiency, then taking a DAO supplement will almost certainly help.

Reducing intake of high-histamine foods will also be important in these cases.

Is it possible to raise your diamine oxidase levels besides those in the small intestine?

Dr. Joneja says no. Like most other enzymes, how much DAO your body makes is determined by your genetics. Currently, there is no known way to increase how much diamine oxidase your body produces endogenously or to raise levels of this enzyme within your bloodstream.

Avoid Histamine Food Sources

Although we cannot stimulate our bodies to make more DAO, we can make changes to reduce our requirements for this enzyme. Eating fewer foods that contain histamine can decrease the amount we need to maintain normal histamine balance.

The following is a list of high-histamine foods to avoid, especially if you are experiencing food intolerance symptoms:

• Pepperoni, bacon, salami, hot dogs, lunch meats, and other cured meat products;
• Buttermilk, sour cream, sour dough bread, and other soured foods;
• Olives, pickles, mayonnaise, and other foods that contain vinegar;
• Sauerkraut, yogurt, kombucha, kefir, and other fermented foods;
• Champagne, wine, beer, and other alcoholic beverages;
• Smoked tuna, anchovies, mackerel, and sardines;
• Tomato, avocado, eggplant, and spinach;
• Apricots, raisins, figs, and prunes;
• Peanuts, walnuts, and cashews;
• Aged cheese;
• Citrus fruit;

Some of the foods listed above may have health benefits associated with them and may be okay for people to consume if they do not have symptoms of intolerance. However, they are known to contain histamine or stimulate its release in the body and are better avoided in those with intolerance symptoms.

Below is a list of some low-histamine foods that you can use in place of those on the list above:

• Fresh vegetables except for tomato, spinach, eggplant, and avocado;
• Fresh fruits like grape, pear, mango, apple, watermelon, and kiwi;
• Gluten-free grains like quinoa, corn, and rice;
• Freshly-cooked beef, pork, and chicken;
• Coconut oil and olive oil;
• Herbs and herbal teas;
• Freshly-caught fish;
• Cooked eggs;

Another way to reduce levels of histamine in the gastrointestinal tract is to consume fewer foods that inhibit the activity of the diamine oxidase enzyme. The following foods are known to block the ability of DAO to break down histamine molecules.

• Energy drinks like Red Bull and Monster;
• Black, green, and mate teas;
• Alcoholic beverages;

DAO Supplements Dosages and Side Effects

There are no known food sources of DAO. Dietary supplements containing this ingredient are made from porcine (pig) kidney protein concentrate.

These supplements are not vegetarian-friendly and may need to be avoided by individuals who follow religions that abstain from pork consumption.

There are no standardized dosage guidelines available for DAO. Dietary supplements containing this ingredient typically provide either 10,000 or 20,000 Histamine Degrading Units (HDU) per serving.

One supplement, Umbrellux DAO, provides 10,000 HDU which is equivalent to 294 mg Diamine Oxidase Enzyme. The supplement is provided in the form of a 7% porcine kidney protein extract.

The manufacturer recommends taking this supplement 15-20 minutes before a meal or as directed by your healthcare professional. They suggest using a 10,000 HDU daily dosage to maintain long-term balance of DAO and histamine in your body.

There is limited research available to determine the safety of this supplement. While it is generally well-tolerated, it may cause negative effects in some users.

Diamine oxidase supplements are not absorbed into the body and have not been associated with any negative effects in currently available research trials. However, other ingredients in some DAO products might cause adverse effects.

Some examples of other ingredients that may be stacked with this compound include Vitamin C (ascorbic acid), Lactase, Vitamin B6 (Pyridoxine Hydrochloride), Serratiopeptidase, Prolyl Endopeptidase, Quercetin and Methylsulfonylmethane.

Dr. Janice Joneja recommends finding a DAO supplement that has fewer additives relative to others.

Diamine Oxidase Interactions

It is possible that a diamine oxidase supplement could interact with various types of medications.

Discuss the safety of taking this supplement with the following types of drugs with your doctor before beginning:

• NSAIDs (nonsteroidal anti-inflammatory drugs) like ibuprofen;
• Antidepressants like Prozac, Zoloft, Effexor, and Cymbalta;
• Antiarrhythmics like Norvasc, propranolol, and Cardizem;
• Immunomodulators like Enbrel, Humira, and Plaquenil;
• Antihistamines like Benadryl, Allegra, and Zyrtec;
• H2 Blockers like Zantac, Tagamet, and Pepcid;

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